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Background: No randomised controlled trials have yet reported on the effectiveness of molnupiravir on longer term outcomes for COVID-19. The PANORAMIC trial found molnupiravir reduced time to recovery in acute COVID-19 over 28 days. We aimed to report the effect of molnupiravir treatment for COVID-19 on wellbeing, severe and persistent symptoms, new infections, health care and social service use, medication use, and time off work at 3 months and 6 months post-randomisation., Methods: This study is a follow-up to the main analysis, which was based on the first 28 days of follow-up and has been previously reported. For this multicentre, primary care, open-label, multi-arm, prospective randomised controlled trial conducted in the UK, participants were eligible if aged at least 50 years, or at least 18 years with a comorbidity, and unwell 5 days or less with confirmed COVID-19 in the community. Participants were randomly assigned to the usual care group or molnupiravir group plus usual care (800 mg twice a day for 5 days), which was stratified by age (<50 years or ≥50 years) and vaccination status (at least one dose: yes or no). The primary outcome was hospitalisation or death (or both) at 28 days; all longer term outcomes were considered to be secondary outcomes and included self-reported ratings of wellness (on a scale of 0-10), experiencing any symptom (fever, cough, shortness of breath, fatigue, muscle ache, nausea and vomiting, diarrhoea, loss of smell or taste, headache, dizziness, abdominal pain, and generally feeling unwell) rated as severe (moderately bad or major problem) or persistent, any health and social care use, health-related quality of life (measured by the EQ-5D-5L), time off work or school, new infections, and hospitalisation., Findings: Between Dec 8, 2021, and April 27, 2022, 25 783 participants were randomly assigned to the molnupiravir plus usual care group (n=12 821) or usual care group (n=12 962). Long-term follow-up data were available for 23 008 (89·2%) of 25 784 participants with 11 778 (91·9%) of 12 821 participants in the molnupiravir plus usual care group and 11 230 (86·6%) of 12 963 in the usual care group. 22 806 (99·1%) of 23 008 had at least one previous dose of a SARS-CoV-2 vaccine. Any severe (3 months: adjusted risk difference -1·6% [-2·6% to -0·6%]; probability superiority [p(sup)]>0·99; number needed to treat [NNT] 62·5; 6 months: -1·9% [-2·9% to -0·9%]; p(sup)>0·99, NNT 52·6) or persistent symptoms (3 months: adjusted risk difference -2·1% [-2·9% to -1·5%]; p(sup)>0·99; NNT 47·6; 6 months: -2·5% [-3·3% to -1·6%]; p(sup)>0·99; NNT 40) were reduced in severity, and health-related quality of life (measured by the EQ-5D-5L) improved in the molnupiravir plus usual care group at 3 months and 6 months (3 months: adjusted mean difference 1·08 [0·65 to 1·53]; p(sup)>0·99; 6 months: 1·09 [0·63 to 1·55]; p(sup)>0·99). Ratings of wellness (3 months: adjusted mean difference 0·15 (0·11 to 0·19); p(sup)>0·99; 6 months: 0·12 (0·07 to 0·16); p(sup)>0·99), experiencing any more severe symptom (3 months; adjusted risk difference -1·6% [-2·6% to -0·6%]; p(sup)=0·99; 6 months: -1·9% [-2·9% to -0·9%]; p(sup)>0·99), and health-care use (3 months: adjusted risk difference -1·4% [-2·3% to -0·4%]; p(sup)>0·99; NNT 71·4; 6 months: -0·5% [-1·5% to 0·4%]; p(sup)>0·99; NNT 200) had high probabilities of superiority with molnupiravir treatment. There were significant differences in persistence of any symptom (910 [8·9%] of 10 190 vs 1027 [11%] of 9332, NNT 67) at 6 months, and reported time off work at 3 months (2017 [17·9%] of 11 274 vs 2385 [22·4%] of 10 628) and 6 months (460 [4·4%] of 10 562 vs 527 [5·4%] of 9846; NNT 100). There were no differences in hospitalisations at long-term follow-up., Interpretation: In a vaccinated population, people treated with molnupiravir for acute COVID-19 felt better, experienced fewer and less severe COVID-19 associated symptoms, accessed health care less often, and took less time off work at 6 months. However, the absolute differences in this open-label design are small with high numbers needed to treat., Funding: UK Research and Innovation and National Institute for Health and Care Research., Competing Interests: Declaration of interests JSN-V-T was seconded to the Department of Health and Social Care, England from Oct 1, 2017, to March 31, 2022. On June 15, 2023, JSN-V-T completed one 3-h paid consultancy assignment for Merck Sharp & Dohme on a subject unrelated to COVID-19, and has given two paid lectures for Gilead who have manufactured COVID-19 treatments in 2022–23, and one paid lecture for AstraZeneca in 2022, who manufacture COVID-19 vaccines. JSN-V-T has consulted occasionally for Moderna (May 1, 2023 onwards) who manufacture COVID-19 vaccines. DML has received personal fees from Gilead for an educational video and from Merck for a roundtable discussion, speaker fees from Biotest, Takeda, and Astra Zeneca, and support to attend a conference from Octapharma. DML holds research grants from GlaxoSmithKline and Bristol Myers Squibb, has received consultancy fees from GlaxoSmithKline paid to his institution, all outside the current work, and reports giving lectures for Biotest, Takeda, and AstraZeneca. JFS has participated in a Data and Safety Monitoring Committee for the sotrovimab paediatric programme