Background: Influenza and influenza-like illness place significant burden on the NHS. Children with underlying health conditions are vulnerable to developing bacterial complications. Objective: To strengthen the evidence base underlying antibiotic use in at-risk children with influenza-like illness. Design: This programme comprised five separate work packages. Work package A investigated published and unpublished data from previously published literature and work package B explored attitudes of parents and general practitioners to influenza-like illness and antibiotics in at-risk children. This was followed by a clinical trial to assess the effectiveness of early co-amoxiclav (Augmentin\u00ae, GlaxoSmithKline UK) use at reducing reconsultation due to clinical deterioration (work package C), a nested sub-study to examine bacterial carriage indicators of antibiotic resistance (work package D) and a within-trial economic evaluation and clinical risk prediction analysis (work package E). Setting: Interviews were conducted by telephone with general practitioners across the UK and parents/ guardians in England (work package B). We conducted the clinical trial (work package C and nested work packages D and E) in general practices and ambulatory care services in England and Wales. Participants: General practitioners and parents/guardians of at-risk children who previously had influenza-like illness participated in work package B. At-risk children with influenza-like illness aged 6 months to 12 years participated in work packages C and E and optionally in work package D. Interventions: The intervention for the clinical trial was a 5-day course of co-amoxiclav 400/57 with dosing regimens based on British National Formulary guidance. Main outcome measures: Hospital admission (work package A); findings from semi-structured interviews with patients and health-care professionals (work package B); proportion of patients who reconsulted owing to clinical deterioration (work package C); respiratory bacterial carriage and antibiotic resistance of potentially pathogenic respiratory tract bacteria at 3, 6, 9 and 12 months (work package D); and risk factors for reconsultation owing to clinical deterioration, quality of life (EuroQol-5 Dimensions, three-level youth version), symptoms (Canadian Acute Respiratory Infection and Flu Scale), health-care use and costs (work package E). Review methods: For work package A, we searched the MEDLINE, MEDLINE In-Process, EMBASE, Science Citation Index and CINAHL (Cumulative Index to Nursing and Allied Health Literature) databases until 3 April 2013 with no language restrictions and requested unpublished data from authors of studies which had collected but not published relevant data. We included studies involving children up to 18 years of age with influenza or influenza-like illness from primary or ambulatory care settings. We used univariable meta-analysis methods to calculate odds ratios with 95% confidence intervals for individual risk factors. We reported our systematic review according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2009 statement. Results: Work package A analysed data from 28 articles reporting data from 27 studies. Neurological disorders, sickle cell disease, immunosuppression, diabetes and an age of <2 years were risk factors for hospital admission. Work package B interviewed 41 general practitioners and found that decision-making in at-risk children with influenza-like illness varies considerably. Parents/guardians were interviewed for work package B and spoke of how quickly their at-risk child could deteriorate. They were supportive of antibiotic use while being aware of antibiotic resistance. The trial (work package C) recruited 271 at-risk children. Primary outcome data were available for 265 children. There was no evidence of benefit from treatment with co-amoxiclav versus placebo (adjusted risk ratio 1.16, 95% confidence interval 0.75 to 1.80). Work package D collected 285 additional throat swabs over 12 months. At 3 months, the proportion of Haemophilus influenzae isolates was greater in the placebo than co-amoxiclav group (29% vs. 18%). No association was found between antibiotic resistance and early co-amoxiclav use. No clinical features were significantly associated with risk of reconsultation due to clinical deterioration except respiratory rate (coefficient 0.046, 95% confidence interval 0.010 to 0.081). Work package E found no evidence that early co-amoxiclav treatment improves quality of life or reduces health-care use and costs. Total costs per patient were highly skewed in both groups (co-amoxiclav: median \u00a34, range \u00a34\u20135258; placebo: median \u00a30, range \u00a30\u20135177). Limitations: We were not able to recruit our target sample size for the trial. This impacted the data available for microbiology, health economics and risk reduction score analyses. Conclusions: Our results do not support early antibiotic prescribing to at-risk children with influenza-like illness during influenza season. Future work: Further research is required to determine if antibiotic treatment would be beneficial during periods of higher influenza activity such as influenza pandemics, to identify children who would gain most clinical benefit and to better understand families\u2019 reconsultation decisions. Trial registration: This trial is registered as ISRCTN70714783 and EudraCT 2013-002822-21.
