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\"An amiable Navy veteran loses his comfortable job at a big-box store, enrolls in community college, and seeks to reinvent himself while falling for his apathetic speech professor in this romantic comedy re-teaming Academy Award-winning Charlie Wilson's War co-stars Tom Hanks and Julia Roberts. Larry Crowne (Hanks) has just been downsized. The unfortunate victim of a failing economy, Larry decides that his best option to avoid becoming idle is to take some classes at his local community college. In no time, Larry befriends a colorful group of moped-obsessed outcasts on the road to self-improvement, and begins working to sharpen his communication skills in a public speaking class taught by Mercedes Tainot (Roberts). Disenchanted with her job and bored in her marriage, Mercedes has begun to feel as if she's missing out on life. But whenever she's with Larry, all of her problems seem to disappear. Now, just as Larry and Mercedes are feeling as if their lives have been put on hold, they both discover that fate sometimes has a way of giving us exactly what we need, at precisely the right time\"--Allmovie.com, December 27, 2019.

Women are under-represented in academic medicine. We reviewed the empirical evidence focusing on the reasons for women's choice or rejection of careers in academic medicine. Using a systematic search, we identified 52 studies published between 1985, and 2015. More than half had methodological limitations and most were from North America. Eight main themes were explored in these studies. There was consistent evidence for four of these themes: women are interested in teaching more than in research; participation in research can encourage women into academic medicine; women lack adequate mentors and role models; and women experience gender discrimination and bias. The evidence was conflicting on four themes: women are less interested in research than men; women lose commitment to research as their education and training progress; women are deterred from academic careers by financial considerations; and women are deterred by concerns about work–life balance. Inconsistency of findings across studies suggests significant opportunities to overcome barriers by providing a more enabling environment. We identified substantial gaps in the scientific literature that could form the focus of future research, including shifting the focus from individuals' career choices to the societal and organisational contexts and cultures within which those choices are made; extending the evidence base to include a wider range of countries and settings; and testing the efficacy of interventions.

Leptospirosis is a leading zoonotic disease worldwide with more than 1 million cases in the general population per year. With leptospirosis being an emerging infectious disease and as the world's environment changes with more floods and environmental disasters, the burden of leptospirosis is expected to increase. The objectives of the systematic review were to explore how leptospirosis affects pregnancy, its burden in this population, its effects on maternal and fetal outcomes and the evidence base surrounding treatment options. We performed a systematic review of published and unpublished literature using automated and manual methods to screen nine electronic databases since inception, with no language restriction. Two reviewers independently screened articles, completed the data extraction and assessment of risk of bias. Due to significant heterogeneity and paucity of data, we were unable to carry out a meta-analysis, but we conducted a pooled analysis of individual patient data from the case reports and case series to examine the patient and disease characteristics, diagnostic methods, differential diagnoses, antibiotic treatments, and outcomes of leptospirosis in pregnancy. The protocol for this review was registered on the International Prospective Register of Systematic Reviews, PROSPERO: CRD42020151501. We identified 419 records, of which we included eight observational studies, 21 case reports, three case series and identified four relevant ongoing studies. Overall the studies were with moderate bias and of 'fair' quality. We estimated the incidence of leptospirosis in pregnancy to be 1.3 per 10,000 in women presenting with fever or with jaundice, but this is likely to be higher in endemic areas. Adverse fetal outcomes were found to be more common in pregnant patients who presented in the second trimester compared with patients who presented in the third trimester. There is overlap between how leptospirosis presents in pregnancy and in the general population. There is also overlap between the signs, symptoms and biochemical disturbances associated with leptospirosis in pregnancy and the presentation of pregnancy associated conditions, such as Pre-Eclampsia (PET), Acute Fatty Liver of Pregnancy (AFLP) and HELLP Syndrome (Haemolysis Elevated Liver enzymes Low Platelets). In 94% of identified cases with available data, there was an indicator in the patient history regarding exposure that could have helped include leptospirosis in the clinician's differential diagnosis. We also identified a range of suitable antibiotic therapies for treating leptospirosis in pregnancy, most commonly used were penicillins. This is the first systematic review of leptospirosis in pregnancy and it clearly shows the need to improve early diagnosis and treatment by asking early, treating early, and reporting well. Ask early-broaden differential diagnoses and ask early for potential leptospirosis exposures and risk factors. Treat early-increase index of suspicion in pregnant patients with fever in endemic areas and combine with rapid field diagnosis and early treatment. Report well-need for more good quality epidemiological studies on leptospirosis in pregnancy and better quality reporting of cases in literature.

