BACKGROUND: The artemisinin derivatives are the preferred antimalaria drugs for treating severe Plasmodium falciparum malaria. However, their clinical effectiveness compared to each other is unknown. Our objective, therefore, was to evaluate the efficacy and safety of the artemisinin derivatives and quinine for treating severe P. falciparum malaria in children and adults using a network meta-analysis. METHODS AND FINDINGS: Review protocol was registered with PROSPERO, CRD42020218190. We updated the search strategies of three Cochrane systematic reviews which included published and unpublished randomised control trials (RCTs) that have compared specific artemisinin derivatives to quinine in treating severe malaria. Search included CENTRAL, MEDLINE, Embase, LILACS, ISI Web of Science and trial registries up to February 2021. We screened studies, extracted data, assessed risk of bias, and quality of evidence in duplicate. Separate network meta-analyses in the frequentist framework, using a random effects model, with quinine as reference, were conducted for adults and children, and rankings were produced using p-scores to assess mortality, parasite clearance, coma recovery, fever clearance, neurological sequela and adverse events. Searches identified 818 citations, 33 RCTs were eligible. We pooled 7795 children and 3182 adults. The networks involved artesunate, artemether, rectal artemisinin, arteether and quinine. Compared to quinine, artesunate reduced mortality in children (risk ratio (RR), 0.76; 95%CI [0.65 to 0.89], moderate quality), adults (RR, 0.55; 95%CI [0.40 to 0.75], moderate quality) and in cerebral malaria (RR, 0.72; 95%CI [0.55 to 0.94], moderate quality). Compared to rectal artemisinin and intramuscular arteether, the efficacy and safety of parenteral artesunate, and intramuscular artemether in treating severe malaria are not clear. Rankings showed that none of the artemisinin drugs were consistently superior in all the outcomes assessed. Indirect evidence produced were of very low ratings due to suspected publication bias and imprecision. CONCLUSIONS: Artesunate reduces mortality compared to quinine for both adults and children in Asia and Africa including cerebral malaria. The artemisinin derivatives remain the best treatment for severe malaria but their comparative clinical effectiveness is yet to be fully explored.
\n \n\n \n \nBackground: Given equivocal findings from existing nationally representative studies, the authors sought to determine associations between vitamin D levels and caries experience in US children using updated National Health and Nutrition Examination Survey data. Methods: The authors used data from 2011-2016 National Health and Nutrition Examination Survey. Vitamin D status was assessed on the basis of the sufficiency thresholds of 50 and 75 nmol/L for serum 25-hydroxyvitamin D (25[OH]D) recommended by the Institute of Medicine (now National Academy of Medicine) and Endocrine Society, respectively. Caries experience was defined as the total number of decayed or filled tooth surfaces (dfs) and decayed, missing, or filled tooth surfaces (DMFS) and a binary measure of any dfs and DMFS. Associations between 25(OH)D and any or total dfs and DMFS were examined in children aged 2 through 5, 6 through 8, 9 through 11, and 12 through 18 years, using multivariable logistic and linear regression models after adjustment for covariates. Results: Children aged 2 through 5 years with 25(OH)D above 75 nmol/L experienced fewer total dfs (\u03b2 = \u20131.94; 95% CI, \u20133.60 to \u20130.28) than those with 25(OH)D below 75 nmol/L. Children 6 through 8 years with 25(OH)D above 75 nmol/L had lower presence of any dfs (odds ratio, 0.59; 95% CI, 0.36 to 0.95) than those with 25(OH)D below 75 nmol/L, and those with 25(OH)D above 50 nmol/L had lower presence of any DMFS (odds ratio, 0.38; 95% CI, 0.19 to 0.79) than those with 25(OH)D below 50 nmol/L. There were no associations of 25(OH)D status with either any or total DMFS in children 12 through 18 years Conclusions: There were no consistent associations of 25(OH)D status with caries experience across age groups. Practical Implications: Vitamin D status was not associated consistently with reduced caries experience.