\n \n\n \n \nBackground: Thrombosis associated with thrombocytopenia was a matter of concern post first and second doses of BNT162b2 and ChAdOx1 COVID-19 vaccines. Therefore, it is important to investigate the risk of thrombocytopenic, thromboembolic and haemorrhagic events following a second dose of BNT162b2 and ChAdOx1 COVID-19 vaccines. Methods: We conducted a large-scale self-controlled case series analysis, using routine primary care data linked to hospital data, among 12.3 million individuals (16 years old and above) in England. We used the nationally representative Oxford-Royal College of General Practitioners (RCGP) sentinel network database with baseline and risk periods between 8th December 2020 and 11th June 2022. We included individuals who received two vaccine (primary) doses of the BNT162b2 mRNA (Pfizer-BioNTech) and two vaccine doses of ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccines in our analyses. We carried out a self-controlled case series (SCCS) analysis for each outcome using a conditional Poisson regression model with an offset for the length of risk period. We reported the incidence rate ratios (IRRs) and 95% confidence intervals (CI) of thrombocytopenic, thromboembolic (including arterial and venous events) and haemorrhagic events, in the period of 0\u201327 days after receiving a second dose of BNT162b2 or ChAdOx1 vaccines compared to the baseline period (14 or more days prior to first dose, 28 or more days after the second dose and the time between 28 or more days after the first and 14 or more days prior to the second dose). We adjusted for a range of potential confounders, including age, sex, comorbidities and deprivation. Findings: Between December 8, 2020 and February 11, 2022, 6,306,306 individuals were vaccinated with two doses of BNT162b2 and 6,046,785 individuals were vaccinated with two doses of ChAdOx1. Compared to the baseline, our analysis show no increased risk of venous thromboembolic events (VTE) for both BNT162b2 (IRR 0.71, 95% CI: 0.65\u20130.770) and ChAdOx1 (IRR 0.91, 95% CI: 0.84\u20130.98); and similarly there was no increased risk for cerebral venous sinus thrombosis (CVST) for both BNT162b2 (IRR 0.87, 95% CI: 0.41\u20131.85) and ChAdOx1 (IRR 1.73, 95% CI: 0.82\u20133.68). We additionally report no difference in IRR for pulmonary embolus, and deep vein thrombosis, thrombocytopenia, including idiopathic thrombocytopenic purpura (ITP), and haemorrhagic events post second dose for both BNT162b2. Interpretation: Reassuringly, we found no associations between increased risk of thrombocytopenic, thromboembolic and haemorrhagic events post vaccination with second dose for either of these vaccines. Funding: Data and Connectivity: COVID-19 Vaccines Pharmacovigilance study.
\n \n\n \n \nSupplementary materials for the Cochrane living review of electronic cigarettes for smoking cessation. Word documents. Created August 2023.\n\nWe included 88 completed studies, representing 27,235 participants, of which 47 were RCTs. Ten of the 88 included studies were new to this review update. Of the included studies, we rated ten (all but one contributing to our main comparisons) at low risk of bias overall, 58 at high risk overall (including all non-randomized studies), and the remainder at unclear risk.\nThere was high certainty that quit rates were higher in people randomized to nicotine EC than in those randomized to nicotine replacement therapy (NRT) (RR 1.59, 95% CI 1.29 to 1.93; I2 = 10%; 7 studies, 2544 participants). In absolute terms, this might translate to an additional four quitters per 100 (95% CI 2 to 6). There was moderate-certainty evidence (limited by imprecision) that the rate of occurrence of AEs was similar between groups (RR 1.03, 95% CI 0.91 to 1.17; I2 = 0%; 5 studies, 2052 participants). SAEs were rare, but there was insufficient evidence to determine whether rates differed between groups due to very serious imprecision (RR 1.20, 95% CI 0.90 to 1.60; I2 = 32%; 6 studies, 2761 participants).\nThere was moderate-certainty evidence, limited by imprecision, that quit rates were higher in people randomized to nicotine EC than to non-nicotine EC (RR 1.46, 95% CI 1.09 to 1.96; I2 = 4%; 6 studies, 1613 participants). In absolute terms, this might lead to an additional seven quitters per 100 (95% CI 2 to 16). There was moderate-certainty evidence of no difference in the rate of AEs between these groups (RR 1.01, 95% CI 0.91 to 1.11; I2 = 0%; 5 studies, 1840 participants). There was insufficient evidence to determine whether rates of SAEs differed between groups, due to very serious imprecision (RR 1.00, 95% CI 0.56 to 1.79; I2 = 0%; 9 studies, 141 participants).