Physical activity for treatment of irritable bowel syndrome.

BACKGROUND: Current recommendations for people with irritable bowel syndrome (IBS) to partake in physical activity are based on low-level evidence, do not incorporate evidence from all available randomised controlled trials (RCTs) and provide little information regarding potential adverse effects. OBJECTIVES: To assess the benefits and harms of physical activity interventions in adults diagnosed with irritable bowel syndrome and to explore possible effect moderators including type, setting and nature of physical activity interventions. SEARCH METHODS: We searched nine electronic databases including CENTRAL, MEDLINE and Embase to 5 November 2021. We handsearched reference lists and sought unpublished studies through trial registries. SELECTION CRITERIA: We included RCTs involving adults (aged 18 years or older) diagnosed with IBS and conducted in any setting comparing a physical activity intervention with no intervention, usual care or wait-list control group or another physical activity intervention group and assessing a validated measure of symptoms, quality of life or bowel movement. DATA COLLECTION AND ANALYSIS: At least two review authors independently selected studies for inclusion, extracted study data, and performed risk of bias and GRADE assessments to assess the certainty of evidence. We pooled studies that evaluated similar outcomes using a random-effects meta-analysis, and synthesised data from other studies narratively. MAIN RESULTS: We included 11 RCTs with data for 622 participants. Most (10/11) were set in high- or middle- to high-income countries, with five involving supervised physical activity, three unsupervised activity and three a mix of supervised and unsupervised activity. No trial was at low risk of bias. Four trials specified a minimally important difference for at least one assessed outcome measure. Data for 10 trials were obtained from published journal articles, with data for one obtained from an unpublished Masters degree thesis. Irritable bowel syndrome symptoms Six RCTs assessed the effectiveness of a physical activity intervention compared with usual care on global symptoms of IBS. Meta-analysis of five studies showed an observed improvement in reported symptoms following physical activity (standardised mean difference (SMD) -0.93, 95% confidence interval (CI) -1.44 to -0.42; 185 participants). We rated the certainty of evidence for this outcome as very low due to unclear and high risk of bias, inconsistency and imprecision from sparse data. This means physical activity may improve IBS symptoms but the evidence is very uncertain. The results of the remaining study supported the meta-analysis but were at unclear risk of bias and sample size was small. Two studies assessed the effectiveness of a yoga intervention compared with a walking intervention on global IBS symptoms. Meta-analysis of these two studies found no conclusive evidence of an effect of yoga compared with walking on IBS symptoms (SMD -1.16, 95% CI -3.93 to 1.62; 124 participants). We rated the certainty of evidence as very low, meaning the evidence is very uncertain about the effect of yoga interventions compared with walking interventions on IBS symptoms. Two studies assessed the effectiveness of a physical activity intervention (yoga) compared with medication. One reported no observed difference in global IBS symptoms, though CIs were wide, suggesting uncertainty in the observed estimates and risk of bias was high (MD -1.20, 95% CI -2.65 to 0.25; 21 participants). We excluded IBS symptom data for the remaining study as it used a non-validated method. One study compared a yoga intervention with a dietary intervention and reported an observed improvement in symptoms with both interventions but neither intervention was superior to the other. Quality of life Five RCTs assessed the impact of physical activity on self-reported quality of life compared with usual care. Meta-analysis of data from four studies found no improvement in quality of life following a physical activity intervention (SMD 1.17, 95% CI -0.30 to 2.64; 134 participants; very low certainty due to risk of bias, inconsistency and imprecision). We rated the certainty of evidence as very low, meaning the evidence is very uncertain about the effect of physical activity interventions on quality-of-life outcomes in people with IBS. One study assessed the impact on quality of life of a yoga intervention compared with walking and observed an improvement in the yoga group (MD 53.45, 95% CI 38.85 to 68.05; 97 participants ).  One study reported no observed difference in quality of life between a yoga and a dietary intervention. Abdominal pain Two trials assessed the impact of physical activity compared with usual care on reported abdominal pain. Meta-analysis found no improvement in abdominal pain with physical activity compared with usual care (SMD 0.01, 95% CI -0.48 to 0.50; 64 participants). We rated the certainty of the evidence as very low due to risk of bias and imprecision, meaning the evidence is very uncertain about the effect of physical activity interventions on abdominal pain in people with IBS. One study assessing the impact of a yoga intervention compared with walking advice reported no observed differences between groups on abdominal pain. One study comparing a yoga intervention with a dietary intervention found neither intervention had a more beneficial impact than the other and both interventions did not conclusively reduce abdominal pain. There was insufficient evidence to adequately assess adverse effects associated with physical activity due to a lack of reporting in trials. One study reported a musculoskeletal injury in a yoga intervention group but this did not result in withdrawal from the study. AUTHORS' CONCLUSIONS: Findings from a small body of evidence suggest that physical activity comprising of yoga, treadmill exercise or support to increase physical activity may improve symptoms but not quality of life or abdominal pain in people diagnosed with IBS but we have little confidence in these conclusions due to the very low certainty of evidence. The numbers of reported adverse events were low and the certainty of these findings was very low for all comparisons, so no conclusions can be drawn. Discussions with patients considering physical activity as part of symptom management should address the uncertainty in the evidence to ensure fully informed decisions. If deemed sufficiently important to patients and healthcare providers, higher quality research is needed to enable more certain conclusions.