Background Tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral ribonucleic acid (RNA) using reverse transcription polymerase chain reaction (RT-PCR) are pivotal to detecting current coronavirus disease (COVID-19) and duration of detectable virus indicating potential for infectivity. Methods We conducted an individual participant data (IPD) systematic review of longitudinal studies of RT-PCR test results in symptomatic SARS-CoV-2. We searched PubMed, LitCOVID, medRxiv, and COVID-19 Living Evidence databases. We assessed risk of bias using a QUADAS-2 adaptation. Outcomes were the percentage of positive test results by time and the duration of detectable virus, by anatomical sampling sites. Results Of 5078 studies screened, we included 32 studies with 1023 SARS-CoV-2 infected participants and 1619 test results, from − 6 to 66 days post-symptom onset and hospitalisation. The highest percentage virus detection was from nasopharyngeal sampling between 0 and 4 days post-symptom onset at 89% (95% confidence interval (CI) 83 to 93) dropping to 54% (95% CI 47 to 61) after 10 to 14 days. On average, duration of detectable virus was longer with lower respiratory tract (LRT) sampling than upper respiratory tract (URT). Duration of faecal and respiratory tract virus detection varied greatly within individual participants. In some participants, virus was still detectable at 46 days post-symptom onset. Conclusions RT-PCR misses detection of people with SARS-CoV-2 infection; early sampling minimises false negative diagnoses. Beyond 10 days post-symptom onset, lower RT or faecal testing may be preferred sampling sites. The included studies are open to substantial risk of bias, so the positivity rates are probably overestimated.

This study carried out a systematic literature review of economic evaluations of varicella vaccination programmes from the earliest publication to the present day, including programmes in the workplace and in special risk groups as well as universal childhood vaccination and catch up programmes. Articles published from 1985 until 2022 were sourced from PubMed/Medline, Embase, Web of Science, NHSEED and Econlit. Eligible economic evaluations, which included posters and conference abstracts, were identified by two reviewers who scrutinised each other's selections at both title and abstract and full report stages. The studies are described in terms of their methodological characteristics. Their results are aggregated by type of vaccination programme and the nature of the economic outcome. A total of 2575 articles were identified of which 79 qualified as economic evaluations. A total of 55 studies focused on universal childhood vaccination, 10 on the workplace and 14 on high risk groups. Twenty-seven studies reported estimates of incremental cost per quality-adjusted life year (QALY) gained, 16 reported benefit-cost ratios, 20 reported cost-effectiveness outcomes in terms of incremental cost per event or life saved and 16 reported cost-cost offset results. Most studies of universal childhood vaccination reported an increase in overall costs to health services, but often a reduction in cost from a societal perspective. The evidence surrounding the cost-effectiveness of varicella vaccination programmes remains sparse with contrasting conclusions in some areas. Future research should particularly aim to encompass the impact of universal childhood vaccination programmes on herpes zoster among adults.

Background. Antibiotic use is the main driver for carriage of antibiotic-resistant bacteria. The perception exists that failure of antibiotic treatment due to antibiotic resistance has little clinical impact in the community. Methods. We searched MEDLINE, EMBASE, PubMed, Cochrane Central Register of Controlled Trials, and Web of Science from inception to 15 April 2016 without language restriction. We included studies conducted in community settings that reported patient-level data on laboratory-confirmed infections (respiratory tract, urinary tract, skin or soft tissue), antibiotic resistance, and clinical outcomes. Our primary outcome was clinical response failure. Secondary outcomes were reconsultation, further antibiotic prescriptions, symptom duration, and symptom severity. Where possible, we calculated odds ratios with 95% confidence intervals by performing meta-analysis using random effects models. Results. We included 26 studies (5659 participants). Clinical response failure was significantly more likely in participants with antibiotic-resistant Escherichia coli urinary tract infections (odds ratio [OR] = 4.19; 95% confidence interval [CI] = 3.27–5.37; n = 2432 participants), Streptococcus pneumoniae otitis media (OR = 2.51; 95% CI = 1.29–4.88; n = 921 participants), and S. pneumoniae community-acquired pneumonia (OR = 2.15; 95% CI = 1.32–3.51; n = 916 participants). Clinical heterogeneity precluded primary outcome meta-analysis for Staphylococcus aureus skin or soft-tissue infections. Conclusions. Antibiotic resistance significantly impacts on patients' illness burden in the community. Patients with laboratory-confirmed antibiotic-resistant urinary and respiratory-tract infections are more likely to experience delays in clinical recovery after treatment with antibiotics. A better grasp of the risk of antibiotic resistance on outcomes that matter to patients should inform more meaningful discussions between healthcare professionals and patients about antibiotic treatment for common infections.