for GlaxoSmithKline (fee paid to the institution). JB reports being the Principle Investigator on The Medicines and Healthcare products Regulatory Agency commissioned study with GlaxoSmithKline to look at the evolution of variants in sotrovimab treated patients, and consulting fees from GlaxoSmithKline, hVIVO, Moderna, and Symbios (donated to UCL). SK has been a speaker for Pfizer and ViiV Healthcare. KH reports a grant to Cardiff University (via University of Oxford), and was on the National Institute for Health and Care Research (NIHR) Health Technology Assessment General Committee and Health Technology Assessment Funding Strategy Group until November, 2022, and is currently Deputy Chair of the Research Professors panel. BRS reports consulting fees were paid to his former employer (Berry Consultants) for tiral design and implementation. NPBT reports being on a single advisory board in July, 2021, with Merck & Co. OvH reports consulting fees from MindGap. AU reports honoria from Merck & Co, Gilead Sciences, Pfizer, and Astra Zeneca in relation to this disease area and manuscript. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Brain arteriovenous malformation (AVM) is a rare congenital disorder affecting young adults with an incidence of 0.94 per 100,000 population. Intracranial digital subtraction angiography has to be done in all patients and grading of AVM is done as per Spetzler-Martin grading. We report a rare case of left basal ganglia large AVM treated by endovascular embolization. Our experience with endovascular embolization using Onyx is successful in the treatment of large brain AVM. Endovascular embolization with Onyx is safe and feasible in deeply located large AVMs of the brain. Our patient has postoperatively recovered completely without any neurological deficit., Competing Interests: Conflict of Interest None., (Asian Congress of Neurological Surgeons. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Background: The evidence for whether ivermectin impacts recovery, hospital admissions, and longer-term outcomes in COVID-19 is contested. The WHO recommends its use only in the context of clinical trials., Methods: In this multicentre, open-label, multi-arm, adaptive platform randomised controlled trial, we included participants aged ≥18 years in the community, with a positive SARS-CoV-2 test, and symptoms lasting ≤14 days. Participants were randomised to usual care, usual care plus ivermectin tablets (target 300-400 μg/kg per dose, once daily for 3 days), or usual care plus other interventions. Co-primary endpoints were time to first self-reported recovery, and COVID-19 related hospitalisation/death within 28 days, analysed using Bayesian models. Recovery at 6 months was the primary, longer term outcome., Trial Registration: ISRCTN86534580., Findings: The primary analysis included 8811 SARS-CoV-2 positive participants (median symptom duration 5 days), randomised to ivermectin (n = 2157), usual care (n = 3256), and other treatments (n = 3398) from June 23, 2021 to July 1, 2022. Time to self-reported recovery was shorter in the ivermectin group compared with usual care (hazard ratio 1·15 [95% Bayesian credible interval, 1·07 to 1·23], median decrease 2.06 days [1·00 to 3·06]), probability of meaningful effect (pre-specified hazard ratio ≥1.2) 0·192). COVID-19-related hospitalisations/deaths (odds ratio 1·02 [0·63 to 1·62]; estimated percentage difference 0% [-1% to 0·6%]), serious adverse events (three and five respectively), and the proportion feeling fully recovered were similar in both groups at 6 months (74·3% and 71·2% respectively (RR = 1·05, [1·02 to 1·08]) and also at 3 and 12 months., Interpretation: Ivermectin for COVID-19 is unlikely to provide clinically meaningful improvement in recovery, hospital admissions, or longer-term outcomes. Further trials of ivermectin for SARS-Cov-2 infection in vaccinated community populations appear unwarranted., Funding: UKRI/National Institute of Health Research (MC&#95;PC&#95;19079)., Competing Interests: Declaration of Competing Interest Drs. Saville, Berry, Detry, Fitzgerald and Saunders report grants from The University of Oxford, for the Sponsor's grant from the UK NIHR, for statistical design and analyses for the PRINCIPLE trial during the conduct of the study. Prof de Lusignan is Director of the Oxford-RCGP Research and Surveillance Centre and reports that through his University he has had grants outside the submitted work from AstraZeneca, GSK, Sanofi, Seqirus and Takeda for vaccine related research, and membership of advisory boards for AstraZeneca, Sanofi and Seqirus. Profs Hobbs and Butler report grants from UKRI, during the conduct of the study. All other authors have no competing interests to declare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Type 2 diabetes mellitus (T2DM) has been traditionally considered a chronic, progressive disease. Since 2017, guidelines from the US Department of Veterans Affairs and US Department of Defense have included low-carbohydrate (LC) dietary patterns in managing T2DM. Recently, carbohydrate reduction, including ketogenic diets, has gained renewed interest in the management and remission of T2DM., Observations: This narrative review examines the evidence behind carbohydrate reduction in T2DM and a practical guide for clinicians starting patients on therapeutic LC diets. We present an