Buy diflucan online

Conversely, we fear that if text-to-988 is not buy diflucan online available, Americans in crisis may be confused by efforts to promote 988 as the Lifeline's telephone number and mistakenly believe that they can reach the Lifeline by texting 988, putting lives at risk. We seek comment on this preliminary analysis. 4. As the Commission noted in the 988 Report and Order, young people are disproportionately buy diflucan online at risk for mental health crises.

They are also more likely to be most comfortable communicating via text. According to the National Alliance on Mental Illness, “[n]early 95% of teens have access to smart phones and say that texting is the primary way that they connect.” For this reason, the International Council for Helplines describes the increasing use of “chat and text services. . .

For those who are in a mental health crisis,” pointing to a recent survey indicating that “75% of millennials prefer texting over talking.” According to Mental Health America, “[m]ultiple sources of data demonstrate youth prefer communicating by text rather than calls,” including a study finding that young people “were more likely to forgo psychological support than talk in person or over the phone.” As a result, Mental Health America argues, the “data strongly support[ ] the implementation of texting for providing resources to individuals experiencing suicidal ideation.” We seek comment on these views and whether adopting a text-to-988 mandate would provide particular benefits for young Americans. Are young people more inclined to seek help by text than by telephone, and if Start Printed Page 31405so, would making it easier to text the Lifeline save lives?. 5. In our preliminary view, facilitating Lifeline accessibility by text message to 988 is also likely to provide significant benefits to many other at-risk communities as well, further justifying our proposed mandate.

As the Commission explained in the 988 Report and Order, a broad range of American communities are disproportionately impacted by suicide, including Veterans, LGBTQ individuals, racial and ethnic minorities, and rural Americans. Many members of these affected communities may prefer to seek help through text messages. For example, Mental Health America reports that data they collect demonstrate that individuals “who identify as Black or African American are more likely to report that they would like to receive a phone number they can immediately call or text for help” than members of any other race or ethnicity. Do commenters agree with Mental Health America that making crisis counseling services available via text message “may mean the difference between accessing psychological support and forgoing it, especially among youth of color?.

€ Is Mental Health America correct that easy access to crisis services via text may be the difference between seeking and forgoing help for such groups, and if so would use of a 3-digit dialing code for the Lifeline make a significant difference in widespread understanding that such crisis services are available?. 6. Indeed, demographic evidence regarding usage of currently available non-governmental text and chat options indicate that texting is a particularly valuable means to obtain help, not only for young people, but also for many members of low income, minority, and other communities that are disproportionately impacted by mental health crises. Several commenters in this proceeding have pointed to the successes that private non-profit services like the Trevor Project have had in providing crisis counseling to at-risk communities through text messages, offering that their experiences demonstrate the need to provide text access to 988.

In addition, as one commenter to the 988 notice of proposed rulemaking argued, adding text access to 988 could allow the Lifeline and Veterans Crisis Line “to more efficiently route those in need to specialized services,” further leveraging the expertise of organizations like the Trevor Project, which provides mental health support and counseling specific to the needs of LGBTQ youth. We preliminarily agree with this assessment and believe that establishing text access to 988 will complement the important work already being done by these and other private sector organizations, and further facilitate access to the lifesaving resources offered by the Lifeline and Veterans Crisis Line. We seek comment on these views and on the benefits of text-to-988 for at-risk groups. Are there additional at-risk communities that may benefit from texting as an option to access the Lifeline?.

7. Likewise, we preliminarily believe that our tentative conclusion is further justified because implementing text-to-988 capability will provide substantial benefits for individuals with disabilities who uniquely rely on text-based media to communicate. As the Communications Equality Advocates and others note, texting is an indispensable means of communication for individuals with disabilities. These individuals have increasingly adopted widely available text messaging platforms such as those offered by CMRS providers and interconnected text messaging services in lieu of specialized legacy devices.

Further, texting may be the only means for such individuals to contact 988 directly and efficiently. Access to telecommunications for individuals with disabilities is a longstanding Commission priority and statutory obligation, and facilitating access to 988 for deaf and hard of hearing individuals is a particularly important policy objective in light of studies finding a significantly increased risk of suicide among deaf and hard of hearing people when compared to those without hearing loss. We seek comment on these views and whether our proposal would ease access to lifesaving counseling for individuals with disabilities. Do commenters agree with the Communications Equality Advocates that the ability for individuals normally using text for the bulk of their communications, including people with disabilities, to access trained mental health professionals using text-to-988 will be of “paramount importance”?.

Currently, how do people with disabilities reach the Lifeline?. How would texting grant access or enhance their ability to communicate with the Lifeline?. We seek comment on whether texting would be more accessible than the options currently available, including the Lifeline's online chat portal. 8.

We tentatively conclude that the potential lifesaving benefits of expanding access to suicide prevention and mental health crisis services for all Americans—and particularly the at-risk groups discussed above—justifies a text-to-988 mandate, and we seek comment on this view. The Commission's designation of 988 as the 3-digit telephone number for the Lifeline reflected its expectation that a simple, easy-to-remember, 3-digit dialing code for suicide prevention and mental health crisis counseling would “help increase the effectiveness of suicide prevention efforts, ease access to crisis services, reduce the stigma surrounding suicide and mental health conditions, and ultimately save lives.” We preliminarily believe that establishing text access to 988 will further advance these important objectives by providing mental health crisis counseling through a nationally available, easy-to-remember number that Americans will also associate with the telephonic Lifeline. Do commenters agree with the Communications Equality Advocates that individuals in crisis “are likely to first use their preferred, familiar mode of communication to reach out for help?. € We seek comment on this analysis, and on our proposed conclusion that a text-to-988 mandate is likely to offer substantial, lifesaving benefits to all Americans affected by mental health crises, particularly for many members of at-risk communities.

Is a text-to-988 mandate likely to have a significant impact on the likelihood of Americans considering suicide or in a mental health crisis to contact the Lifeline?. Would mandating text-to-988 amplify the benefits of promoting 988 as the telephone number for the Lifeline?. What are the costs or drawbacks to our proposal?. 9.

In our preliminary view, the Lifeline's soft launch of a texting capability is a significant changed circumstance that supports mandating text-to-988. When the Commission adopted the 988 Report and Order, the Lifeline was not capable of receiving or responding to text messages. The Commission, stating that it has no authority to require the Lifeline to develop texting capability, deferred “consideration of mandating text-to-988 at this time so that we could revisit the issue promptly should the Lifeline develop integrated texting.” Now, the Lifeline is capable of responding to texts sent to the Lifeline. The Lifeline's ability to respond to texts significantly strengthens the case for imposing a text-to-988 mandate on providers.

We seek comment on this evaluation. 10. We preliminarily expect many of the same lifesaving benefits from texting to 911 to accrue from texting to 988. In its comments in support of adopting a text-to-988 requirement, CTIA notes that text-to-911 functionality “has saved countless lives and enabled public safety to keep pace with the modern Start Printed Page 31406communications preferences of consumers.” Given the parallels between the Commission's efforts to promote text access to 911 and our proposals in this FNPRM, are there lessons learned in the context of establishing text-to-911 capability that would be instructive here?.

CTIA states that there are “significant technical and policy differences between the national 9-8-8 service that will be administered by the Lifeline and the local 9-1-1 services that are administered by thousands of PSAPs.” For example, unlike calls to 911, which carriers route to one of thousands of local PSAPs across the country based on the caller's geographic location, all calls to 988 are routed to a central toll free number, and are then directed within the Lifeline network to a local crisis center. How might these or other differences between the 911 and 988 networks affect our proposal to adopt a text-to-988 requirement?. B. Proposed Implementation of Text-to-988 1.

Scope of Text-to-988 Requirement 11. Text Formats. We seek comment on an appropriate scope of text messages that covered text providers must transmit to 988. At present, the Lifeline is capable of receiving text messages sent to the existing 10-digit number in “short message service” (SMS) format.

The Commission's Truth in Caller ID rules define the term `short message service' or SMS as “a wireless messaging service that enables users to send and receive short text messages, typically 160 characters or fewer, to or from mobile phones and can support a host of applications.” We recognize, however, that our federal partners may incorporate additional capabilities for receiving and responding to text messages in the future. We seek to adopt a forward-looking, flexible scope that can expand with the capabilities of the Lifeline without unnecessarily burdening covered text providers by requiring support of formats that the Lifeline is not yet capable of receiving. To that end, we propose (1) establishing a definition that sets the outer bound of text messages sent to 988 that covered text providers may be required to support. And (2) directing the Wireline Competition Bureau (Bureau) to identify text formats within the scope of that definition that the Lifeline can receive and thus covered text providers must support by routing to the 10-digit Lifeline number.

We seek comment on this proposal in detail below. 12. First, we propose to define the outer bound of text messages that covered text providers may be required to transmit to 988 based on the definition of “text message” that Congress enacted in 2018 in the context of Truth in Caller ID requirements. The term “text message” (i) means a message consisting of text, images, sounds, or other information that is transmitted to or from a device that is identified as the receiving or transmitting device by means of a 10-digit telephone number or N11 service code.

(ii) includes a [SMS] message and a multimedia message service (commonly referred to as `MMS') message. And (iii) does not include—(I) a real-time, two-way voice or video communication. Or (II) a message sent over an IP-enabled messaging service to another user of the same messaging service, except a message described in clause (ii). The Commission's Truth in Caller ID rules define MMS as “a wireless messaging service that is an extension of the SMS protocol and can deliver a variety of media, and enables users to send pictures, videos, and attachments over wireless messaging channels.” We seek comment on this proposed scope.

We believe this definition has several advantages—it incorporates multimedia messages. It is not limited to specific technologies. And it reflects a recent determination by Congress, albeit in a different policy context. For the purpose of our text-to-988 rules, we propose adding “or 988” to the phrase “10-digit telephone number or N11 service code” so that text messages from the Lifeline identified by the 3-digit code 988 are included within the scope of covered text providers' obligations, and we seek comment on this proposal.

We seek comment on whether using the Truth in Caller ID definition appropriately sets an outer bound that would achieve our goals of adopting a forward-looking, flexible scope that can expand with the capabilities of the Lifeline without unnecessarily burdening covered text providers. 13. We note that the Truth in Caller ID statutory definition of “text message” excludes “real-time, two-way voice or video communications,” as well as “messages sent over. .

. IP-enabled messaging services to another user of the same messaging service.” If we adopt the Truth in Caller ID definition, we seek comment on how we should interpret each of these two exclusions here. Is there any reason to adopt a different interpretation of the relevant exclusions in this context compared to the Truth in Caller ID context?. € Would adopting the Truth in Caller ID definition of “text message,” with the exclusions specified above, prevent us from possibly adding “next-generation” text messages to our requirements in the future?.

14. We also seek comment on alternative outer scopes of required texts. For instance, should we adopt the scope of our text-to-911 rules, which require providers to route “a message, consisting of text characters, sent to the short code `911' and intended to be delivered to a PSAP by a covered text provider, regardless of the text messaging platform used”?. In the Text-to-911 Second Report and Order, the Commission identified SMS and MMS messages as examples of text messages included within the scope of this proposed rule.

We seek comment on whether the Truth in Caller ID definition, the text-to-911 definition, or another definition offers the best model here. We note that the Truth in Caller ID model is newer than the text-to-911 definition, originates with Congress rather than the Commission, and unlike the text-to-911 definition explicitly includes images, sounds, and other non-textual information. On the other hand, the Commission developed the text-to-911 definition in a more analogous policy context than the Truth in Caller ID definition. Do these or other considerations suggest that one or the other model is superior?.

15. Should we ensure that any definition we adopt encompasses next-generation forms of text messaging, such as MMS, Rich Communications Services (RCS), and/or real-time text (RTT), and what modifications—if any—would we need to make to the definitions we are considering to ensure that such forms are within our proposed scope?. RCS has been described as a “successor protocol” to SMS, or as “next-generation” SMS. What are the fundamental differences between SMS, MMS, and RCS?.

How would the costs to implement SMS, MMS, and RCS differ?. The Commission has previously concluded that “messages sent over other IP-enabled messaging services that are not SMS or MMS—such as [RCS]—are excluded from” the Truth in Caller ID definition of text message “to the extent such messages are sent to other users of the same messaging service.” Would it be necessary to modify the Truth in Caller ID definition for our purposes to ensure that it includes RCS or other next-generation services?. 16. We also seek comment on whether we should ensure that our proposed outer bound definition of text message encompasses RTT.

Telecommunications for the Deaf and Hard of Hearing, Inc., et al. Have urged us to mandate the ability to reach 988 by RTT, noting that the Commission “has acknowledged the benefits of RTT in crisis situations such as `allow[ing] for interruption and reduc[ing] the risk of crossed messages Start Printed Page 31407because the. . .

Call taker is able to read the caller's message as it is being typed, rather than waiting until the caller presses the `send' key.” We seek comment on this assertion and other potential benefits and drawbacks of RTT to 988. We note that pursuant to the 2016 RTT Order, all wireless service providers are permitted to support RTT on their IP networks for purposes of 911 compliance (and for purposes of complying with the general accessibility requirements of Parts 6, 7, and 14 of the Commission's rules) as an alternative to supporting TTY communications over IP. In light of the deployment of such RTT capabilities in wireless IP networks, are there any impediments to wireless service providers routing RTT texts to the 988 number, in the event that Lifeline chooses to support RTT?. Do newer text messaging protocols like RTT and RCS represent a significant portion of the text messaging ecosystem, or are they likely to in the near future?.

Are consumers likely to expect the ability to use these kinds of platforms to send text messages to 988?. Do these texting solutions make texting more accessible for individuals with disabilities?. Are there other reasons to include, or exclude, these types of applications from our definition?. Are there any text message formats that we should specifically exclude from the definition we adopt?.

For example, in crafting the text-to-911 rules, the Commission chose to exclude from its requirements a variety of services, including “relay service. . . , mobile satellite service (MSS), and in-flight text messaging services,” as well as “text messages that originate from Wi-Fi only locations or that are transmitted from devices that cannot access the CMRS network.” Should we adopt any similar exclusions here?.

17. Second, we seek comment on how to structure our delegation to the Bureau to ensure that covered text providers support formats within the scope of the definition we adopt that the Lifeline can receive. We propose, as an initial matter, requiring covered text providers to support transmission of SMS messages to 988, since that is what the Lifeline can presently receive. We further propose directing the Bureau, after consultation with our federal partners at SAMHSA and the VA, to issue a Public Notice no less frequently than annually proposing and seeking comment on requiring covered text providers to transmit any new message formats to 988 that the Lifeline can receive and that are within the scope of the definition we adopt.

If the Bureau proposes requiring implementation of a new message format, we further propose directing the Bureau, after notice and comment, to issue a second Public Notice, requiring covered text providers to transmit the new message format to 988 by a fixed deadline that we specify unless the record demonstrates that implementation is not technically feasible. We seek comment on this proposal. Does it appropriately balance the need for expedient implementation with avoiding unduly burdening covered text providers with implementing formats that the Lifeline cannot receive?. Should we require the Bureau to issue a Public Notice more or less often than annually?.

Or is there another mechanism, such as one similar to the Commission's Text-to-911 PSAP registry, whereby PSAPs issue a valid request for texting service from covered text providers, that we should consider?. Is technical feasibility an appropriate standard for exclusion, or do commenters recommend a different standard?. Should we have a standard for exclusion by the Bureau at all?. If we do not have a standard for excluding certain technologies, is notice and comment necessary?.

What is an appropriate implementation deadline for us to specify after the Bureau issues its Public Notice requiring implementation?. For instance, would six months be sufficient?. Should we instead allow the Bureau flexibility to set an appropriate deadline?. Should we provide any further direction to the Bureau regarding the evaluation we propose to require?.

18. We also seek comment on structuring the scope of covered text messages differently. For instance, should we simply adopt a definition of “text message” and require covered text providers to support all such formats, regardless of whether the Lifeline can support that format presently?. Should we adopt a narrower definition of “text message” that conforms to what the Lifeline can support at present?.

While we appreciate the simplicity of either of these approaches compared to our proposal, how would commenters address our concern that the former is unnecessarily burdensome, and the latter is not adequately future-proofed?. 19. Covered Text Providers. We propose to apply our text-to-988 requirement to “covered text providers” as that term is defined in the text-to-911 rules, to “include[ ] all CMRS providers as well as all providers of interconnected text messaging services that enable consumers to send text messages to and receive text messages from all or substantially all text-capable U.S.

Telephone numbers, including through the use of applications downloaded or otherwise installed on mobile phones.” We note that the term “covered text provider” used in this notice of proposed rulemaking differs from the term “covered providers” used in the rules the Commission adopted in the 988 Order, which refers to all telecommunications carriers, interconnected VoIP providers, and one-way VoIP providers. We seek comment on this proposal, and on any alternative approaches to the scope of entities that must establish text-to-988 transmission capability. For example, if we can apply the definition of “text message” in the Truth in Caller ID rules to texting to 988, should we apply our text-to-988 rules to providers of “text messaging services,” as defined in section 227 of the Act and our Truth in Caller ID rules?. In that context, we define “text messaging service” as “a service that enables the transmission or receipt of a text message.” Is the Truth in Caller ID model preferable, for instance because it may incorporate a broader range of providers that support text messaging service, or is our proposal preferable, for instance because it is more specific?.

We also seek comment on other possible models and scopes of covered providers. Would using “CMRS providers” exclude services over certain spectrum bands or non-switched wireless services that transmit text messages to 988, and should we instead include “wireless carriers,” or a different term, in our definition of “covered text providers?. € 20. Interconnected Text Messaging Services.

In adopting the text-to-911 rules, the Commission observed that there are a variety of widely available text messaging services and platforms with different technological capabilities, including SMS, MMS, and “over-the-top” (OTT) applications delivered over internet protocol (IP)-based mobile data networks. As the Commission explained in the Text-to-911 Second Report and Order, “SMS requires use of an underlying carrier's SMS Center (SMSC) to send and receive messages from other users” while “[MMS]-based messaging makes use of the SMSC but also involves the use of different functional elements to enable transport of the message over IP networks.” A third category, OTT applications, may be offered by CMRS providers or third parties and allow consumers “to send text messages using SMS, MMS or directly via IP over a data connection to dedicated messaging servers and gateways.” These OTT services, which are often downloaded through mobile app stores, are increasingly popular with consumers and may be interconnected with the publicly Start Printed Page 31408switched telephone network (PSTN) or not. For purposes of the Commission's text-to-911 rules, interconnected text messaging applications enable consumers to “send text messages to all or substantially all text-capable U.S. Telephone numbers and receive text messages from the same,” while non-interconnected applications “only support communication with a defined set of users of compatible applications but do not support general communication with text-capable telephone numbers.” The Commission's text-to-911 rules include interconnected text messaging services but exclude non-interconnected applications because they do not provide the ability to communicate with text-capable U.S.

Telephone numbers. 21. As in the text-to-911 rules, we propose to apply our text-to-988 requirements to interconnected text messaging services, thereby excluding non-interconnected applications from the requirements. We seek comment on this approach.

This approach is also analogous to the Commission's decision in the 988 Report and Order to apply to “providers that access the [PSTN] on an interconnected basis to reach all Americans” and any “providers that access the [PSTN] on an interconnected basis to reach all Americans.” We note that the Commission's Truth in Caller ID rules provide an exemption for messages “sent over an IP-enabled messaging service to another user of the same messaging service, except [for an SMS or MMS message],” which similarly operates to exclude non-interconnected text messaging services. Since the services provided by the Lifeline require two-way communication and, by definition, non-interconnected text messaging applications cannot support two-way texting with “all or substantially all text-capable U.S. Telephone numbers,” we believe it is unlikely that these services would be technically capable of supporting text-to-988 functionality. We seek comment on this view.

Are there any tools available to the Commission to mitigate the potential for consumer confusion regarding the availability of text-to-988 across different text messaging platforms and technologies, particularly with respect to non-interconnected text messaging applications?. 2. Routing Texts to 988 22. We propose to require that covered text providers route covered 988 text messages to the Lifeline's current 10-digit number, 1-800-273-8255 (TALK), and we seek comment on this proposal.

This proposal is consistent with the Commission's decision for routing calls to 988 in the 988 Report and Order. In the 988 Report and Order, the Commission required “that service providers transmit all calls initiated by an end user dialing 988 to the current toll free access number for the Lifeline,” finding that a centralized routing solution will allow for faster implementation of the 988 3-digit dialing code, lower costs to maintain 988 routing, and provide continued easy access to Lifeline by callers with disabilities. We preliminarily believe that there are similar benefits to routing texts to 988 to a single, centralized number and seek comment on this view. 23.

There is support in the record thus far for routing to the Lifeline. CTIA supports directing texts sent to 988 to the Lifeline as a “central point for receiving such communications,” consistent with the Commission's mandate for routing 988 voice calls. Vibrant Emotional Health, the administrator of the Lifeline, argues in support of text-to-988 functionality integrated into the current Lifeline structure for routing voice and chat services, with oversight squarely within the role of the Lifeline's administrator. We seek comment on these assessments.

24. We anticipate that requiring covered text providers to route to a single destination provides SAMHSA and the VA with flexibility to develop their own routing solutions among the local crisis centers, including adding new crisis centers in the future, as compared to requiring covered text providers to implement additional updates or routing changes as more centers are added. Callers to 1-800-273-8255 (TALK) can reach the Veterans Crisis Line by pressing option 1 to connect with one of three linked call centers in New York, Georgia, or Kansas. For other calls, calls to the Lifeline from anywhere in the United States are routed to the closest certified local crisis center according to the caller's area code or, should the closest center be overwhelmed by call volume, experience a disruption of service, or if the call is placed from part of a state not covered by Lifeline's network, the system automatically routes calls to a backup center.

We seek comment on this preliminary analysis. Do the current obligations to route voice calls to 988 to the Lifeline 10-digit number offer any opportunities for streamlining implementation or reducing costs associated with routing texts to 988 to the same number?. 25. In the alternative, we seek comment on whether instead to follow a model more comparable to the text-to-911 architecture, whereby covered text providers route directly to a PSAP by requiring routing directly to a Lifeline local crisis center or to a Veterans Crisis Line crisis center.

We anticipate that this approach would be significantly more costly than centralized routing and seek comment on this preliminary view. Is it easier to route texts to a single number than to individual crisis centers?. As the Veterans Crisis Line is not currently set up for geographic distribution, would this architecture be appropriate for messages by Veterans or Service Members?. Are covered text providers able to leverage existing text-to-911 systems to reduce costs if required to route texts to 988 directly to local crisis centers?.

In the 988 Report and Order, the Commission recognized that some commenters expressed there may be benefits to routing voice calls to individual crisis centers, such as familiarity with a caller's area and potentially easier coordination with local emergency services, but ultimately concluded that the advantages associated with routing to a single number outweighed the benefits of localized routing. Does that rationale apply here?. Are there benefits to routing texts to the individual crisis centers that are unique to text messages, such as providing localized support to the public in the vicinity of the crisis center?. What are the costs or drawbacks to covered text providers to route texts to the Lifeline 10-digit number versus the local crisis centers?.

Which approach will lead to speedier implementation, and how should that impact our analysis?. Is there another alternative approach, other than centralized routing or routing by crisis center, that we should consider?. 26. Currently, Veterans and Service Members may dial the Lifeline to reach the Veterans Crisis Line via voice call, but the Lifeline texting service and the VA's short code texting service require contacting separate numbers.

How should we account for this distinction in evaluating what rules to adopt to ensure that Veterans, Service Members, and their families are able to reach the Veterans Crisis Line directly and promptly?. We seek comment on whether and how we can act to facilitate integration of the Veterans Crisis Line's separate short code-based texting service into text-to-988 routing. Are there specific actions that the Commission should take to allow users to text 988 and reach both the Lifeline and Veteran-specific assistance?. For instance, should we require covered text providers to provide an automated inquiry as to whether the texter is a Veteran or Service Member and route Start Printed Page 31409the text to either the existing Lifeline number or the existing short code for Veterans depending on the response?.

Alternatively, would it be feasible to immediately prompt individuals texting to 988 to reply with the number “1” or “Vet” to be routed to the Veterans Crisis Line, similar to the experience for voice callers?. Are other prompts preferable?. We seek comment on possible solutions to ensure that texts are routed to the proper counseling services via the Lifeline or the Veterans Crisis Line, including input on technical feasibility, ways to minimize consumer confusion, and implementation costs. Should other text or chat services be integrated into 988 text routing, and if so, how?.

27. We seek comment on whether we should require covered text providers to enable text-to-988 messages to include location information. As required by the National Suicide Hotline Designation Act of 2020, the Bureau will report to Congress on the costs and feasibility of providing location information with 988 calls on April 17, 2021. In our preliminary view, given that we have not adopted a location mandate in the context of calls to 988, we believe it would be premature to adopt a mandate here, and we seek comment on this view.

Does someone who sends a text message to 988 expect that their location will be transmitted to the Lifeline?. If consumers generally are aware that calls and texts to 911 include their location, would the same expectation apply to texts to 988?. Would including location information deter at-risk individuals from texting to 988?. We seek comment on any complications inherent in this plan and on ways for covered text providers to work with SAMHSA and the VA to limit misrouting of texts.

3. Implementation Timeframe for Text-to-988 28. Uniform Nationwide Deadline. We seek comment on an appropriate implementation timeframe for requiring covered text providers to support texting to 988 on a nationwide basis.

We preliminarily propose adopting a uniform nationwide deadline for implementation for all covered text providers and for all covered 988 text messages, as determined by the Bureau. In the 988 Report and Order, the Commission determined that the “rollout of 988 will be most effective if [it] set a single implementation deadline so that stakeholders can clearly and consistently communicate to the American public when 988 will be universally available.” We preliminarily believe that the same holds true here, and we seek comment on this view. Are there other benefits to a uniform nationwide implementation deadline?. What drawbacks, if any, exist?.

29. Although we propose adopting a uniform nationwide deadline, we seek comment on whether we should adopt any extensions or exemptions for certain classes of providers or categories of text messages. Should we adopt any extensions or exemptions for smaller, rural, or regional covered text providers?. If so, under what circumstances would such exemptions be appropriate?.

Are there unique technical considerations that necessitate different implementation timelines for certain covered text providers?. If so, what are they and why?. Are there any other considerations, such as any existing contractual obligations between our federal partners and other entities, that we should take into account in setting a deadline or deadlines?. 30.

Appropriate Deadline. We observe that CTIA and other commenters have previously argued that the Commission should not mandate text-to-988 before the Lifeline is capable of receiving and responding to texts, in part because the Lifeline's readiness to receive and respond to text messages is crucial to implementing text-to-988 successfully. We seek comment on this assertion. We also seek comment on CTIA's proposal to require covered text providers to “deliver text-to-988 to the Lifeline by July 16, 2022, or six months after the Lifeline demonstrates its readiness to accept text messages, whichever is later.” Is the Lifeline's pilot program sufficient to demonstrate that it is ready to accept text messages?.

If not, how should we determine that the Lifeline has demonstrated readiness to accept text messages, both from a technical and operational standpoint?. How should we take into account the capabilities of the Veterans Crisis Line in establishing a deadline?. Understanding that the Lifeline and Veterans Crisis Line successfully accepting and responding to text messages to 988 will require coordination between several stakeholders, we emphasize that the Commission will continue to coordinate closely with our federal partners, SAMHSA and the VA, in their efforts to enable crisis centers to respond to text messages to 988 and establish a reasonable implementation timeframe for text-to-988. We reiterate that the Commission does not wish to determine for SAMHSA how it allocates the Lifeline's resources, nor do we have the authority to require the Lifeline and its crisis centers to be capable of receiving and responding to text messages to 988.