\nCompared to behavioral support only/no support, quit rates were higher for participants randomized to nicotine EC (RR 1.88, 95% CI 1.56 to 2.25; I2 = 0%; 9 studies, 5024 participants). In absolute terms, this represents an additional two quitters per 100 (95% CI 1 to 3). However, this finding was of low certainty, due to issues with risk of bias. There was some evidence that (non-serious) AEs were more common in people randomized to nicotine EC (RR 1.22, 95% CI 1.12 to 1.32; I2 = 41%, low certainty; 4 studies, 765 participants) and, again, insufficient evidence to determine whether rates of SAEs differed between groups (RR 0.89, 95% CI 0.59 to 1.34; I2 = 23%; 10 studies, 3263 participants). \nData from non-randomized studies were consistent with RCT data. The most commonly reported AEs were throat/mouth irritation, headache, cough, and nausea, which tended to dissipate with continued EC use. Very few studies reported data on other outcomes or comparisons, hence evidence for these is limited, with CIs often encompassing clinically significant harm and benefit.
\n \n\n \n \nBACKGROUND: Opioid deaths have increased in England and Wales. Coroners' Prevention of Future Deaths reports (PFDs) provide important insights that may enable safer use and avert harms, yet reports implicating opioids have not been synthesized. We aimed to identify opioid-related PFDs and explore coroners' concerns to prevent future deaths. METHODS: In this systematic case series, we screened 3897 coronial PFDs dated between 01 July 2013 and 23 February 2022, obtained by web scraping the UK's Courts and Tribunals Judiciary website. PFDs were included when an opioid was implicated in the death. Included PFDs were descriptively analysed, and content analysis was used to assess concerns reported by coroners. RESULTS: Opioids were involved in 219 deaths reported in PFDs (5\u00b76% of PFDs), equating to 4418\u00a0years of life lost (median 33\u00a0years/person). Morphine (29%), methadone (23%) and diamorphine (16%) were the most common implicated opioids. Coroners most frequently raised concerns regarding systems and protocols (52%) or safety issues (15%). These concerns were most often addressed to National Health Service (NHS) organizations (51%), but response rates were low overall (47%). CONCLUSIONS: Opioids could be used more safely if coroners' concerns in PFDs were addressed by national organizations such as NHS bodies, government agencies and policymakers, as well as individual prescribing clinicians.
\n \n\n \n \nBackground: This study investigated NHS Health Check programme delivery before and after the Covid-19 pandemic response, with a focus on support services and referral methods available to Health Check attendees. The NHS Health Check is an important part of England\u2019s Cardiovascular Disease (CVD) prevention programme. Methods: Public health commissioners from all 151 local authorities responsible for commissioning the NHS Health Check programme were surveyed in 2021, using an online questionnaire to capture detail about programme delivery, changes in delivery because of the pandemic response, and monitoring of programme outcomes. Four-point rating scales were used to obtain level of confidence in capacity, accessibility and usage of follow-on support services for Health Check attendees. A typology of programme delivery was developed, and associations between delivery categories and a range of relevant variables were assessed using one-way analysis of variance. Results: Sixty-eight responses were received on behalf of 74 (of 151) local authorities (49%), across all geographical regions. Our findings suggest a basic typology of delivery, though with considerable variation in who is providing the Checks, where and how, and with continued changes prompted by the Covid-19 pandemic. Support for risk management is highly varied with notable gaps in some areas. Local authorities using a model of delivery that includes community venues tended to have a higher number of services to support behaviour change following the Check, and greater confidence in the accessibility and usage of these services. A minority of local authorities gather data on referrals for Health Check attendees, or on outcomes of referrals. Conclusions: The Covid-19 pandemic has prompted continued changes in delivery, which are likely to influence patient experience and outcomes; these need careful evaluation. The programme\u2019s delivery and commissioners' intentions to follow through risk communication with appropriate support is challenged by the complexity of the commissioning landscape.