At what times during infection is SARS-CoV-2 detectable and no longer detectable using RT-PCR-based tests? A systematic review of individual participant data.

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.

Interventions outside the workplace for reducing sedentary behaviour in adults under 60 years of age.

BACKGROUND: Adults spend a majority of their time outside the workplace being sedentary. Large amounts of sedentary behaviour increase the risk of type 2 diabetes, cardiovascular disease, and both all-cause and cardiovascular disease mortality. OBJECTIVES: Primary • To assess effects on sedentary time of non-occupational interventions for reducing sedentary behaviour in adults under 60 years of age Secondary • To describe other health effects and adverse events or unintended consequences of these interventions • To determine whether specific components of interventions are associated with changes in sedentary behaviour • To identify if there are any differential effects of interventions based on health inequalities (e.g. age, sex, income, employment) SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Cochrane Database of Systematic Reviews, CINAHL, PsycINFO, SportDiscus, and ClinicalTrials.gov on 14 April 2020. We checked references of included studies, conducted forward citation searching, and contacted authors in the field to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and cluster RCTs of interventions outside the workplace for community-dwelling adults aged 18 to 59 years. We included studies only when the intervention had a specific aim or component to change sedentary behaviour. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles/abstracts and full-text articles for study eligibility. Two review authors independently extracted data and assessed risk of bias. We contacted trial authors for additional information or data when required. We examined the following primary outcomes: device-measured sedentary time, self-report sitting time, self-report TV viewing time, and breaks in sedentary time. MAIN RESULTS: We included 13 trials involving 1770 participants, all undertaken in high-income countries. Ten were RCTs and three were cluster RCTs. The mean age of study participants ranged from 20 to 41 years. A majority of participants were female. All interventions were delivered at the individual level. Intervention components included personal monitoring devices, information or education, counselling, and prompts to reduce sedentary behaviour. We judged no study to be at low risk of bias across all domains. Seven studies were at high risk of bias for blinding of outcome assessment due to use of self-report outcomes measures. Primary outcomes Interventions outside the workplace probably show little or no difference in device-measured sedentary time in the short term (mean difference (MD) -8.36 min/d, 95% confidence interval (CI) -27.12 to 10.40; 4 studies; I² = 0%; moderate-certainty evidence). We are uncertain whether interventions reduce device-measured sedentary time in the medium term (MD -51.37 min/d, 95% CI -126.34 to 23.59; 3 studies; I² = 84%; very low-certainty evidence) We are uncertain whether interventions outside the workplace reduce self-report sitting time in the short term (MD -64.12 min/d, 95% CI -260.91 to 132.67; I² = 86%; very low-certainty evidence). Interventions outside the workplace may show little or no difference in self-report TV viewing time in the medium term (MD -12.45 min/d, 95% CI -50.40 to 25.49; 2 studies; I² = 86%; low-certainty evidence) or in the long term (MD 0.30 min/d, 95% CI -0.63 to 1.23; 2 studies; I² = 0%; low-certainty evidence). It was not possible to pool the five studies that reported breaks in sedentary time given the variation in definitions used. Secondary outcomes Interventions outside the workplace probably have little or no difference on body mass index in the medium term (MD -0.25 kg/m², 95% CI -0.48 to -0.01; 3 studies; I² = 0%; moderate-certainty evidence). Interventions may have little or no difference in waist circumference in the medium term (MD -2.04 cm, 95% CI -9.06 to 4.98; 2 studies; I² = 65%; low-certainty evidence). Interventions probably have little or no difference on glucose in the short term (MD -0.18 mmol/L, 95% CI -0.30 to -0.06; 2 studies; I² = 0%; moderate-certainty evidence) and medium term (MD -0.08 mmol/L, 95% CI -0.21 to 0.05; 2 studies, I² = 0%; moderate-certainty evidence) Interventions outside the workplace may have little or no difference in device-measured MVPA in the short term (MD 1.99 min/d, 95% CI -4.27 to 8.25; 4 studies; I² = 23%; low-certainty evidence). We are uncertain whether interventions improve device-measured MVPA in the medium term (MD 6.59 min/d, 95% CI -7.35 to 20.53; 3 studies; I² = 70%; very low-certainty evidence). We are uncertain whether interventions outside the workplace improve self-reported light-intensity PA in the short-term (MD 156.32 min/d, 95% CI 34.34 to 278.31; 2 studies; I² = 79%; very low-certainty evidence). Interventions may have little or no difference on step count in the short-term (MD 226.90 steps/day, 95% CI -519.78 to 973.59; 3 studies; I² = 0%; low-certainty evidence) No data on adverse events or symptoms were reported in the included studies. AUTHORS' CONCLUSIONS: Interventions outside the workplace to reduce sedentary behaviour probably lead to little or no difference in device-measured sedentary time in the short term, and we are uncertain if they reduce device-measured sedentary time in the medium term. We are uncertain whether interventions outside the workplace reduce self-reported sitting time in the short term. Interventions outside the workplace may result in little or no difference in self-report TV viewing time in the medium or long term. The certainty of evidence is moderate to very low, mainly due to concerns about risk of bias, inconsistent findings, and imprecise results. Future studies should be of longer duration; should recruit participants from varying age, socioeconomic, or ethnic groups; and should gather quality of life, cost-effectiveness, and adverse event data. We strongly recommend that standard methods of data preparation and analysis are adopted to allow comparison of the effects of interventions to reduce sedentary behaviour.