31. We seek comment on whether the Commission should require all covered text providers to support text-to-988 by July 16, 2022, the same implementation deadline for telecommunications carriers, interconnected VoIP providers, and one-way VoIP providers to support voice calls to 988. Is this technically, economically and operationally feasible?. Are there benefits to requiring a uniform implementation timeline for all voice and text communications to 988?.

We observe that some covered text providers have already implemented voice calling to 988. For those providers, will requiring covered text providers to implement text-to-988 on the same timeline as voice calling to 988 create any efficiencies, such as reducing fixed costs?. Is there an expectation that once 988 is deployed nationwide for voice communications that texting to 988 will be similarly available?. Will a uniform implementation deadline discourage covered text providers from potentially supporting text to 988 before July 16, 2022?.

Are there other potential benefits or drawbacks to uniform implementation deadlines for providers supporting voice calling and texting to 988?. 32. Alternatively, we seek comment on whether we should separate the timeline for implementing text-to-988 from the implementation timeline for voice-to-988. Is a phased-in approach preferable?.

Would it be beneficial to consider balance of telecommunications activation needs and organizational response needs by SAMHSA and the VA?. Would it be less burdensome on providers working to implement 988 for voice calls in accordance with the 988 Report and Order?. Would a phased-in implementation timeline create consumer confusion regarding the availability of texting to 988?. If phased-in implementation deadlines would create consumer confusion, would requiring certain covered text providers to implement text-to-988 more quickly minimize consumer confusion?.

For example, if a covered text provider has already implemented voice calling to 988 and is advertising the availability of 988 to its customers, should the provider be required to implement text-to-988 before other covered text providers?. Are there other risks associated with a phased-in approach to an implementation timeline for voice and text communications to 988 as compared to uniform implementation timeline?. What, if any, phased-in deadlines should the Commission consider?. 33.

We also seek comment on whether we should we adopt the same timeline for all covered text providers, regardless of the text messaging technology they use. Are there other preparedness concerns that we should take into Start Printed Page 31410consideration when determining an implementation timeframe?. 4. Technical Considerations 34.

We seek comment on the specific technical considerations for covered text providers and equipment and software vendors—including those providers who are rural or small businesses—necessary to implement text-to-988. We propose to allow covered text providers to use any reliable method or methods (e.g., mobile-switched, IP-based) to support text routing and transmission to 988, similar to text-to-911 implementation. We seek comment on this proposal. 35.

Network Upgrades. We seek comment on possible upgrades covered text providers would have to make to their networks to support text-to-988 capability. Since we propose to allow covered text providers to use any reliable method or methods to support text routing and delivery to 988, are any necessary network hardware or software upgrades small in scope?. What specific components would require upgrading?.

Can the current solutions to enable text-to-911 capability be leveraged to support text-to-988, or are the implementation options for covered text providers to support text-to-988 significantly different?. CTIA notes “there are significant technical and policy differences between national 9-8-8 service that will be administered by the Lifeline and the local 9-1-1 services that are administered by thousands of PSAPs.” We seek comment on CTIA's view, especially with regard to any “significant” technical differences. Conversely, do commenters agree with Communications Equality Advocates that the costs to covered text providers for implementation of text-to-988 should be substantially lower than those associated with implementing text-to-911?. We seek further comment on the potential integration of text-to-988 solutions with existing systems, as well as other network considerations specific to covered text providers to support text-to-988.

36. We also seek comment on whether there are unique network considerations for different text messaging service technologies within the proposed outer bound scope of text-to-988 service that impact implementation. CTIA comments that its member companies are “optimistic about the technical feasibility of supporting text-to-988,” provided that implementation is consistent with existing capabilities of native SMS messaging. Do commenters agree?.

Are there fewer network upgrades necessary to support SMS-only texts to 988?. What specific network upgrades would be required should we obligate covered text providers to support other text messaging formats, such as MMS, RTT, or RCS?. Given that the Commission has recognized MMS as “an extension of the SMS protocol,” would support for MMS messaging be comparably feasible to support for SMS?. How does the evolution of texting services to new or future formats affect network upgrade options and implementation, and how should our rules account for such evolution?.

Would requiring support for certain text messaging formats be more feasible for covered text providers to implement than others?. 37. We specifically seek comment on the technical implementation capability and network upgrades necessary for interconnected text messaging service providers. Similar to the Commission's conclusion in the Text-to-911 proceeding, we anticipate that many interconnected text messaging service providers may choose to use a CMRS network-based solution to deliver texts to 988 and seek comment on this expectation.

Have there been developments in text-to-911 delivery by interconnected text messaging service providers that such providers can use in text-to-988 implementation?. In the text-to-911 context, the Commission's rules state. To the extent that CMRS providers offer Short Message Service (SMS), they shall allow access by any other covered text provider to the capabilities necessary for transmission of 911 text messages originating on such other covered text providers' application services. Covered text providers using the CMRS network to deliver 911 text messages must clearly inform consumers that, absent an SMS plan with the consumer's underlying CMRS provider, the covered text provider may be unable to deliver 911 text messages.

CMRS providers may migrate to other technologies and need not retain SMS networks solely for other covered text providers' 911 use, but must notify the affected covered text providers not less than 90 days before the migration is to occur. We seek comment on adopting this or a comparable requirement here. We recognize that text-to-911 network integration is necessary to facilitate a CMRS network-based solution, and we seek comment on whether the same integration is necessary for transmission of text-to-988 communications by other covered text providers using that solution. We seek comment on the relationship between CMRS providers and interconnected text messaging service providers to maintain support and capability for text-to-988 service based on the technical solutions available.

We emphasize that, as in the text-to-911 proceeding, even if we were to adopt a rule comparable to the text-to-911 rule above, we do not intend to establish an open-ended obligation for CMRS providers to maintain underlying SMS network support merely for the use of other providers. Further, similar to the Commission's position in the Text-to-911 Second Report and Order, if we adopt a rule comparable to the text-to-911 rule above, we propose concluding that it is the responsibility of the covered text provider using the CMRS-based solution to ensure that its text messaging service is technically compatible with the CMRS providers' SMS-based network and devices, and in conformance with any applicable technical standards. We seek comment on this proposal. Finally, as in the text-to-911 context, if we adopt a rule comparable to the text-to-911 rule above, we propose requiring CMRS providers to make any necessary specifications for accessing their SMS networks available to other covered text providers upon request, and to inform such covered text providers in advance of any changes to these specifications.

We seek comment on this proposal. 38. We also seek comment on specific technical considerations for covered text providers that are rural or regional providers, or small businesses. Are there unique impediments or challenges to implementation that these types of providers face that warrant further consideration?.

39. Equipment Upgrades. We seek comment on possible equipment or software upgrades required for covered text providers to implement text-to-988. What challenges will equipment (e.g., handsets, network infrastructure) and software vendors face with respect to the implementation and deployment of text-to-988?.

For example, are upgrades required for operating systems, firmware, or other software on mobile devices to support text-to-988 capability?. Are there upgrades necessary by vendors that are beyond the covered text providers' control that require additional coordination?. Will new standards need to be defined to ensure interoperability?. 40.

In the Text-to-911 proceeding, the Commission clarified that legacy devices that are incapable of sending texts via 3-digit codes are not subject to the text-to-911 requirements, provided the software for these devices cannot be upgraded over the air to allow text-to-911. If the device's text messaging software can be upgraded over the air to support a text to 911, however, then the Commission required the covered text provider to make the necessary software upgrade available. Should we include a Start Printed Page 31411similar exemption for legacy devices under any text-to-988 requirements we may adopt?. Have circumstances changed in the past seven years such that we should adopt a different approach here?.

5. Cost Recovery 41. Consistent with the Commission's decision in the 988 Report and Order, we propose to require that all covered text providers bear their own costs to implement text-to-988 capability to the Lifeline 10-digit number. As with call routing to 988, we do not anticipate any shared industry costs are necessary to implement text-to-988, in contrast to previous non-988 numbering proceedings where the Commission established a cost recovery mechanism.

As proposed, costs to support text-to-988 would be borne by each provider, specific to the solutions each has adopted to route texts to 988 ultimately to the Lifeline's current toll free access number, presently 1-800-273-8255 (TALK). We seek comment on this proposal. 42. We believe this approach promotes efficiency in implementation and avoids unnecessary administrative costs.

Section 251(e)(2) of the Act states that “[t]he cost of establishing telecommunications numbering administration arrangements and number portability shall be borne by all telecommunications carriers on a competitively neutral basis.” The Commission typically applies cost recovery mechanisms in situations involving some type of numbering administration arrangement, such as when the Commission hires a third party to develop a database for industry use, to ensure that the statutory cost neutrality requirements are met. Here, as with implementation of voice calls to 988, circumstances do not require establishment of a numbering administration arrangement as there will not be shared costs. Therefore, we believe the section 251(e)(2) requirements do not apply. Furthermore, even if section 251(e)(2) applies, we believe it is satisfied if we require each provider to bear its own costs because each provider's costs will be proportional to the size and quality of its network.

We seek comment on this analysis. 6. Bounce-Back Messages 43. We seek comment on whether and in what circumstances to require covered text providers to send automatic bounce-back messages where text-to-988 service is unavailable.

Throughout the ongoing roll-out of text-to-911 services across the U.S., the Commission has required covered text providers to send an automatic reply, or bounce-back, text message when a consumer attempts to send a text message to a PSAP by means of the 3-digit code “911” and the covered text provider cannot deliver the text because (1) the consumer is located in an area where text-to-911 is not available, or (2) the covered text provider either does not support text-to-911 generally or does not support it in the particular area at the time of the consumer's attempted text. Unlike in the text-to-911 context, where availability varies by geography and is based on whether the local PSAP can receive texts, our proposals herein would require covered text providers to support nationwide texting to the Lifeline via the 988 3-digit code on a uniform nationwide deadline. If we were to adopt our proposal, should we nonetheless require bounce-back messages?. If so, when and under what circumstances?.

Should we require covered text providers to make available bounce-back messages sooner than we require implementation of text-to-988?. Would requiring bounce-back messages be appropriate if we adopt a uniform nationwide deadline for text-to-988 capability later than July 16, 2022—the uniform nationwide deadline for covered providers to support calls to 988?. Would requiring bounce-back messages be appropriate if we adopt exemptions or extensions for some providers?. 44.

We seek comment on the potential benefits and costs of a bounce-back requirement. In the text-to-911 context, the Commission determined that “there is a clear benefit and present need for persons who attempt to send emergency text messages to know immediately if their text cannot be delivered to the proper authorities,” noting that feedback where text-to-911 is not available may be lifesaving by directing a person to seek out an alternative means of communicating with emergency services. Is that the case here as well?. Because some individuals with disabilities may rely exclusively on texting for communicating, are there unique benefits of a bounce-back requirement for these individuals?.

Since the Commission designated 988 as the 3-digit dialing code to access the Lifeline, efforts have been underway to educate the public about using this 3-digit code to reach help by telephone in times of mental health crisis, including its availability for routing voice calls to the Lifeline by July 16, 2022. In the absence of a bounce-back, might such advertising confuse the public about the availability of texting to 988?. Would an automated bounce-back help to prevent such confusion?. Are there other advantages to requiring covered text providers to send bounce-back messages for attempts to text 988 where service is unavailable?.

Are any providers included under the proposed “covered text providers” definition currently sending bounce-back messages to texts sent to 988?. 45. What are the costs of requiring a bounce-back message?. What work or upgrades would be necessary for text service providers to implement an automatic bounce-back reply?.

Given that covered text providers must provide a bounce-back in circumstances in which text-to-911 is unavailable, would adding a comparable bounce-back message for 988 be easier than if that existing infrastructure were not in place?. Would requiring text service providers to build bounce-back capabilities deter resources from more rapid deployment of text-to-988?. 46. We seek comment on how requiring bounce-back messages may impact the public's ability to seek help from the Lifeline in times of mental crisis.

What are the potential benefits to receiving an automatic bounce-back message when text-to-988 service is unavailable?. Are there any drawbacks to the public of requiring covered text providers to send bounce-back messages when text-to-988 is not available?. One commenter contends that if at-risk texters receive a bounce-back message regarding the unavailability of services, “the risks of disengagement and adverse outcomes increase.” Do commenters agree with the assessment that an automatic bounce-back message will negatively impact individuals seeking help during a crisis?. Would a bounce-back message have the effect of making the sender more discouraged, such that it that could increase, not decrease, the likelihood of suicide?.

Alternatively, if there is no automatic reply, and the sender is left wondering whether the Lifeline received the text message, would that uncertainty also increase sender's likelihood of suicide?. We seek comment on whether the benefits of receiving an automatic bounce-back message outweigh the potential risk of disengagement. 47. If we were to adopt a bounce-back requirement, we seek comment on the specific requirement we should adopt.

To align with the scope of the proposed outer bound text-to-988 capability requirements, we propose that if we were to adopt a bounce-back requirement, we would require all covered text providers to provide automatic bounce-back messages to text messages, as defined by our outer bound Start Printed Page 31412proposal herein, sent to 988 where text-to-988 service is unavailable. We seek comment on this approach. Are there unique considerations for different technologies within the outer bound scope of text message that we should consider under our bounce-back message proposal, including such impact on technical implementation or costs?. Should we consider requiring covered text providers to send automatic bounce-back messages in reply to messages outside the scope of the outer bound definition?.

Are there additional text or chat service providers that offer services beyond the proposed outer bound definition that we should include within the scope of our proposed bounce-back requirement?. Should we limit any bounce-back requirement to covered text providers, as proposed, or should the requirement sweep more broadly?. CTIA asserts that text-to-988 implementation should be consistent with existing SMS capabilities. Should any bounce-back requirement we may explore likewise remain consistent with SMS?.

Is sending a bounce-back message in response to texts to 988 feasible on legacy SMS systems?. We seek comment on the impact including other text or chat service providers, or other forms of messages, may have on the implementation costs, technical feasibility, and timeframe for our proposed bounce-back message requirements. 48. Should we adopt a bounce-back requirement, we seek comment on whether and how to expand on the circumstances in which a covered text provider must provide a bounce-back message due to unavailability of text-to-988.

In the text-to-911 context, when a customer is roaming away from his or her “home network” (i.e., the network of the customer's mobile carrier), the CMRS provider operating the customer's home network is nonetheless responsible for providing a bounce-back message when required. And the provider operating the network on which the customer is roaming must not impede the bounce-back response by the home network operator. We seek comment on adopting a similar requirement here. Additionally, we anticipate that there may be circumstances in which the Lifeline is unable to receive and respond to texts, including where demand may exceed its capacity to respond.

In instances amounting essentially to a “busy signal” for text delivery, are covered text providers capable of determining that the text cannot be delivered to 988?. Would covered text providers be able to determine if a text to 988 is undeliverable due to the Lifeline's inability, whether temporary or sustained, to receive and respond to the texts?. Or should we establish a mechanism whereby the Lifeline may inform providers of a temporary suspension of text-to-988 service, and should the bounce-back requirement apply until the suspension is lifted?. Lastly, we seek comment on considerations, either within the control of the covered text provider or the Lifeline's administrators, in which a message from an individual in crisis attempting to reach 988 may not be delivered, and therefore may benefit from receipt of a bounce-back message directing the individual to contact 988 by alternative means.

Are there additional circumstances where we should require covered text providers to send bounce-back messages in response to 988 texts?. 49. If we were to adopt a bounce-back requirement, we propose to adopt the same exceptions to our bounce-back notification requirement for text-to-988 as currently exist for the Commission's text-to-911 rules. If we adopt that same approach, a covered text provider would not be required to provide an automatic bounce-back message when.

(1) Transmission of the text message is not controlled by the provider. (2) a consumer is attempting to text 988, through a text messaging application that requires CMRS service, from a non-service initialized handset. (3) the text-to-988 message cannot be delivered due to a failure in the Lifeline's routing network that has not been reported to the provider. Or (4) a consumer is attempting to text 988 through a device that is incapable of sending texts via 3-digit codes, provided that the software for the device cannot be upgraded over the air to allow text-to-988.

We seek comment on this approach. Are there other situations where a covered text provider should not be required to send bounce-back messages to consumers attempting to text to 988?. Furthermore, we seek comment on the circumstances in which the provider of a pre-installed or downloaded interconnected text application would be considered to have “control” over the transmission of text messages for the purposes of any requirements we adopt. If a user or third party modifies or manipulates the application after it is installed or downloaded so that it no longer supports bounce-back messaging, should the application provider be presumed not to have control?.

50. If we adopt a bounce-back requirement, should we specify or provide guidance regarding the content of the bounce-back message, and if so, what should we specify or encourage?. Similar to automatic messages sent in response to undeliverable texts to 911, we propose that any bounce-back messages to consumers attempting to text 988 would not require all covered text providers to use identical wording for their automatic responses. Rather, if we were to adopt a bounce-back requirement, we propose that a covered text provider would be deemed to have met its obligation so long as the bounce-back message to 988 includes, at a minimum, two essential points of information.

(1) That text-to-988 is not available. And (2) identify other means to reach the Lifeline, such as by telephone. We seek comment on this approach and on alternatives. We seek comment on what role our federal partners and non-governmental mental health organizations could play in developing best practices regarding the content of messages.

7. Role of the Substance Abuse and Mental Health Services Administration and the Department of Veterans Affairs 51. Although the Commission has an important role to play in expanding access to crisis counseling through its implementation of 988, SAMHSA and the VA are ultimately responsible for ensuring the continued success of these lifesaving resources. As such, we propose to direct the Bureau to continue to coordinate the implementation of 988 with SAMHSA and the VA, including any issues pertaining to the delivery of text messages to 988.

52. We seek comment on this proposal. How we can best support the work of our federal partners in administering the Lifeline and Veterans Crisis Line?. We recognize that many commenters have stressed the importance of ensuring adequate funding and staffing for the Lifeline and the Veterans Crisis Line over the course of this proceeding.

Although these issues are beyond our jurisdiction, are there unique considerations pertaining to staffing, funding, or the availability of other resources at the Lifeline or Veterans Crisis Line that we should be aware of as we consider adopting rules to require the delivery of text messages to 988?. How should we account for the possibility that text-to-988 may be popular and increase demands on the Lifeline and Veterans Crisis Line?. What resources will be needed for the Lifeline and Veterans Crisis Line to ensure that text-to-988 is a success?. How should we account for our federal partners' budget cycles?.

We are cognizant of the potential burdens our proposals may impose upon our federal partners, Start Printed Page 31413including personnel, equipment, and resource allocation, and we seek comment on the impact the possible implementation solutions may have on SAMHSA and the VA when supporting text-to-988 service. To that end, we intend to coordinate with SAMHSA and the VA, and we encourage other industry stakeholders in the wireless and texting service industry to coordinate with these agencies as well. Assuming that our adoption of rules implementing text-to-988 capability will require expenditure of additional resources by SAMHSA and the VA, are there ways that we can structure our rules to minimize the burden on our federal partners?. Are there any steps we should take to deter misuse of text-to-988, so as to limit the unnecessary expenditure of resources by our federal partners?.

Are there any solutions that have been employed in other contexts, such as text-to-911, that we or others should adapt here to deter misuse of text-to-988?. 53. In addition, we encourage SAMHSA and the VA to coordinate with outside organizations that have expertise in providing crisis counseling via text message as they develop the infrastructure to receive and respond to text messages which may one day be delivered to the Lifeline and Veterans Crisis Line via 988. Many commenters in this proceeding have urged collaboration between private entities like the Trevor Project and federal agencies providing similar services.

We therefore seek comment on how to facilitate such coordination across federal agencies and the private sector, as we work towards our shared goal of ensuring that all Americans have ready access to mental health counseling and support services. C. Legal Authority 54. We propose concluding that we have the authority to adopt the rules proposed and for which we seek comment in this further notice of proposed rulemaking under Title III of the Act and the Twenty-First Century Communications and Video Accessibility Act (CVAA).

We seek comment on these and any other sources of authority available to us. In particular, we seek comment on whether, and if so, to what extent, our numbering authority under section 251(e) of the Act provides an additional source of authority for the rules proposed and for which we seek comment in this further notice of proposed rulemaking. Finally, we also seek comment on whether we should employ our ancillary authority. We note that, in our preliminary review, the National Suicide Hotline Designation Act of 2020 does not provide additional support for—nor does it hinder—the actions proposed in this further notice of proposed rulemaking.

We seek comment on these views. 55. The rules we propose and for which we seek comment in this further notice of proposed rulemaking are analogous to those the Commission has adopted to facilitate text-to-911 communications, which relied, in part, on the Commission's Title III authority over wireless carriers, including sections 301, 303, 307, 309, and 316. We propose concluding that, with respect to CMRS providers, Title III provides us with appropriate authority to require wireless carriers to support text-to-988 service and to require delivery of a bounce-back message to consumers in cases where delivery of a text to 988 cannot be completed.

As the Supreme Court has long recognized, Title III grants the Commission a “comprehensive mandate” regarding regulation of spectrum usage, and courts have routinely found that Title III provides the Commission with “broad authority to manage spectrum. . . In the public interest.” As we explain, we believe the rules we propose in this further notice of proposed rulemaking are likely to have significant public interest benefits.

And, the Commission has previously found that its Title III licensing authority supported adoption of a similar set of obligations in the text-to-911 context. Therefore, we believe that with respect to CMRS providers, Title III provides sufficient authority here. We note that, following the release of the Text-to-911 Order, the Commission released a Declaratory Ruling classifying SMS and MMS services as “information services” under the Act. However, as the Commission explicitly noted in the Declaratory Ruling, this determination “does not affect the general applicability of the spectrum allocation and licensing provisions of Title III and the Commission's rules” to SMS and MMS services, nor does it affect the specific application of sections 301, 303, 307, 309, and 316 to the Commission's text-to-911 rules.

We seek comment on this analysis. 56. With respect to interconnected text messaging service providers, we propose to find that the CVAA provides us with authority to adopt the proposals in this further notice of proposed rulemaking, as some commenters in this proceeding suggest. Congress enacted the CVAA to increase the accessibility of modern communications technologies to people with disabilities, including access related to emergency services, and the Commission relied, in part, on this authority when it adopted similar text-to-911 requirements.

The CVAA provides the Commission with authority to “achiev[e] equal access to emergency services by individuals with disabilities, as a part of the migration to a national internet protocol-enabled emergency network.” In particular, the CVAA granted the Commission the authority to adopt regulations to implement recommendations proposed by the Emergency Access Advisory Committee established by the CVAA, which concern access to 911 and NG911 services, and to adopt “other regulations” as are necessary to achieve reliable, interoperable communication that ensures access by persons with disabilities to an IP-enabled emergency services network. We tentatively conclude that the CVAA provides authority for our proposals because access to 988 is similar to 911 access for the purposes of our CVAA authority. We seek comment on this tentative conclusion. Do commenters agree that access to the Lifeline or Veterans Crisis Line through 988 constitute “access to emergency services” under the CVAA?.

Do commenters agree that text-to-988 is necessary to achieve reliable, interoperable communication that ensures access by persons with disabilities to an IP-enabled emergency services network?. More generally, does the CVAA provide us with authority to adopt the rules proposed in this further notice of proposed rulemaking?. 57. We seek comment on any other sources of authority available to the Commission to adopt the proposals detailed in this further notice of proposed rulemaking.

In particular, we seek comment on whether our section 251(e) authority over numbering provides authority to require support for text-to-988 service. Section 251(e)(1) of the Act grants us “exclusive jurisdiction over those portions of the North American Numbering Plan that pertain to the United States” and provides that numbers must be made “available on an equitable basis.” This provision gives the Commission “authority to set policy with respect to all facets of numbering administration in the United States.” The Commission found in the 988 Report and Order that section 251(e) provides us with the ability to regulate interconnected and one-way VoIP providers that make use of numbering resources when they connect with the PSTN. We seek comment on whether our numbering authority provides an additional, independent basis to adopt rules with respect to CMRS providers Start Printed Page 31414and interconnected text messaging services. 58.

We also seek comment on the Commission's authority to mandate location information with text-to-988 service. Section 222 of the Communications Act, as amended, provides strong legal protections for customer proprietary network information (CPNI), including geolocation information. Section 222(d) provides exceptions to allow CPNI and call location data to be shared for “emergency services.” We seek comment on whether this could encompass the transmission of geolocation information with 988 calls. Should we choose to require covered text providers to include location information with texts to 988, does section 222 authorize the disclosure of location information with texts to 988?.

Are there other privacy concerns that we should consider with regard to texts to 988?. 59. Finally, we seek comment on whether exercise of our ancillary authority would be necessary or appropriate to support any of our proposed rules. The Commission relied in part on ancillary authority to apply the bounce-back notification requirement to providers of interconnected text messaging services when it adopted text-to-911 requirements.

Would a similar finding be appropriate with respect to any aspect of our text-to-988 rules?. D. Benefits and Costs of Text-to-988 60. We expect to find that the benefits of requiring service providers to support text-to-988 service will exceed the costs of implementation.

We seek comment on this proposal, and any specific data regarding both the benefits of facilitating access to the Lifeline via texts to 988 and on the costs or burdens implementation of text-to-988 may impose upon covered text providers. 61. Suicide causes shock, anguish, grief, and guilt among victims' families and friends. Suicide attempts exact a similarly heavy toll on the community and the victim.

The long-lasting damage from mental distress and suicide can extend deep into communities. As outlined above, we preliminarily believe that enabling text-to-988 service will improve access to lifesaving resources for individuals contemplating suicide or experiencing mental health crises, especially for members of at-risk communities such as young people, LGBTQ, people of color, and individuals with disabilities, thereby saving lives. By expanding access to counseling, text-to-988 may help break the cycle of pain, suffering, and suicide. We seek comment generally on these and other important benefits that may follow from increased access to mental health resources via texting to 988.

62. We further seek comment on ways to quantify these benefits. Of course, the benefits to individuals who the Lifeline or Veterans Crisis Line places on a path to recovery, much less to their families and friends, cannot be reduced to dollars and cents. That being said, even if text-to-988 service could annually place just one-per-one-thousand suicide victims on a path to long-term recovery, the economic gain would be $19.2 million in any single year, for a present-value of $78.7 million over five years and $134.9 million over ten years.

In estimating benefits, we focus on teens and individuals with disabilities, as individuals in these groups are more likely to use a text-to-988 capability. Based on the most recent CDC data from 2015-2019, 11,283 youth (ages 15-19) and an estimated 13,101 individuals who are deaf, hard of hearing, deafblind or speech disabled committed suicide (using an estimated incidence among adults of 6%), or an average of more than 2,000 per year for each group. To calculate the estimated benefits for a single year, we multiply the annual average by 0.1% and the VSL (2,000 * 0.001 * $9.6 million = $19.2 million). We discount over five years and ten years at a 7% discount rate.

We seek comment on this analysis. 63. Our proposed analysis does not examine certain categories of benefits. For example, we have not estimated the cost savings from medical expenses and loss-of-work avoided through reduced suicides and suicide attempts.

We also have not estimated the cost savings of reduced burdens on PSAPs, police, ambulance, and fire and rescue services, which currently respond to some 911 texts that will be routed to the Lifeline, where they will be more effectively and efficiently de-escalated or otherwise resolved. Moreover, we have not examined the benefits of text-to-988 usage by every demographic group. For example, smartphone ownership and suicide are particularly common in younger age groups. According to the Common Sense Census.

Media Use by Tweens and Teens, 2019, 53% of children have their own smartphone by age 11, and 69% have one at age 12. Currently, our estimated benefits analysis looks at youth ages 15-19. To accurately estimate these benefits, we seek comment on how broadly we should define youth who may text to 988. Relatedly, there is the possibility that adults without hearing or speech disabilities may rely exclusively on text-to-988 for added privacy or convenience, meriting inclusion in our benefit estimates.