\n \n\n \n \nBACKGROUND: The potential of the electronic health record to support safety netting has been recognised and a number of electronic safety-netting (E-SN) tools developed. AIM: To establish the most important features of E-SN tools. DESIGN & SETTING: User-experience interviews followed by a Delphi study in a primary care setting in the UK. METHOD: The user-experience interviews were carried out remotely with primary care staff who had trialled the EMIS E-SN toolkit for suspected cancer. An electronic modified Delphi approach was used, with primary care staff involved in safety netting in any capacity, to measure consensus on tool features. RESULTS: Thirteen user-experience interviews were carried out and features of E-SN tools seen as important formed the majority of the features included in the Delphi study. Three rounds of Delphi survey were administered. Sixteen responders (64%) completed all three rounds, and 28 out of 44 (64%) features reached consensus. Primary care staff preferred tools that were general in scope. CONCLUSION: Primary care staff indicated that tools that were not specific to cancer or any other disease, and had features that promoted their flexible, efficient, and integrated use, were important. However, when the important features were discussed with the patient and public involvement (PPI) group, they expressed disappointment that features they believed would make E-SN tools robust and provide a safety net that is difficult to fall through did not reach consensus. The successful adoption of E-SN tools will rely on an evidence base of their effectiveness. Efforts should be made to assess the impact of these tools on patient outcomes.
\n \n\n \n \nBACKGROUND: Insomnia is prevalent and distressing but access to the first-line treatment, cognitive behavioural therapy (CBT), is extremely limited. We aimed to assess the clinical and cost-effectiveness of sleep restriction therapy, a key component of CBT, which has the potential to be widely implemented. METHODS: We did a pragmatic, superiority, open-label, randomised controlled trial of sleep restriction therapy versus sleep hygiene. Adults with insomnia disorder were recruited from 35 general practices across England and randomly assigned (1:1) using a web-based randomisation programme to either four sessions of nurse-delivered sleep restriction therapy plus a sleep hygiene booklet or a sleep hygiene booklet only. There was no restriction on usual care for either group. Outcomes were assessed at 3 months, 6 months, and 12 months. The primary endpoint was self-reported insomnia severity at 6 months measured with the insomnia severity index (ISI). The primary analysis included participants according to their allocated group and who contributed at least one outcome measurement. Cost-effectiveness was evaluated from the UK National Health Service and personal social services perspective and expressed in terms of incremental cost per quality-adjusted life year (QALY) gained. The trial was prospectively registered (ISRCTN42499563). FINDINGS: Between Aug 29, 2018, and March 23, 2020 we randomly assigned 642 participants to sleep restriction therapy (n=321) or sleep hygiene (n=321). Mean age was 55\u00b74 years (range 19-88), with 489 (76\u00b72%) participants being female and 153 (23\u00b78%) being male. 580 (90\u00b73%) participants provided data for at least one outcome measurement. At 6 months, mean ISI score was 10\u00b79 (SD 5\u00b75) for sleep restriction therapy and 13\u00b79 (5\u00b72) for sleep hygiene (adjusted mean difference -3\u00b705, 95% CI -3\u00b783 to -2\u00b728; p<0\u00b70001; Cohen's d -0\u00b774), indicating that participants in the sleep restriction therapy group reported lower insomnia severity than the sleep hygiene group. The incremental cost per QALY gained was \u00a32076, giving a 95\u00b73% probability that treatment was cost-effective at a cost-effectiveness threshold of \u00a320\u2009000. Eight participants in each group had serious adverse events, none of which were judged to be related to intervention. INTERPRETATION: Brief nurse-delivered sleep restriction therapy in primary care reduces insomnia symptoms, is likely to be cost-effective, and has the potential to be widely implemented as a first-line treatment for insomnia disorder. FUNDING: The National Institute for Health and Care Research Health Technology Assessment Programme.