illustrative case and provide practical approaches to prescribing a very LC ketogenic (< 50 g), LC (50-100 g), or a moderate LC (101-150 g) dietary plan and discuss adverse effects and management of LC diets. We provide a medication management and deprescription approach and discuss strategies to consider in conjunction with LC diets. As patients adopt LC diets, glycemia improves, and medications are deprescribed, hemoglobin A 1c levels and fasting glucose may drop below the diagnostic threshold for T2DM. Remission of T2DM may occur with LC diets (hemoglobin A 1c < 6.5% for ≥ 3 months without T2DM medications). Finally, we describe barriers and limitations to applying therapeutic carbohydrate reduction in a federal health care system., Conclusions: The effective use of LC diets with close and intensive lifestyle counseling and a safe approach to medication management and deprescribing can improve glycemic control, reduce the overall need for insulin and medication and provide sustained weight loss. The efficacy and continuation of therapeutic carbohydrate reduction for patients with T2DM appears promising. Further research on LC diets, emerging strategies, and long-term effects on cardiometabolic risk factors, morbidity, and mortality will continue to inform practice., Competing Interests: Author disclosures: CM Jenks is married to an employee of Virta Medical, which provides care related to type 2 diabetes and ketogenic diets., (Copyright © 2024 Frontline Medical Communications Inc., Parsippany, NJ, USA.)

Background: Type 2 diabetes mellitus (T2DM) is a significant health problem around the world., Objective: This review aims to define missed opportunities and how they apply to patients with T2DM., Method: This narrative review describes the natural history of T2DM and also describes where missed opportunities may arise., Results: Missed opportunities may relate to prevention, early detection, diagnosis, and treatment of diabetes. The cornerstone of T2DM prevention is the control of modifiable risk factors and lifestyle changes to potentially prevent diabetes. Early detection of T2DM is important as it is a chronic condition that can progress rapidly if untreated. Missed opportunities related to the diagnosis of T2DM draw attention to the heterogeneous presentation of diabetes. The condition can be incidentally identified in asymptomatic patients, so all healthcare professionals should be aware of the disease. Furthermore, it is not unexpected that patients with atypical symptoms may have a delay in diagnosis. The treatment-related missed opportunities in T2DM are broad and include self-care, education, remission of T2DM, risk factor management, prevention of complications, medication therapy and compliance, as well as individualized care. Considering patient pathways is a useful approach to evaluate missed opportunities in patient care., Conclusion: Missed opportunities are a concept that is not often considered in diabetes care, which calls upon reflection of real-world activities and consideration of whether patient outcomes could have been improved with changes in decision-making. Future studies that aim to improve patient care should consider this concept., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: There is an urgent need to determine the safety, effectiveness and cost-effectiveness of novel antiviral treatments for COVID-19 in vaccinated patients in the community at increased risk of morbidity and mortality from COVID-19., Methods and Analysis: PANORAMIC is a UK-wide, open-label, prospective, adaptive, multiarm platform, randomised clinical trial that evaluates antiviral treatments for COVID-19 in the community. A master protocol governs the addition of new antiviral treatments as they become available, and the introduction and cessation of existing interventions via interim analyses. The first two interventions to be evaluated are molnupiravir (Lagevrio) and nirmatrelvir/ritonavir (Paxlovid)., Eligibility Criteria: community-dwelling within 5 days of onset of symptomatic COVID-19 (confirmed by PCR or lateral flow test), and either (1) aged 50 years and over, or (2) aged 18-49 years with qualifying comorbidities. Registration occurs via the trial website and by telephone. Recruitment occurs remotely through the central trial team, or in person through clinical sites. Participants are randomised to receive either usual care or a trial drug plus usual care. Outcomes are collected via a participant-completed daily electronic symptom diary for 28 days post randomisation. Participants and/or their Trial Partner are contacted by the research team after days 7, 14 and 28 if the diary is not completed, or if the participant is unable to access the diary. The primary efficacy endpoint is all-cause, non-elective hospitalisation and/or death within 28 days of randomisation. Multiple prespecified interim analyses allow interventions to be stopped for futility or superiority based on prespecified decision criteria. A prospective economic evaluation is embedded within the trial., Ethics and Dissemination: Ethical approval granted by South Central-Berkshire REC number: 21/SC/0393; IRAS project ID: 1004274. Results will be presented to policymakers and at conferences, and published in peer-reviewed journals., Trial Registration Number: ISRCTN30448031; EudraCT number: 2021-005748-31., Competing Interests: Competing interests: JN-V-T was seconded to the Department of Health and Social Care, England (DHSC) from October 2017 to March 2022. The views expressed in this paper are those of its authors and not necessarily those of DHSC. JN-V-T reports a lecture fee from Gilead Sciences Ltd (manufacturer of remdesivir) and a paid Influenza Advisory Board for F. Hoffmann-La Roche (manufacturer of tocilizumab), both after March 2022. KH is a member of the following NIHR committees: HTA General Committee, HTA Funding Strategy Group, Research Professors Funding Committee. KH is co-investigator on the grant provided by UKRI/NIHR, Grant number NIHR135366 (subcontract from University of Oxford to Cardiff University). KH received a grant from AstraZeneca to support a trial of Evusheld for the prevention of COVID in high-risk individuals (to Cardiff University). KH is an independent member of the IDMC for the OCTAVE-DUO trial of vaccines for COVID in high-risk individuals (unpaid). DML has received grants/contracts from LifeArc, Medical Research Council, Bristol Myers Squibb and Blood Cancer UK. DML received personal fees/honoraria for a lecture from Biotest UK, for an educational video from Gilead and for a ‘round table’ discussion with Merck. SP is co-investigator on the grant provided by UKRI/NIHR, Grant number NIHR135366. DR has received consulting fees from OMASS therapeutics. DR has a leadership/fiduciary role in the Heal-COVID trial TMG. BRS reports grant money paid to his employer (Berry Consultants, LLC) from The University of Oxford, from the Sponsor’s grant from the UKRI/NIHR, per the statistical design and analyses for the PANORAMIC trial. GH reports that the NIHR funded this study. ML reports funding directly from the PANORAMIC trial (NIHR). ML reports being a RAPIS-TEST (NIHR EME) DMC member. JM reports that this is part of his consulting work for Berry Consultants. SK reports research funding from GSK, ViiV Healthcare, Ridgeback Biotherapeutics, Vir and Merck unrelated to this work. SK reports speaker’s fees from ViiV Healthcare and participation on ViiV Healthcare, Pfizer advisory boards. SK reports receiving donation of drugs for clinical studies from ViiV Healthcare, Toyama and GSK. JFS reports receiving research grants from MRC (MR/X004724/1), Wellcome, NIHR, DNDi, Gates and MRC (MR/W015560/1) paid to his institution. JFS reports receiving Pharmacometric consultancy fees from Adrenomed Ltd paid to his institution. JFS reports participation on a Data Safety Monitoring board/Advisory Board for GSK Sotrovimab paediatric programme. MIA reports receiving grants from BTRU – GEMS, Janssen – Cartography, Pfizer – Myst, Prenetics, Dunhill Medical Trust, BMA Trust – Kathleen Harper Fund and Antibiotic Research UK – all paid to the institution. MIA reports receiving consultancy fees from Prenetics and OxDx. MIA reports a planned patent for Ramanomics. MIA reports participation on a Data Safety Monitoring board/Advisory Board for Prenetics. MIA has an unpaid leadership/fiduciary role in the E3 Initiative. NPBT reports his current affiliations with RCGP and NIHR TVSM. NPBT reports a payment for a single episode of participation on the MSD advisory board in July 2021, prior to any knowledge or planning of this trial. OvH reports receiving an NIHR Development and Skills Personal Award. OvH reports receiving consulting fees for MINDGAP BV, with the fees paid to Oxford University lnnovation Limited. OvH reports unpaid participation on a Data Safety Monitoring board/Advisory Board for The CHIldren with COugh Cluster Randomised Controlled Trial (CHICO). OvH has an unpaid leadership/fiduciary role in the British Society of Antimicrobial Chemotherapy. CB reports full employment with the Nuffield Department of Primary Care Health Sciences. AU reports receiving consulting fees and payment/honoraria from Merck/MSD and Gilead Sciences. RH reports receiving expenses reimbursed for talks on COVID monoclonal antibodies. PL reports support from the NIHR for the grant to do the PANORAMIC study. NF reports receiving consulting fees from Abbott Diagnostics and GSK, a presentation fee from Abbott Diagnostics, and has stocks in Synairgen PLC., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Endodontic mistakes, also known as procedural accidents, are those bad events that occur during treatment, some of which are attributable to a lack of attention to detail and others of which are completely unforeseeable. The second most frequent reason for root canal failure is perforation., Aims and Objective: The current in vitro study's objective was to assess the furcal perforation's potential to be sealed with and without internal matrix by MTA flow, Biodentine, and pro-root MTA., Materials and Methods: 60 samples were allocated into six groups at random (10 each). In intact permanent mandibular first and second teeth, furcal perforation sites were made and sealed with various materials. Following perforation sealing, the specimens' capacity for sealing was evaluated using the dye penetration method., Result: The current study's findings indicated that Group 2 has the least amount of microleakage and Group 5 has the most., Conclusion: Biodentine has excellent sealing capabilities and can be utilised to heal furcation perforations with or without internal matrix., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Pharmacy and Bioallied Sciences.)