We also seek comment on ways to better assess the long-term impact of text-to-988 service. Without longitudinal studies evaluating the long-term effectiveness of suicide call centers, we cannot pinpoint how many suicides text-to-988 will prevent in the long run. Available survey-based studies, however, reveal call centers can substantially reduce suicides during the initial call and follow-up periods. We seek comment on the types and magnitudes of these and other benefits not covered in this further notice of proposed rulemaking, as well as any overlooked categories of costs.

64. In the Text-to-911 proceeding, the Commission estimated that the total cost for covered providers to implement text-to-911 service amounted to less than $21 million. The costs of nationwide deployment of text-to-911 fell into three categories. CMRS and PSAP system cost components.

Interconnected text providers' software upgrades. And bounce-back messaging application alterations and server platform modifications. Assuming that all or most of the software and equipment necessary to receive and transmit 911 texts will again be needed to deploy text-to-988, we expect that the implementation costs for text-to-988 service will be comparable to the costs for text-to-911 service. Using cost estimates from the Text-to-911 proceeding as a model, we estimate it will cost $19,024,916 for CMRS providers to implement text-to-988, $613,275 for interconnected text messaging service providers to implement text-to-988, and $7,310,340 for Lifeline to route texts to local crisis centers.

We convert the estimate for CMRS providers to implement text-to-911 service to 2021 dollars by multiplying by a Consumer Price Index (CPI) factor of 1.16, then discounting over five years at a 7% discount rate. Similarly, we convert the estimate for interconnected text messaging providers to implement text-to-911 service into 2021 dollars by using a CPI factor of 1.105. To soberly assess Lifeline capability, we assume that 100% of Lifeline call centers may require SMS upgrades and thus multiply PSAP software estimates by 2.22. To estimate the costs to equip the more than 180 Lifeline crisis centers, we calculate an average cost based on an estimated per PSAP cost of $40,613 (=($263,277,595 + $12,891,283)/6,800), for a total of $7,310,340 (=180 * $40,613).

Therefore, we preliminarily estimate that total costs for implementing text-to-988 will be approximately $27 million. We seek Start Printed Page 31415comment on this analysis, including our preliminary assumption that text-to-911 software and equipment can be leveraged for texting to 988. Do commenters agree with CTIA that there are “significant technical and policy differences” between 988 and 911 service, and if so, how might those differences impact our evaluation?. Furthermore, we seek comment on whether cost estimates for PSAPs from the Text-to-911 proceeding reflect an appropriate estimate for costs to the Lifeline or Veterans Crisis Line.

Are there other costs borne by the Lifeline or Veterans Crisis Line needed to implement text-to-988 service?. 65. We preliminarily assume that some costs may be streamlined or reduced due to the previous implementation of text-to-911, which may be leveraged to facilitate text-to-988 capability and seek comment on this assumption. As a result, we anticipate that costs for covered text providers to implement text-to-988 may be less than what we estimate above and seek comment on this finding.

We further seek comment on what extent covered text providers may rely upon existing text-to-911 services and how to quantify the costs needed to upgrade such systems to support text-to-988. 66. Deterring suicide has benefits that simply cannot be reduced to numbers—saving lives has value beyond measure. While recognizing this fact, to illustrate how the benefits of our proposal relate to the more aptly quantified costs, we attempt to estimate the quantifiable value of suicide prevention using a measure of collective willingness to pay.

We propose calculating that the level of suicide prevention needed to generate benefits exceeding our preliminary estimate of $27 million in text-to-988 costs is a total of four suicides avoided over five years. Specifically, the level of teen suicide prevention needed to generate benefits exceeding $27 million is one per 2,821, and the level of suicide prevention among individuals with disabilities to generate benefits exceeding $27 million is one per 3,275. Even assuming that text-to-988 prevented no suicides in its inaugural year as the service rolled out but prevented one suicide in each of the ensuing four years, measured in terms of the public's willingness to pay for that mortality reduction, the present value of the benefit would be $30.39 million, more than three million dollars greater than the total cost. The present value would be an uneven stream of payments of $9.6 million ($0 in Year 1 + $9.6 million per year in Year 2 through Year 5) at a 7% discount rate.

We seek comment on our analysis. 67. Using break-even points and highly attainable suicide reductions that are well below those suggested by survey studies, we estimate that the benefits of text-to-988 will far exceed the costs. Pooling teenagers and individuals with disabilities, we estimate that text-to-988 would need to prevent one suicide out of every six thousand in order to break-even in the first five years of deployment.

Slightly raising the bar to preventing one suicide per one thousand, we further estimate that the more than $157.5 million estimated benefit from modestly reducing suicides in two vulnerable populations far exceeds the text-to-988 deployment costs of $19.6 million incurred by CMRS and interconnected text providers. Even if sizable Lifeline deployment costs are added, increasing estimated total cost to nearly $27 million, the estimated benefits of text-to-988 remain greater by a multiple of nearly six. Over ten years, the benefits rise to $269.8 million, exceeding costs by a multiple of nearly ten. We seek comment on these estimates.

We also seek comment on the methods and underlying benefits and costs estimates, including those submitted by third parties, used to arrive at our overall proposed conclusion. II. Initial Regulatory Flexibility Analysis 1. As required by the Regulatory Flexibility Act of 1980, as amended (RFA), the Commission has prepared this Initial Regulatory Flexibility Analysis (IRFA) of the possible significant economic impact on small entities by the policies and rules proposed in this Implementation of the National Suicide Hotline Improvement Act of 2018 further notice of proposed rulemaking (FNPRM).

The Commission requests written public comments on this IRFA. Comments must be identified as responses to the IRFA and must be filed by the deadlines for comments provided on the first page of the further notice of proposed rulemaking. The Commission will send a copy of the further notice of proposed rulemaking, including this IRFA, to the Chief Counsel for Advocacy of the Small Business Administration (SBA). In addition, the further notice of proposed rulemaking and IRFA (or summaries thereof) will be published in the Federal Register.

A. Need for, and Objectives of, the Proposed Rules 2. In this FNPRM, the Commission proposes and seeks comment on requiring CMRS providers and providers of interconnected text messaging services that enable consumers to send text messages to, and receive text messages from, the PSTN (covered text providers) to enable delivery of text messages to 988. The Commission proposes to require that covered text providers route 988 text messages to the National Suicide Prevention Lifeline's (Lifeline) 10-digit number, currently 1-800-273-8255 (TALK).

The Commission believes these proposed rules will expand the availability of mental health and crisis counseling resources to Americans who suffer from depressive or suicidal thoughts, by allowing individuals in crisis to reach the Lifeline by texting 988. B. Legal Basis 3. The legal basis for any action that may be taken pursuant to this FNPRM is contained in sections 201, 251, 301, 303, 307, 309, and 316 of the Communications Act of 1934, as amended, 47 U.S.C.

201, 251, 301, 303, 307, 309, 316. C. Description and Estimate of the Number of Small Entities to Which the Proposed Rules Will Apply 4. The RFA directs agencies to provide a description of, and where feasible, an estimate of the number of small entities that may be affected by the proposed rules and by the rule revisions on which the Notice seeks comment, if adopted.

The RFA generally defines the term “small entity” as having the same meaning as the terms “small business,” “small organization,” and “small governmental jurisdiction.” In addition, the term “small business” has the same meaning as the term “small-business concern” under the Small Business Act. A “small-business concern” is one which. (1) Is independently owned and operated. (2) is not dominant in its field of operation.

And (3) satisfies any additional criteria established by the SBA. 5. Small Businesses, Small Organizations, Small Governmental Jurisdictions. Our actions, over time, may affect small entities that are not easily categorized at present.

We therefore describe here, at the outset, three broad groups of small entities that could be directly affected herein. First, while there are industry specific size standards for small businesses that are used in the regulatory flexibility analysis, according to data from the Small Business Administration's (SBA) Office of Advocacy, in general a small business is an independent business having fewer than 500 employees. These types of small businesses represent 99.9% of all businesses in the United Start Printed Page 31416States, which translates to 30.7 million businesses. 6.

Next, the type of small entity described as a “small organization” is generally “any not-for-profit enterprise which is independently owned and operated and is not dominant in its field.” The Internal Revenue Service (IRS) uses a revenue benchmark of $50,000 or less to delineate its annual electronic filing requirements for small exempt organizations. Nationwide, for tax year 2018, there were approximately 571,709 small exempt organizations in the U.S. Reporting revenues of $50,000 or less according to the registration and tax data for exempt organizations available from the IRS. 7.

Finally, the small entity described as a “small governmental jurisdiction” is defined generally as “governments of cities, counties, towns, townships, villages, school districts, or special districts, with a population of less than fifty thousand.” U.S. Census Bureau data from the 2017 Census of Governments indicate that there were 90,075 local governmental jurisdictions consisting of general purpose governments and special purpose governments in the United States. Of this number there were 36,931 general purpose governments (county, municipal and town or township) with populations of less than 50,000 and 12,040 special purpose governments—independent school districts with enrollment populations of less than 50,000. Accordingly, based on the 2017 U.S.

Census of Governments data, we estimate that at least 48,971 entities fall into the category of “small governmental jurisdictions.” 8. Wired Telecommunications Carriers. The U.S. Census Bureau defines this industry as “establishments primarily engaged in operating and/or providing access to transmission facilities and infrastructure that they own and/or lease for the transmission of voice, data, text, sound, and video using wired communications networks.

Transmission facilities may be based on a single technology or a combination of technologies. Establishments in this industry use the wired telecommunications network facilities that they operate to provide a variety of services, such as wired telephony services, including VoIP services, wired (cable) audio and video programming distribution, and wired broadband internet services. By exception, establishments providing satellite television distribution services using facilities and infrastructure that they operate are included in this industry.” The SBA has developed a small business size standard for Wired Telecommunications Carriers, which consists of all such companies having 1,500 or fewer employees. U.S.

Census Bureau data for 2012 show that there were 3,117 firms that operated that year. Of this total, 3,083 operated with fewer than 1,000 employees. Thus, under this size standard, the majority of firms in this industry can be considered small. 9.

Local Exchange Carriers (LECs). Neither the Commission nor the SBA has developed a size standard for small businesses specifically applicable to local exchange services. The closest applicable NAICS Code category is Wired Telecommunications Carriers. Under the applicable SBA size standard, such a business is small if it has 1,500 or fewer employees.

U.S. Census Bureau data for 2012 show that there were 3,117 firms that operated for the entire year. Of that total, 3,083 operated with fewer than 1,000 employees. Thus under this category and the associated size standard, the Commission estimates that the majority of local exchange carriers are small entities.

10. Incumbent LECs. Neither the Commission nor the SBA has developed a small business size standard specifically for incumbent local exchange services. The closest applicable NAICS Code category is Wired Telecommunications Carriers.

Under the applicable SBA size standard, such a business is small if it has 1,500 or fewer employees. U.S. Census Bureau data for 2012 indicate that 3,117 firms operated the entire year. Of this total, 3,083 operated with fewer than 1,000 employees.

Consequently, the Commission estimates that most providers of incumbent local exchange service are small businesses that may be affected by our actions. According to Commission data, one thousand three hundred and seven (1,307) Incumbent Local Exchange Carriers reported that they were incumbent local exchange service providers. Of this total, an estimated 1,006 have 1,500 or fewer employees. Thus, using the SBA's size standard the majority of incumbent LECs can be considered small entities.

11. Competitive Local Exchange Carriers (Competitive LECs). Competitive Access Providers (CAPs), Shared-Tenant Service Providers, and Other Local Service Providers. Neither the Commission nor the SBA has developed a small business size standard specifically for these service providers.

The appropriate NAICS Code category is Wired Telecommunications Carriers and under that size standard, such a business is small if it has 1,500 or fewer employees. U.S. Census Bureau data for 2012 indicate that 3,117 firms operated during that year. Of that number, 3,083 operated with fewer than 1,000 employees.

Based on these data, the Commission concludes that the majority of Competitive LECS, CAPs, Shared-Tenant Service Providers, and Other Local Service Providers, are small entities. According to Commission data, 1,442 carriers reported that they were engaged in the provision of either competitive local exchange services or competitive access provider services. Of these 1,442 carriers, an estimated 1,256 have 1,500 or fewer employees. In addition, 17 carriers have reported that they are Shared-Tenant Service Providers, and all 17 are estimated to have 1,500 or fewer employees.

Also, 72 carriers have reported that they are Other Local Service Providers. Of this total, 70 have 1,500 or fewer employees. Consequently, based on internally researched FCC data, the Commission estimates that most providers of competitive local exchange service, competitive access providers, Shared-Tenant Service Providers, and Other Local Service Providers are small entities. 12.

We have included small incumbent LECs in this present RFA analysis. As noted above, a “small business” under the RFA is one that, inter alia, meets the pertinent small business size standard (e.g., a telephone communications business having 1,500 or fewer employees), and “is not dominant in its field of operation.” The SBA's Office of Advocacy contends that, for RFA purposes, small incumbent LECs are not dominant in their field of operation because any such dominance is not “national” in scope. We have therefore included small incumbent LECs in this RFA analysis, although we emphasize that this RFA action has no effect on Commission analyses and determinations in other, non-RFA contexts. 13.

Interexchange Carriers (IXCs). Neither the Commission nor the SBA has developed a small business size standard specifically for Interexchange Carriers. The closest applicable NAICS Code category is Wired Telecommunications Carriers. The applicable size standard under SBA rules is that such a business is small if it has 1,500 or fewer employees.

U.S. Census Bureau data for 2012 indicate that 3,117 firms operated for the entire year. Of that number, 3,083 operated with fewer than 1,000 employees. According to internally developed Commission data, 359 companies reported that their primary telecommunications service activity was the provision of interexchange services.

Of this total, an estimated 317 have 1,500 or fewer employees. Start Printed Page 31417Consequently, the Commission estimates that the majority of interexchange service providers are small entities. 14. Local Resellers.

The SBA has not developed a small business size standard specifically for Local Resellers. The SBA category of Telecommunications Resellers is the closest NAICs code category for local resellers. The Telecommunications Resellers industry comprises establishments engaged in purchasing access and network capacity from owners and operators of telecommunications networks and reselling wired and wireless telecommunications services (except satellite) to businesses and households. Establishments in this industry resell telecommunications.

They do not operate transmission facilities and infrastructure. Mobile virtual network operators (MVNOs) are included in this industry. Under the SBA's size standard, such a business is small if it has 1,500 or fewer employees. U.S.

Census Bureau data from 2012 show that 1,341 firms provided resale services during that year. Of that number, all operated with fewer than 1,000 employees. Thus, under this category and the associated small business size standard, the majority of these resellers can be considered small entities. According to Commission data, 213 carriers have reported that they are engaged in the provision of local resale services.

Of these, an estimated 211 have 1,500 or fewer employees and two have more than 1,500 employees. Consequently, the Commission estimates that the majority of local resellers are small entities. 15. Toll Resellers.

The Commission has not developed a definition for Toll Resellers. The closest NAICS Code Category is Telecommunications Resellers. The Telecommunications Resellers industry comprises establishments engaged in purchasing access and network capacity from owners and operators of telecommunications networks and reselling wired and wireless telecommunications services (except satellite) to businesses and households. Establishments in this industry resell telecommunications.

They do not operate transmission facilities and infrastructure. MVNOs are included in this industry. The SBA has developed a small business size standard for the category of Telecommunications Resellers. Under that size standard, such a business is small if it has 1,500 or fewer employees.

2012 U.S. Census Bureau data show that 1,341 firms provided resale services during that year. Of that number, 1,341 operated with fewer than 1,000 employees. Thus, under this category and the associated small business size standard, the majority of these resellers can be considered small entities.

According to Commission data, 881 carriers have reported that they are engaged in the provision of toll resale services. Of this total, an estimated 857 have 1,500 or fewer employees. Consequently, the Commission estimates that the majority of toll resellers are small entities. 16.

Other Toll Carriers. Neither the Commission nor the SBA has developed a definition for small businesses specifically applicable to Other Toll Carriers. This category includes toll carriers that do not fall within the categories of interexchange carriers, operator service providers, prepaid calling card providers, satellite service carriers, or toll resellers. The closest applicable size standard under SBA rules is for Wired Telecommunications Carriers.

The applicable SBA size standard consists of all such companies having 1,500 or fewer employees. U.S. Census Bureau data for 2012 indicates that 3,117 firms operated during that year. Of that number, 3,083 operated with fewer than 1,000 employees.

Thus, under this category and the associated small business size standard, the majority of Other Toll Carriers can be considered small. According to internally developed Commission data, 284 companies reported that their primary telecommunications service activity was the provision of other toll carriage. Of these, an estimated 279 have 1,500 or fewer employees. Consequently, the Commission estimates that most Other Toll Carriers are small entities.

17. Prepaid Calling Card Providers. Neither the Commission nor the SBA has developed a small business definition specifically for prepaid calling card providers. The most appropriate NAICS code-based category for defining prepaid calling card providers is Telecommunications Resellers.

This industry comprises establishments engaged in purchasing access and network capacity from owners and operators of telecommunications networks and reselling wired and wireless telecommunications services (except satellite) to businesses and households. Establishments in this industry resell telecommunications. They do not operate transmission facilities and infrastructure. Mobile virtual networks operators (MVNOs) are included in this industry.

Under the applicable SBA size standard, such a business is small if it has 1,500 or fewer employees. U.S. Census Bureau data for 2012 show that 1,341 firms provided resale services during that year. Of that number, 1,341 operated with fewer than 1,000 employees.

Thus, under this category and the associated small business size standard, the majority of these prepaid calling card providers can be considered small entities. According to the Commission's Form 499 Filer Database, 86 active companies reported that they were engaged in the provision of prepaid calling cards. The Commission does not have data regarding how many of these companies have 1,500 or fewer employees, however, the Commission estimates that the majority of the 86 active prepaid calling card providers that may be affected by these rules are likely small entities. 18.

Wireless Telecommunications Carriers (except Satellite). Neither the SBA nor the Commission has developed a size standard specifically applicable to Wireless Carriers and Service Providers. The closest applicable is Wireless Telecommunications Carriers (except Satellite), which the SBA small business size standard is such a business is small if it 1,500 persons or less. For this industry, U.S.

Census Bureau data for 2012 show that there were 967 firms that operated for the entire year. Of this total, 955 firms had employment of 999 or fewer employees and 12 had employment of 1000 employees or more. Thus under this category and the associated size standard, the Commission estimates that the majority of Wireless Carriers and Service Providers are small entities. 19.

According to internally developed Commission data for all classes of Wireless Service Providers, there are 970 carriers that reported they were engaged in the provision of wireless services. Of this total, an estimated 815 have 1,500 or fewer employees, and 155 have more than 1,500 employees. Thus, using available data, we estimate that the majority of Wireless Carriers and Service Providers can be considered small. 20.

Cable and Other Subscription Programming. The U.S. Census Bureau defines this industry as establishments primarily engaged in operating studios and facilities for the broadcasting of programs on a subscription or fee basis. The broadcast programming is typically narrowcast in nature (e.g., limited format, such as news, sports, education, or youth-oriented).

These establishments produce programming in their own facilities or acquire programming from external sources. The programming material is usually delivered to a third party, such as cable systems or direct-to-home satellite Start Printed Page 31418systems, for transmission to viewers.” The SBA size standard for this industry establishes as small any company in this category with annual receipts less than $41.5 million. Based on U.S. Census Bureau data for 2012, 367 firms operated for the entire year.

Of that number, 319 firms operated with annual receipts of less than $25 million a year and 48 firms operated with annual receipts of $25 million or more. Based on this data, the Commission estimates that a majority of firms in this industry are small. 21. Cable Companies and Systems (Rate Regulation).

The Commission has also developed its own small business size standards, for the purpose of cable rate regulation. Under the Commission's rules, a “small cable company” is one serving 400,000 or fewer subscribers nationwide. Industry data indicate that there are 4,600 active cable systems in the United States. Of this total, all but five cable operators nationwide are small under the 400,000-subscriber size standard.

In addition, under the Commission's rate regulation rules, a “small system” is a cable system serving 15,000 or fewer subscribers. Commission records show 4,600 cable systems nationwide. Of this total, 3,900 cable systems have fewer than 15,000 subscribers, and 700 systems have 15,000 or more subscribers, based on the same records. Thus, under this standard as well, we estimate that most cable systems are small entities.

22. Cable System Operators (Telecom Act Standard). The Communications Act of 1934, as amended, also contains a size standard for small cable system operators, which is “a cable operator that, directly or through an affiliate, serves in the aggregate fewer than one percent of all subscribers in the United States and is not affiliated with any entity or entities whose gross annual revenues in the aggregate exceed $250,000,000.” As of 2019, there were approximately 48,646,056 basic cable video subscribers in the United States. Accordingly, an operator serving fewer than 486,460 subscribers shall be deemed a small operator if its annual revenues, when combined with the total annual revenues of all its affiliates, do not exceed $250 million in the aggregate.

Based on available data, we find that all but five cable operators are small entities under this size standard. We note that the Commission neither requests nor collects information on whether cable system operators are affiliated with entities whose gross annual revenues exceed $250 million. Therefore, we are unable at this time to estimate with greater precision the number of cable system operators that would qualify as small cable operators under the definition in the Communications Act. 23.

All Other Telecommunications. The “All Other Telecommunications” category is comprised of establishments primarily engaged in providing specialized telecommunications services, such as satellite tracking, communications telemetry, and radar station operation. This industry also includes establishments primarily engaged in providing satellite terminal stations and associated facilities connected with one or more terrestrial systems and capable of transmitting telecommunications to, and receiving telecommunications from, satellite systems. Establishments providing internet services or voice over internet protocol (VoIP) services via client-supplied telecommunications connections are also included in this industry.

The SBA has developed a small business size standard for “All Other Telecommunications”, which consists of all such firms with annual receipts of $35 million or less. For this category, U.S. Census Bureau data for 2012 show that there were 1,442 firms that operated for the entire year. Of those firms, a total of 1,400 had annual receipts less than $25 million and 15 firms had annual receipts of $25 million to $49,999,999.

Thus, the Commission estimates that the majority of “All Other Telecommunications” firms potentially affected by our action can be considered small. 24. Radio and Television Broadcasting and Wireless Communications Equipment Manufacturing. This industry comprises establishments primarily engaged in manufacturing radio and television broadcast and wireless communications equipment.

Examples of products made by these establishments are. Transmitting and receiving antennas, cable television equipment, GPS equipment, pagers, cellular phones, mobile communications equipment, and radio and television studio and broadcasting equipment. The SBA has established a small business size standard for this industry of 1,250 or fewer employees. U.S.

Census Bureau data for 2012 show that 841 establishments operated in this industry in that year. Of that number, 828 establishments operated with fewer than 1,000 employees, 7 establishments operated with between 1,000 and 2,499 employees and 6 establishments operated with 2,500 or more employees. Based on this data, we conclude that a majority of manufacturers in this industry are small. 25.

Semiconductor and Related Device Manufacturing. This industry comprises establishments primarily engaged in manufacturing semiconductors and related solid state devices. Examples of products made by these establishments are integrated circuits, memory chips, microprocessors, diodes, transistors, solar cells and other optoelectronic devices. The SBA has developed a small business size standard for Semiconductor and Related Device Manufacturing, which consists of all such companies having 1,250 or fewer employees.

U.S. Census Bureau data for 2012 show that there were 862 establishments that operated that year. Of this total, 843 operated with fewer than 1,000 employees. Thus, under this size standard, the majority of firms in this industry can be considered small.

26. Software Publishers. This industry comprises establishments primarily engaged in computer software publishing or publishing and reproduction. Establishments in this industry carry out operations necessary for producing and distributing computer software, such as designing, providing documentation, assisting in installation, and providing support services to software purchasers.

These establishments may design, develop, and publish, or publish only. The SBA has established a size standard for this industry of annual receipts of $41.5 million or less per year. U.S. Census data for 2012 indicates that 5,079 firms operated for the entire year.

Of that number 4,691 firms had annual receipts of less than $25 million and 166 firms had annual receipts of $25,000,000 to $49,999,999. Based on this data, we conclude that a majority of firms in this industry are small. 27. Internet Service Providers (Broadband).

Broadband internet service providers include wired (e.g., cable, DSL) and VoIP service providers using their own operated wired telecommunications infrastructure fall in the category of Wired Telecommunication Carriers. Wired Telecommunications Carriers are comprised of establishments primarily engaged in operating and/or providing access to transmission facilities and infrastructure that they own and/or lease for the transmission of voice, data, text, sound, and video using wired telecommunications networks. Transmission facilities may be based on a single technology or a combination of technologies. The SBA size standard for this category classifies a business as small if it has 1,500 or fewer employees.

U.S. Census Bureau data for 2012 show that there were 3,117 firms that operated Start Printed Page 31419that year. Of this total, 3,083 operated with fewer than 1,000 employees. Consequently, under this size standard the majority of firms in this industry can be considered small.

28. Internet Service Providers (Non-Broadband). Internet access service providers such as Dial-up internet service providers, VoIP service providers using client-supplied telecommunications connections and internet service providers using client-supplied telecommunications connections (e.g., dial-up ISPs) fall in the category of All Other Telecommunications. The SBA has developed a small business size standard for All Other Telecommunications which consists of all such firms with gross annual receipts of $35 million or less.

For this category, U.S. Census Bureau data for 2012 show that there were 1,442 firms that operated for the entire year. Of these firms, a total of 1,400 had gross annual receipts of less than $25 million. Consequently, under this size standard a majority of firms in this industry can be considered small.

29. All Other Information Services. The U.S. Census Bureau has determined that this category “comprises establishments primarily engaged in providing other information services (except news syndicates, libraries, archives, internet publishing and broadcasting, and Web search portals).” The SBA has developed a small business size standard for this category, which consists of all such firms with annual receipts of $30 million or less.

U.S. Census Bureau data for 2012 show that there were 512 firms that operated for the entire year. Of those firms, a total of 498 had annual receipts less than $25 million and 7 firms had annual receipts of $25 million to $49, 999,999. Consequently, we estimate that the majority of these firms are small entities that may be affected by our action.

D. Description of Projected Reporting, Recordkeeping, and Other Compliance Requirements for Small Entities 30. The FNPRM proposes and seeks comment on rules to require covered text providers to support text messaging to 988. It tentatively concludes that text-to-988 functionality will greatly improve consumer access to the Lifeline, particularly for at-risk populations, and thereby save lives.

The proposed rules would require CMRS providers and interconnected text messaging service providers to route texts sent to 988 to the 10-digit Lifeline number, presently 1-800-273-8255 (TALK). The FNPRM proposes (1) establishing a definition that sets the outer bound of text messages sent to 988 that covered text providers may be required to support. And (2) directing the Wireline Competition Bureau (Bureau) to identify text formats within the scope of that definition that the Lifeline can receive and thus covered text providers must support by routing to the 10-digit Lifeline number. The FNPRM seeks comment on this proposal.

The Commission preliminarily believes that applying the same rules equally to all entities in this context is necessary to alleviate potential consumer confusion from adopting different rules for different covered text providers. The Commission proposes that the costs and/or administrative burdens associated with the rules will not unduly burden small entities. E. Steps Taken To Minimize the Significant Economic Impact on Small Entities, and Significant Alternatives Considered 31.

The RFA requires an agency to describe any significant alternatives that it has considered in reaching its proposed approach, which may include the following four alternatives (among others). (1) The establishment of differing compliance or reporting requirements or timetables that take into account the resources available to small entities. (2) the clarification, consolidation, or simplification of compliance and reporting requirements under the rules for such small entities. (3) the use of performance rather than design standards.

And (4) an exemption from coverage of the rule, or any part thereof, for such small entities. 32. In the FNPRM, the Commission seeks comment from all entities, including small entities, regarding the impact of these proposed rules on small entities. The Commission seeks comment on the impact, cost or otherwise, that requiring text messaging to 988 capability will impose on regional and rural carriers and small businesses.