\n \n\n \n \nOBJECTIVE: To compare the effectiveness of the BNT162b2 mRNA (Pfizer-BioNTech) and the ChAdOx1 (Oxford-AstraZeneca) covid-19 vaccines against infection and covid-19 disease in health and social care workers. DESIGN: Cohort study, emulating a comparative effectiveness trial, on behalf of NHS England. SETTING: Linked primary care, hospital, and covid-19 surveillance records available within the OpenSAFELY-TPP research platform, covering a period when the SARS-CoV-2 Alpha variant was dominant. PARTICIPANTS: 317\u2009341 health and social care workers vaccinated between 4 January and 28 February 2021, registered with a general practice using the TPP SystmOne clinical information system in England, and not clinically extremely vulnerable. INTERVENTIONS: Vaccination with either BNT162b2 or ChAdOx1 administered as part of the national covid-19 vaccine roll-out. MAIN OUTCOME MEASURES: Recorded SARS-CoV-2 positive test, or covid-19 related attendance at an accident and emergency (A&E) department or hospital admission occurring within 20 weeks of receipt of the first vaccine dose. RESULTS: Over the duration of 118\u2009771 person-years of follow-up there were 6962 positive SARS-CoV-2 tests, 282 covid-19 related A&E attendances, and 166 covid-19 related hospital admissions. The cumulative incidence of each outcome was similar for both vaccines during the first 20 weeks after vaccination. The cumulative incidence of recorded SARS-CoV-2 infection 20 weeks after first-dose vaccination with BNT162b2 was 21.7 per 1000 people (95% confidence interval 20.9 to 22.4) and with ChAdOx1 was 23.7 (21.8 to 25.6), representing a difference of 2.04 per 1000 people (0.04 to 4.04). The difference in the cumulative incidence per 1000 people of covid-19 related A&E attendance at 20 weeks was 0.06 per 1000 people (95% CI -0.31 to 0.43). For covid-19 related hospital admission, this difference was 0.11 per 1000 people (-0.22 to 0.44). CONCLUSIONS: In this cohort of healthcare workers where we would not anticipate vaccine type to be related to health status, we found no substantial differences in the incidence of SARS-CoV-2 infection or covid-19 disease up to 20 weeks after vaccination. Incidence dropped sharply at 3-4 weeks after vaccination, and there were few covid-19 related hospital attendance and admission events after this period. This is in line with expected onset of vaccine induced immunity and suggests strong protection against Alpha variant covid-19 disease for both vaccines in this relatively young and healthy population of healthcare workers.
\n \n\n \n \nOBJECTIVE: To estimate waning of covid-19 vaccine effectiveness over six months after second dose. DESIGN: Cohort study, approved by NHS England. SETTING: Linked primary care, hospital, and covid-19 records within the OpenSAFELY-TPP database. PARTICIPANTS: Adults without previous SARS-CoV-2 infection were eligible, excluding care home residents and healthcare professionals. EXPOSURES: People who had received two doses of BNT162b2 or ChAdOx1 (administered during the national vaccine rollout) were compared with unvaccinated people during six consecutive comparison periods, each of four weeks. MAIN OUTCOME MEASURES: Adjusted hazard ratios for covid-19 related hospital admission, covid-19 related death, positive SARS-CoV-2 test, and non-covid-19 related death comparing vaccinated with unvaccinated people. Waning vaccine effectiveness was quantified as ratios of adjusted hazard ratios per four week period, separately for subgroups aged \u226565 years, 18-64 years and clinically vulnerable, 40-64 years, and 18-39 years. RESULTS: 1\u2009951\u2009866 and 3\u2009219\u2009349 eligible adults received two doses of BNT162b2 and ChAdOx1, respectively, and 2\u2009422\u2009980 remained unvaccinated. Waning of vaccine effectiveness was estimated to be similar across outcomes and vaccine brands. In the \u226565 years subgroup, ratios of adjusted hazard ratios for covid-19 related hospital admission, covid-19 related death, and positive SARS-CoV-2 test ranged from 1.19 (95% confidence interval 1.14 to 1.24)to 1.34 (1.09 to 1.64) per four weeks. Despite waning vaccine effectiveness, rates of covid-19 related hospital admission and death were substantially lower among vaccinated than unvaccinated adults up to 26 weeks after the second dose, with estimated vaccine effectiveness \u226580% for BNT162b2, and \u226575% for ChAdOx1. By weeks 23-26, rates of positive SARS-CoV-2 test in vaccinated people were similar to or higher than in unvaccinated people (adjusted hazard ratios up to 1.72 (1.11 to 2.68) for BNT162b2 and 1.86 (1.79 to 1.93) for ChAdOx1). CONCLUSIONS: The rate at which estimated vaccine effectiveness waned was consistent for covid-19 related hospital admission, covid-19 related death, and positive SARS-CoV-2 test and was similar across subgroups defined by age and clinical vulnerability. If sustained to outcomes of infection with the omicron variant and to booster vaccination, these findings will facilitate scheduling of booster vaccination.