Background Social prescribing is a way of addressing the ‘non-medical’ needs (e.g. loneliness, debt, housing problems) that can affect people’s health and well-being. Connector schemes (e.g. delivered by care navigators or link workers) have become a key component to social prescribing’s delivery. Those in this role support patients by either (a) signposting them to relevant local assets (e.g. groups, organisations, charities, activities, events) or (b) taking time to assist them in identifying and prioritising their ‘non-medical’ needs and connecting them to relevant local assets. To understand how such connector schemes work, for whom, why and in what circumstances, we conducted a realist review. Method A search of electronic databases was supplemented with Google alerts and reference checking to locate grey literature. In addition, we sent a Freedom of Information request to all Clinical Commissioning Groups in England to identify any further evaluations of social prescribing connector schemes. Included studies were from the UK and focused on connector schemes for adult patients (18+ years) related to primary care. Results Our searches resulted in 118 included documents, from which data were extracted to produce context-mechanism-outcome configurations (CMOCs). These CMOCs underpinned our emerging programme theory that centred on the essential role of ‘buy-in’ and connections. This was refined further by turning to existing theories on (a) social capital and (b) patient activation. Conclusion Our realist review highlights how connector roles, especially link workers, represent a vehicle for accruing social capital (e.g. trust, sense of belonging, practical support). We propose that this then gives patients the confidence, motivation, connections, knowledge and skills to manage their own well-being, thereby reducing their reliance on GPs. We also emphasise within the programme theory situations that could result in unintended consequences (e.g. increased demand on GPs).

BACKGROUND AND OBJECTIVE: Walking and cycling have shown beneficial effects on population risk of all-cause mortality (ACM). This paper aims to review the evidence and quantify these effects, adjusted for other physical activity (PA). DATA SOURCES: We conducted a systematic review to identify relevant studies. Searches were conducted in November 2013 using the following health databases of publications: Embase (OvidSP); Medline (OvidSP); Web of Knowledge; CINAHL; SCOPUS; SPORTDiscus. We also searched reference lists of relevant texts and reviews. STUDY ELIGIBILITY CRITERIA AND PARTICIPANTS: Eligible studies were prospective cohort design and reporting walking or cycling exposure and mortality as an outcome. Only cohorts of individuals healthy at baseline were considered eligible. STUDY APPRAISAL AND SYNTHESIS METHODS: Extracted data included study population and location, sample size, population characteristics (age and sex), follow-up in years, walking or cycling exposure, mortality outcome, and adjustment for other co-variables. We used random-effects meta-analyses to investigate the beneficial effects of regular walking and cycling. RESULTS: Walking (18 results from 14 studies) and cycling (8 results from 7 studies) were shown to reduce the risk of all-cause mortality, adjusted for other PA. For a standardised dose of 11.25 MET.hours per week (or 675 MET.minutes per week), the reduction in risk for ACM was 11% (95% CI = 4 to 17%) for walking and 10% (95% CI = 6 to 13%) for cycling. The estimates for walking are based on 280,000 participants and 2.6 million person-years and for cycling they are based on 187,000 individuals and 2.1 million person-years. The shape of the dose–response relationship was modelled through meta-analysis of pooled relative risks within three exposure intervals. The dose–response analysis showed that walking or cycling had the greatest effect on risk for ACM in the first (lowest) exposure interval. CONCLUSIONS AND IMPLICATIONS: The analysis shows that walking and cycling have population-level health benefits even after adjustment for other PA. Public health approaches would have the biggest impact if they are able to increase walking and cycling levels in the groups that have the lowest levels of these activities. REVIEW REGISTRATION: The review protocol was registered with PROSPERO (International database of prospectively registered systematic reviews in health and social care) PROSPERO 2013: CRD42013004266.