The Commission also seeks comment on whether to adopt any exemptions for small businesses and if so, under what circumstances. The Commission asks and will consider alternatives to the proposals and on alternative ways of implementing the proposals. F. Federal Rules That May Duplicate, Overlap, or Conflict With the Proposed Rules 33.

None. III. Procedural Matters 34. Ex Parte Rules.

This proceeding shall be treated as a “permit-but-disclose” proceeding in accordance with the Commission's ex parte rules. Persons making ex parte presentations must file a copy of any written presentation or a memorandum summarizing any oral presentation within two business days after the presentation (unless a different deadline applicable to the Sunshine period applies). Persons making oral ex parte presentations are reminded that memoranda summarizing the presentation must (1) list all persons attending or otherwise participating in the meeting at which the ex parte presentation was made, and (2) summarize all data presented and arguments made during the presentation. If the presentation consisted in whole or in part of the presentation of data or arguments already reflected in the presenter's written comments, memoranda or other filings in the proceeding, the presenter may provide citations to such data or arguments in his or her prior comments, memoranda, or other filings (specifying the relevant page and/or paragraph numbers where such data or arguments can be found) in lieu of summarizing them in the memorandum.

Documents shown or given to Commission staff during ex parte meetings are deemed to be written ex parte presentations and must be filed consistent with Rule 1.1206(b). In proceedings governed by Rule 1.49(f) or for which the Commission has made available a method of electronic filing, written ex parte presentations and memoranda summarizing oral ex parte presentations, and all attachments thereto, must be filed through the electronic comment filing system available for that proceeding, and must be filed in their native format (e.g., .doc, .xml, .ppt, searchable .pdf). Participants in this proceeding should familiarize themselves with the Commission's ex parte rules. 35.

Initial Regulatory Flexibility Analysis. Pursuant to the Regulatory Flexibility Act (RFA), the Commission has prepared an Initial Regulatory Flexibility Analysis (IRFA) of the possible significant economic impact on small entities of the policies and actions considered in this FNPRM. Written public comments are requested on this IRFA. Comments must be identified as responses to the IRFA and must be filed by the deadlines for comments on the FNPRM.

The Commission's Consumer and Governmental Affairs Bureau, Reference Information Center, will send a copy of the FNPRM, including the IRFA, to the Chief Counsel for Advocacy of the Small Business Administration.Start Printed Page 31420 36. Comment Filing Procedures. Pursuant to §§ 1.415 and 1.419 of the Commission's rules, 47 CFR 1.415, 1.419, interested parties may file comments and reply comments on or before the dates indicated on the first page of this document. Comments may be filed using the Commission's Electronic Comment Filing System (ECFS).

See Electronic Filing of Documents in Rulemaking Proceedings, 63 FR 24121 (1998). Electronic Filers. Comments may be filed electronically using the internet by accessing ECFS. Https://www.fcc.gov/​ecfs/​.

Paper Filers. Parties who choose to file by paper must file an original and one copy of each filing. Filings can be sent by commercial overnight courier, or by first-class or overnight U.S. Postal Service mail.

All filings must be addressed to the Commission's Secretary, Office of the Secretary, Federal Communications Commission. Commercial overnight mail (other than U.S. Postal Service Express Mail and Priority Mail) must be sent to 9050 Junction Drive, Annapolis Junction, MD 20701. U.S.

Postal Service first-class, Express, and Priority mail must be addressed to 45 L Street NE, Washington, DC 20554. Effective March 19, 2020, and until further notice, the Commission no longer accepts any hand or messenger delivered filings. This is a temporary measure taken to help protect the health and safety of individuals, and to mitigate the transmission of antifungal medication. See FCC Announces Closure of FCC Headquarters Open Window and Change in Hand-Delivery Policy, Public Notice, 35 FCC Rcd 2788 (OS 2020), https://www.fcc.gov/​document/​fcc-closes-headquarters-open-window-and-changes-hand-delivery-policy.

37. People with Disabilities. To request materials in accessible formats for people with disabilities (braille, large print, electronic files, audio format), send an email to fcc504@fcc.gov or call the Consumer &. Governmental Affairs Bureau at (202) 418-0530 (voice).

38. Paperwork Reduction Act of 1995 Analysis. This document may contain proposed new or modified information collection requirements. The Commission, as part of its continuing effort to reduce paperwork burdens, invites the general public and the Office of Management and Budget (OMB) to comment on the information collection requirements contained in this document, as required by the Paperwork Reduction Act of 1995, Public Law 104-13.

In addition, pursuant to the Small Business Paperwork Relief Act of 2002, Public Law 107-198, we seek specific comment on how we might further reduce the information collection burden for small business concerns with fewer than 25 employees. 39. Contact Person. For further information about this rulemaking proceeding, please contact Michelle Sclater, Competition Policy Division, Wireline Competition Bureau, at (202) 418-0388 or michelle.sclater@fcc.gov.

IV. Ordering Clauses 40. It is ordered, pursuant to sections 201, 251, 301, 303, 307, 309, and 316 of the Communications Act of 1934, as amended, 47 U.S.C. 201, 251, 301, 303, 307, 309, 316, that the FNPRM in WC Docket No.

18-336 is adopted. 41. It is further ordered that the Petition for Reconsideration filed by Communications Equality Advocates is granted in part to the extent described herein. 42.

It is further ordered that the Commission's Consumer and Governmental Affairs Bureau, Reference Information Center, shall send a copy of this FNPRM, including the Initial Regulatory Flexibility Analysis, to the Chief Counsel for Advocacy of the Small Business Administration. Start List of Subjects Communications common carriersTelecommunicationsTelephone End List of Subjects Start Signature Federal Communications Commission. Marlene Dortch, Secretary. End Signature Proposed Rules For the reasons discussed in the preamble, the Federal Communications Commission proposes to amend 47 CFR part 52 as follows.

Start Part End Part Start Amendment Part1. The authority citation for part 52 is revised to read as follows. End Amendment Part Start Authority 47 U.S.C. 151, 152, 153, 154, 155, 201-205, 207-209, 218, 225-227, 251-252, 271, 301, 303, 307, 309, 316, 332, unless otherwise noted.

End Authority Start Amendment Part2. Add § 52.201 to subpart E to read as follows. End Amendment Part Texting to the National Suicide Prevention and Mental Health Crisis Hotline. (a) Support for 988 text message service.

Beginning [[DATE]], all covered text providers must have the capability to route a covered 988 text message to the current toll free access number for the National Suicide Prevention Lifeline, presently 1-800-273-8255 (TALK). (b) Definitions. For purposes of this section. 988 text message.

(i) Means a message consisting of text, images, sounds, or other information that is transmitted to or from a device that is identified as the receiving or transmitting device by means of a 10-digit telephone number, N11 service code, or 988. (ii) Includes a SMS message and a MMS message. And (iii) Does not include— (A) A real-time, two-way voice or video communication. Or (B) A message sent over an IP-enabled messaging service to another user of the same messaging service, except a message described in paragraph (b)(2) of this section.

Covered 988 text message means a 988 text message in SMS format and any other format that the Wireline Competition Bureau has determined must be supported by covered text providers. Covered text provider shall mean all Commercial Mobile Radio Services (CMRS) providers and providers of interconnected text messaging services that enable consumers to send text messages to and receive text messages from all or substantially all text-capable U.S. Telephone numbers, including through the use of applications downloaded or otherwise installed on mobile phones. Multimedia message service (MMS) shall have the same definition as the term in § 64.1600(k) of the Commission's rules.

Short message service (SMS) shall have the same definition as the term in § 64.1600(m) of the Commission's rules. End Supplemental Information [FR Doc. 2021-09855 Filed 6-9-21. 4:15 pm]BILLING CODE 6712-01-P.

Buy diflucan canada

	Diflucan	Sporanox	Mentax	Micatin	Lotrisone
Does work at first time	Ask your Doctor	Ask your Doctor	Ask your Doctor	Ask your Doctor	Ask your Doctor
Male dosage	Yes	No	Yes	Online	Online
Can women take	No	Online	Yes	Yes	Yes
Average age to take	No	Yes	Yes	Yes	No
How long does stay in your system	Canadian pharmacy only	In online pharmacy	Canadian pharmacy only	Canadian pharmacy only	Register first
Buy without prescription	No	Online	Yes	Online	Yes

Shutterstock buy diflucan canada U.S Visit Your URL. Sens. Elizabeth Warren (D-MA), Richard Blumenthal (D-CT), Dick Durbin (D-IL), buy diflucan canada and U.S.

Reps. Raja Krishnamoorthi (D-IL) and Dianna DeGette (D-CO) are questioning tobacco companies on their use of social media advertising to market e-cigarettes to youths buy diflucan canada and adolescents during the antifungal medication diflucan. Warren is a member of the Senate Health, Education, Labor, and Pensions Committee, while Krishnamoorthi is the Chair of the House Committee on Oversight and Reform’s Subcommittee on Economic and Consumer Policy and DeGette is Chair of the House Energy and Commerce Committee’s Oversight and Investigations Subcommittee.

In letters to British American Tobacco (BAT), Philip Morris International (PMI), the Food and Drug Administration (FDA), and the Federal Trade Commission (FTC), the Congressmembers buy diflucan canada said the tobacco companies had have “chosen to exploit a global diflucan for marketing purposes.” The Congressmembers said the subsidiaries of the companies used the public health emergency to promote their e-cigarette products. Citing research done by public health experts at Stanford, the Congressmembers said the companies produced over 300 antifungal medication-themed e-cigarette advertisements, several of which offered things in short supply, like hand sanitizer, face masks, and toilet paper, as free gifts with the purchase of vaping products. Others falsely claimed that vaping is not associated with an increased risk of contracting antifungal medication, the legislators said.

Additionally, they wrote, the companies appear to have specifically targeted underage users, placing the vast majority of their ads on Instagram and Twitter, a potential violation of federal law buy diflucan canada. €œThese advertisements are a blatant exploitation of a diflucan that has killed nearly two million people across the world and devastated the lives of countless more. They are reckless and endanger millions, especially buy diflucan canada as countries around the globe are experiencing yet another surge in cases,” the lawmakers wrote in their letters.

€œThis attempt to profit off the back of a global health crisis, reminiscent of decades of false and misleading advertising about cigarettes by tobacco companies, represents a callous indifference to the lives and well-being of millions of people across the world.”The Congressmembers asked both tobacco companies for copies of the company’s advertisements, a list of subsidiaries that distribute their products, internal documentation of the companies’ antifungal medication marketing strategies and communications with federal health officials regarding the content of these advertisements. The lawmakers asked the FTC and FDA for a staff-level briefing and buy diflucan canada information on the agencies’ enforcement authority related to e-cigarette advertising and promotional activities.Friday, the U.S. Food and Drug Administration announced that it was taking further steps to combat the opioid crisis through risk evaluation and mitigation strategy programs.

FDA Commissioner Stephen M buy diflucan canada. Hahn announced that while the FDA’s day-to-day focus continues to be the antifungal medication diflucan, the agency continues to work on other public health issues, like the opioid epidemic. “We remain committed to using all facets of our regulatory authority to lessen the impact of opioid addiction, misuse, and abuse while also striking a careful balance between patient access and safety to ensure that patients suffering from significant pain have access to appropriate medication,” he said in a statement.

To do that, he said, the agency has worked to decrease unnecessary exposure to prescription opioids and prevent new addictions, supported the treatment of those with opioid use disorder, fostered the development of new pain therapies, and taken action against those who buy diflucan canada contribute to illegal import and sale of opioids. The agency took further steps to strengthen the risk evaluation and mitigation strategies for opioid analgesics by looking at transmucosal immediate-release fentanyl (TIRF) products and toughening the requirements for prescribing practices. These changes include requiring prescribers buy diflucan canada to document a patient’s opioid tolerance.

Requiring outpatient pharmacies dispensing TIRF medicines to document a patient’s opioid tolerance. Requiring inpatient pharmacies to develop internal policies and procedures to buy diflucan canada very opioid tolerance in patients requiring TIRF medicines while hospitalized, and requiring a new patient registry for use, along with other sources, in monitoring accidental exposure, misuse, abuse, addiction, and overdose. “Today, we took further steps to strengthen the REMS program for transmucosal immediate-release fentanyl (TIRF) products to help ensure that the benefits of these drugs continue to outweigh the risks,” Hahn said.

€œTIRF medicines contain fentanyl, a powerful opioid, and are used to manage breakthrough pain in adults with cancer who are routinely taking other opioid pain medicines around-the-clock for buy diflucan canada pain. To use the TIRF medicines safely, these patients must be opioid tolerant based on concurrent regular use of another opioid medication.Shutterstock The U.S. Department of Health and Human Services (HHS) recently awarded West Virginia $1.9 million for research and programs addressing opioid misuse.Funding was divided among four organizations.

The Morgan County Partnership received $45,436, United Way of the River Cities received $54,500, West Virginia University’s Drug Abuse and Addiction Research received $222,568, and the West Virginia Department of Health and Human Resources received $1.5 million.“The drug epidemic has ravaged our state, impacting every West Virginian buy diflucan canada and taking thousands from us too soon, and the antifungal medication diflucan has only made this crisis worse,” Sen. Joe Manchin (D-WV) said. €œThis funding supports research and programs that help West Virginians with substance use disorder across the state… Together we can manage both crises in the Mountain States.”“The opioid crisis has affected lives and communities across the country, but some states—including West buy diflucan canada Virginia—have been hit harder than others,” Sen.

Shelley Moore Capito (R-WV) said. €œUnfortunately, the current diflucan has brought new challenges for those in recovery and living with addiction, resulting in rising overdoses and treatment needs, which makes these funds even more critical.”Capito thanked HHS for its support, which will have a positive buy diflucan canada impact on West Virginians. Both senators are members of the Senate Appropriations Committee.Shutterstock A new report from the Centers for Disease Control and Prevention (CDC) shows that while drug overdose deaths from prescription opioids are dropping, overdose deaths for 2019 are up compared to 2018.

According to the report, deaths due to opioid-related drugs like oxycodone, hydrocodone, and morphine are down 5 buy diflucan canada percent over 2018. Opioid-related deaths declined 13 percent between 2017 and 2018. But overdose deaths due to fentanyl, stimulants including methamphetamine and cocaine, and deaths due to poly-drug involvements are up, the report showed.

Between 2012 and 2019, buy diflucan canada the report said drug overdoses involving cocaine increased from 1.4 deaths per 100,000 Americans to 4.9 per every 100,000, while those involving psychostimulants increased from .8 per 100,000 to 5.0 per 100,000. The White House’s Office of National Drug Control Policy’s Director Jim Carroll said the new data suggests America should address drug smuggling across the Mexican border. €œLast year’s drug mortality data makes it buy diflucan canada clear.

Innovations in illicit substance combinations, and a stark spike in the amount of lethal methamphetamine smuggled into the United States from Mexico, took a heartbreaking toll on the United States in 2019,” Carroll said in a press release. €œAlmost all of the illegal drugs killing people and shattering families are buy diflucan canada coming from outside of the United States. It is apparent that continued vigilance at our Nation’s Borders is necessary to keep illicit substances off of American soil and out of our communities.”Carroll said the dropping opioid death numbers could be linked to the Trump administration’s declaration of the opioid crisis as a public health emergency in 2017.

€œYet within the grim buy diflucan canada overall numbers, there are rays of hope. Opioid-related deaths involving opioid analgesics excluding fentanyl continue to fall year-over-year since President Trump declared the opioid crisis a public health emergency in 2017,” Carroll said. €œBy taking the whole-of-government approach championed by the Trump Administration to address the opioid crisis, and applying it to the scourge of methamphetamine, fentanyl, and other deadly synthetics, we can begin to turn the tide and ensure fewer American lives are lost, and those suffering from substance use disorder are connected with treatment and hope.”Shutterstock Congress recently included $850 million in funding for the national Certified Community Behavioral Health Clinic (CCBHC) Expansion Grants program in the Consolidated Appropriations Act of 2021.

Congress also extended the Excellence in Mental Health and buy diflucan canada Addiction Treatment Act by three years.“CCBHCs play a vital role in meeting the mental health and substances use care needs of communities and represent a lifeline for so many vulnerable people as our nation copes with a diflucan and an opioid crisis,” Chuck Ingoglia, National Council for Behavioral Health president and CEO, said. Approximately one in five Americans suffer from substance use or mental illness. Of those who have a mental illness, 43 percent receive treatment, whereas 12 percent buy diflucan canada of addicts receive treatment.

Drug overdose is the leading cause of death for Americans younger than 50, while suicide is the second-leading cause of death for those between 10 and 34 years old.CCBHCs provide immediate screenings, risk assessments, diagnoses. Outpatient mental health and buy diflucan canada substance abuse treatment services. Crisis services.

And care coordination with emergency rooms, law enforcement, and veteran groups.In the first year of operation, 87 percent of CCBHCs increased the number of patients served, 93 percent provided staff training in suicide prevention and response, and 94 percent increased the number of patients treated for addiction, according to the National Council for Behavioral Health..

Shutterstock buy diflucan online U.S. Sens. Elizabeth Warren buy diflucan online (D-MA), Richard Blumenthal (D-CT), Dick Durbin (D-IL), and U.S. Reps. Raja Krishnamoorthi (D-IL) and Dianna DeGette (D-CO) are questioning tobacco companies on their use of buy diflucan online social media advertising to market e-cigarettes to youths and adolescents during the antifungal medication diflucan.

Warren is a member of the Senate Health, Education, Labor, and Pensions Committee, while Krishnamoorthi is the Chair of the House Committee on Oversight and Reform’s Subcommittee on Economic and Consumer Policy and DeGette is Chair of the House Energy and Commerce Committee’s Oversight and Investigations Subcommittee. In letters to British American Tobacco (BAT), Philip Morris International (PMI), the Food and Drug Administration (FDA), and the Federal Trade Commission buy diflucan online (FTC), the Congressmembers said the tobacco companies had have “chosen to exploit a global diflucan for marketing purposes.” The Congressmembers said the subsidiaries of the companies used the public health emergency to promote their e-cigarette products. Citing research done by public health experts at Stanford, the Congressmembers said the companies produced over 300 antifungal medication-themed e-cigarette advertisements, several of which offered things in short supply, like hand sanitizer, face masks, and toilet paper, as free gifts with the purchase of vaping products. Others falsely claimed that vaping is not associated with an increased risk of contracting antifungal medication, the legislators said. Additionally, they wrote, the companies buy diflucan online appear to have specifically targeted underage users, placing the vast majority of their ads on Instagram and Twitter, a potential violation of federal law.

€œThese advertisements are a blatant exploitation of a diflucan that has killed nearly two million people across the world and devastated the lives of countless more. They are reckless and endanger millions, especially as countries around the globe are experiencing yet another surge in cases,” buy diflucan online the lawmakers wrote in their letters. €œThis attempt to profit off the back of a global health crisis, reminiscent of decades of false and misleading advertising about cigarettes by tobacco companies, represents a callous indifference to the lives and well-being of millions of people across the world.”The Congressmembers asked both tobacco companies for copies of the company’s advertisements, a list of subsidiaries that distribute their products, internal documentation of the companies’ antifungal medication marketing strategies and communications with federal health officials regarding the content of these advertisements. The lawmakers asked the FTC and FDA for buy diflucan online a staff-level briefing and information on the agencies’ enforcement authority related to e-cigarette advertising and promotional activities.Friday, the U.S. Food and Drug Administration announced that it was taking further steps to combat the opioid crisis through risk evaluation and mitigation strategy programs.

FDA Commissioner Stephen M buy diflucan online. Hahn announced that while the FDA’s day-to-day focus continues to be the antifungal medication diflucan, the agency continues to work on other public health issues, like the opioid epidemic. “We remain committed to using all facets of our regulatory authority to lessen the impact of opioid addiction, misuse, and abuse while also striking a careful balance between patient access and safety to ensure that patients suffering from significant pain have access to appropriate medication,” he said in a statement. To do that, he said, the agency has worked to decrease unnecessary exposure to prescription opioids and prevent new addictions, supported the treatment of those with opioid use disorder, fostered the development of new pain therapies, and taken buy diflucan online action against those who contribute to illegal import and sale of opioids. The agency took further steps to strengthen the risk evaluation and mitigation strategies for opioid analgesics by looking at transmucosal immediate-release fentanyl (TIRF) products and toughening the requirements for prescribing practices.

These changes include requiring buy diflucan online prescribers to document a patient’s opioid tolerance. Requiring outpatient pharmacies dispensing TIRF medicines to document a patient’s opioid tolerance. Requiring inpatient pharmacies to develop internal policies and procedures to very opioid tolerance in patients requiring TIRF medicines while hospitalized, and requiring a new patient registry for use, along with other sources, buy diflucan online in monitoring accidental exposure, misuse, abuse, addiction, and overdose. “Today, we took further steps to strengthen the REMS program for transmucosal immediate-release fentanyl (TIRF) products to help ensure that the benefits of these drugs continue to outweigh the risks,” Hahn said. €œTIRF medicines contain fentanyl, a powerful buy diflucan online opioid, and are used to manage breakthrough pain in adults with cancer who are routinely taking other opioid pain medicines around-the-clock for pain.

To use the TIRF medicines safely, these patients must be opioid tolerant based on concurrent regular use of another opioid medication.Shutterstock The U.S. Department of Health and Human Services (HHS) recently awarded West Virginia $1.9 million for research and programs addressing opioid misuse.Funding was divided among four organizations. The Morgan County Partnership received $45,436, United Way of the River Cities received $54,500, West Virginia University’s Drug Abuse and Addiction Research received $222,568, and the West Virginia Department of Health and Human Resources buy diflucan online received $1.5 million.“The drug epidemic has ravaged our state, impacting every West Virginian and taking thousands from us too soon, and the antifungal medication diflucan has only made this crisis worse,” Sen. Joe Manchin (D-WV) said. €œThis funding supports research and programs that help West Virginians with substance use disorder across the state… Together we can manage both crises in the Mountain States.”“The opioid crisis has affected lives and communities across the country, but some buy diflucan online states—including West Virginia—have been hit harder than others,” Sen.

Shelley Moore Capito (R-WV) said. €œUnfortunately, the buy diflucan online current diflucan has brought new challenges for those in recovery and living with addiction, resulting in rising overdoses and treatment needs, which makes these funds even more critical.”Capito thanked HHS for its support, which will have a positive impact on West Virginians. Both senators are members of the Senate Appropriations Committee.Shutterstock A new report from the Centers for Disease Control and Prevention (CDC) shows that while drug overdose deaths from prescription opioids are dropping, overdose deaths for 2019 are up compared to 2018. According to the report, deaths due to opioid-related drugs like oxycodone, hydrocodone, buy diflucan online and morphine are down 5 percent over 2018. Opioid-related deaths declined 13 percent between 2017 and 2018.

But overdose deaths due to fentanyl, stimulants including methamphetamine and cocaine, and deaths due to poly-drug involvements are up, the report showed. Between 2012 and 2019, the report said drug overdoses involving cocaine increased from 1.4 deaths per 100,000 Americans to 4.9 per every 100,000, while those buy diflucan online involving psychostimulants increased from .8 per 100,000 to 5.0 per 100,000. The White House’s Office of National Drug Control Policy’s Director Jim Carroll said the new data suggests America should address drug smuggling across the Mexican border. €œLast year’s drug buy diflucan online mortality data makes it clear. Innovations in illicit substance combinations, and a stark spike in the amount of lethal methamphetamine smuggled into the United States from Mexico, took a heartbreaking toll on the United States in 2019,” Carroll said in a press release.

€œAlmost all of the illegal drugs killing people and shattering families are coming from outside of the buy diflucan online United States. It is apparent that continued vigilance at our Nation’s Borders is necessary to keep illicit substances off of American soil and out of our communities.”Carroll said the dropping opioid death numbers could be linked to the Trump administration’s declaration of the opioid crisis as a public health emergency in 2017. €œYet within the grim overall numbers, buy diflucan online there are rays of hope. Opioid-related deaths involving opioid analgesics excluding fentanyl continue to fall year-over-year since President Trump declared the opioid crisis a public health emergency in 2017,” Carroll said. €œBy taking the whole-of-government approach championed by the Trump Administration to address the opioid crisis, and applying it to the scourge of methamphetamine, fentanyl, and other deadly synthetics, we can begin to turn the tide and ensure fewer American lives are lost, and those suffering from substance use disorder are connected with treatment and hope.”Shutterstock Congress recently included $850 million in funding for the national Certified Community Behavioral Health Clinic (CCBHC) Expansion Grants program in the Consolidated Appropriations Act of 2021.

Congress also extended the Excellence in Mental Health and Addiction Treatment Act by three years.“CCBHCs play a vital role in meeting the mental health and buy diflucan online substances use care needs of communities and represent a lifeline for so many vulnerable people as our nation copes with a diflucan and an opioid crisis,” Chuck Ingoglia, National Council for Behavioral Health president and CEO, said. Approximately one in five Americans suffer from substance use or mental illness. Of those who have a mental illness, 43 percent receive treatment, whereas 12 percent of addicts receive treatment. Drug overdose is the leading cause of death for Americans younger than 50, while suicide is the second-leading cause of death for those between 10 and 34 years old.CCBHCs provide immediate screenings, risk assessments, diagnoses. Outpatient mental health and substance abuse treatment services.

Crisis services. And care coordination with emergency rooms, law enforcement, and veteran groups.In the first year of operation, 87 percent of CCBHCs increased the number of patients served, 93 percent provided staff training in suicide prevention and response, and 94 percent increased the number of patients treated for addiction, according to the National Council for Behavioral Health..

What may interact with Diflucan?

Do not take Diflucan with any of the following medications:

• cisapride
• pimozide
• red yeast rice

Diflucan may also interact with the following medications:

• birth control pills
• cyclosporine
• diuretics like hydrochlorothiazide
• medicines for diabetes that are taken by mouth
• medicines for high cholesterol like atorvastatin, lovastatin or simvastatin
• phenytoin
• ramelteon
• rifabutin
• rifampin
• some medicines for anxiety or sleep
• tacrolimus
• terfenadine
• theophylline
• warfarin

This list may not describe all possible interactions. Give your health care provider a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.

Buy diflucan tablets

Abstract Thiamine is essential buy diflucan tablets for the activity of several enzymes associated with energy metabolism in humans. Chronic alcohol use is associated with deficiency of thiamine along with other vitamins through several mechanisms. Several neuropsychiatric syndromes have been associated with thiamine deficiency in the context of alcohol use disorder including Wernicke–Korsakoff buy diflucan tablets syndrome, alcoholic cerebellar syndrome, alcoholic peripheral neuropathy, and possibly, Marchiafava–Bignami syndrome. High-dose thiamine replacement is suggested for these neuropsychiatric syndromes.Keywords.

Alcohol use disorder, alcoholic cerebellar syndrome, alcoholic peripheral neuropathy, Marchiafava–Bignami syndrome, thiamine, Wernicke–Korsakoff syndromeHow to cite this article:Praharaj buy diflucan tablets SK, Munoli RN, Shenoy S, Udupa ST, Thomas LS. High-dose thiamine strategy in Wernicke–Korsakoff syndrome and related thiamine deficiency conditions associated with alcohol use disorder. Indian J Psychiatry 2021;63:121-6How to buy diflucan tablets cite this URL:Praharaj SK, Munoli RN, Shenoy S, Udupa ST, Thomas LS. High-dose thiamine strategy in Wernicke–Korsakoff syndrome and related thiamine deficiency conditions associated with alcohol use disorder.