Death audits and reviews for reducing maternal, perinatal and child mortality.

BACKGROUND: The United Nations' Sustainable Development Goals (SDGs) include reducing the global maternal mortality rate to less than 70 per 100,000 live births and ending preventable deaths of newborns and children under five years of age, in every country, by 2030. Maternal and perinatal death audit and review is widely recommended as an intervention to reduce maternal and perinatal mortality, and to improve quality of care, and could be key to attaining the SDGs. However, there is uncertainty over the most cost-effective way of auditing and reviewing deaths: community-based audit (verbal and social autopsy), facility-based audits (significant event analysis (SEA)) or a combination of both (confidential enquiry). OBJECTIVES: To assess the impact and cost-effectiveness of different types of death audits and reviews in reducing maternal, perinatal and child mortality. SEARCH METHODS: We searched the following from inception to 16 January 2019: CENTRAL, Ovid MEDLINE, Embase OvidSP, and five other databases. We identified ongoing studies using ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform, and searched reference lists of included articles. SELECTION CRITERIA: Cluster-randomised trials, cluster non-randomised trials, controlled before-and-after studies and interrupted time series studies of any form of death audit or review that involved reviewing individual cases of maternal, perinatal or child deaths, identifying avoidable factors, and making recommendations. To be included in the review, a study needed to report at least one of the following outcomes: perinatal mortality rate; stillbirth rate; neonatal mortality rate; mortality rate in children under five years of age or maternal mortality rate. DATA COLLECTION AND ANALYSIS: We used standard Cochrane Effective Practice and Organisation of Care (EPOC) group methodological procedures. Two review authors independently extracted data, assessed risk of bias and assessed the certainty of the evidence using GRADE. We planned to perform a meta-analysis using a random-effects model but included studies were not homogeneous enough to make pooling their results meaningful. MAIN RESULTS: We included two cluster-randomised trials. Both introduced death review and audit as part of a multicomponent intervention, and compared this to current care. The QUARITE study (QUAlity of care, RIsk management, and TEchnology) concerned maternal death reviews in hospitals in West Africa, which had very high maternal and perinatal mortality rates. In contrast, the OPERA trial studied perinatal morbidity/mortality conferences (MMCs) in maternity units in France, which already had very low perinatal mortality rates at baseline. The OPERA intervention in France started with an outreach visit to brief obstetricians, midwives and anaesthetists on the national guidelines on morbidity/mortality case management, and was followed by a series of perinatal MMCs. Half of the intervention units were randomised to receive additional support from a clinical psychologist during these meetings. The OPERA intervention may make little or no difference to overall perinatal mortality (low certainty evidence), however we are uncertain about the effect of the intervention on perinatal mortality related to suboptimal care (very low certainty evidence).The intervention probably reduces perinatal morbidity related to suboptimal care (unadjusted odds ratio (OR) 0.62, 95% confidence interval (CI) 0.40 to 0.95; 165,353 births; moderate-certainty evidence). The effect of the intervention on stillbirth rate, neonatal mortality, mortality rate in children under five years of age, maternal mortality or adverse effects was not reported. The QUARITE intervention in West Africa focused on training leaders of hospital obstetric teams using the ALARM (Advances in Labour And Risk Management) course, which included one day of training about conducting maternal death reviews. The leaders returned to their hospitals, established a multidisciplinary committee and started auditing maternal deaths, with the support of external facilitators. The intervention probably reduces inpatient maternal deaths (adjusted OR 0.85, 95% CI 0.73 to 0.98; 191,167 deliveries; moderate certainty evidence) and probably also reduces inpatient neonatal mortality within 24 hours following birth (adjusted OR 0.74, 95% CI 0.61 to 0.90; moderate certainty evidence). However, QUARITE probably makes little or no difference to the inpatient stillbirth rate (moderate certainty evidence) and may make little or no difference to the inpatient neonatal mortality rate after 24 hours, although the 95% confidence interval includes both benefit and harm (low certainty evidence). The QUARITE intervention probably increases the percent of women receiving high quality of care (OR 1.87, 95% CI 1.35 - 2.57, moderate-certainty evidence). The effect of the intervention on perinatal mortality, mortality rate in children under five years of age, or adverse effects was not reported. We did not find any studies that evaluated child death audit and review or community-based death reviews or costs. AUTHORS' CONCLUSIONS: A complex intervention including maternal death audit and review, as well as development of local leadership and training, probably reduces inpatient maternal mortality in low-income country district hospitals, and probably slightly improves quality of care. Perinatal death audit and review, as part of a complex intervention with training, probably improves quality of care, as measured by perinatal morbidity related to suboptimal care, in a high-income setting where mortality was already very low. The WHO recommends that maternal and perinatal death reviews should be conducted in all hospitals globally. However, conducting death reviews in isolation may not be sufficient to achieve the reductions in mortality observed in the QUARITE trial. This review suggests that maternal death audit and review may need to be implemented as part of an intervention package which also includes elements such as training of a leading doctor and midwife in each hospital, annual recertification, and quarterly outreach visits by external facilitators to provide supervision and mentorship. The same may also apply to perinatal and child death reviews. More operational research is needed on the most cost-effective ways of implementing maternal, perinatal and paediatric death reviews in low- and middle-income countries.

Nutritional labelling for healthier food or non-alcoholic drink purchasing and consumption.