Objectives: Across diverse ethnic groups in the UK, explore attitudes and intentions towards COVID-19 vaccination and sources of COVID-19 information., Design: Remote qualitative interviews and focus groups (FGs) conducted June-October 2020 before UK COVID-19 vaccine approval. Data were transcribed and analysed through inductive thematic analysis and mapped to the Theoretical Domains Framework., Setting: England and Wales., Participants: 100 participants from 19 self-identified ethnic groups., Results: Mistrust and doubt were reported across ethnic groups. Many participants shared concerns about perceived lack of information about COVID-19 vaccine safety and efficacy. There were differences within each ethnic group, with factors such as occupation and perceived health status influencing intention to accept a vaccine once made available. Across ethnic groups, participants believed that public contact occupations, older adults and vulnerable groups should be prioritised for vaccination. Perceived risk, social influences, occupation, age, comorbidities and engagement with healthcare influenced participants' intentions to accept vaccination once available. All Jewish FG participants intended to accept, while all Traveller FG participants indicated they probably would not.Facilitators to COVID-19 vaccine uptake across ethnic groups included: desire to return to normality and protect health and well-being; perceived higher risk of infection; evidence of vaccine safety and efficacy; vaccine availability and accessibility.COVID-19 information sources were influenced by social factors and included: friends and family; media and news outlets; research literature; and culture and religion. Participants across most different ethnic groups were concerned about misinformation or had negative attitudes towards the media., Conclusions: During vaccination rollout, including boosters, commissioners and providers should provide accurate information, authentic community outreach and use appropriate channels to disseminate information and counter misinformation. Adopting a context-specific approach to vaccine resources, interventions and policies and empowering communities has potential to increase trust in the programme., Competing Interests: Competing interests: AKamal participates in the UK’s Scientific Advisory Group for Emergencies (SAGE) behavioural science subgroup SPI-B. LFJ and CM have been involved in the review of Public Health England/UK Health Security Agency COVID-19 guidance. All other authors have no conflicts of interest to declare., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To explore public reactions to the COVID-19 pandemic across diverse ethnic groups., Design: Remote qualitative interviews and focus groups in English or Punjabi. Data were transcribed and analysed through inductive thematic analysis., Setting: England and Wales, June to October 2020., Participants: 100 participants from 19 diverse 'self-identified' ethnic groups., Results: Dismay, frustration and altruism were reported across all ethnic groups during the first 6-9 months of the COVID-19 pandemic. Dismay was caused by participants' reported individual, family and community risks, and loss of support networks. Frustration was caused by reported lack of recognition of the efforts of ethnic minority groups (EMGs), inaction by government to address COVID-19 and inequalities, rule breaking by government advisors, changing government rules around: border controls, personal protective equipment, social distancing, eating out, and perceived poor communication around COVID-19 and the Public Health England COVID-19 disparities report (leading to reported increased racism and social isolation). Altruism was felt by all, in the resilience of National Health Service (NHS) staff and their communities and families pulling together. Data, participants' suggested actions and the behaviour change wheel informed suggested interventions and policies to help control COVID-19., Conclusion: To improve trust and compliance future reports or guidance should clearly explain any stated differences in health outcomes by ethnicity or other risk group, including specific messages for these groups and concrete actions to minimise any risks. Messaging should reflect the uncertainty in data or advice and how guidance may change going forward as new evidence becomes available. A contingency plan is needed to mitigate the impact of COVID-19 across all communities including EMGs, the vulnerable and socially disadvantaged individuals, in preparation for any rise in cases and for future pandemics. Equality across ethnicities for healthcare is essential, and the NHS and local communities will need to be supported to attain this., Competing Interests: Competing interests: AKam participates in the UK Scientific Advisory Group for Emergencies (SAGE) behavioural science subgroup SPI-B. The views expressed are those of the authors. LFJ and CM have been involved in the review of PHE/UKHSA COVID-19 guidance., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Pharmacists are uniquely positioned to provide tobacco cessation interventions given their medication expertise and accessibility to the public. The purpose of this study was to evaluate the efficacy and safety of management of varenicline by clinical pharmacy specialists (CPSs) compared with other clinicians., Methods: This retrospective chart review included patients with a varenicline prescription between July 1, 2019, and July 31, 2020. Primary outcomes were reduction in tobacco use at 12 weeks from baseline, continuous abstinence at 12 weeks, adherence to varenicline therapy, and time to first follow-up. For safety evaluation, charts were reviewed for documented adverse drug reactions., Results: Management by CPS compared with other clinicians was associated with similar mean (SD) reductions of tobacco use (-7.9 [10.4] vs -5.4 [9.8] cigarettes per day, respectively; P = .15) and rates of complete abstinence (34% vs 38%, respectively; P = .73) and higher adherence (42% vs 31%, respectively; P = .01). Mean (SD) time to first follow-up was shorter for patients in the CPS group: 52 (66) vs 163 (110) days; P < .001. Adverse events were more common in the CPS group compared with the other clinicians group (42% vs 23%; P = .02)., Conclusions: These results suggest that CPS management of varenicline is as safe and effective as management by other clinicians. Additional research is needed to fully characterize the impact of pharmacist management of varenicline, justify expansion of CPS scope of practice, and ultimately enhance patient outcomes regarding tobacco cessation., Competing Interests: Author disclosures The authors report no actual or potential conflicts of interest with regard to this article., (Copyright © 2022 Frontline Medical Communications Inc., Parsippany, NJ, USA.)