Indian J Psychiatry [serial online] 2021 buy diflucan tablets [cited 2021 May 13];63:121-6. Available from. Https://www.indianjpsychiatry.org/text.asp?. 2021/63/2/121/313716 Introduction Thiamine is a water-soluble vitamin (B1) that plays a key role in the activity of several enzymes associated with energy metabolism.

Thiamine pyrophosphate (or diphosphate) is the active form that acts as a cofactor for enzymes. The daily dietary requirement of thiamine in adults is 1–2 mg and is dependent on carbohydrate intake.[1],[2] The requirement increases if basal metabolic rate is higher, for example, during alcohol withdrawal state. Dietary sources include pork (being the major source), meat, legume, vegetables, and enriched foods. The body can store between 30 and 50 mg of thiamine and is likely to get depleted within 4–6 weeks if the diet is deficient.[2] In those with alcohol-related liver damage, the ability to store thiamine is gradually reduced.[1],[2]Lower thiamine levels are found in 30%–80% of chronic alcohol users.[3] Thiamine deficiency occurs due to poor intake of vitamin-rich foods, impaired intestinal absorption, decreased storage capacity of liver, damage to the renal epithelial cells due to alcohol, leading to increased loss from the kidneys, and excessive loss associated with medical conditions.[2],[3] Furthermore, alcohol decreases the absorption of colonic bacterial thiamine, reduces the enzymatic activity of thiamine pyrophosphokinase, and thereby, reducing the amount of available thiamine pyrophosphate.[4] Since facilitated diffusion of thiamine into cells is dependent on a concentration gradient, reduced thiamine pyrophosphokinase activity further reduces thiamine uptake into cells.[4] Impaired utilization of thiamine is seen in certain conditions (e.g., hypomagnesemia) which are common in alcohol use disorder.[2],[3],[4] This narrative review discusses the neuropsychiatric syndromes associated with thiamine deficiency in the context of alcohol use disorder, and the treatment regimens advocated for these conditions.

A PubMed search supplemented with manual search was used to identify neuropsychiatric syndromes related to thiamine deficiency in alcohol use disorder patients. Neuropsychiatric Syndromes Associated With Thiamine Deficiency Wernicke–Korsakoff syndromeWernicke encephalopathy is associated with chronic alcohol use, and if not identified and treated early, could lead to permanent brain damage characterized by an amnestic syndrome known as Korsakoff syndrome. Inappropriate treatment of Wernicke encephalopathy with lower doses of thiamine can lead to high mortality rates (~20%) and Korsakoff syndrome in ~ 80% of patients (ranges from 56% to 84%).[5],[6] The classic triad of Wernicke includes oculomotor abnormalities, cerebellar dysfunction, and confusion. Wernicke lesions are found in 12.5% of brain samples of patients with alcohol dependence.[7] However, only 20%–30% of them had a clinical diagnosis of Wernicke encephalopathy antemortem.

It has been found that many patients develop Wernicke–Korsakoff syndrome (WKS) following repeated subclinical episodes of thiamine deficiency.[7] In an autopsy report of 97 chronic alcohol users, only16% had all the three “classical signs,” 29% had two signs, 37% presented with one sign, and 19% had none.[8] Mental status changes are the most prevalent sign (seen in 82% of the cases), followed by eye signs (in 29%) and ataxia (23%).[8] WKS should be suspected in persons with a history of alcohol use and presenting with signs of ophthalmoplegia, ataxia, acute confusion, memory disturbance, unexplained hypotension, hypothermia, coma, or unconsciousness.[9] Operational criteria for the diagnosis of Wernicke encephalopathy have been proposed by Caine et al.[10] that requires two out of four features, i.e., (a) dietary deficiency (signs such as cheilitis, glossitis, and bleeding gums), (b) oculomotor abnormalities (nystagmus, opthalmoplegia, and diplopia), (c) cerebellar dysfunction (gait ataxia, nystagmus), and (d) either altered mental state (confusion) or mild memory impairment.As it is very difficult to clinically distinguish Wernicke encephalopathy from other associated conditions such as delirium tremens, hepatic encephalopathy, or head injury, it is prudent to have a lower threshold to diagnose this if any of the clinical signs is seen. Magnetic resonance imaging (MRI) brain scan during Wernicke encephalopathy shows mammillary body atrophy and enlarged third ventricle, lesions in the medial portions of thalami and mid brain and can be used to aid diagnosis.[11],[12] However, most clinical situations warrant treatment without waiting for neuroimaging report. The treatment suggestions in the guidelines vary widely. Furthermore, hardly any evidence-based recommendations exist on a more general use of thiamine as a preventative intervention in individuals with alcohol use disorder.[13] There are very few studies that have evaluated the dose and duration of thiamine for WKS, but higher doses may result in a greater response.[6],[14] With thiamine administration rapid improvement is seen in eye movement abnormalities (improve within days or weeks) and ataxia (may take months to recover), but the effects on memory, in particular, are unclear.[4],[14] Severe memory impairment is the core feature of Korsakoff syndrome.

Initial stages of the disease can present with confabulation, executive dysfunction, flattened affect, apathy, and poor insight.[15] Both the episodic and semantic memory are affected, whereas, procedural memory remains intact.[15]Thomson et al.[6] suggested the following should be treated with thiamine as they are at high risk for developing WKS. (1) all patients with any evidence of chronic alcohol misuse and any of the following. Acute confusion, decreased conscious level, ataxia, ophthalmoplegia, memory disturbance, and hypothermia with hypotension. (2) patients with delirium tremens may often also have Wernicke encephalopathy, therefore, all of these patients should be presumed to have Wernicke encephalopathy and treated, preferably as inpatients.

And (3) all hypoglycemic patients (who are treated with intravenous glucose) with evidence of chronic alcohol ingestion must be given intravenous thiamine immediately because of the risk of acutely precipitating Wernicke encephalopathy.Alcoholic cerebellar syndromeChronic alcohol use is associated with the degeneration of anterior superior vermis, leading to a clinical syndrome characterized by the subacute or chronic onset of gait ataxia and incoordination in legs, with relative sparing of upper limbs, speech, and oculomotor movements.[16] In severe cases, truncal ataxia, mild dysarthria, and incoordination of the upper limb is also found along with gait ataxia. Thiamine deficiency is considered to be the etiological factor,[17],[18] although direct toxic effects of alcohol may also contribute to this syndrome. One-third of patients with chronic use of alcohol have evidence of alcoholic cerebellar degeneration. However, population-based studies estimate prevalence to be 14.6%.[19] The effect of alcohol on the cerebellum is graded with the most severe deficits occurring in alcohol users with the longest duration and highest severity of use.

The diagnosis of cerebellar degeneration is largely clinical. MRI can be used to evaluate for vermian atrophy but is unnecessary.[20] Anterior portions of vermis are affected early, with involvement of posterior vermis and adjacent lateral hemispheres occurring late in the course could be used to differentiate alcoholic cerebellar degeneration from other conditions that cause more diffuse involvement.[21] The severity of cerebellar syndrome is more in the presence of WKS, thus could be related to thiamine deficiency.[22],[23] Therefore, this has been considered as a cerebellar presentation of WKS and should be treated in a similar way.[16] There are anecdotal evidence to suggest improvement in cerebellar syndrome with high-dose thiamine.[24]Alcoholic peripheral neuropathyPeripheral neuropathy is common in alcohol use disorder and is seen in 44% of the users.[25] It has been associated predominantly with thiamine deficiency. However, deficiency of other B vitamins (pyridoxine and cobalamin) and direct toxic effect of alcohol is also implicated.[26] Clinically, onset of symptoms is gradual with the involvement of both sensory and motor fibers and occasionally autonomic fibers. Neuropathy can affect both small and large peripheral nerve fibers, leading to different clinical manifestations.

Thiamine deficiency-related neuropathy affects larger fiber types, which results in motor deficits and sensory ataxia. On examination, large fiber involvement is manifested by distal limb muscle weakness and loss of proprioception and vibratory sensation. Together, these can contribute to the gait unsteadiness seen in chronic alcohol users by creating a superimposed steppage gait and reduced proprioceptive input back to the movement control loops in the central nervous system. The most common presentations include painful sensations in both lower limbs, sometimes with burning sensation or numbness, which are early symptoms.

Typically, there is a loss of vibration sensation in distal lower limbs. Later symptoms include loss of proprioception, gait disturbance, and loss of reflexes. Most advanced findings include weakness and muscle atrophy.[20] Progression is very gradual over months and involvement of upper limbs may occur late in the course. Diagnosis begins with laboratory evaluation to exclude other causes of distal, sensorimotor neuropathy including hemoglobin A1c, liver function tests, and complete blood count to evaluate for red blood cell macrocytosis.

Cerebrospinal fluid studies may show increased protein levels but should otherwise be normal in cases of alcohol neuropathy and are not recommended in routine evaluation. Electromyography and nerve conduction studies can be used to distinguish whether the neuropathy is axonal or demyelinating and whether it is motor, sensory, or mixed type. Alcoholic neuropathy shows reduced distal, sensory amplitudes, and to a lesser extent, reduced motor amplitudes on nerve conduction studies.[20] Abstinence and vitamin supplementation including thiamine are the treatments advocated for this condition.[25] In mild-to-moderate cases, near-complete improvement can be achieved.[20] Randomized controlled trials have showed a significant improvement in alcoholic polyneuropathy with thiamine treatment.[27],[28]Marchiafava–Bignami syndromeThis is a rare but fatal condition seen in chronic alcohol users that is characterized by progressive demyelination and necrosis of the corpus callosum. The association of this syndrome with thiamine deficiency is not very clear, and direct toxic effects of alcohol are also suggested.[29] The clinical syndrome is variable and presentation can be acute, subacute, or chronic.

In acute forms, it is predominantly characterized by the altered mental state such as delirium, stupor, or coma.[30] Other clinical features in neuroimaging confirmed Marchiafava–Bignami syndrome (MBS) cases include impaired gait, dysarthria, mutism, signs of split-brain syndrome, pyramidal tract signs, primitive reflexes, rigidity, incontinence, gaze palsy, diplopia, and sensory symptoms.[30] Neuropsychiatric manifestations are common and include psychotic symptoms, depression, apathy, aggressive behavior, and sometimes dementia.[29] MRI scan shows lesions of the corpus callosum, particularly splenium. Treatment for this condition is mostly supportive and use of nutritional supplements and steroids. However, there are several reports of improvement of this syndrome with thiamine at variable doses including reports of beneficial effects with high-dose strategy.[29],[30],[31] Early initiation of thiamine, preferably within 2 weeks of the onset of symptoms is associated with a better outcome. Therefore, high-dose thiamine should be administered to all suspected cases of MBS.

Laboratory Diagnosis of Thiamine Deficiency Estimation of thiamine and thiamine pyrophosphate levels may confirm the diagnosis of deficiency. Levels of thiamine in the blood are not reliable indicators of thiamine status. Low erythrocyte transketolase activity is also helpful.[32],[33] Transketolase concentrations of <120 nmol/L have also been used to indicate deficiency, while concentrations of 120–150 nmol/L suggest marginal thiamine status.[1] However, these tests are not routinely performed as it is time consuming, expensive, and may not be readily available.[34] The ETKA assay is a functional test rather than a direct measurement of thiamin status and therefore may be influenced by factors other than thiamine deficiency such as diabetes mellitus and polyneuritis.[1] Hence, treatment should be initiated in the absence of laboratory confirmation of thiamine deficiency. Furthermore, treatment should not be delayed if tests are ordered, but the results are awaited.

Electroencephalographic abnormalities in thiamine deficiency states range from diffuse mild-to-moderate slow waves and are not a good diagnostic option, as the prevalence of abnormalities among patients is inconsistent.[35]Surrogate markers, which reflect chronic alcohol use and nutritional deficiency other than thiamine, may be helpful in identifying at-risk patients. This includes gamma glutamate transferase, aspartate aminotransferase. Alanine transaminase ratio >2:1, and increased mean corpuscular volume.[36] They are useful when a reliable history of alcohol use is not readily available, specifically in emergency departments when treatment needs to be started immediately to avoid long-term consequences. Thiamine Replacement Therapy Oral versus parenteral thiamineIntestinal absorption of thiamine depends on active transport through thiamine transporter 1 and 2, which follow saturation kinetics.[1] Therefore, the rate and amount of absorption of thiamine in healthy individuals is limited.

In healthy volunteers, a 10 mg dose results in maximal absorption of thiamine, and any doses higher than this do not increase thiamine levels. Therefore, the maximum amount of thiamine absorbed from 10 mg or higher dose is between 4.3 and 5.6 mg.[37] However, it has been suggested that, although thiamine transport occurs through the energy-requiring, sodium-dependent active process at physiologic concentrations, at higher supraphysiologic concentrations thiamine uptake is mostly a passive process.[38] Smithline et al. Have demonstrated that it is possible to achieve higher serum thiamine levels with oral doses up to 1500 mg.[39]In chronic alcohol users, intestinal absorption is impaired. Hence, absorption rates are expected to be much lower.

It is approximately 30% of that seen in healthy individuals, i.e., 1.5 mg of thiamine is absorbed from 10 mg oral thiamine.[3] In those consuming alcohol and have poor nutrition, not more than 0.8 mg of thiamine is absorbed.[2],[3],[6] The daily thiamine requirement is 1–1.6 mg/day, which may be more in alcohol-dependent patients at risk for Wernicke encephalopathy.[1] It is highly likely that oral supplementation with thiamine will be inadequate in alcohol-dependent individuals who continue to drink. Therefore, parenteral thiamine is preferred for supplementation in deficiency states associated with chronic alcohol use. Therapy involving parenteral thiamine is considered safe except for occasional circumstances of allergic reactions involving pruritus and local irritation.There is a small, but definite risk of anaphylaxis with parenteral thiamine, specifically with intravenous administration (1/250,000 intravenous injections).[40] Diluting thiamine in 50–100 mg normal saline for infusion may reduce the risk. However, parenteral thiamine should always be administered under observation with the necessary facilities for resuscitation.A further important issue involves the timing of administration of thiamine relative to the course of alcohol abuse or dependence.

Administration of thiamine treatment to patients experiencing alcohol withdrawal may also be influenced by other factors such as magnesium depletion, N-methyl-D-aspartate (NMDA) receptor upregulation, or liver impairment, all of which may alter thiamine metabolism and utilization.[6],[14]Thiamine or other preparations (e.g., benfotiamine)The thiamine transporters limit the rate of absorption of orally administered thiamine. Allithiamines (e.g., benfotiamine) are the lipid-soluble thiamine derivatives that are absorbed better, result in higher thiamine levels, and are retained longer in the body.[41] The thiamine levels with orally administered benfotiamine are much higher than oral thiamine and almost equals to intravenous thiamine given at the same dosage.[42]Benfotiamine has other beneficial effects including inhibition of production of advanced glycation end products, thus protecting against diabetic vascular complications.[41] It also modulates nuclear transcription factor κB (NK-κB), vascular endothelial growth factor receptor 2, glycogen synthase kinase 3 β, etc., that play a role in cell repair and survival.[41] Benfotiamine has been found to be effective for the treatment of alcoholic peripheral neuropathy.[27]Dosing of thiamineAs the prevalence of thiamine deficiency is very common in chronic alcohol users, the requirement of thiamine increases in active drinkers and it is difficult to rapidly determine thiamine levels using laboratory tests, it is prudent that all patients irrespective of nutritional status should be administered parenteral thiamine. The dose should be 100 mg thiamine daily for 3–5 days during inpatient treatment. Commonly, multivitamin injections are added to intravenous infusions.

Patients at risk for thiamine deficiency should receive 250 mg of thiamine daily intramuscularly for 3–5 days, followed by oral thiamine 100 mg daily.[6]Thiamine plasma levels reduce to 20% of peak value after approximately 2 h of parenteral administration, thus reducing the effective “window period” for passive diffusion to the central nervous system.[6] Therefore, in thiamine deficient individuals with features of Wernicke encephalopathy should receive thiamine thrice daily.High-dose parenteral thiamine administered thrice daily has been advocated in patients at risk for Wernicke encephalopathy.[43] The Royal College of Physicians guideline recommends that patients with suspected Wernicke encephalopathy should receive 500 mg thiamine diluted in 50–100 ml of normal saline infusion over 30 min three times daily for 2–3 days and sometimes for longer periods.[13] If there are persistent symptoms such as confusion, cerebellar symptoms, or memory impairment, this regimen can be continued until the symptoms improve. If symptoms improve, oral thiamine 100 mg thrice daily can be continued for prolonged periods.[6],[40] A similar treatment regimen is advocated for alcoholic cerebellar degeneration as well. Doses more than 500 mg intramuscular or intravenous three times a day for 3–5 days, followed by 250 mg once daily for a further 3–5 days is also recommended by some guidelines (e.g., British Association for Psychopharmacology).[44]Other effects of thiamineThere are some data to suggest that thiamine deficiency can modulate alcohol consumption and may result in pathological drinking. Benfotiamine 600 mg/day as compared to placebo for 6 months was well tolerated and found to decrease psychiatric distress in males and reduce alcohol consumption in females with severe alcohol dependence.[45],[46] Other Factors During Thiamine Therapy Correction of hypomagnesemiaMagnesium is a cofactor for many thiamine-dependent enzymes in carbohydrate metabolism.

Patients may fail to respond to thiamine supplementation in the presence of hypomagnesemia.[47] Magnesium deficiency is common in chronic alcohol users and is seen in 30% of individuals.[48],[49] It can occur because of increased renal excretion of magnesium, poor intake, decreased absorption because of Vitamin D deficiency, the formation of undissociated magnesium soaps with free fatty acids.[48],[49]The usual adult dose is 35–50 mmol of magnesium sulfate added to 1 L isotonic (saline) given over 12–24 h.[6] The dose has to be titrated against plasma magnesium levels. It is recommended to reduce the dose in renal failure. Contraindications include patients with documented hypersensitivity and those with heart block, Addison's disease, myocardial damage, severe hepatitis, or hypophosphatemia. Do not administer intravenous magnesium unless hypomagnesemia is confirmed.[6]Other B-complex vitaminsMost patients with deficiency of thiamine will also have reduced levels of other B vitamins including niacin, pyridoxine, and cobalamin that require replenishment.

For patients admitted to the intensive care unit with symptoms that may mimic or mask Wernicke encephalopathy, based on the published literature, routine supplementation during the 1st day of admission includes 200–500 mg intravenous thiamine every 8 h, 64 mg/kg magnesium sulfate (≈4–5 g for most adult patients), and 400–1000 μg intravenous folate.[50] If alcoholic ketoacidosis is suspected, dextrose-containing fluids are recommended over normal saline.[50] Precautions to be Taken When Administering Parenteral Thiamine It is recommended to monitor for anaphylaxis and has appropriate facilities for resuscitation and for treating anaphylaxis readily available including adrenaline and corticosteroids. Anaphylaxis has been reported at the rate of approximately 4/1 million pairs of ampoules of Pabrinex (a pair of high potency vitamins available in the UK containing 500 mg of thiamine (1:250,000 I/V administrations).[40] Intramuscular thiamine is reported to have a lower incidence of anaphylactic reactions than intravenous administration.[40] The reaction has been attributed to nonspecific histamine release.[51] Administer intravenous thiamine slowly, preferably by slow infusion in 100 ml normal saline over 15–30 min. Conclusions Risk factors for thiamine deficiency should be assessed in chronic alcohol users. A high index of suspicion and a lower threshold to diagnose thiamine deficiency states including Wernicke encephalopathy is needed.

Several other presentations such as cerebellar syndrome, MBS, polyneuropathy, and delirium tremens could be related to thiamine deficiency and should be treated with protocols similar to Wernicke encephalopathy. High-dose thiamine is recommended for the treatment of suspected Wernicke encephalopathy and related conditions [Figure 1]. However, evidence in terms of randomized controlled trials is lacking, and the recommendations are based on small studies and anecdotal reports. Nevertheless, as all these conditions respond to thiamine supplementation, it is possible that these have overlapping pathophysiology and are better considered as Wernicke encephalopathy spectrum disorders.Figure 1.

Thiamine recommendations for patients with alcohol use disorder. AHistory of alcohol use, but no clinical features of WE. BNo clinical features of WE, but with risk factors such as complicated withdrawal (delirium, seizures). CClinical features of WE (ataxia, opthalmoplegia, global confusion)Click here to viewFinancial support and sponsorshipNil.Conflicts of interestThere are no conflicts of interest.

References 1.Frank LL. Thiamin in clinical practice. JPEN J Parenter Enteral Nutr 2015;39:503-20. 2.Thomson AD, Marshall EJ.

The natural history and pathophysiology of Wernicke's Encephalopathy and Korsakoff's Psychosis. Alcohol Alcohol 2006;41:151-8. 3.Thomson AD, Guerrini I, Marshall EJ. Wernicke's encephalopathy.

Role of thiamine. Pract Gastroenterol 2009;33:21-30. 4.Isenberg-Grzeda E, Kutner HE, Nicolson SE. Wernicke-Korsakoff-syndrome.

Under-recognized and under-treated. Psychosomatics 2012;53:507-16. 5.Wood B, Currie J, Breen K. Wernicke's encephalopathy in a metropolitan hospital.

A prospective study of incidence, characteristics and outcome. Med J Aust 1986;144:12-6. 6.Thomson AD, Cook CC, Touquet R, Henry JA, Royal College of Physicians, London. The Royal College of Physicians report on alcohol.

Guidelines for managing Wernicke's encephalopathy in the accident and Emergency Department. Alcohol Alcohol 2002;37:513-21. 7.Harper C. Thiamine (vitamin B1) deficiency and associated brain damage is still common throughout the world and prevention is simple and safe!.

Eur J Neurol 2006;13:1078-82. 8.Harper CG, Giles M, Finlay-Jones R. Clinical signs in the Wernicke-Korsakoff complex. A retrospective analysis of 131 cases diagnosed at necropsy.

J Neurol Neurosurg Psychiatry 1986;49:341-5. 9.Cook CC. Prevention and treatment of Wernicke-Korsakoff syndrome. Alcohol Alcohol 2000;35:19-20.

10.Caine D, Halliday GM, Kril JJ, Harper CG. Operational criteria for the classification of chronic alcoholics. Identification of Wernicke's encephalopathy. J Neurol Neurosurg Psychiatry 1997;62:51-60.

11.Sullivan EV, Pfefferbaum A. Neuroimaging of the Wernicke-Korsakoff syndrome. Alcohol Alcohol 2009;44:155-65. 12.Jung YC, Chanraud S, Sullivan EV.

Neuroimaging of Wernicke's encephalopathy and Korsakoff's syndrome. Neuropsychol Rev 2012;22:170-80. 13.Pruckner N, Baumgartner J, Hinterbuchinger B, Glahn A, Vyssoki S, Vyssoki B. Thiamine substitution in alcohol use disorder.

A narrative review of medical guidelines. Eur Addict Res 2019;25:103-10. 14.Day E, Bentham PW, Callaghan R, Kuruvilla T, George S. Thiamine for prevention and treatment of Wernicke-Korsakoff Syndrome in people who abuse alcohol.

Cochrane Database Syst Rev 2013;7:CD004033. Doi. 10.1002/14651858.CD004033.pub3. 15.Arts NJ, Walvoort SJ, Kessels RP.

Korsakoff's syndrome. A critical review. Neuropsychiatr Dis Treat 2017;13:2875-90. 16.Laureno R.

Nutritional cerebellar degeneration, with comments on its relationship to Wernicke disease and alcoholism. Handb Clin Neurol 2012;103:175-87. 17.Maschke M, Weber J, Bonnet U, Dimitrova A, Bohrenkämper J, Sturm S, et al. Vermal atrophy of alcoholics correlate with serum thiamine levels but not with dentate iron concentrations as estimated by MRI.

J Neurol 2005;252:704-11. 18.Mulholland PJ, Self RL, Stepanyan TD, Little HJ, Littleton JM, Prendergast MA. Thiamine deficiency in the pathogenesis of chronic ethanol-associated cerebellar damage in vitro. Neuroscience 2005;135:1129-39.

19.Del Brutto OH, Mera RM, Sullivan LJ, Zambrano M, King NR. Population-based study of alcoholic cerebellar degeneration. The Atahualpa Project. J Neurol Sci 2016;367:356-60.

20.Hammoud N, Jimenez-Shahed J. Chronic neurologic effects of alcohol. Clin Liver Dis 2019;23:141-55. 21.Lee JH, Heo SH, Chang DI.

Early-stage alcoholic cerebellar degeneration. Diagnostic imaging clues. J Korean Med Sci 2015;30:1539. 22.Phillips SC, Harper CG, Kril JJ.

The contribution of Wernicke's encephalopathy to alcohol-related cerebellar damage. Drug Alcohol Rev 1990;9:53-60. 23.Baker KG, Harding AJ, Halliday GM, Kril JJ, Harper CG. Neuronal loss in functional zones of the cerebellum of chronic alcoholics with and without Wernicke's encephalopathy.

Neuroscience 1999;91:429-38. 24.Graham JR, Woodhouse D, Read FH. Massive thiamine dosage in an alcoholic with cerebellar cortical degeneration. Lancet 1971;2:107.

25.Julian T, Glascow N, Syeed R, Zis P. Alcohol-related peripheral neuropathy. A systematic review and meta-analysis. J Neurol 2018;22:1-3.

26.Chopra K, Tiwari V. Alcoholic neuropathy. Possible mechanisms and future treatment possibilities. Br J Clin Pharmacol 2012;73:348-62.

27.Woelk H, Lehrl S, Bitsch R, Köpcke W. Benfotiamine in treatment of alcoholic polyneuropathy. An 8-week randomized controlled study (BAP I Study). Alcohol Alcohol 1998;33:631-8.

28.Peters TJ, Kotowicz J, Nyka W, Kozubski W, Kuznetsov V, Vanderbist F, et al. Treatment of alcoholic polyneuropathy with vitamin B complex. A randomised controlled trial. Alcohol Alcohol 2006;41:636-42.

29.Fernandes LM, Bezerra FR, Monteiro MC, Silva ML, de Oliveira FR, Lima RR, et al. Thiamine deficiency, oxidative metabolic pathways and ethanol-induced neurotoxicity. How poor nutrition contributes to the alcoholic syndrome, as Marchiafava-Bignami disease. Eur J Clin Nutr 2017;71:580-6.

30.Hillbom M, Saloheimo P, Fujioka S, Wszolek ZK, Juvela S, Leone MA. Diagnosis and management of Marchiafava-Bignami disease. A review of CT/MRI confirmed cases. J Neurol Neurosurg Psychiatry 2014;85:168-73.

31.Nemlekar SS, Mehta RY, Dave KR, Shah ND. Marchiafava. Bignami disease treated with parenteral thiamine. Indian J Psychol Med 2016;38:147-9.

[Full text] 32.Brin M. Erythrocyte transketolase in early thiamine deficiency. Ann N Y Acad Sci 1962;98:528-41. 33.Dreyfus PM.

Clinical application of blood transketolase determinations. N Engl J Med 1962;267:596-8. 34.Edwards KA, Tu-Maung N, Cheng K, Wang B, Baeumner AJ, Kraft CE. Thiamine assays – Advances, challenges, and caveats.

ChemistryOpen 2017;6:178-91. 35.Chandrakumar A, Bhardwaj A, 't Jong GW. Review of thiamine deficiency disorders. Wernicke encephalopathy and Korsakoff psychosis.

J Basic Clin Physiol Pharmacol 2018;30:153-62. 36.Torruellas C, French SW, Medici V. Diagnosis of alcoholic liver disease. World J Gastroenterol 2014;20:11684-99.

37.Thomson AD, Leevy CM. Observations on the mechanism of thiamine hydrochloride absorption in man. Clin Sci 1972;43:153-63. 38.Hoyumpa AM Jr., Strickland R, Sheehan JJ, Yarborough G, Nichols S.