BACKGROUND: Nutritional labelling is advocated as a means to promote healthier food purchasing and consumption, including lower energy intake. Internationally, many different nutritional labelling schemes have been introduced. There is no consensus on whether such labelling is effective in promoting healthier behaviour. OBJECTIVES: To assess the impact of nutritional labelling for food and non-alcoholic drinks on purchasing and consumption of healthier items. Our secondary objective was to explore possible effect moderators of nutritional labelling on purchasing and consumption. SEARCH METHODS: We searched 13 electronic databases including CENTRAL, MEDLINE and Embase to 26 April 2017. We also handsearched references and citations and sought unpublished studies through websites and trials registries. SELECTION CRITERIA: Eligible studies: were randomised or quasi-randomised controlled trials (RCTs/Q-RCTs), controlled before-and-after studies, or interrupted time series (ITS) studies; compared a labelled product (with information on nutrients or energy) with the same product without a nutritional label; assessed objectively measured purchasing or consumption of foods or non-alcoholic drinks in real-world or laboratory settings. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies for inclusion and extracted study data. We applied the Cochrane 'Risk of bias' tool and GRADE to assess the quality of evidence. We pooled studies that evaluated similar interventions and outcomes using a random-effects meta-analysis, and we synthesised data from other studies in a narrative summary. MAIN RESULTS: We included 28 studies, comprising 17 RCTs, 5 Q-RCTs and 6 ITS studies. Most (21/28) took place in the USA, and 19 took place in university settings, 14 of which mainly involved university students or staff. Most (20/28) studies assessed the impact of labelling on menus or menu boards, or nutritional labelling placed on, or adjacent to, a range of foods or drinks from which participants could choose. Eight studies provided participants with only one labelled food or drink option (in which labelling was present on a container or packaging, adjacent to the food or on a display board) and measured the amount consumed. The most frequently assessed labelling type was energy (i.e. calorie) information (12/28).Eleven studies assessed the impact of nutritional labelling on purchasing food or drink options in real-world settings, including purchases from vending machines (one cluster-RCT), grocery stores (one ITS), or restaurants, cafeterias or coffee shops (three RCTs, one Q-RCT and five ITS). Findings on vending machines and grocery stores were not interpretable, and were rated as very low quality. A meta-analysis of the three RCTs, all of which assessed energy labelling on menus in restaurants, demonstrated a statistically significant reduction of 47 kcal in energy purchased (MD -46.72 kcal, 95% CI -78.35, -15.10, N = 1877). Assuming an average meal of 600 kcal, energy labelling on menus would reduce energy purchased per meal by 7.8% (95% CI 2.5% to 13.1%). The quality of the evidence for these three studies was rated as low, so our confidence in the effect estimate is limited and may change with further studies. Of the remaining six studies, only two (both ITS studies involving energy labels on menus or menus boards in a coffee shop or cafeteria) were at low risk of bias, and their results support the meta-analysis. The results of the