Background Primary care has been described as the ‘bedrock’ of the National Health Service (NHS) accounting for approximately 90% of patient contacts but is facing significant challenges. Against a backdrop of a rapidly ageing population with increasingly complex health challenges, policy-makers have encouraged primary care commissioners to increase the usage of data when making commissioning decisions. Purported benefits include cost savings and improved population health. However, research on evidence-based commissioning has concluded that commissioners work in complex environments and that closer attention should be paid to the interplay of contextual factors and evidence use. The aim of this review was to understand how and why primary care commissioners use data to inform their decision making, what outcomes this leads to, and understand what factors or contexts promote and inhibit their usage of data. Methods We developed initial programme theory by identifying barriers and facilitators to using data to inform primary care commissioning based on the findings of an exploratory literature search and discussions with programme implementers. We then located a range of diverse studies by searching seven databases as well as grey literature. Using a realist approach, which has an explanatory rather than a judgemental focus, we identified recurrent patterns of outcomes and their associated contexts and mechanisms related to data usage in primary care commissioning to form context-mechanism-outcome (CMO) configurations. We then developed a revised and refined programme theory. Results Ninety-two studies met the inclusion criteria, informing the development of 30 CMOs. Primary care commissioners work in complex and demanding environments, and the usage of data are promoted and inhibited by a wide range of contexts including specific commissioning activities, commissioners’ perceptions and skillsets, their relationships with external providers of data (analysis), and the characteristics of data themselves. Data are used by commissioners not only as a source of evidence but also as a tool for stimulating commissioning improvements and as a warrant for convincing others about decisions commissioners wish to make. Despite being well-intentioned users of data, commissioners face considerable challenges when trying to use them, and have developed a range of strategies to deal with ‘imperfect’ data. Conclusions There are still considerable barriers to using data in certain contexts. Understanding and addressing these will be key in light of the government’s ongoing commitments to using data to inform policy-making, as well as increasing integrated commissioning.

Non-communicable diseases (NCDs) are the leading cause of death globally. Eighty-two percent of premature NCD deaths occur within low- and lower middle-income countries (LLMICs). Research to date, largely drawn from high-income countries, suggests that disadvantaged and marginalized groups have a higher NCD burden, but there has been a dearth of research studying this relationship within LLMICs. The purpose of this systematic review is to map the literature on evidence from LLMICs on the socio-economic status (SES) gradient of four particular NCDs: cardiovascular disease, cancer, diabetes, and chronic respiratory diseases. We conducted a comprehensive literature search for primary research published between 1 January 1990 and 27 April 2015 using six bibliographic databases and web resources. We included studies that reported SES and morbidity or mortality from cardiovascular disease, cancer, diabetes and chronic respiratory diseases within LLMICs. Fifty-seven studies from 17 LLMICs met our inclusion criteria. Fourteen of the 18 papers that reported significant associations between cancer and SES suggested that low SES groups had the highest cancer risk. Eleven of 15 papers reporting significant relationships between CVD and SES suggested that low SES groups have higher risk. In contrast, seven of 12 papers reporting significant findings related to diabetes found that higher SES groups had higher diabetes risk. We identified just three studies on the relationship between chronic respiratory diseases and SES; none of them reported significant findings. Only 17 of the 84 LLMICs were represented, highlighting the need for more research on NCDs within these countries. The majority of studies were medium to high quality cross-sectional studies. When we restricted our analyses to high quality studies only, for both cancer and cardiovascular disease more than half of studies found a significantly higher risk for those of lower SES. The opposite was true for diabetes, whilst there was a paucity of high quality research on chronic respiratory disease. Development programmes must consider health alongside other aims and NCD prevention interventions must target all members of the population. Prospero: CRD42015020169.