Dual system of intestinal thiamine transport in humans. J Lab Clin Med 1982;99:701-8. 39.Smithline HA, Donnino M, Greenblatt DJ. Pharmacokinetics of high-dose oral thiamine hydrochloride in healthy subjects.

BMC Clin Pharmacol 2012;12:4. 40.Latt N, Dore G. Thiamine in the treatment of Wernicke encephalopathy in patients with alcohol use disorders. Intern Med J 2014;44:911-5.

41.Raj V, Ojha S, Howarth FC, Belur PD, Subramanya SB. Therapeutic potential of benfotiamine and its molecular targets. Eur Rev Med Pharmacol Sci 2018;22:3261-73. 42.Xie F, Cheng Z, Li S, Liu X, Guo X, Yu P, et al.

Pharmacokinetic study of benfotiamine and the bioavailability assessment compared to thiamine hydrochloride. J Clin Pharmacol 2014;54:688-95. 43.Cook CC, Hallwood PM, Thomson AD. B Vitamin deficiency and neuropsychiatric syndromes in alcohol misuse.

Alcohol Alcohol 1998;33:317-36. 44.Lingford-Hughes AR, Welch S, Peters L, Nutt DJ, British Association for Psychopharmacology, Expert Reviewers Group. BAP updated guidelines. Evidence-based guidelines for the pharmacological management of substance abuse, harmful use, addiction and comorbidity.

Recommendations from BAP. J Psychopharmacol 2012;26:899-952. 45.Manzardo AM, He J, Poje A, Penick EC, Campbell J, Butler MG. Double-blind, randomized placebo-controlled clinical trial of benfotiamine for severe alcohol dependence.

Drug Alcohol Depend 2013;133:562-70. 46.Manzardo AM, Pendleton T, Poje A, Penick EC, Butler MG. Change in psychiatric symptomatology after benfotiamine treatment in males is related to lifetime alcoholism severity. Drug Alcohol Depend 2015;152:257-63.

47.Dingwall KM, Delima JF, Gent D, Batey RG. Hypomagnesaemia and its potential impact on thiamine utilisation in patients with alcohol misuse at the Alice Springs Hospital. Drug Alcohol Rev 2015;34:323-8. 48.Flink EB.

Magnesium deficiency in alcoholism. Alcohol Clin Exp Res 1986;10:590-4. 49.Grochowski C, Blicharska E, Baj J, Mierzwińska A, Brzozowska K, Forma A, et al. Serum iron, magnesium, copper, and manganese levels in alcoholism.

A systematic review. Molecules 2019;24:E1361. 50.Flannery AH, Adkins DA, Cook AM. Unpeeling the evidence for the banana bag.

Evidence-based recommendations for the management of alcohol-associated vitamin and electrolyte deficiencies in the ICU. Crit Care Med 2016;44:1545-52. 51.Lagunoff D, Martin TW, Read G. Agents that release histamine from mast cells.

Annu Rev Pharmacol Toxicol 1983;23:331-51. Correspondence Address:Samir Kumar PraharajDepartment of Psychiatry, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka IndiaSource of Support. None, Conflict of Interest. NoneDOI.

10.4103/psychiatry.IndianJPsychiatry_440_20 Figures [Figure 1].

Abstract Thiamine What do i need to buy seroquel is essential for the activity of several enzymes buy diflucan online associated with energy metabolism in humans. Chronic alcohol use is associated with deficiency of thiamine along with other vitamins through several mechanisms. Several neuropsychiatric syndromes have been associated with thiamine deficiency in the context of alcohol use disorder including Wernicke–Korsakoff syndrome, alcoholic cerebellar syndrome, alcoholic peripheral buy diflucan online neuropathy, and possibly, Marchiafava–Bignami syndrome.

High-dose thiamine replacement is suggested for these neuropsychiatric syndromes.Keywords. Alcohol use disorder, alcoholic cerebellar syndrome, alcoholic peripheral neuropathy, Marchiafava–Bignami syndrome, thiamine, Wernicke–Korsakoff syndromeHow to cite this article:Praharaj SK, Munoli RN, Shenoy S, Udupa ST, buy diflucan online Thomas LS. High-dose thiamine strategy in Wernicke–Korsakoff syndrome and related thiamine deficiency conditions associated with alcohol use disorder.

Indian J Psychiatry 2021;63:121-6How to buy diflucan online cite this URL:Praharaj SK, Munoli RN, Shenoy S, Udupa ST, Thomas LS. High-dose thiamine strategy in Wernicke–Korsakoff syndrome and related thiamine deficiency conditions associated with alcohol use disorder. Indian J Psychiatry [serial buy diflucan online online] 2021 [cited 2021 May 13];63:121-6.

Available from. Https://www.indianjpsychiatry.org/text.asp?. 2021/63/2/121/313716 Introduction Thiamine is a water-soluble vitamin (B1) that plays a key role in the activity of several enzymes associated with energy metabolism.

Thiamine pyrophosphate (or diphosphate) is the active form that acts as a cofactor for enzymes. The daily dietary requirement of thiamine in adults is 1–2 mg and is dependent on carbohydrate intake.[1],[2] The requirement increases if basal metabolic rate is higher, for example, during alcohol withdrawal state. Dietary sources include pork (being the major source), meat, legume, vegetables, and enriched foods.

The body can store between 30 and 50 mg of thiamine and is likely to get depleted within 4–6 weeks if the diet is deficient.[2] In those with alcohol-related liver damage, the ability to store thiamine is gradually reduced.[1],[2]Lower thiamine levels are found in 30%–80% of chronic alcohol users.[3] Thiamine deficiency occurs due to poor intake of vitamin-rich foods, impaired intestinal absorption, decreased storage capacity of liver, damage to the renal epithelial cells due to alcohol, leading to increased loss from the kidneys, and excessive loss associated with medical conditions.[2],[3] Furthermore, alcohol decreases the absorption of colonic bacterial thiamine, reduces the enzymatic activity of thiamine pyrophosphokinase, and thereby, reducing the amount of available thiamine pyrophosphate.[4] Since facilitated diffusion of thiamine into cells is dependent on a concentration gradient, reduced thiamine pyrophosphokinase activity further reduces thiamine uptake into cells.[4] Impaired utilization of thiamine is seen in certain conditions (e.g., hypomagnesemia) which are common in alcohol use disorder.[2],[3],[4] This narrative review discusses the neuropsychiatric syndromes associated with thiamine deficiency in the context of alcohol use disorder, and the treatment regimens advocated for these conditions. A PubMed search supplemented with manual search was used to identify neuropsychiatric syndromes related to thiamine deficiency in alcohol use disorder patients. Neuropsychiatric Syndromes Associated With Thiamine Deficiency Wernicke–Korsakoff syndromeWernicke encephalopathy is associated with chronic alcohol use, and if not identified and treated early, could lead to permanent brain damage characterized by an amnestic syndrome known as Korsakoff syndrome.

Inappropriate treatment of Wernicke encephalopathy with lower doses of thiamine can lead to high mortality rates (~20%) and Korsakoff syndrome in ~ 80% of patients (ranges from 56% to 84%).[5],[6] The classic triad of Wernicke includes oculomotor abnormalities, cerebellar dysfunction, and confusion. Wernicke lesions are found in 12.5% of brain samples of patients with alcohol dependence.[7] However, only 20%–30% of them had a clinical diagnosis of Wernicke encephalopathy antemortem. It has been found that many patients develop Wernicke–Korsakoff syndrome (WKS) following repeated subclinical episodes of thiamine deficiency.[7] In an autopsy report of 97 chronic alcohol users, only16% had all the three “classical signs,” 29% had two signs, 37% presented with one sign, and 19% had none.[8] Mental status changes are the most prevalent sign (seen in 82% of the cases), followed by eye signs (in 29%) and ataxia (23%).[8] WKS should be suspected in persons with a history of alcohol use and presenting with signs of ophthalmoplegia, ataxia, acute confusion, memory disturbance, unexplained hypotension, hypothermia, coma, or unconsciousness.[9] Operational criteria for the diagnosis of Wernicke encephalopathy have been proposed by Caine et al.[10] that requires two out of four features, i.e., (a) dietary deficiency (signs such as cheilitis, glossitis, and bleeding gums), (b) oculomotor abnormalities (nystagmus, opthalmoplegia, and diplopia), (c) cerebellar dysfunction (gait ataxia, nystagmus), and (d) either altered mental state (confusion) or mild memory impairment.As it is very difficult to clinically distinguish Wernicke encephalopathy from other associated conditions such as delirium tremens, hepatic encephalopathy, or head injury, it is prudent to have a lower threshold to diagnose this if any of the clinical signs is seen.

Magnetic resonance imaging (MRI) brain scan during Wernicke encephalopathy shows mammillary body atrophy and enlarged third ventricle, lesions in the medial portions of thalami and mid brain and can be used to aid diagnosis.[11],[12] However, most clinical situations warrant treatment without waiting for neuroimaging report. The treatment suggestions in the guidelines vary widely. Furthermore, hardly any evidence-based recommendations exist on a more general use of thiamine as a preventative intervention in individuals with alcohol use disorder.[13] There are very few studies that have evaluated the dose and duration of thiamine for WKS, but higher doses may result in a greater response.[6],[14] With thiamine administration rapid improvement is seen in eye movement abnormalities (improve within days or weeks) and ataxia (may take months to recover), but the effects on memory, in particular, are unclear.[4],[14] Severe memory impairment is the core feature of Korsakoff syndrome.

Initial stages of the disease can present with confabulation, executive dysfunction, flattened affect, apathy, and poor insight.[15] Both the episodic and semantic memory are affected, whereas, procedural memory remains intact.[15]Thomson et al.[6] suggested the following should be treated with thiamine as they are at high risk for developing WKS. (1) all patients with any evidence of chronic alcohol misuse and any of the following. Acute confusion, decreased conscious level, ataxia, ophthalmoplegia, memory disturbance, and hypothermia with hypotension.

(2) patients with delirium tremens may often also have Wernicke encephalopathy, therefore, all of these patients should be presumed to have Wernicke encephalopathy and treated, preferably as inpatients. And (3) all hypoglycemic patients (who are treated with intravenous glucose) with evidence of chronic alcohol ingestion must be given intravenous thiamine immediately because of the risk of acutely precipitating Wernicke encephalopathy.Alcoholic cerebellar syndromeChronic alcohol use is associated with the degeneration of anterior superior vermis, leading to a clinical syndrome characterized by the subacute or chronic onset of gait ataxia and incoordination in legs, with relative sparing of upper limbs, speech, and oculomotor movements.[16] In severe cases, truncal ataxia, mild dysarthria, and incoordination of the upper limb is also found along with gait ataxia. Thiamine deficiency is considered to be the etiological factor,[17],[18] although direct toxic effects of alcohol may also contribute to this syndrome.

One-third of patients with chronic use of alcohol have evidence of alcoholic cerebellar degeneration. However, population-based studies estimate prevalence to be 14.6%.[19] The effect of alcohol on the cerebellum is graded with the most severe deficits occurring in alcohol users with the longest duration and highest severity of use. The diagnosis of cerebellar degeneration is largely clinical.

MRI can be used to evaluate for vermian atrophy but is unnecessary.[20] Anterior portions of vermis are affected early, with involvement of posterior vermis and adjacent lateral hemispheres occurring late in the course could be used to differentiate alcoholic cerebellar degeneration from other conditions that cause more diffuse involvement.[21] The severity of cerebellar syndrome is more in the presence of WKS, thus could be related to thiamine deficiency.[22],[23] Therefore, this has been considered as a cerebellar presentation of WKS and should be treated in a similar way.[16] There are anecdotal evidence to suggest improvement in cerebellar syndrome with high-dose thiamine.[24]Alcoholic peripheral neuropathyPeripheral neuropathy is common in alcohol use disorder and is seen in 44% of the users.[25] It has been associated predominantly with thiamine deficiency. However, deficiency of other B vitamins (pyridoxine and cobalamin) and direct toxic effect of alcohol is also implicated.[26] Clinically, onset of symptoms is gradual with the involvement of both sensory and motor fibers and occasionally autonomic fibers. Neuropathy can affect both small and large peripheral nerve fibers, leading to different clinical manifestations.

Thiamine deficiency-related neuropathy affects larger fiber types, which results in motor deficits and sensory ataxia. On examination, large fiber involvement is manifested by distal limb muscle weakness and loss of proprioception and vibratory sensation. Together, these can contribute to the gait unsteadiness seen in chronic alcohol users by creating a superimposed steppage gait and reduced proprioceptive input back to the movement control loops in the central nervous system.

The most common presentations include painful sensations in both lower limbs, sometimes with burning sensation or numbness, which are early symptoms. Typically, there is a loss of vibration sensation in distal lower limbs. Later symptoms include loss of proprioception, gait disturbance, and loss of reflexes.

Most advanced findings include weakness and muscle atrophy.[20] Progression is very gradual over months and involvement of upper limbs may occur late in the course. Diagnosis begins with laboratory evaluation to exclude other causes of distal, sensorimotor neuropathy including hemoglobin A1c, liver function tests, and complete blood count to evaluate for red blood cell macrocytosis. Cerebrospinal fluid studies may show increased protein levels but should otherwise be normal in cases of alcohol neuropathy and are not recommended in routine evaluation.

Electromyography and nerve conduction studies can be used to distinguish whether the neuropathy is axonal or demyelinating and whether it is motor, sensory, or mixed type. Alcoholic neuropathy shows reduced distal, sensory amplitudes, and to a lesser extent, reduced motor amplitudes on nerve conduction studies.[20] Abstinence and vitamin supplementation including thiamine are the treatments advocated for this condition.[25] In mild-to-moderate cases, near-complete improvement can be achieved.[20] Randomized controlled trials have showed a significant improvement in alcoholic polyneuropathy with thiamine treatment.[27],[28]Marchiafava–Bignami syndromeThis is a rare but fatal condition seen in chronic alcohol users that is characterized by progressive demyelination and necrosis of the corpus callosum. The association of this syndrome with thiamine deficiency is not very clear, and direct toxic effects of alcohol are also suggested.[29] The clinical syndrome is variable and presentation can be acute, subacute, or chronic.

In acute forms, it is predominantly characterized by the altered mental state such as delirium, stupor, or coma.[30] Other clinical features in neuroimaging confirmed Marchiafava–Bignami syndrome (MBS) cases include impaired gait, dysarthria, mutism, signs of split-brain syndrome, pyramidal tract signs, primitive reflexes, rigidity, incontinence, gaze palsy, diplopia, and sensory symptoms.[30] Neuropsychiatric manifestations are common and include psychotic symptoms, depression, apathy, aggressive behavior, and sometimes dementia.[29] MRI scan shows lesions of the corpus callosum, particularly splenium. Treatment for this condition is mostly supportive and use of nutritional supplements and steroids. However, there are several reports of improvement of this syndrome with thiamine at variable doses including reports of beneficial effects with high-dose strategy.[29],[30],[31] Early initiation of thiamine, preferably within 2 weeks of the onset of symptoms is associated with a better outcome.

Therefore, high-dose thiamine should be administered to all suspected cases of MBS. Laboratory Diagnosis of Thiamine Deficiency Estimation of thiamine and thiamine pyrophosphate levels may confirm the diagnosis of deficiency. Levels of thiamine in the blood are not reliable indicators of thiamine status.

Low erythrocyte transketolase activity is also helpful.[32],[33] Transketolase concentrations of <120 nmol/L have also been used to indicate deficiency, while concentrations of 120–150 nmol/L suggest marginal thiamine status.[1] However, these tests are not routinely performed as it is time consuming, expensive, and may not be readily available.[34] The ETKA assay is a functional test rather than a direct measurement of thiamin status and therefore may be influenced by factors other than thiamine deficiency such as diabetes mellitus and polyneuritis.[1] Hence, treatment should be initiated in the absence of laboratory confirmation of thiamine deficiency. Furthermore, treatment should not be delayed if tests are ordered, but the results are awaited. Electroencephalographic abnormalities in thiamine deficiency states range from diffuse mild-to-moderate slow waves and are not a good diagnostic option, as the prevalence of abnormalities among patients is inconsistent.[35]Surrogate markers, which reflect chronic alcohol use and nutritional deficiency other than thiamine, may be helpful in identifying at-risk patients.

This includes gamma glutamate transferase, aspartate aminotransferase. Alanine transaminase ratio >2:1, and increased mean corpuscular volume.[36] They are useful when a reliable history of alcohol use is not readily available, specifically in emergency departments when treatment needs to be started immediately to avoid long-term consequences. Thiamine Replacement Therapy Oral versus parenteral thiamineIntestinal absorption of thiamine depends on active transport through thiamine transporter 1 and 2, which follow saturation kinetics.[1] Therefore, the rate and amount of absorption of thiamine in healthy individuals is limited.

In healthy volunteers, a 10 mg dose results in maximal absorption of thiamine, and any doses higher than this do not increase thiamine levels. Therefore, the maximum amount of thiamine absorbed from 10 mg or higher dose is between 4.3 and 5.6 mg.[37] However, it has been suggested that, although thiamine transport occurs through the energy-requiring, sodium-dependent active process at physiologic concentrations, at higher supraphysiologic concentrations thiamine uptake is mostly a passive process.[38] Smithline et al. Have demonstrated that it is possible to achieve higher serum thiamine levels with oral doses up to 1500 mg.[39]In chronic alcohol users, intestinal absorption is impaired.

Hence, absorption rates are expected to be much lower. It is approximately 30% of that seen in healthy individuals, i.e., 1.5 mg of thiamine is absorbed from 10 mg oral thiamine.[3] In those consuming alcohol and have poor nutrition, not more than 0.8 mg of thiamine is absorbed.[2],[3],[6] The daily thiamine requirement is 1–1.6 mg/day, which may be more in alcohol-dependent patients at risk for Wernicke encephalopathy.[1] It is highly likely that oral supplementation with thiamine will be inadequate in alcohol-dependent individuals who continue to drink. Therefore, parenteral thiamine is preferred for supplementation in deficiency states associated with chronic alcohol use.

Therapy involving parenteral thiamine is considered safe except for occasional circumstances of allergic reactions involving pruritus and local irritation.There is a small, but definite risk of anaphylaxis with parenteral thiamine, specifically with intravenous administration (1/250,000 intravenous injections).[40] Diluting thiamine in 50–100 mg normal saline for infusion may reduce the risk. However, parenteral thiamine should always be administered under observation with the necessary facilities for resuscitation.A further important issue involves the timing of administration of thiamine relative to the course of alcohol abuse or dependence. Administration of thiamine treatment to patients experiencing alcohol withdrawal may also be influenced by other factors such as magnesium depletion, N-methyl-D-aspartate (NMDA) receptor upregulation, or liver impairment, all of which may alter thiamine metabolism and utilization.[6],[14]Thiamine or other preparations (e.g., benfotiamine)The thiamine transporters limit the rate of absorption of orally administered thiamine.

Allithiamines (e.g., benfotiamine) are the lipid-soluble thiamine derivatives that are absorbed better, result in higher thiamine levels, and are retained longer in the body.[41] The thiamine levels with orally administered benfotiamine are much higher than oral thiamine and almost equals to intravenous thiamine given at the same dosage.[42]Benfotiamine has other beneficial effects including inhibition of production of advanced glycation end products, thus protecting against diabetic vascular complications.[41] It also modulates nuclear transcription factor κB (NK-κB), vascular endothelial growth factor receptor 2, glycogen synthase kinase 3 β, etc., that play a role in cell repair and survival.[41] Benfotiamine has been found to be effective for the treatment of alcoholic peripheral neuropathy.[27]Dosing of thiamineAs the prevalence of thiamine deficiency is very common in chronic alcohol users, the requirement of thiamine increases in active drinkers and it is difficult to rapidly determine thiamine levels using laboratory tests, it is prudent that all patients irrespective of nutritional status should be administered parenteral thiamine. The dose should be 100 mg thiamine daily for 3–5 days during inpatient treatment. Commonly, multivitamin injections are added to intravenous infusions.

Patients at risk for thiamine deficiency should receive 250 mg of thiamine daily intramuscularly for 3–5 days, followed by oral thiamine 100 mg daily.[6]Thiamine plasma levels reduce to 20% of peak value after approximately 2 h of parenteral administration, thus reducing the effective “window period” for passive diffusion to the central nervous system.[6] Therefore, in thiamine deficient individuals with features of Wernicke encephalopathy should receive thiamine thrice daily.High-dose parenteral thiamine administered thrice daily has been advocated in patients at risk for Wernicke encephalopathy.[43] The Royal College of Physicians guideline recommends that patients with suspected Wernicke encephalopathy should receive 500 mg thiamine diluted in 50–100 ml of normal saline infusion over 30 min three times daily for 2–3 days and sometimes for longer periods.[13] If there are persistent symptoms such as confusion, cerebellar symptoms, or memory impairment, this regimen can be continued until the symptoms improve. If symptoms improve, oral thiamine 100 mg thrice daily can be continued for prolonged periods.[6],[40] A similar treatment regimen is advocated for alcoholic cerebellar degeneration as well. Doses more than 500 mg intramuscular or intravenous three times a day for 3–5 days, followed by 250 mg once daily for a further 3–5 days is also recommended by some guidelines (e.g., British Association for Psychopharmacology).[44]Other effects of thiamineThere are some data to suggest that thiamine deficiency can modulate alcohol consumption and may result in pathological drinking.

Benfotiamine 600 mg/day as compared to placebo for 6 months was well tolerated and found to decrease psychiatric distress in males and reduce alcohol consumption in females with severe alcohol dependence.[45],[46] Other Factors During Thiamine Therapy Correction of hypomagnesemiaMagnesium is a cofactor for many thiamine-dependent enzymes in carbohydrate metabolism. Patients may fail to respond to thiamine supplementation in the presence of hypomagnesemia.[47] Magnesium deficiency is common in chronic alcohol users and is seen in 30% of individuals.[48],[49] It can occur because of increased renal excretion of magnesium, poor intake, decreased absorption because of Vitamin D deficiency, the formation of undissociated magnesium soaps with free fatty acids.[48],[49]The usual adult dose is 35–50 mmol of magnesium sulfate added to 1 L isotonic (saline) given over 12–24 h.[6] The dose has to be titrated against plasma magnesium levels. It is recommended to reduce the dose in renal failure.

Contraindications include patients with documented hypersensitivity and those with heart block, Addison's disease, myocardial damage, severe hepatitis, or hypophosphatemia. Do not administer intravenous magnesium unless hypomagnesemia is confirmed.[6]Other B-complex vitaminsMost patients with deficiency of thiamine will also have reduced levels of other B vitamins including niacin, pyridoxine, and cobalamin that require replenishment. For patients admitted to the intensive care unit with symptoms that may mimic or mask Wernicke encephalopathy, based on the published literature, routine supplementation during the 1st day of admission includes 200–500 mg intravenous thiamine every 8 h, 64 mg/kg magnesium sulfate (≈4–5 g for most adult patients), and 400–1000 μg intravenous folate.[50] If alcoholic ketoacidosis is suspected, dextrose-containing fluids are recommended over normal saline.[50] Precautions to be Taken When Administering Parenteral Thiamine It is recommended to monitor for anaphylaxis and has appropriate facilities for resuscitation and for treating anaphylaxis readily available including adrenaline and corticosteroids.

Anaphylaxis has been reported at the rate of approximately 4/1 million pairs of ampoules of Pabrinex (a pair of high potency vitamins available in the UK containing 500 mg of thiamine (1:250,000 I/V administrations).[40] Intramuscular thiamine is reported to have a lower incidence of anaphylactic reactions than intravenous administration.[40] The reaction has been attributed to nonspecific histamine release.[51] Administer intravenous thiamine slowly, preferably by slow infusion in 100 ml normal saline over 15–30 min. Conclusions Risk factors for thiamine deficiency should be assessed in chronic alcohol users. A high index of suspicion and a lower threshold to diagnose thiamine deficiency states including Wernicke encephalopathy is needed.

Several other presentations such as cerebellar syndrome, MBS, polyneuropathy, and delirium tremens could be related to thiamine deficiency and should be treated with protocols similar to Wernicke encephalopathy. High-dose thiamine is recommended for the treatment of suspected Wernicke encephalopathy and related conditions [Figure 1]. However, evidence in terms of randomized controlled trials is lacking, and the recommendations are based on small studies and anecdotal reports.

Nevertheless, as all these conditions respond to thiamine supplementation, it is possible that these have overlapping pathophysiology and are better considered as Wernicke encephalopathy spectrum disorders.Figure 1. Thiamine recommendations for patients with alcohol use disorder. AHistory of alcohol use, but no clinical features of WE.

BNo clinical features of WE, but with risk factors such as complicated withdrawal (delirium, seizures). CClinical features of WE (ataxia, opthalmoplegia, global confusion)Click here to viewFinancial support and sponsorshipNil.Conflicts of interestThere are no conflicts of interest. References 1.Frank LL.

Thiamin in clinical practice. JPEN J Parenter Enteral Nutr 2015;39:503-20. 2.Thomson AD, Marshall EJ.

The natural history and pathophysiology of Wernicke's Encephalopathy and Korsakoff's Psychosis. Alcohol Alcohol 2006;41:151-8. 3.Thomson AD, Guerrini I, Marshall EJ.

Wernicke's encephalopathy. Role of thiamine. Pract Gastroenterol 2009;33:21-30.

4.Isenberg-Grzeda E, Kutner HE, Nicolson SE. Wernicke-Korsakoff-syndrome. Under-recognized and under-treated.

Psychosomatics 2012;53:507-16. 5.Wood B, Currie J, Breen K. Wernicke's encephalopathy in a metropolitan hospital.

A prospective study of incidence, characteristics and outcome. Med J Aust 1986;144:12-6. 6.Thomson AD, Cook CC, Touquet R, Henry JA, Royal College of Physicians, London.

The Royal College of Physicians report on alcohol. Guidelines for managing Wernicke's encephalopathy in the accident and Emergency Department. Alcohol Alcohol 2002;37:513-21.

7.Harper C. Thiamine (vitamin B1) deficiency and associated brain damage is still common throughout the world and prevention is simple and safe!. Eur J Neurol 2006;13:1078-82.

8.Harper CG, Giles M, Finlay-Jones R. Clinical signs in the Wernicke-Korsakoff complex. A retrospective analysis of 131 cases diagnosed at necropsy.

J Neurol Neurosurg Psychiatry 1986;49:341-5. 9.Cook CC. Prevention and treatment of Wernicke-Korsakoff syndrome.

Alcohol Alcohol 2000;35:19-20. 10.Caine D, Halliday GM, Kril JJ, Harper CG. Operational criteria for the classification of chronic alcoholics.

Identification of Wernicke's encephalopathy. J Neurol Neurosurg Psychiatry 1997;62:51-60. 11.Sullivan EV, Pfefferbaum A.

Neuroimaging of the Wernicke-Korsakoff syndrome. Alcohol Alcohol 2009;44:155-65. 12.Jung YC, Chanraud S, Sullivan EV.

Neuroimaging of Wernicke's encephalopathy and Korsakoff's syndrome. Neuropsychol Rev 2012;22:170-80. 13.Pruckner N, Baumgartner J, Hinterbuchinger B, Glahn A, Vyssoki S, Vyssoki B.

Thiamine substitution in alcohol use disorder. A narrative review of medical guidelines. Eur Addict Res 2019;25:103-10.

14.Day E, Bentham PW, Callaghan R, Kuruvilla T, George S. Thiamine for prevention and treatment of Wernicke-Korsakoff Syndrome in people who abuse alcohol. Cochrane Database Syst Rev 2013;7:CD004033.

Doi. 10.1002/14651858.CD004033.pub3. 15.Arts NJ, Walvoort SJ, Kessels RP.