other four studies which were conducted in a restaurant, cafeterias (2 studies) or a coffee shop, were not clearly reported and were at high risk of bias.Seventeen studies assessed the impact of nutritional labels on consumption in artificial settings or scenarios (henceforth referred to as laboratory studies or settings). Of these, eight (all RCTs) assessed the effect of labels on menus or placed on a range of food options. A meta-analysis of these studies did not conclusively demonstrate a reduction in energy consumed during a meal (MD -50 kcal, 95% CI -104.41, 3.88, N = 1705). We rated the quality of the evidence as low, so our confidence in the effect estimate is limited and may change with further studies.Six laboratory studies (four RCTs and two Q-RCTs) assessed the impact of labelling a single food or drink option (such as chocolate, pasta or soft drinks) on energy consumed during a snack or meal. A meta-analysis of these studies did not demonstrate a statistically significant difference in energy (kcal) consumed (SMD 0.05, 95% CI -0.17 to 0.27, N = 732). However, the confidence intervals were wide, suggesting uncertainty in the true effect size. We rated the quality of the evidence as low, so our confidence in the effect estimate is limited and may change with further studies.There was no evidence that nutritional labelling had the unintended harm of increasing energy purchased or consumed. Indirect evidence came from five laboratory studies that involved mislabelling single nutrient content (i.e. placing low energy or low fat labels on high-energy foods) during a snack or meal. A meta-analysis of these studies did not demonstrate a statistically significant increase in energy (kcal) consumed (SMD 0.19, 95% CI -0.14to 0.51, N = 718). The effect was small and the confidence intervals wide, suggesting uncertainty in the true effect size. We rated the quality of the evidence from these studies as very low, providing very little confidence in the effect estimate. AUTHORS' CONCLUSIONS: Findings from a small body of low-quality evidence suggest that nutritional labelling comprising energy information on menus may reduce energy purchased in restaurants. The evidence assessing the impact on consumption of energy information on menus or on a range of food options in laboratory settings suggests a similar effect to that observed for purchasing, although the evidence is less definite and also of low quality.Accordingly, and in the absence of observed harms, we tentatively suggest that nutritional labelling on menus in restaurants could be used as part of a wider set of measures to tackle obesity. Additional high-quality research in real-world settings is needed to enable more certain conclusions.Further high-quality research is also needed to address the dearth of evidence from grocery stores and vending machines and to assess potential moderators of the intervention effect, including socioeconomic status.

Implications of Antibiotic Resistance for Patients' Recovery From Common Infections in the Community: A Systematic Review and Meta-analysis.

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.

Why do women choose or reject careers in academic medicine? A narrative review of empirical evidence.

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.

Clinician-targeted interventions to influence antibiotic prescribing behaviour for acute respiratory infections in primary care: an overview of systematic reviews.