\n \n\n \n \nSocial prescribing is an approach that aims to improve health and well-being. It connects individuals to non-clinical services and supports that address social needs, such as those related to loneliness, housing instability and mental health. At the person level, social prescribing can give individuals the knowledge, skills, motivation and confidence to manage their own health and well-being. At the society level, it can facilitate greater collaboration across health, social, and community sectors to promote integrated care and move beyond the traditional biomedical model of health. While the term social prescribing was first popularised in the UK, this practice has become more prevalent and widely publicised internationally over the last decade. This paper aims to illuminate the ways social prescribing has been conceptualised and implemented across 17 countries in Europe, Asia, Australia and North America. We draw from the 'Beyond the Building Blocks' framework to describe the essential inputs for adopting social prescribing into policy and practice, related to service delivery; social determinants and household production of health; workforce; leadership and governance; financing, community organisations and societal partnerships; health technology; and information, learning and accountability. Cross-cutting lessons can inform country and regional efforts to tailor social prescribing models to best support local needs.
\n \n\n \n \nIntroductionFailure to recognise and respond to patient deterioration in an appropriate and timely manner has been highlighted as a global patient safety concern. Early Warning Scores (EWSs) using vital signs were introduced to address this concern, with the aim of getting the patient timely and appropriate treatment. The National Early Warning Score 2 (NEWS2) is in use across the NHS, and many other settings globally. While patient improvements have been shown, research has identified that the NEWS2 is not always used as intended. Therefore, this review will use a realist approach to understand what the mechanisms are that influence appropriate use (or not) of the NEWS2 in acute care settings, how, for whom and in which contexts. The findings will inform clinicians of what helps and/or hinders appropriate use of the NEWS2 in clinical practice, thus helping to facilitate successful implementation.Methods and analysisOur realist review will follow Pawson\u2019s iterative six step process: (1) Development of initial programme theory. (2) Searching the literature; an information scientist will develop, pilot and refine the search strategy. A systematic search will be completed, based on subject relevancy on the following databases: Cumulative Index to Nursing and Allied Health Literature (CINAHL), Medline, Embase (OvidSP), Web of Science (Science Citation Index and Social Science Citation), Cochrane Database of Systematic Reviews, Joanna Briggs Institute, Ethos, Proquest Dissertations and Theses Global, and Google Scholar for documents dating from 1997 (date of the first published EWS) to present. To retrieve additional relevant data \u2018snowballing\u2019 (finding references and authors by hand, contacting authors, searching reference lists and citation-tracking using Google Scholar) will be used. Inclusion criteria include all documents (including grey literature) that relate to the use of EWSs/NEWS2 in the English language only. Documents set in the paediatric, maternity and primary care settings will be excluded. (3) Selecting documents and quality appraisal. (4) Extracting and organising the data. (5) Synthesising the data. (6) Disseminating the findings. We will recruit a group of stakeholders comprised of experienced clinicians who use the NEWS2 as part of their clinical practice to provide feedback throughout the review. Step 1 has already begun with the development of an initial programme theory. This initial programme theory presents how the NEWS2 is supposed to work (or not), it will now be developed, tested and refined.Ethics and disseminationEthical approval is not required for this study as it is secondary research. Dissemination will include a peer-reviewed publication and conference presentations. Findings will also be amplified through social media platforms with user friendly summaries. Our stakeholder group will also contribute to dissemination of findings in their clinical areas and among existing networks.PROSPERO registration numberCRD42022304497.