Korsakoff's syndrome. A critical review. Neuropsychiatr Dis Treat 2017;13:2875-90.

16.Laureno R. Nutritional cerebellar degeneration, with comments on its relationship to Wernicke disease and alcoholism. Handb Clin Neurol 2012;103:175-87.

17.Maschke M, Weber J, Bonnet U, Dimitrova A, Bohrenkämper J, Sturm S, et al. Vermal atrophy of alcoholics correlate with serum thiamine levels but not with dentate iron concentrations as estimated by MRI. J Neurol 2005;252:704-11.

18.Mulholland PJ, Self RL, Stepanyan TD, Little HJ, Littleton JM, Prendergast MA. Thiamine deficiency in the pathogenesis of chronic ethanol-associated cerebellar damage in vitro. Neuroscience 2005;135:1129-39.

19.Del Brutto OH, Mera RM, Sullivan LJ, Zambrano M, King NR. Population-based study of alcoholic cerebellar degeneration. The Atahualpa Project.

J Neurol Sci 2016;367:356-60. 20.Hammoud N, Jimenez-Shahed J. Chronic neurologic effects of alcohol.

Clin Liver Dis 2019;23:141-55. 21.Lee JH, Heo SH, Chang DI. Early-stage alcoholic cerebellar degeneration.

Diagnostic imaging clues. J Korean Med Sci 2015;30:1539. 22.Phillips SC, Harper CG, Kril JJ.

The contribution of Wernicke's encephalopathy to alcohol-related cerebellar damage. Drug Alcohol Rev 1990;9:53-60. 23.Baker KG, Harding AJ, Halliday GM, Kril JJ, Harper CG.

Neuronal loss in functional zones of the cerebellum of chronic alcoholics with and without Wernicke's encephalopathy. Neuroscience 1999;91:429-38. 24.Graham JR, Woodhouse D, Read FH.

Massive thiamine dosage in an alcoholic with cerebellar cortical degeneration. Lancet 1971;2:107. 25.Julian T, Glascow N, Syeed R, Zis P.

Alcohol-related peripheral neuropathy. A systematic review and meta-analysis. J Neurol 2018;22:1-3.

26.Chopra K, Tiwari V. Alcoholic neuropathy. Possible mechanisms and future treatment possibilities.

Br J Clin Pharmacol 2012;73:348-62. 27.Woelk H, Lehrl S, Bitsch R, Köpcke W. Benfotiamine in treatment of alcoholic polyneuropathy.

An 8-week randomized controlled study (BAP I Study). Alcohol Alcohol 1998;33:631-8. 28.Peters TJ, Kotowicz J, Nyka W, Kozubski W, Kuznetsov V, Vanderbist F, et al.

Treatment of alcoholic polyneuropathy with vitamin B complex. A randomised controlled trial. Alcohol Alcohol 2006;41:636-42.

29.Fernandes LM, Bezerra FR, Monteiro MC, Silva ML, de Oliveira FR, Lima RR, et al. Thiamine deficiency, oxidative metabolic pathways and ethanol-induced neurotoxicity. How poor nutrition contributes to the alcoholic syndrome, as Marchiafava-Bignami disease.

Eur J Clin Nutr 2017;71:580-6. 30.Hillbom M, Saloheimo P, Fujioka S, Wszolek ZK, Juvela S, Leone MA. Diagnosis and management of Marchiafava-Bignami disease.

A review of CT/MRI confirmed cases. J Neurol Neurosurg Psychiatry 2014;85:168-73. 31.Nemlekar SS, Mehta RY, Dave KR, Shah ND.

Marchiafava. Bignami disease treated with parenteral thiamine. Indian J Psychol Med 2016;38:147-9.

[Full text] 32.Brin M. Erythrocyte transketolase in early thiamine deficiency. Ann N Y Acad Sci 1962;98:528-41.

33.Dreyfus PM. Clinical application of blood transketolase determinations. N Engl J Med 1962;267:596-8.

34.Edwards KA, Tu-Maung N, Cheng K, Wang B, Baeumner AJ, Kraft CE. Thiamine assays – Advances, challenges, and caveats. ChemistryOpen 2017;6:178-91.

35.Chandrakumar A, Bhardwaj A, 't Jong GW. Review of thiamine deficiency disorders. Wernicke encephalopathy and Korsakoff psychosis.

J Basic Clin Physiol Pharmacol 2018;30:153-62. 36.Torruellas C, French SW, Medici V. Diagnosis of alcoholic liver disease.

World J Gastroenterol 2014;20:11684-99. 37.Thomson AD, Leevy CM. Observations on the mechanism of thiamine hydrochloride absorption in man.

Clin Sci 1972;43:153-63. 38.Hoyumpa AM Jr., Strickland R, Sheehan JJ, Yarborough G, Nichols S. Dual system of intestinal thiamine transport in humans.

J Lab Clin Med 1982;99:701-8. 39.Smithline HA, Donnino M, Greenblatt DJ. Pharmacokinetics of high-dose oral thiamine hydrochloride in healthy subjects.

BMC Clin Pharmacol 2012;12:4. 40.Latt N, Dore G. Thiamine in the treatment of Wernicke encephalopathy in patients with alcohol use disorders.

Intern Med J 2014;44:911-5. 41.Raj V, Ojha S, Howarth FC, Belur PD, Subramanya SB. Therapeutic potential of benfotiamine and its molecular targets.

Eur Rev Med Pharmacol Sci 2018;22:3261-73. 42.Xie F, Cheng Z, Li S, Liu X, Guo X, Yu P, et al. Pharmacokinetic study of benfotiamine and the bioavailability assessment compared to thiamine hydrochloride.

J Clin Pharmacol 2014;54:688-95. 43.Cook CC, Hallwood PM, Thomson AD. B Vitamin deficiency and neuropsychiatric syndromes in alcohol misuse.

Alcohol Alcohol 1998;33:317-36. 44.Lingford-Hughes AR, Welch S, Peters L, Nutt DJ, British Association for Psychopharmacology, Expert Reviewers Group. BAP updated guidelines.

Evidence-based guidelines for the pharmacological management of substance abuse, harmful use, addiction and comorbidity. Recommendations from BAP. J Psychopharmacol 2012;26:899-952.

45.Manzardo AM, He J, Poje A, Penick EC, Campbell J, Butler MG. Double-blind, randomized placebo-controlled clinical trial of benfotiamine for severe alcohol dependence. Drug Alcohol Depend 2013;133:562-70.

46.Manzardo AM, Pendleton T, Poje A, Penick EC, Butler MG. Change in psychiatric symptomatology after benfotiamine treatment in males is related to lifetime alcoholism severity. Drug Alcohol Depend 2015;152:257-63.

47.Dingwall KM, Delima JF, Gent D, Batey RG. Hypomagnesaemia and its potential impact on thiamine utilisation in patients with alcohol misuse at the Alice Springs Hospital. Drug Alcohol Rev 2015;34:323-8.

48.Flink EB. Magnesium deficiency in alcoholism. Alcohol Clin Exp Res 1986;10:590-4.

49.Grochowski C, Blicharska E, Baj J, Mierzwińska A, Brzozowska K, Forma A, et al. Serum iron, magnesium, copper, and manganese levels in alcoholism. A systematic review.

Molecules 2019;24:E1361. 50.Flannery AH, Adkins DA, Cook AM. Unpeeling the evidence for the banana bag.

Evidence-based recommendations for the management of alcohol-associated vitamin and electrolyte deficiencies in the ICU. Crit Care Med 2016;44:1545-52. 51.Lagunoff D, Martin TW, Read G.

Agents that release histamine from mast cells. Annu Rev Pharmacol Toxicol 1983;23:331-51. Correspondence Address:Samir Kumar PraharajDepartment of Psychiatry, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka IndiaSource of Support.

None, Conflict of Interest. NoneDOI. 10.4103/psychiatry.IndianJPsychiatry_440_20 Figures [Figure 1].

Diflucan half life

Researchers used single-molecule imaging to compare cheap diflucan online canada the diflucan half life genome-editing tools CRISPR-Cas9 and TALEN. Their experiments revealed that TALEN is up to five times more efficient than CRISPR-Cas9 in parts of the genome, called heterochromatin, that are densely packed. Fragile X syndrome, sickle cell anemia, beta-thalassemia and other diseases are the result of genetic diflucan half life defects in the heterochromatin.The researchers report their findings in the journal Nature Communications.The study adds to the evidence that a broader selection of genome-editing tools is needed to target all parts of the genome, said Huimin Zhao, a professor of chemical and biomolecular engineering at the University of Illinois Urbana-Champaign who led the new research."CRISPR is a very powerful tool that led to a revolution in genetic engineering," Zhao said. "But it still has some limitations."CRISPR is a bacterial molecule that detects invading diflucanes.

It can carry one of several enzymes, such as Cas-9, that allow it to cut viral genomes at specific sites diflucan half life. TALEN also scans DNA to find and target specific genes. Both CRISPR and TALEN can be engineered to target specific genes to fight disease, improve crop plant characteristics or for other applications.Zhao and his colleagues used single-molecule fluorescence microscopy to diflucan half life directly observe how the two genome-editing tools performed in living mammalian cells. Fluorescent-labeled tags enabled the researchers to measure how long it took CRISPR and TALEN to move along the DNA and to detect and cut target sites."We found that CRISPR works better in the less-tightly wound regions of the genome, but TALEN can access those genes in the heterochromatin region better than CRISPR," Zhao said.

"We also saw that TALEN can have higher diflucan half life editing efficiency than CRISPR. It can cut the DNA and then make changes more efficiently than CRISPR."TALEN was as much as five times more efficient than CRISPR in multiple experiments.The findings will lead to improved approaches for targeting various parts of the genome, Zhao said."Either we can use TALEN for certain applications, or we could try to make CRISPR work better in the heterochromatin," he said. Story Source diflucan half life. Materials provided by University of Illinois at Urbana-Champaign, News Bureau.

Original written diflucan half life by Diana Yates. Note. Content may be edited for style and length.Multi-disciplinary researchers at The University of Manchester have helped develop a powerful diflucan half life physics-based tool to map the pace of language development and human innovation over thousands of years -- even stretching into pre-history before records were kept.Tobias Galla, a professor in theoretical physics, and Dr Ricardo Bermúdez-Otero, a specialist in historical linguistics, from The University of Manchester, have come together as part of an international team to share their diverse expertise to develop the new model, revealed in a paper entitled 'Geospatial distributions reflect temperatures of linguistic feature' authored by Henri Kauhanen, Deepthi Gopal, Tobias Galla and Ricardo Bermúdez-Otero, and published by the journal Science Advances.Professor Galla has applied statistical physics -- usually used to map atoms or nanoparticles -- to help build a mathematically-based model that responds to http://counterbalancebeer.com/single-project-2/ the evolutionary dynamics of language. Essentially, the forces that drive language change can operate across thousands of years and leave a measurable "geospatial signature," determining how languages of different types are distributed over the surface of the Earth.Dr Bermúdez-Otero explained.

"In our model each language has a collection of properties or features and some of those features are what we describe as 'hot' or 'cold'."So, if a language puts the object before the verb, then it is relatively likely to get stuck with that order for a diflucan half life long period of time -- so that's a 'cold' feature. In contrast, markers like the English article 'the' come and go a lot faster. They may be here in one historical period, diflucan half life and be gone in the next. In that sense, definite articles are 'hot' features."The striking thing is that languages with 'cold' properties tend to form big clumps, whereas languages with 'hot' properties tend to be more scattered geographically."This method therefore works like a thermometer, enabling researchers to retrospectively tell whether one linguistic property is more prone to change in historical time than another.

This modelling could also provide a similar benchmark for the pace of change in other social behaviours or practices over time and space."For example, suppose that you have a map showing the spatial distribution of some variable cultural practice for which you don't have any historical records -- this could be be anything, like different rules on marriage or on the inheritance of possessions," added Dr Bermúdez-Otero."Our method could, in principle, be used to ascertain whether one practice changes in the course of historical time faster than another, ie whether people are more innovative in one area diflucan half life than in another, just by looking at how the present-day variation is distributed in space."The source data for the linguistic modelling comes from present-day languages and the team relied on The World Atlas of Language Structures (WALS). This records information of 2,676 contemporary languages.Professor Galla explained. "We were interested in diflucan half life emergent phenomena, such as how large-scale effects, for example patterns in the distribution of language features arise from relatively simple interactions. This is a common theme in complex systems research."I was able to help with my expertise in the mathematical tools we used to analyse the language model and in simulation techniques.

I also contributed to setting up the model diflucan half life in the first place, and by asking questions that a linguist would perhaps not ask in the same way." Story Source. Materials provided by University of Manchester. Note. Content may be edited for style and length..

Researchers used buy diflucan online http://howyouruletheworld.com/atlanta-play-to-your-strengths/ single-molecule imaging to compare the genome-editing tools CRISPR-Cas9 and TALEN. Their experiments revealed that TALEN is up to five times more efficient than CRISPR-Cas9 in parts of the genome, called heterochromatin, that are densely packed. Fragile X syndrome, sickle cell anemia, beta-thalassemia and other diseases buy diflucan online are the result of genetic defects in the heterochromatin.The researchers report their findings in the journal Nature Communications.The study adds to the evidence that a broader selection of genome-editing tools is needed to target all parts of the genome, said Huimin Zhao, a professor of chemical and biomolecular engineering at the University of Illinois Urbana-Champaign who led the new research."CRISPR is a very powerful tool that led to a revolution in genetic engineering," Zhao said. "But it still has some limitations."CRISPR is a bacterial molecule that detects invading diflucanes. It can carry one of several enzymes, such as Cas-9, that allow it to buy diflucan online cut viral genomes at specific sites.

TALEN also scans DNA to find and target specific genes. Both CRISPR and TALEN can be engineered to target specific genes to fight disease, improve crop plant characteristics or for other applications.Zhao and his colleagues used single-molecule buy diflucan online fluorescence microscopy to directly observe how the two genome-editing tools performed in living mammalian cells. Fluorescent-labeled tags enabled the researchers to measure how long it took CRISPR and TALEN to move along the DNA and to detect and cut target sites."We found that CRISPR works better in the less-tightly wound regions of the genome, but TALEN can access those genes in the heterochromatin region better than CRISPR," Zhao said. "We also saw that TALEN can have higher buy diflucan online editing efficiency than CRISPR. It can cut the DNA and then make changes more efficiently than CRISPR."TALEN was as much as five times more efficient than CRISPR in multiple experiments.The findings will lead to improved approaches for targeting various parts of the genome, Zhao said."Either we can use TALEN for certain applications, or we could try to make CRISPR work better in the heterochromatin," he said.

Story Source buy diflucan online. Materials provided by University of Illinois at Urbana-Champaign, News Bureau. Original written buy diflucan online by Diana Yates. Note. Content may be edited for style and length.Multi-disciplinary researchers at The University of Manchester have helped develop a powerful physics-based tool to map the pace of language development and human innovation over thousands of years -- even stretching into pre-history before records were kept.Tobias Galla, a professor in theoretical physics, and Dr Ricardo Bermúdez-Otero, a specialist in historical linguistics, from The University of Manchester, have come together as part of an international team to share their diverse expertise to develop the new model, revealed buy diflucan online in a paper entitled 'Geospatial distributions reflect temperatures of linguistic feature' authored by Henri Kauhanen, Deepthi Gopal, Tobias Galla and Ricardo Bermúdez-Otero, and published by the journal Science Advances.Professor Galla has applied statistical physics -- usually used to map atoms or nanoparticles -- to help build a mathematically-based model that responds to the evolutionary dynamics of language.

Essentially, the forces that drive language change can operate across thousands of years and leave a measurable "geospatial signature," determining how languages of different types are distributed over the surface of the Earth.Dr Bermúdez-Otero explained. "In our buy diflucan online model each language has a collection of properties or features and some of those features are what we describe as 'hot' or 'cold'."So, if a language puts the object before the verb, then it is relatively likely to get stuck with that order for a long period of time -- so that's a 'cold' feature. In contrast, markers like the English article 'the' come and go a lot faster. They may be here in one historical period, and be gone in buy diflucan online the next. In that sense, definite articles are 'hot' features."The striking thing is that languages with 'cold' properties tend to form big clumps, whereas languages with 'hot' properties tend to be more scattered geographically."This method therefore works like a thermometer, enabling researchers to retrospectively tell whether one linguistic property is more prone to change in historical time than another.

This modelling could also provide a similar benchmark for the pace of change in other social behaviours or practices over time and space."For example, suppose that you have a map showing the buy diflucan online spatial distribution of some variable cultural practice for which you don't have any historical records -- this could be be anything, like different rules on marriage or on the inheritance of possessions," added Dr Bermúdez-Otero."Our method could, in principle, be used to ascertain whether one practice changes in the course of historical time faster than another, ie whether people are more innovative in one area than in another, just by looking at how the present-day variation is distributed in space."The source data for the linguistic modelling comes from present-day languages and the team relied on The World Atlas of Language Structures (WALS). This records information of 2,676 contemporary languages.Professor Galla explained. "We were interested in emergent phenomena, such as how large-scale effects, for example patterns in the distribution of language features buy diflucan online arise from relatively simple interactions. This is a common theme in complex systems research."I was able to help with my expertise in the mathematical tools we used to analyse the language model and in simulation techniques. I also contributed to setting up the model in the buy diflucan online first place, and by asking questions that a linguist would perhaps not ask in the same way." Story Source.

Materials provided by University of Manchester. Note. Content may be edited for style and length..

Is fluconazole and diflucan the same

Full-page version of http://www.smhgg.org.uk/levitra-for-sale-online/ the is fluconazole and diflucan the same map. Nonmetropolitan counties completed an average of 30,000 is fluconazole and diflucan the same vaccinations per day from July 6-15. That raised the rural vaccination rate to 35.5% of the total nonmetropolitan population, an increase of 0.7 percentage points since the last Daily Yonder vaccination report. The vaccination rate in metropolitan counties increased at a slightly quicker pace, rising by 0.9 percentage points to is fluconazole and diflucan the same 46.2% of the total population. Utah had the highest percentage-point increase in rural vaccinations, raising its is fluconazole and diflucan the same rate by 5.6 points to 37.4%.

Utah’s metropolitan vaccination rate climbed even more, rising 6.2 percentage points to 42.9%. Like this story? is fluconazole and diflucan the same. Sign up for our is fluconazole and diflucan the same newsletter. Mississippi raised its rural vaccination rate by 3.6 points to 31.8% from July 6-15. The state’s metropolitan vaccination rate climbed by 3.8 is fluconazole and diflucan the same points to 34.5%.

Mississippi, which is fluconazole and diflucan the same previously ranked 41st in the nation for its rural vaccination rate, climbed to 37th. Other states that added a percentage point or more to their rural vaccination rate last week were. Alaska, up is fluconazole and diflucan the same 2.4 points to 49.3%.Hawaii, up 2.2 points to 55.3%, the highest rural vaccination rate of any state outside New England.And West Virginia, up 1 point to 20.3%. States with the smallest increases in is fluconazole and diflucan the same their rural vaccination rates were Georgia, Virginia, Nevada, North Dakota, and Ohio. Each of those states increased their rural vaccination rate by about 0.3 points.

Those increases could be higher, especially in Georgia and Virginia, where the number of is fluconazole and diflucan the same unallocated vaccinations is high. Unallocated vaccinations are is fluconazole and diflucan the same not assigned to a county and aren’t included in our metropolitan/nonmetropolitan analysis. Georgia continued to have the lowest rural vaccination rate, at 13.2%, although unallocated vaccinations likely mean the real rate is higher. The gap between the nonmetropolitan and is fluconazole and diflucan the same metropolitan vaccination rates climbed by 0.1 point last week, to 10.7 points. You Might Also Like.

Full-page version buy diflucan online of the Levitra for sale online map. Nonmetropolitan counties completed an average of 30,000 vaccinations per buy diflucan online day from July 6-15. That raised the rural vaccination rate to 35.5% of the total nonmetropolitan population, an increase of 0.7 percentage points since the last Daily Yonder vaccination report. The vaccination rate in metropolitan counties increased at a slightly quicker pace, rising by 0.9 percentage points to 46.2% of buy diflucan online the total population. Utah had the highest percentage-point increase in rural vaccinations, raising its rate buy diflucan online by 5.6 points to 37.4%.

Utah’s metropolitan vaccination rate climbed even more, rising 6.2 percentage points to 42.9%. Like this buy diflucan online story?. Sign up for our buy diflucan online newsletter. Mississippi raised its rural vaccination rate by 3.6 points to 31.8% from July 6-15. The state’s metropolitan vaccination rate climbed by 3.8 points to 34.5% buy diflucan online.

Mississippi, which previously ranked 41st in the nation for its rural buy diflucan online vaccination rate, climbed to 37th. Other states that added a percentage point or more to their rural vaccination rate last week were. Alaska, up 2.4 points to 49.3%.Hawaii, up 2.2 points to 55.3%, the highest rural vaccination rate of any state outside New England.And West Virginia, buy diflucan online up 1 point to 20.3%. States with the buy diflucan online smallest increases in their rural vaccination rates were Georgia, Virginia, Nevada, North Dakota, and Ohio. Each of those states increased their rural vaccination rate by about 0.3 points.

Those increases could be higher, especially in Georgia and Virginia, where the buy diflucan online number of unallocated vaccinations is high. Unallocated vaccinations are not assigned to a county and aren’t included in our metropolitan/nonmetropolitan analysis. Georgia continued to have the lowest rural vaccination rate, at 13.2%, although unallocated vaccinations likely mean the real rate is higher. The gap between the nonmetropolitan and metropolitan vaccination rates climbed by 0.1 point last week, to 10.7 points. You Might Also Like.

Diflucan side effects reddit

Kristy Nishimoto, (206) 615-2367—Beneficiary here are the findings Enrollment and Appeals Issues diflucan side effects reddit. Danielle Blaser, (410) 786-3487—Program Integrity Issues. Tobey Oliver, (202) 260-1113—D-SNP Appeals and Grievances. End Further Info End Preamble Start diflucan side effects reddit Supplemental Information I. Background In FR Doc.

2021-00538 of January 19, 2021 (86 FR 5864), the final rule titled “Medicare and Medicaid Programs. Contract Year 2022 Policy and Technical Changes to the Medicare Advantage Program, Medicare Prescription Drug Benefit Program, Medicaid diflucan side effects reddit Program, Medicare Cost Plan Program, and Programs of All Inclusive Care for the Elderly”, there were technical errors that are identified and corrected in this correcting amendment. II. Summary of Errors A. Summary of Errors in the Preamble On pages 5870, 5895, 5950, 5975, 5983, diflucan side effects reddit 5985, 5987, 6007, 6016, and 6088, we made inadvertent grammatical and typographical errors.

On page 5938, in our discussion of tiering exceptions requests and the complaint tracking module, we inadvertently included an incorrect link. On pages 5962 and 6058, we made typographical errors in several regulatory citations. On pages 5977 and 5990, made typographical errors in cross-references to diflucan side effects reddit other sections of the final rule. On page 6062, in our discussion of the information collection requirements (ICRs) regarding beneficiaries' education on opioid risks and alternative treatments (§ 423.128), we mistakenly referred to “Part D sponsors” rather than “Part D parent organizations.” B. Summary of Errors in the Regulations Text On page 6094, in the amendatory instructions for § 422.101, we inadvertently omitted changes that would move existing paragraph (f)(2)(vi) to paragraph (f)(3)(i) This error caused a duplication of those paragraphs.

Therefore, we diflucan side effects reddit are removing paragraph (f)(2)(vi) to correct this error. On page 6103, we inadvertently changed the format in the regulation text for § 422.760(b)(3)(ii)(C) that was inconsistent with the language in § 423.760(b)(3)(ii)(C). In addition, we made a typographical error in § 422.760(b)(3)(ii)(A). On page 6120, in the regulation text for § 423.568(j)(2) and (3) and (k), we inadvertently use language applicable to MA plans instead of diflucan side effects reddit Part D plan sponsors. On page 6128, in the regulations text for § 423.2267, we inadvertently misnumbered a paragraph.

III. Waiver of Proposed Rulemaking and Delay in Effective Date Under 5 diflucan side effects reddit U.S.C. 553(b) of the Administrative Procedure Act (APA), the agency is required to publish a notice of the proposed rule in the Federal Register before the provisions of a rule take effect. Specifically, 5 U.S.C. 553 requires the agency to publish a notice of the proposed rule in the Federal Register that includes a reference to the legal authority under which the rule is proposed, and the terms and substance of diflucan side effects reddit the proposed rule or a description of the subjects and issues involved.

Further, 5 U.S.C. 553 requires the agency to give interested parties the opportunity to participate in the rulemaking through public comment before the provisions of the rule take effect. Similarly, section 1871(b)(1) of the Act requires the Secretary to provide for diflucan side effects reddit notice of the proposed rule in the Federal Register and provide a period of not less than 60 days for public comment for rulemaking to carry out the administration of the Medicare program under title XVIII of the Act. In addition, section 553(d) of the APA, and section 1871(e)(1)(B)(i) of the Social Security Act (the Act) mandate a 30-day delay in effective date after issuance or publication of a rule. Sections 553(b)(B) and 553(d)(3) of the APA provide for exceptions from the notice and comment and delay in effective date APA requirements.

In cases in which these exceptions apply, sections 1871(b)(2)(C) and 1871(e)(1)(B)(ii) of the Act, also provide exceptions from the notice and diflucan side effects reddit 60-day comment period and delay in effective date requirements of the Act. Section 553(b)(B) of the APA and section 1871(b)(2)(C) of the Act authorize an agency to dispense with normal rulemaking requirements for good cause if the agency makes a finding that the notice and comment process are impracticable, unnecessary, or contrary to the public interest. In addition, both section 553(d)(3) of the APA and section 1871(e)(1)(B)(ii) of the Act allow the agency to avoid the 30-day delay in effective date where such delay is contrary to the public interest and an agency includes a statement of support. We believe that this correcting document does not constitute a rule that would diflucan side effects reddit be subject to the notice and comment or delayed effective date requirements of the APA or section 1871 of the Act. This correcting document corrects technical errors in the preamble and regulations text of the final rule but does not make substantive changes to the policies that were adopted in the final rule.

As a result, this correcting document is intended to ensure that the information in the final rule accurately reflects the policies adopted in that final rule. In addition, even if this were a rule to which the notice and comment procedures and delayed effective date requirements applied, we find that there diflucan side effects reddit is good cause to waive such requirements. Undertaking further notice and comment procedures to incorporate the corrections in this document into the final rule or delaying the effective date would be contrary to the public interest because it is in the public's interest to ensure that final rule accurately reflects our policies. Furthermore, such procedures would be unnecessary, as we are not altering payment eligibility or benefit methodologies or policies, but rather, simply implementing correctly the policies that we previously proposed, received comment on, and subsequently finalized. This correcting document is intended solely diflucan side effects reddit to ensure that the final rule accurately reflects these policies.

Therefore, we believe we have good cause to waive the requirements for notice and comment and delay of effective date. IV. Correction of Errors in the Preamble In FR Doc diflucan side effects reddit. 2021-00538, published in the Federal Register of January 19, 2021, beginning on page 5864, the following corrections are made. 1.

On page 5870, second column of the table, first paragraph, line 3, the phrase “he RTBTI” is corrected diflucan side effects reddit to read “The RTBT”. 2. On page 5895, third column, second full paragraph, line 6, the terms “thatthis” are corrected to read “that this”. 3. On page 5938, second column, second full paragraph, lines 8 through 10, the website link “https://Start Printed Page 29528www.cms.gov/​files/​document/​cy2020part-d-reportingrequirements.pdf” is corrected to read “https://www.cms.gov/​files/​document/​cy2020part-d-reporting-requirements082719.pdf”.