BACKGROUND: Antibiotic resistance is a worldwide health threat. Interventions that reduce antibiotic prescribing by clinicians are expected to reduce antibiotic resistance. Disparate interventions to change antibiotic prescribing behaviour for acute respiratory infections (ARIs) have been trialled and meta-analysed, but not yet synthesised in an overview. This overview synthesises evidence from systematic reviews, rather than individual trials. OBJECTIVES: To systematically review the existing evidence from systematic reviews on the effects of interventions aimed at influencing clinician antibiotic prescribing behaviour for ARIs in primary care. METHODS: We searched the Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects (DARE), MEDLINE, Embase, CINAHL, PsycINFO, and Science Citation Index to June 2016. We also searched the reference lists of all included reviews. We ran a pre-publication search in May 2017 and placed additional studies in 'awaiting classification'.We included both Cochrane and non-Cochrane reviews of randomised controlled trials evaluating the effect of any clinician-focussed intervention on antibiotic prescribing behaviour in primary care. Two overview authors independently extracted data and assessed the methodological quality of included reviews using the ROBIS tool, with disagreements reached by consensus or by discussion with a third overview author. We used the GRADE system to assess the quality of evidence in included reviews. The results are presented as a narrative overview. MAIN RESULTS: We included eight reviews in this overview: five Cochrane Reviews (33 included trials) and three non-Cochrane reviews (11 included trials). Three reviews (all Cochrane Reviews) scored low risk across all the ROBIS domains in Phase 2 and low risk of bias overall. The remaining five reviews scored high risk on Domain 4 of Phase 2 because the 'Risk of bias' assessment had not been specifically considered and discussed in the review Results and Conclusions. The trials included in the reviews varied in both size and risk of bias. Interventions were compared to usual care.Moderate-quality evidence indicated that C-reactive protein (CRP) point-of-care testing (risk ratio (RR) 0.78, 95% confidence interval (CI) 0.66 to 0.92, 3284 participants, 6 trials), shared decision making (odds ratio (OR) 0.44, 95% CI 0.26 to 0.75, 3274 participants, 3 trials; RR 0.64, 95% CI 0.49 to 0.84, 4623 participants, 2 trials; risk difference -18.44, 95% CI -27.24 to -9.65, 481,807 participants, 4 trials), and procalcitonin-guided management (adjusted OR 0.10, 95% CI 0.07 to 0.14, 1008 participants, 2 trials) probably reduce antibiotic prescribing in general practice. We found moderate-quality evidence that procalcitonin-guided management probably reduces antibiotic prescribing in emergency departments (adjusted OR 0.34, 95% CI 0.28 to 0.43, 2605 participants, 7 trials). The overall effect of these interventions was small (few achieving greater than 50% reduction in antibiotic prescribing, most about a quarter or less), but likely to be clinically important.Compared to usual care, shared decision making probably makes little or no difference to reconsultation for the same illness (RR 0.87, 95% CI 0.74 to 1.03, 1860 participants, 4 trials, moderate-quality evidence), and may make little or no difference to patient satisfaction (RR 0.86, 95% CI 0.57 to 1.30, 1110 participants, 2 trials, low-quality evidence). Similarly, CRP testing probably has little or no effect on patient satisfaction (RR 0.79, 95% CI 0.57 to 1.08, 689 participants, 2 trials, moderate-quality evidence) or reconsultation (RR 1.08, 95% CI 0.93 to 1.27, 5132 participants, 4 trials, moderate-quality evidence). Procalcitonin-guided management probably results in little or no difference in treatment failure in general practice compared to normal care (adjusted OR 0.95, 95% CI 0.73 to 1.24, 1008 participants, 2 trials, moderate-quality evidence), however it probably reduces treatment failure in the emergency department compared to usual care (adjusted OR 0.76, 95% CI 0.61 to 0.95, 2605 participants, 7 trials, moderate-quality evidence).The quality of evidence for interventions focused on clinician educational materials and decision support in reducing antibiotic prescribing in general practice was either low or very low (no pooled result reported) and trial results were highly heterogeneous, therefore we were unable draw conclusions about the effects of these interventions. The use of rapid viral diagnostics in emergency departments may have little or no effect on antibiotic prescribing (RR 0.86, 95% CI 0.61 to 1.22, 891 participants, 3 trials, low-quality evidence) and may result in little to no difference in reconsultation (RR 0.86, 95% CI 0.59 to 1.25, 200 participants, 1 trial, low-quality evidence).None of the trials in the included reviews reported on management costs for the treatment of an ARI or any associated complications. AUTHORS' CONCLUSIONS: We found evidence that CRP testing, shared decision making, and procalcitonin-guided management reduce antibiotic prescribing for patients with ARIs in primary care. These interventions may therefore reduce overall antibiotic consumption and consequently antibiotic resistance. There do not appear to be negative effects of these interventions on the outcomes of patient satisfaction and reconsultation, although there was limited measurement of these outcomes in the trials. This should be rectified in future trials.We could gather no information about the costs of management, and this along with the paucity of measurements meant that it was difficult to weigh the benefits and costs of implementing these interventions in practice.Most of this research was undertaken in high-income countries, and it may not generalise to other settings. The quality of evidence for the interventions of educational materials and tools for patients and clinicians was either low or very low, which prevented us from drawing any conclusions. High-quality trials are needed to further investigate these interventions.