Background: Colchicine has been proposed as a COVID-19 treatment., Aim: To determine whether colchicine reduces time to recovery and COVID-19-related admissions to hospital and/or deaths among people in the community., Design and Setting: Prospective, multicentre, open-label, multi-arm, randomised, controlled, adaptive platform trial (PRINCIPLE)., Method: Adults aged ≥65 years or ≥18 years with comorbidities or shortness of breath, and unwell for ≤14 days with suspected COVID-19 in the community, were randomised to usual care, usual care plus colchicine (500 µg daily for 14 days), or usual care plus other interventions. The co-primary endpoints were time to first self-reported recovery and admission to hospital/death related to COVID-19, within 28 days, analysed using Bayesian models., Results: The trial opened on 2 April 2020. Randomisation to colchicine started on 4 March 2021 and stopped on 26 May 2021 because the prespecified time to recovery futility criterion was met. The primary analysis model included 2755 participants who were SARS-CoV-2 positive, randomised to colchicine ( n = 156), usual care ( n = 1145), and other treatments ( n = 1454). Time to first self-reported recovery was similar in the colchicine group compared with usual care with an estimated hazard ratio of 0.92 (95% credible interval (CrI) = 0.72 to 1.16) and an estimated increase of 1.4 days in median time to self-reported recovery for colchicine versus usual care. The probability of meaningful benefit in time to recovery was very low at 1.8%. COVID-19-related admissions to hospital/deaths were similar in the colchicine group versus usual care, with an estimated odds ratio of 0.76 (95% CrI = 0.28 to 1.89) and an estimated difference of -0.4% (95% CrI = -2.7 to 2.4)., Conclusion: Colchicine did not improve time to recovery in people at higher risk of complications with COVID-19 in the community., (© The Authors.)

Introduction: There is an urgent need to idenfy treatments for COVID-19 that reduce illness duration and hospital admission in those at higher risk of a longer illness course and complications., Methods and Analysis: The Platform Randomised trial of INterventions against COVID-19 In older peoPLE trial is an open-label, multiarm, prospective, adaptive platform, randomised clinical trial to evaluate potential treatments for COVID-19 in the community. A master protocol governs the addition of new interventions as they become available, as well as the inclusion and cessation of existing intervention arms via frequent interim analyses. The first three interventions are hydroxychloroquine, azithromycin and doxycycline. Eligible participants must be symptomatic in the community with possible or confirmed COVID-19 that started in the preceding 14 days and either (1) aged 65 years and over or (2) aged 50-64 years with comorbidities. Recruitment is through general practice, health service helplines, COVID-19 'hot hubs' and directly through the trial website. Participants are randomised to receive either usual care or a study drug plus usual care, and outcomes are collected via daily online symptom diary for 28 days from randomisation. The research team contacts participants and/or their study partner following days 7, 14 and 28 if the online diary is not completed. The trial has two coprimary endpoints: time to first self-report of feeling recovered from possible COVID-19 and hospital admission or death from possible COVID-19 infection, both within 28 days from randomisation. Prespecified interim analyses assess efficacy or futility of interventions and to modify randomisation probabilities that allocate more participants to interventions with better outcomes., Ethics and Dissemination: Ethical approval Ref: 20/SC/0158 South Central - Berkshire Research Ethics Committee; IRAS Project ID: 281958; EudraCT Number: 2020-001209-22. Results will be presented to policymakers and at conferences and published in peer-reviewed journals., Trial Registration Number: ISRCTN86534580., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

We chose to understand the cyclic instability and rate instability issues in the promising class of Na + conversion and alloying anodes with Sb 2 Se 3 as a typical example. We employ a synthetic strategy that ensures efficient rGO (reduced graphene oxide) wrapping over Sb 2 Se 3 material. By utilization of the minimum weight of additive (5 wt.% of rGO), we achieved a commendable performance with a reversible capacity of 550 mAh g -1 at a specific current of 100 mA g -1 and an impressive rate performance with 100 % capacity retention after high current cycling involving a 2 Ag -1 intermediate current step. The electrochemical galvanostatic intermittent titration technique (GITT) has been employed for the first time to draw a rationale between the enhanced performance and the increased mobility in the rGO wrapped composite (Sb 2 Se 3 -rGO) compared to bare Sb 2 Se 3 . GITT analysis reveals higher Na + diffusion coefficients (approx. 