\n \n\n \n \nBACKGROUND: While the vaccines against COVID-19 are highly effective, COVID-19 vaccine breakthrough is possible despite being fully vaccinated. With SARS-CoV-2 variants still circulating, describing the characteristics of individuals who have experienced COVID-19 vaccine breakthroughs could be hugely important in helping to determine who may be at greatest risk. METHODS: With the approval of NHS England, we conducted a retrospective cohort study using routine clinical data from the OpenSAFELY-TPP database of fully vaccinated individuals, linked to secondary care and death registry data and described the characteristics of those experiencing COVID-19 vaccine breakthroughs. RESULTS: As of 1st November 2021, a total of 15,501,550 individuals were identified as being fully vaccinated against COVID-19, with a median follow-up time of 149 days (IQR: \u200b107-179). From within this population, a total of 579,780 (<4%) individuals reported a positive SARS-CoV-2 test. For every 1000 years of patient follow-up time, the corresponding incidence rate (IR) was 98.06 (95% CI 97.93-98.19). There were 28,580 COVID-19-related hospital admissions, 1980 COVID-19-related critical care admissions and 6435 COVID-19-related deaths; corresponding IRs 4.77 (95% CI 4.74-4.80), 0.33 (95% CI 0.32-0.34) and 1.07 (95% CI 1.06-1.09), respectively. The highest rates of breakthrough COVID-19 were seen in those in care homes and in patients with chronic kidney disease, dialysis, transplant, haematological malignancy or who were immunocompromised. CONCLUSIONS: While the majority of COVID-19 vaccine breakthrough cases in England were mild, some differences in rates of breakthrough cases have been identified in several clinical groups. While it is important to note that these findings are simply descriptive and cannot be used to answer why certain groups have higher rates of COVID-19 breakthrough than others, the emergence of the Omicron variant of COVID-19 coupled with the number of positive SARS-CoV-2 tests still occurring is concerning and as numbers of fully vaccinated (and boosted) individuals increases and as follow-up time lengthens, so too will the number of COVID-19 breakthrough cases. Additional analyses, to assess vaccine waning and rates of breakthrough COVID-19 between different variants, aimed at identifying individuals at higher risk, are needed.
\n \n\n \n \nAlthough risk assessment tools have been widely used to inform sentencing decisions, there is uncertainty about the extent and quality of evidence of their predictive performance when validated in new samples. Following PRISMA guidelines, we conducted a systematic review of validation studies of 11 commonly used risk assessment tools for sentencing. We identified 36 studies with 597,665 participants, among which were 27 independent validation studies with 177,711 individuals. Overall, the predictive performance of the included risk assessment tools was mixed, and ranged from poor to moderate. Tool performance was typically overestimated in studies with smaller sample sizes or studies in which tool developers were co-authors. Most studies only reported area under the curve (AUC), which ranged from 0.57 to 0.75 in independent studies with more than 500 participants. The majority did not report key performance measures, such as calibration and rates of false positives and negatives. In addition, most validation studies had a high risk of bias, partly due to inappropriate analytical approach used. We conclude that the research priority is for future investigations to address the key methodological shortcomings identified in this review, and policy makers should enable this research. More sufficiently powered independent validation studies are necessary.
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