B-type natriuretic peptide-guided treatment for heart failure.

BACKGROUND: Heart failure is a condition in which the heart does not pump enough blood to meet all the needs of the body. Symptoms of heart failure include breathlessness, fatigue and fluid retention. Outcomes for patients with heart failure are highly variable; however on average, these patients have a poor prognosis. Prognosis can be improved with early diagnosis and appropriate use of medical treatment, use of devices and transplantation. Patients with heart failure are high users of healthcare resources, not only due to drug and device treatments, but due to high costs of hospitalisation care. B-type natriuretic peptide levels are already used as biomarkers for diagnosis and prognosis of heart failure, but could offer to clinicians a possible tool to guide drug treatment. This could optimise drug management in heart failure patients whilst allaying concerns over potential side effects due to drug intolerance. OBJECTIVES: To assess whether treatment guided by serial BNP or NT-proBNP (collectively referred to as NP) monitoring improves outcomes compared with treatment guided by clinical assessment alone. SEARCH METHODS: Searches were conducted up to 15 March 2016 in the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library; MEDLINE (OVID), Embase (OVID), the Database of Abstracts of Reviews of Effects (DARE) and the NHS Economic Evaluation Database in the Cochrane Library. Searches were also conducted in the Science Citation Index Expanded, the Conference Proceedings Citation Index on Web of Science (Thomson Reuters), World Health Organization International Clinical Trials Registry and ClinicalTrials.gov. We applied no date or language restrictions. SELECTION CRITERIA: We included randomised controlled trials of NP-guided treatment of heart failure versus treatment guided by clinical assessment alone with no restriction on follow-up. Adults treated for heart failure, in both in-hospital and out-of-hospital settings, and trials reporting a clinical outcome were included. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, extracted data and evaluated risk of bias. Risk ratios (RR) were calculated for dichotomous data, and pooled mean differences (MD) (with 95% confidence intervals (CI)) were calculated for continuous data. We contacted trial authors to obtain missing data. Using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, we assessed the quality of the evidence and GRADE profiler (GRADEPRO) was used to import data from Review Manager to create a 'Summary of findings' table. MAIN RESULTS: We included 18 randomised controlled trials with 3660 participants (range of mean age: 57 to 80 years) comparing NP-guided treatment with clinical assessment alone. The evidence for all-cause mortality using NP-guided treatment showed uncertainty (RR 0.87, 95% CI 0.76 to 1.01; patients = 3169; studies = 15; low quality of the evidence), and for heart failure mortality (RR 0.84, 95% CI 0.54 to 1.30; patients = 853; studies = 6; low quality of evidence).The evidence suggested heart failure admission was reduced by NP-guided treatment (38% versus 26%, RR 0.70, 95% CI 0.61 to 0.80; patients = 1928; studies = 10; low quality of evidence), but the evidence showed uncertainty for all-cause admission (57% versus 53%, RR 0.93, 95% CI 0.84 to 1.03; patients = 1142; studies = 6; low quality of evidence).Six studies reported on adverse events, however the results could not be pooled (patients = 1144; low quality of evidence). Only four studies provided cost of treatment results, three of these studies reported a lower cost for NP-guided treatment, whilst one reported a higher cost (results were not pooled; patients = 931, low quality of evidence). The evidence showed uncertainty for quality of life data (MD -0.03, 95% CI -1.18 to 1.13; patients = 1812; studies = 8; very low quality of evidence).We completed a 'Risk of bias' assessment for all studies. The impact of risk of bias from lack of blinding of outcome assessment and high attrition levels was examined by restricting analyses to only low 'Risk of bias' studies. AUTHORS' CONCLUSIONS: In patients with heart failure low-quality evidence showed a reduction in heart failure admission with NP-guided treatment while low-quality evidence showed uncertainty in the effect of NP-guided treatment for all-cause mortality, heart failure mortality, and all-cause admission. Uncertainty in the effect was further shown by very low-quality evidence for patient's quality of life. The evidence for adverse events and cost of treatment was low quality and we were unable to pool results.

Blood CEA levels for detecting recurrent colorectal cancer.