30 fold higher) in the case of Sb 2 Se 3 -rGO as compared to bare Sb 2 Se 3 throughout the operating voltage window. For Sb 2 Se 3 -rGO the diffusion coefficients in the range of 8.0×10 -15  cm 2  s -1 to 2.2×10 -12  cm 2  s -1 were observed, while in case of bare Sb 2 Se 3 the diffusion coefficients in the range of 1.6×10 -15  cm 2  s -1 to 9.4×10 -15  cm 2  s -1 were observed., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Alcohol and drug abuse continue to be major causes of morbidity and mortality and have significant social and economic ramifications. Studies have shown that for every $1 spent on substance use disorder treatment, $4 are saved on healthcare costs. Characterizing the healthcare resource utilization of these patients may shed light on the burden of disease and opportunities for intervention. A retrospective chart review of all patients admitted to the ICU between July 1, 2017 and December 31, 2017 was completed. Variables regarding demographic and clinical characteristics as well as healthcare resource utilization were collected. Of 737 admissions to the ICU, 158 (21%) were due to acute or chronic complications of alcohol or drug abuse. Even though alcohol and drug users were significantly younger (average age 50 years) than the general ICU cohort (average age 66 years), resource utilization was similar between these patients. The median length of stay in the ICU was similar. The number of patients transferred to in-patient rehab was low (8%), and all of those were due to comorbid psychiatric illness. The total hospital charges for the alcohol and drug abuse cohort was over 7 million dollars for the 6 months observed. A significant number of patients had at least one ER visit (49%) during the previous year, and most of these had numerous visits. ICU resource utilization by patients with acute and chronic sequelae of drug or alcohol abuse disorders continues to be high. These patients utilize resources at rates similar to an older group with other disease processes. Patients are unlikely to receive intervention for their disorder unless they have a comorbid psychiatric illness. Patients admitted to the ICU with alcohol or drug-related illness were frequently seen in the ER or were admitted to the hospital in the year prior to ICU admission, providing opportunities for intervention., Competing Interests: Declaration of Conflicting Interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: To compare the diagnostic ability of pharmacists, nurses and general practitioners (GPs) for a range of skin conditions., Methods: An online study comprising 10 specifically developed dermatological case studies containing a digital image of the skin condition and a short case history. A total of 60 participants (20 representing each of pharmacists, GPs and primary care nurses) were required to identify the skin condition as well as the features in the case history that supported the diagnosis and the recommended first-line management approach for the condition., Key Findings: The mean diagnostic scores for each group were GPs = 8.8 (95% confidence interval, CI, 7.9-9.6), pharmacists = 6.2 (95% CI, 5.4-6.9) and nurses = 7.0 (95% CI, 6.1-7.9). Post hoc analysis revealed that the difference in mean diagnostic scores was significant (P < 0.05) between GPs and both pharmacists and nurses. However, pharmacists' diagnostic accuracy was similar to GPs' for some skin conditions such as tinea corporis, scabies and plantar warts and overall at least 40% of pharmacists correctly identified all conditions., Conclusion: This small study has demonstrated that for all of the skin conditions considered, pharmacists' overall diagnostic scores were significantly different from those of GPs but similar to those of nurses for the conditions assessed. However, further work with a larger sample is required to determine the accuracy of these preliminary findings and to establish whether advice given by pharmacists in practice results in the appropriate course of action being taken., (© 2013 Royal Pharmaceutical Society.)

This study investigated the possible anti-inflammatory, analgesic, and antipyretic effects of ethanolic extract of Pedalium murex Linn. fruits in selected experimental animal models. Anti-inflammatory activity of Pedalium murex Linn., with doses of 200 mg/kg and 400 mg/kg, p.o., was evaluated by Lambda-carrageenan induced paw oedema in Wistar albino rats; analgesic activity with doses of 280 mg/kg and 560 mg/kg, p.o., was evaluated by hot plate method and acetic acid induced writhing method in Swiss albino mice; and antipyretic activity with doses of 110 mg/kg and 220 mg/kg, p.o., was evaluated in New Zealand white rabbits by injecting gram -ve lipopolysaccharide obtained from E. coli. Results were analysed by one way ANOVA followed by Dunnet's multiple comparison test. Pedalium murex Linn. showed significant anti-inflammatory activity from 15 min to 180 min as compared to vehicle treated animals. It was comparable to diclofenac sodium at 180 min. The extract did not prolong the reaction time on hot plate method but significantly reduced the number of writhing after acetic acid administration. Also the extract did not show any antipyretic activity on lipopolysaccharide induced pyrexia. It is therefore concluded that the ethanolic extract of Pedalium murex Linn. fruits has an anti-inflammatory and peripheral analgesic effects.