4. On page 5950, third column, third full paragraph, lines 23 and 24, the phrase “will become” is corrected to “became”. 5. On page 5962, third column, second partial paragraph, line 7, the citation “§ 422.509 or § 423.510” is corrected to read “§ 422.510 or § 423.509”. 6.

On page 5975, first column, fifth paragraph, line 18, the word “reward” is corrected to read “rewards”. 7. On page 5977, third column, second full paragraph, line 19, the phrase “Section IIIC” is corrected to read “Section III.C.”. 8. On page 5983, second column, first partial paragraph, line 37, the word “provider” is corrected to read “provides”.

9. On page 5985, third column, first full paragraph, line 6, the word “are” is corrected to read “is”. 10. On page 5987, first column, second partial paragraph, line 17, the word “of” is corrected to read “or”. 11.

On page 5990, second column, first full paragraph, line 25, the reference “section D.” is corrected to read “section V.D.”. 12. On page 6007, first column, second partial paragraph, lines 26 and 27, the phrase “used evaluating” is corrected to read “use in evaluating”. 13. On page 6016, first column, first full paragraph, line 1, the word “toe” is corrected to read “to”.

14. On page 6058, third column, first full paragraph, line 4. A. The reference “0938-10396” is corrected to “0938-1154”. B.

The reference “CMS-1154” is corrected to read “CMS-10396”. 15. On page 6062, first column, first full paragraph, line 1, “288 Part D sponsors” is corrected to read “288 Part D parent organizations”. 16. On page 6088, second column, first full paragraph, line 12, “positon” is corrected to “position”.

Start List of Subjects 42 CFR Part 422 Administrative practice and procedureHealth facilitiesHealth maintenance organizations (HMO)MedicarePenaltiesPrivacyReporting and recordkeeping requirements 42 CFR Part 423 Administrative practice and procedureEmergency medical servicesHealth facilitiesHealth maintenance organizations (HMO)MedicarePenaltiesPrivacyReporting and recordkeeping requirements End List of Subjects Accordingly, 42 CFR parts 422 and 423 are corrected by making the following correcting amendments. Start Part End Part Start Amendment Part1. The authority citation for part 422 continues to read as follows. End Amendment Part Start Authority 42 U.S.C. 1302 and 1395hh.

End Authority Start Amendment Part2. Section 422.101 is amended by removing paragraph (f)(2)(vi). End Amendment Part Start Amendment Part3. Section 422.760 is amended as follows. End Amendment Part Start Amendment Parta.

In paragraph (b)(3)(ii)(A) by removing the word “increases” and adding in its place the phrase “are increased”. End Amendment Part Start Amendment Partb. By revising paragraph (b)(3)(ii)(C). End Amendment Part The revision reads as follows. Determinations regarding the amount of civil money penalties and assessment imposed by CMS.

* * * * * (b) * * * (3) * * * (ii) * * * (C) CMS tracks the calculation and accrual of the standard minimum penalty and aggravating factor amounts and announces them on an annual basis. * * * * * Start Part End Part Start Amendment Part4. The authority citation for part 423 continues to read as follows. End Amendment Part Start Authority 42 U.S.C. 1302, 1306, 1395w-101 through 1395w-152, and 1395hh.

End Authority Start Amendment Part5. Section 423.568 is amended as follows. End Amendment Part Start Amendment Parta. In paragraph (j)(2) by removing the phrase “MA organization” and adding in its place the phrase “Part D plan sponsor”. End Amendment Part Start Amendment Partb.

In paragraph (j)(3) by removing the term “reconsideration” adding in its place the term “redetermination”. End Amendment Part Start Amendment Partc. In paragraph (k) by removing the term “redetermination” adding in its place the term “coverage determination”. End Amendment Part Start Amendment Part6. Section 423.2267 is amended by redesignating paragraph (e)(13)(ii)(H) as paragraph (e)(13)(ii)(G).

End Amendment Part Start Signature Dated. May 25, 2021. Karuna Seshasai, Executive Secretary to the Department, Department of Health and Human Services. End Signature End Supplemental Information [FR Doc. 2021-11446 Filed 6-1-21.

8:45 am]BILLING CODE 4120-01-PStart Preamble Centers for Medicare &. Medicaid Services, Health and Human Services (HHS). Notice. The Centers for Medicare &. Medicaid Services (CMS) is announcing an opportunity for the public to comment on CMS' intention to collect information from the public.

Under the Paperwork Reduction Act of 1995 (PRA), federal agencies are required to publish notice in the Federal Register concerning each proposed collection of information, including each proposed extension or reinstatement of an existing collection of information, and to allow a second opportunity for public comment on the notice. Interested persons are invited to send comments regarding the burden estimate or any other aspect of this collection of information, including the necessity and utility of the proposed information collection for the proper performance of the agency's functions, the accuracy of the estimated burden, ways to enhance the quality, utility, and clarity of the information to be collected, and the use of automated collection techniques or other forms of information technology to minimize the information collection burden. Comments on the collection(s) of information must be received by the OMB desk officer by July 1, 2021. Written comments and recommendations for the proposed information collection should be sent within 30 days of publication of this notice to www.reginfo.gov/​public/​do/​PRAMain. Find this particular information collection by selecting “Currently under 30-day Review—Open for Public Comments” or by using the search function.

To obtain copies of a supporting statement and any related forms for the proposed collection(s) summarized in this notice, you may make your request using one of following. 1. Access CMS' website address at website address at. Https://www.cms.gov/​Regulations-and-Guidance/​Legislation/​PaperworkReductionActof1995/​PRA-Listing.html. Start Further Info Start Printed Page 29265 William Parham at (410) 786-4669.

End Further Info End Preamble Start Supplemental Information Under the Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 3501-3520), federal agencies must obtain approval from the Office of Management and Budget (OMB) for each collection of information they conduct or sponsor. The term “collection of information” is defined in 44 U.S.C. 3502(3) and 5 CFR 1320.3(c) and includes agency requests or requirements that members of the public submit reports, keep records, or provide information to a third party. Section 3506(c)(2)(A) of the PRA (44 U.S.C.

3506(c)(2)(A)) requires federal agencies to publish a 30-day notice in the Federal Register concerning each proposed collection of information, including each proposed extension or reinstatement of an existing collection of information, before submitting the collection to OMB for approval. To comply with this requirement, CMS is publishing this notice that summarizes the following proposed collection(s) of information for public comment. 1. Type of Information Collection Request. Extension of a currently approved collection.

Title of Information Collection. Verification of Clinic Data—Rural Health Clinic Form and Supporting Regulations. Use. The form is utilized as an application to be completed by suppliers of Rural Health Clinic (RHC) services requesting participation in the Medicare program. This form initiates the process of obtaining a decision as to whether the conditions for certification are met as a supplier of RHC services.

It also promotes data reduction or introduction to and retrieval from the Automated Survey Process Environment (ASPEN) and related survey and certification databases by the CMS Regional Offices. Should any question arise regarding the structure of the organization, this information is readily available. Form Number. CMS-29 (OMB control number 0938-0074). Frequency.

Occasionally (initially and then every six years). Affected Public. Private Sector (Business or other for-profit and Not-for-profit institutions). Number of Respondents. 1,887.

Total Annual Responses. 5,661. Total Annual Hours. 1,269. (For policy questions regarding this collection contact Shonte Carter at 410-786-3532.) 2.

Type of Information Collection Request. Extension of a currently approved collection. Title of Information Collection. Psychiatric Unit Criteria Work Sheet. Use.

Certain specialty hospitals and hospital specialty distinct-part units may be excluded from the Inpatient Medicare Prospective Payment System (IPPS) and be paid at a different rate. These specialty hospitals and distinct-part units of hospitals include Inpatient Rehabilitation Facilities (IRFs) units, Inpatient Rehabilitation Facilities (IRFs) hospitals and Inpatient Psychiatric Facilities (IPFs). CMS regulations at 42 CFR 412.20 through 412.29 describe the criteria under which these specialty hospitals and specialty distinct-part hospital units are excluded from the IPPS. Form CMS-437 is used by Inpatient Psychiatric Facilities (IPFs) to attest to meeting the necessary requirements that make them exempt for receiving payment from Medicare under the IPPS. These IPFs must use CMS-437 to attest that they meet the requirements for IPPS exempt status prior to being placed into excluded status.

The IPFs must re-attest to meeting the exclusion criteria annually. Form Number. CMS-437 (OMB control number. 0938-0358). Frequency.

Annually. Affected Public. Private sector—Business or other for-profits. Number of Respondents. 1,598.

Total Annual Responses. 1,598. Total Annual Hours. 1,732. (For policy questions regarding this collection contact Caroline Gallaher at 410-786-8705.) 3.

Type of Information Collection Request. Extension of a previously approved collection. Title of Information Collection. CMS Identity Management (IDM) System. Use.

HIPAA regulations require covered entities to verify the identity of the person requesting Personal Health Information (PHI) and the person's authority to have access to that information. Per the HIPAA Security Rule, covered entities, regardless of their size, are required under Section 164.312(a)(2)(i) to “assign a unique name and/or number for identifying and tracking user identity.” A `user' is defined in Section 164.304 as a “person or entity with authorized access”. Accordingly, the Security Rule requires covered entities to assign a unique name and/or number to each employee or workforce member who uses a system that receives, maintains or transmits electronic PHI, so that system access and activity can be identified and tracked by user. This pertains to workforce members within health plans, group health plans, small or large provider offices, clearinghouses and beneficiaries. The information collected will be gathered and used solely by CMS, approved contractor(s), and state health insurance exchanges to prove the identity of an individual requesting electronic access to CMS protected information or services.

Information confidentiality will conform to the Health Insurance Portability and Accountability Act (HIPAA) of 1996 and the Federal Information Security Management Act (FISMA) requirements. Respondents may also access CMS' Terms of Service and Privacy Statement on the CMS Portal and IDM websites. CMS has moved from this centralized on premise model for enterprise identity management to a cloud-based solution, IDM, with multiple products providing specialized services. Okta Identity as a Service (IDaaS), which includes Multi-Factor Authentication (MFA) services. Experian Remote Identity Proofing (RIDP) services.

And Cloud Computing Services-Amazon Web Services/Information Technology Operations (CCS-AWS/ITOps) Hub Hosting. In order to prove the identity of an individual requesting electronic access to CMS protected information or services, IDM (leveraging Experian Precise ID RIDP services) will collect a core set of attributes about that individual. Form Number. CMS-10452 (OMB control number. 0938-1236).

Frequency. Yearly. Affected Public. Individuals and Households. Number of Respondents.

560,000. Total Annual Responses. 560,000. Total Annual Hours. 186,667.

(For policy questions regarding this collection contact Malachi Robinson at 410-786-1849).

Start Preamble check over here Centers buy diflucan online for Medicare &. Medicaid Services (CMS), Department of Health and Human Services (HHS). Final rule.

Correction and correcting amendment buy diflucan online. This document corrects technical and typographical errors in the final rule that appeared in the January 19, 2021 Federal Register titled “Medicare and Medicaid Programs. Contract Year 2022 Policy and Technical Changes to the Medicare Start Printed Page 29527Advantage Program, Medicare Prescription Drug Benefit Program, Medicaid Program, Medicare Cost Plan Program, and Programs of All Inclusive Care for the Elderly.” The effective date of the final rule was March 22, 2021.

This document is effective June buy diflucan online 2, 2021. Start Further Info Cali Diehl, (410) 786-4053 or Christopher McClintick, (410) 786-4682—General Questions. Kimberlee Levin, (410) 786-2549—Part C Issues.

Lucia Patrone, buy diflucan online (410) 786-8621—Part D Issues. Kristy Nishimoto, (206) 615-2367—Beneficiary Enrollment and Appeals Issues. Danielle Blaser, (410) 786-3487—Program Integrity Issues.

Tobey Oliver, (202) 260-1113—D-SNP Appeals and Grievances buy diflucan online. End Further Info End Preamble Start Supplemental Information I. Background In FR Doc.

2021-00538 of January 19, 2021 (86 FR 5864), the final buy diflucan online rule titled “Medicare and Medicaid Programs. Contract Year 2022 Policy and Technical Changes to the Medicare Advantage Program, Medicare Prescription Drug Benefit Program, Medicaid Program, Medicare Cost Plan Program, and Programs of All Inclusive Care for the Elderly”, there were technical errors that are identified and corrected in this correcting amendment. II.

Summary of Errors buy diflucan online A. Summary of Errors in the Preamble On pages 5870, 5895, 5950, 5975, 5983, 5985, 5987, 6007, 6016, and 6088, we made inadvertent grammatical and typographical errors. On page 5938, in our discussion of tiering exceptions requests and the complaint tracking module, we inadvertently included an incorrect link.

On pages 5962 buy diflucan online and 6058, we made typographical errors in several regulatory citations. On pages 5977 and 5990, made typographical errors in cross-references to other sections of the final rule. On page 6062, in our discussion of the information collection requirements (ICRs) regarding beneficiaries' education on opioid risks and alternative treatments (§ 423.128), we mistakenly referred to “Part D sponsors” rather than “Part D parent organizations.” B.

Summary of Errors in the Regulations Text buy diflucan online On page 6094, in the amendatory instructions for § 422.101, we inadvertently omitted changes that would move existing paragraph (f)(2)(vi) to paragraph (f)(3)(i) This error caused a duplication of those paragraphs. Therefore, we are removing paragraph (f)(2)(vi) to correct this error. On page 6103, we inadvertently changed the format in the regulation text for § 422.760(b)(3)(ii)(C) that was inconsistent with the language in § 423.760(b)(3)(ii)(C).

In addition, we buy diflucan online made a typographical error in § 422.760(b)(3)(ii)(A). On page 6120, in the regulation text for § 423.568(j)(2) and (3) and (k), we inadvertently use language applicable to MA plans instead of Part D plan sponsors. On page 6128, in the regulations text for § 423.2267, we inadvertently misnumbered a paragraph.

III. Waiver of Proposed Rulemaking and Delay in Effective Date Under 5 U.S.C. 553(b) of the Administrative Procedure Act (APA), the agency is required to publish a notice of the proposed rule in the Federal Register before the provisions of a rule take effect.

Specifically, 5 U.S.C. 553 requires the agency to publish a notice of the proposed rule in the Federal Register that includes a reference to the legal authority under which the rule is proposed, and the terms and substance of the proposed rule or a description of the subjects and issues involved. Further, 5 U.S.C.

553 requires the agency to give interested parties the opportunity to participate in the rulemaking through public comment before the provisions of the rule take effect. Similarly, section 1871(b)(1) of the Act requires the Secretary to provide for notice of the proposed rule in the Federal Register and provide a period of not less than 60 days for public comment for rulemaking to carry out the administration of the Medicare program under title XVIII of the Act. In addition, section 553(d) of the APA, and section 1871(e)(1)(B)(i) of the Social Security Act (the Act) mandate a 30-day delay in effective date after issuance or publication of a rule.

Sections 553(b)(B) and 553(d)(3) of the APA provide for exceptions from the notice and comment and delay in effective date APA requirements. In cases in which these exceptions apply, sections 1871(b)(2)(C) and 1871(e)(1)(B)(ii) of the Act, also provide exceptions from the notice and 60-day comment period and delay in effective date requirements of the Act. Section 553(b)(B) of the APA and section 1871(b)(2)(C) of the Act authorize an agency to dispense with normal rulemaking requirements for good cause if the agency makes a finding that the notice and comment process are impracticable, unnecessary, or contrary to the public interest.

In addition, both section 553(d)(3) of the APA and section 1871(e)(1)(B)(ii) of the Act allow the agency to avoid the 30-day delay in effective date where such delay is contrary to the public interest and an agency includes a statement of support. We believe that this correcting document does not constitute a rule that would be subject to the notice and comment or delayed effective date requirements of the APA or section 1871 of the Act. This correcting document corrects technical errors in the preamble and regulations text of the final rule but does not make substantive changes to the policies that were adopted in the final rule.

As a result, this correcting document is intended to ensure that the information in the final rule accurately reflects the policies adopted in that final rule. In addition, even if this were a rule to which the notice and comment procedures and delayed effective date requirements applied, we find that there is good cause to waive such requirements. Undertaking further notice and comment procedures to incorporate the corrections in this document into the final rule or delaying the effective date would be contrary to the public interest because it is in the public's interest to ensure that final rule accurately reflects our policies.

Furthermore, such procedures would be unnecessary, as we are not altering payment eligibility or benefit methodologies or policies, but rather, simply implementing correctly the policies that we previously proposed, received comment on, and subsequently finalized. This correcting document is intended solely to ensure that the final rule accurately reflects these policies. Therefore, we believe we have good cause to waive the requirements for notice and comment and delay of effective date.

IV. Correction of Errors in the Preamble In FR Doc. 2021-00538, published in the Federal Register of January 19, 2021, beginning on page 5864, the following corrections are made.

1. On page 5870, second column of the table, first paragraph, line 3, the phrase “he RTBTI” is corrected to read “The RTBT”. 2.

On page 5895, third column, second full paragraph, line 6, the terms “thatthis” are corrected to read “that this”. 3. On page 5938, second column, second full paragraph, lines 8 through 10, the website link “https://Start Printed Page 29528www.cms.gov/​files/​document/​cy2020part-d-reportingrequirements.pdf” is corrected to read “https://www.cms.gov/​files/​document/​cy2020part-d-reporting-requirements082719.pdf”.

4. On page 5950, third column, third full paragraph, lines 23 and 24, the phrase “will become” is corrected to “became”. 5.

On page 5962, third column, second partial paragraph, line 7, the citation “§ 422.509 or § 423.510” is corrected to read “§ 422.510 or § 423.509”. 6. On page 5975, first column, fifth paragraph, line 18, the word “reward” is corrected to read “rewards”.

7. On page 5977, third column, second full paragraph, line 19, the phrase “Section IIIC” is corrected to read “Section III.C.”. 8.

On page 5983, second column, first partial paragraph, line 37, the word “provider” is corrected to read “provides”. 9. On page 5985, third column, first full paragraph, line 6, the word “are” is corrected to read “is”.

10. On page 5987, first column, second partial paragraph, line 17, the word “of” is corrected to read “or”. 11.

On page 5990, second column, first full paragraph, line 25, the reference “section D.” is corrected to read “section V.D.”. 12. On page 6007, first column, second partial paragraph, lines 26 and 27, the phrase “used evaluating” is corrected to read “use in evaluating”.

13. On page 6016, first column, first full paragraph, line 1, the word “toe” is corrected to read “to”. 14.

On page 6058, third column, first full paragraph, line 4. A. The reference “0938-10396” is corrected to “0938-1154”.

B. The reference “CMS-1154” is corrected to read “CMS-10396”. 15.

On page 6062, first column, first full paragraph, line 1, “288 Part D sponsors” is corrected to read “288 Part D parent organizations”. 16. On page 6088, second column, first full paragraph, line 12, “positon” is corrected to “position”.

Start List of Subjects 42 CFR Part 422 Administrative practice and procedureHealth facilitiesHealth maintenance organizations (HMO)MedicarePenaltiesPrivacyReporting and recordkeeping requirements 42 CFR Part 423 Administrative practice and procedureEmergency medical servicesHealth facilitiesHealth maintenance organizations (HMO)MedicarePenaltiesPrivacyReporting and recordkeeping requirements End List of Subjects Accordingly, 42 CFR parts 422 and 423 are corrected by making the following correcting amendments. Start Part End Part Start Amendment Part1. The authority citation for part 422 continues to read as follows.

End Amendment Part Start Authority 42 U.S.C. 1302 and 1395hh. End Authority Start Amendment Part2.

Section 422.101 is amended by removing paragraph (f)(2)(vi). End Amendment Part Start Amendment Part3. Section 422.760 is amended as follows.

End Amendment Part Start Amendment Parta. In paragraph (b)(3)(ii)(A) by removing the word “increases” and adding in its place the phrase “are increased”. End Amendment Part Start Amendment Partb.

By revising paragraph (b)(3)(ii)(C). End Amendment Part The revision reads as follows. Determinations regarding the amount of civil money penalties and assessment imposed by CMS.

* * * * * (b) * * * (3) * * * (ii) * * * (C) CMS tracks the calculation and accrual of the standard minimum penalty and aggravating factor amounts and announces them on an annual basis. * * * * * Start Part End Part Start Amendment Part4. The authority citation for part 423 continues to read as follows.

End Amendment Part Start Authority 42 U.S.C. 1302, 1306, 1395w-101 through 1395w-152, and 1395hh. End Authority Start Amendment Part5.

Section 423.568 is amended as follows. End Amendment Part Start Amendment Parta. In paragraph (j)(2) by removing the phrase “MA organization” and adding in its place the phrase “Part D plan sponsor”.

End Amendment Part Start Amendment Partb. In paragraph (j)(3) by removing the term “reconsideration” adding in its place the term “redetermination”. End Amendment Part Start Amendment Partc.

In paragraph (k) by removing the term “redetermination” adding in its place the term “coverage determination”. End Amendment Part Start Amendment Part6. Section 423.2267 is amended by redesignating paragraph (e)(13)(ii)(H) as paragraph (e)(13)(ii)(G).

End Amendment Part Start Signature Dated. May 25, 2021. Karuna Seshasai, Executive Secretary to the Department, Department of Health and Human Services.

End Signature End Supplemental Information [FR Doc. 2021-11446 Filed 6-1-21. 8:45 am]BILLING CODE 4120-01-PStart Preamble Centers for Medicare &.

Medicaid Services, Health and Human Services (HHS). Notice. The Centers for Medicare &.

Medicaid Services (CMS) is announcing an opportunity for the public to comment on CMS' intention to collect information from the public. Under the Paperwork Reduction Act of 1995 (PRA), federal agencies are required to publish notice in the Federal Register concerning each proposed collection of information, including each proposed extension or reinstatement of an existing collection of information, and to allow a second opportunity for public comment on the notice. Interested persons are invited to send comments regarding the burden estimate or any other aspect of this collection of information, including the necessity and utility of the proposed information collection for the proper performance of the agency's functions, the accuracy of the estimated burden, ways to enhance the quality, utility, and clarity of the information to be collected, and the use of automated collection techniques or other forms of information technology to minimize the information collection burden.

Comments on the collection(s) of information must be received by the OMB desk officer by July 1, 2021. Written comments and recommendations for the proposed information collection should be sent within 30 days of publication of this notice to www.reginfo.gov/​public/​do/​PRAMain. Find this particular information collection by selecting “Currently under 30-day Review—Open for Public Comments” or by using the search function.

To obtain copies of a supporting statement and any related forms for the proposed collection(s) summarized in this notice, you may make your request using one of following. 1. Access CMS' website address at website address at.

Https://www.cms.gov/​Regulations-and-Guidance/​Legislation/​PaperworkReductionActof1995/​PRA-Listing.html. Start Further Info Start Printed Page 29265 William Parham at (410) 786-4669. End Further Info End Preamble Start Supplemental Information Under the Paperwork Reduction Act of 1995 (PRA) (44 U.S.C.

3501-3520), federal agencies must obtain approval from the Office of Management and Budget (OMB) for each collection of information they conduct or sponsor. The term “collection of information” is defined in 44 U.S.C. 3502(3) and 5 CFR 1320.3(c) and includes agency requests or requirements that members of the public submit reports, keep records, or provide information to a third party.

Section 3506(c)(2)(A) of the PRA (44 U.S.C. 3506(c)(2)(A)) requires federal agencies to publish a 30-day notice in the Federal Register concerning each proposed collection of information, including each proposed extension or reinstatement of an existing collection of information, before submitting the collection to OMB for approval. To comply with this requirement, CMS is publishing this notice that summarizes the following proposed collection(s) of information for public comment.

1. Type of Information Collection Request. Extension of a currently approved collection.

Title of Information Collection. Verification of Clinic Data—Rural Health Clinic Form and Supporting Regulations. Use.

The form is utilized as an application to be completed by suppliers of Rural Health Clinic (RHC) services requesting participation in the Medicare program. This form initiates the process of obtaining a decision as to whether the conditions for certification are met as a supplier of RHC services. It also promotes data reduction or introduction to and retrieval from the Automated Survey Process Environment (ASPEN) and related survey and certification databases by the CMS Regional Offices.

Should any question arise regarding the structure of the organization, this information is readily available. Form Number. CMS-29 (OMB control number 0938-0074).

Frequency. Occasionally (initially and then every six years). Affected Public.

Private Sector (Business or other for-profit and Not-for-profit institutions). Number of Respondents. 1,887.

Total Annual Responses. 5,661. Total Annual Hours.

1,269. (For policy questions regarding this collection contact Shonte Carter at 410-786-3532.) 2. Type of Information Collection Request.

Extension of a currently approved collection. Title of Information Collection. Psychiatric Unit Criteria Work Sheet.

Use. Certain specialty hospitals and hospital specialty distinct-part units may be excluded from the Inpatient Medicare Prospective Payment System (IPPS) and be paid at a different rate. These specialty hospitals and distinct-part units of hospitals include Inpatient Rehabilitation Facilities (IRFs) units, Inpatient Rehabilitation Facilities (IRFs) hospitals and Inpatient Psychiatric Facilities (IPFs).

CMS regulations at 42 CFR 412.20 through 412.29 describe the criteria under which these specialty hospitals and specialty distinct-part hospital units are excluded from the IPPS. Form CMS-437 is used by Inpatient Psychiatric Facilities (IPFs) to attest to meeting the necessary requirements that make them exempt for receiving payment from Medicare under the IPPS. These IPFs must use CMS-437 to attest that they meet the requirements for IPPS exempt status prior to being placed into excluded status.

The IPFs must re-attest to meeting the exclusion criteria annually. Form Number. CMS-437 (OMB control number.

Affected Public. Private sector—Business or other for-profits. Number of Respondents.

Total Annual Hours. 1,732. (For policy questions regarding this collection contact Caroline Gallaher at 410-786-8705.) 3.

Type of Information Collection Request. Extension of a previously approved collection. Title of Information Collection.

CMS Identity Management (IDM) System. Use. HIPAA regulations require covered entities to verify the identity of the person requesting Personal Health Information (PHI) and the person's authority to have access to that information.

Per the HIPAA Security Rule, covered entities, regardless of their size, are required under Section 164.312(a)(2)(i) to “assign a unique name and/or number for identifying and tracking user identity.” A `user' is defined in Section 164.304 as a “person or entity with authorized access”. Accordingly, the Security Rule requires covered entities to assign a unique name and/or number to each employee or workforce member who uses a system that receives, maintains or transmits electronic PHI, so that system access and activity can be identified and tracked by user. This pertains to workforce members within health plans, group health plans, small or large provider offices, clearinghouses and beneficiaries.

The information collected will be gathered and used solely by CMS, approved contractor(s), and state health insurance exchanges to prove the identity of an individual requesting electronic access to CMS protected information or services. Information confidentiality will conform to the Health Insurance Portability and Accountability Act (HIPAA) of 1996 and the Federal Information Security Management Act (FISMA) requirements. Respondents may also access CMS' Terms of Service and Privacy Statement on the CMS Portal and IDM websites.

CMS has moved from this centralized on premise model for enterprise identity management to a cloud-based solution, IDM, with multiple products providing specialized services. Okta Identity as a Service (IDaaS), which includes Multi-Factor Authentication (MFA) services. Experian Remote Identity Proofing (RIDP) services.

And Cloud Computing Services-Amazon Web Services/Information Technology Operations (CCS-AWS/ITOps) Hub Hosting. In order to prove the identity of an individual requesting electronic access to CMS protected information or services, IDM (leveraging Experian Precise ID RIDP services) will collect a core set of attributes about that individual. Form Number.

CMS-10452 (OMB control number. 0938-1236). Frequency.