\n \n\n \n \nDrug shortages are repeatedly in the news. The earliest drug shortages were reported during the First World War, but the numbers of shortages have increased in recent years. In the first part of this two-part review we discuss definitions of drug shortages and so-called stock-outs, which are localized shortages, and the harms that they can cause. Drug shortages make it difficult or impossible to meet the therapeutic needs of individual patients or populations, but we lack an adequate definition. The problems are too complicated to be encompassed in a brief intensional dictionary-style definition, and that is reflected in the many different attempts at definition that have been proposed. We therefore propose an extensional operational definition that incorporates the processes by which products are manufactured, the causes of shortages, and the contributory factors. A definition of this sort allows one to identify the main causes of a particular drug shortage and therefore the remedies that might prevent, mitigate, or manage it. In the second part of the review we discuss the causes and solutions in more detail. Adverse drug reactions and medication errors attributable to shortages occur but are not often reported. Adverse reactions to substitute medicines are possible, and errors can occur because of unfamiliarity or unnecessary treatment with replacement medicines. Other harmful outcomes include withdrawal reactions, under-treatment, treatment delays and cancellations, failure of alternatives, and disruption of clinical trials.
\n \n\n \n \nAim: There are direct links between housing and health. However, there is a lack of systematic reviews that bring together the evidence to outline the health impacts of exposures in housing and housing interventions. This article aims to address this gap by synthesising systematic reviews on the themes of housing exposures and interventions. Methods: We searched four databases: Scopus (Elsevier), PsycINFO (OvidSP), Science Citation Index and Social Science Citation Index (Web of Science Core Collection), and the Sociology Collection (Proquest). We used keywords related to \u2018health\u2019 and \u2018city*\u2019 and included all types of reviews. We extracted data into a predesigned extraction form and synthesised information narratively. Results: 745 articles were identified and screened, of which 256 reviews were included and 16 (6%) related to housing. All reviews related to housing exposures found that poor housing, including crowding, coldness, dampness, mould, and indoor air pollution had a negative impact on health. Most reviews found that housing interventions such as housing refurbishment, heating, and energy efficiency interventions positively impacted health outcomes. An online toolkit was developed to disseminate and communicate this research: https://www.healthycitiescommission.org/toolkit/. Conclusion: Governments have a pivotal role in addressing health issues related to housing interventions and exposures in housing. This includes interventions through building regulations following international guidance and financial assistance to encourage housing modifications that will improve health.
\n \n\n \n \nINTRODUCTION: 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\u2009days 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.
\n \n\n \n \nABSTRACT Background Working under pandemic conditions exposes health care workers (HCWs) to infection risk and psychological strain. Protecting the physical and psychological health of HCWs is a key priority. This study assessed the perceptions of European hospital HCWs of local infection prevention and control (IPC) procedures during the COVID-19 pandemic and the impact on their emotional wellbeing. Methods We performed two rounds of an international cross-sectional survey, between 31 March and 17 April 2020 via existing research networks (round 1), and between 14 May and 31 August 2020 via online convenience sampling (round 2). Main outcome measures were (1) behavioural determinants of HCW adherence with IPC procedures, (2) WHO-5 Well-Being Index, a validated scale of 0-100 reflecting emotional wellbeing. The WHO-5 was interpreted as a score below or above 50 points, a cut-off score used in previous literature to screen for depression. Results 2,289 HCWs (round 1: n=190, round 2: n=2,099) from 40 countries in Europe participated. Mean age of respondents was 42 (\u00b111) years, 66% were female, 47% and 39% were medical doctors and nurses, respectively. 74% (n=1699) of HCWs were directly treating patients with COVID-19, of which 32% (n=527) reported they were fearful of caring for these patients. HCWs reported high levels of concern about COVID-19 infection risk to themselves (71%) and their family (82%) as a result of their job. 40% of HCWs considered that getting infected with COVID-19 was not within their control. This was more common among junior than senior HCWs (46% versus 38%, P value Conclusions In Europe, the COVID-19 pandemic has had a differential impact on those providing direct COVID-19 patient care, junior staff and women. Health facilities must be aware of these differential impacts, build trust and provide tailored support for this vital workforce during the current COVID-19 pandemic.
\n \n\n \n \n