Ceramidases cleave the N-acyl linkages of ceramide to generate sphingosine and its subsequent product sphingosine-1-phosphate (S1P). Ceramide and S1P are important bioactive lipids, and ceramidases are important in regulating the availability of these lipids. In this study, we report the purification and characterization of camel brain neutral ceramidase (CBCDase). The novel CBCDase was purified from camel brain using sequential chromatography of DEAE-Sepharose, Phenyl-Sepharose, Superdex, and Mono Q column. The Mono Q fractions containing ceramidase activity were used for enzyme characterization. The purified CBCDase showed a single band corresponding to a molecular weight of ~100 kDa, displaying classical Michaelis-Menten kinetics, with maximum enzymatic activity at pH 7.0. Deglycosylation of the enzyme yields an apparent molecular weight of ~80 kDa. The purified CBCDase was inhibited by Zn(2+) and Cu(2+), while Ca(2+) stimulates the activity. Phosphatidic acid, phosphatidylserine and phosphatidylcholine completely inhibited enzyme activity at low concentrations. Thiol-containing compounds inhibited the CBCDase activity. Among the nucleotides, ADP, UMP, and TMP inhibited the enzyme activity at low concentrations, whereas, ATP inhibited the activity at higher concentrations only. The CBCDase catalysed both ceramide hydrolysis and reverse CDase reactions. For the first time, we have purified to apparent homogeneity of a ~100 kDa nCDase from camel brain.

Background: Public policy and clinical treatment in tobacco addiction in the UK has focused on cessation: an abrupt attempt to stop all cigarettes. However, recent evidence suggests that allowing more gradual withdrawal from tobacco or even permanent partial substitution by nicotine replacement therapy (NRT) could lead to net benefits to public health. No jurisdiction has introduced smoking reduction programmes in normal clinical care and the best methods for their implementation is uncertain. Community pharmacists offering smoking cessation services in the UK are ideally placed to implement reduction programmes.This pilot study aims therefore to examine the feasibility of implementing smoking reduction programme in pharmacies, and also to see if behavioural support and a longer treatment affect the success rate for cessation., Design and Methods: This is a 2 × 2 randomised factorial trial of behavioural support versus no support and short versus standard length reduction programme. The pharmacists will recruit 16 patients per pharmacy, 160 smokers altogether. Pharmacists will randomise each participant by sealed envelopes. In a standard supported programme, the pharmacist will give support for 34 weeks, inviting participants to set a treatment goal and providing advice on how to reduce cigarette use. Participants in the short programme will be given the same advice on how to reduce but will reduce smoking over four weeks. Participants in the no support arms will be given a leaflet that describes the reduction programmes in 4-week and 34-week format. All participants are encouraged to use of NRT to support the reduction. These processes will be measured by recording the number of recruited smokers; percentage of those who reduce and sustain their consumption to at least 50% of baseline value, and the proportion of people who attain 4 weeks abstinence and 6 months abstinence. Interviews will assess smokers' and pharmacists' views on the way the programme ran., Discussion: This is a pilot study to assess the feasibility of offering smoking reduction programme within pharmacies that offer naturalistic setting to show population benefit from these programmes. Findings from this trial will inform the development of evidence-based treatment for smokers who want to reduce and best approaches to engage reluctant quitters onto the programme., Trial Registration: Current Controlled Trials ISRCTN 2010-019259-24.

A simple, sensitive, selective, and rapid high-performance liquid chromatography-tandem mass spectrometry method is developed and validated for the quantitation of naratriptan, using sumatriptan as internal standard (IS). The method included liquid-liquid extraction of naratriptan and IS with methyl-tert-butyl ether and dichloromethane mixture from 100 μL human plasma. The chromatographic separation is achieved on ACE C18 (50 mm × 2.1 mm, 5 μm) analytical column under isocratic conditions, using 0.1% acetic acid and acetonitrile (15:85, v/v) at a flow-rate of 0.4 mL/min. The precursor → product ion transitions for naratriptan (m/z 336.10 → 98.06) and IS (m/z 296.09 → 251.06) were monitored on a triple quadrupole mass spectrometer, operating in the multiple reaction monitoring (MRM) and positive ion mode. The linearity of the method for naratriptan is determined in the range of 103-20690 pg/mL with the analysis time of 1.5 min. The method is fully validated according to USFDA guidelines. A systematic post-column infusion study is conducted for ion-suppression due to endogenous matrix components. The process efficiency of analyte (96%) and IS (93%) from spiked plasma samples was consistent and reproducible. The application of the method is demonstrated by a bioequivalence study of 2.5 mg naratriptan tablet formulation in 31 healthy volunteers under fasting conditions.