BACKGROUND: Testing for carcino-embryonic antigen (CEA) in the blood is a recommended part of follow-up to detect recurrence of colorectal cancer following primary curative treatment. There is substantial clinical variation in the cut-off level applied to trigger further investigation. OBJECTIVES: To determine the diagnostic performance of different blood CEA levels in identifying people with colorectal cancer recurrence in order to inform clinical practice. SEARCH METHODS: We conducted all searches to January 29 2014. We applied no language limits to the searches, and translated non-English manuscripts. We searched for relevant reviews in the MEDLINE, EMBASE, MEDION and DARE databases. We searched for primary studies (including conference abstracts) in the Cochrane Central Register of Controlled Trials (CENTRAL), in MEDLINE, EMBASE, and the Science Citation Index & Conference Proceedings Citation Index - Science. We identified ongoing studies by searching WHO ICTRP and the ASCO meeting library. SELECTION CRITERIA: We included cross-sectional diagnostic test accuracy studies, cohort studies, and randomised controlled trials (RCTs) of post-resection colorectal cancer follow-up that compared CEA to a reference standard. We included studies only if we could extract 2 x 2 accuracy data. We excluded case-control studies, as the ratio of cases to controls is determined by the study design, making the data unsuitable for assessing test accuracy. DATA COLLECTION AND ANALYSIS: Two review authors (BDN, IP) assessed the quality of all articles independently, discussing any disagreements. Where we could not reach consensus, a third author (BS) acted as moderator. We assessed methodological quality against QUADAS-2 criteria. We extracted binary diagnostic accuracy data from all included studies as 2 x 2 tables. We conducted a bivariate meta-analysis. We used the xtmelogit command in Stata to produce the pooled estimates of sensitivity and specificity and we also produced hierarchical summary ROC plots. MAIN RESULTS: In the 52 included studies, sensitivity ranged from 41% to 97% and specificity from 52% to 100%. In the seven studies reporting the impact of applying a threshold of 2.5 µg/L, pooled sensitivity was 82% (95% confidence interval (CI) 78% to 86%) and pooled specificity 80% (95% CI 59% to 92%). In the 23 studies reporting the impact of applying a threshold of 5 µg/L, pooled sensitivity was 71% (95% CI 64% to 76%) and pooled specificity 88% (95% CI 84% to 92%). In the seven studies reporting the impact of applying a threshold of 10 µg/L, pooled sensitivity was 68% (95% CI 53% to 79%) and pooled specificity 97% (95% CI 90% to 99%). AUTHORS' CONCLUSIONS: CEA is insufficiently sensitive to be used alone, even with a low threshold. It is therefore essential to augment CEA monitoring with another diagnostic modality in order to avoid missed cases. Trying to improve sensitivity by adopting a low threshold is a poor strategy because of the high numbers of false alarms generated. We therefore recommend monitoring for colorectal cancer recurrence with more than one diagnostic modality but applying the highest CEA cut-off assessed (10 µg/L).

Interventions to increase the use of electronic health information by healthcare practitioners to improve clinical practice and patient outcomes.

BACKGROUND: There is a large volume of health information available, and, if applied in clinical practice, may contribute to effective patient care. Despite an abundance of information, sub-optimal care is common. Many factors influence practitioners' use of health information, and format (electronic or other) may be one such factor. OBJECTIVES: To assess the effects of interventions aimed at improving or increasing healthcare practitioners' use of electronic health information (EHI) on professional practice and patient outcomes. SEARCH METHODS: We searched The Cochrane Library (Wiley), MEDLINE (Ovid), EMBASE (Ovid), CINAHL (EBSCO), and LISA (EBSCO) up to November 2013. We contacted researchers in the field and scanned reference lists of relevant articles. SELECTION CRITERIA: We included studies that evaluated the effects of interventions to improve or increase the use of EHI by healthcare practitioners on professional practice and patient outcomes. We defined EHI as information accessed on a computer. We defined 'use' as logging into EHI. We considered any healthcare practitioner involved in patient care. We included randomized, non-randomized, and cluster randomized controlled trials (RCTs, NRCTs, CRCTs), controlled clinical trials (CCTs), interrupted time series (ITS), and controlled before-and-after studies (CBAs).The comparisons were: electronic versus printed health information; EHI on different electronic devices (e.g. desktop, laptop or tablet computers, etc.; cell / mobile phones); EHI via different user interfaces; EHI provided with or without an educational or training component; and EHI compared to no other type or source of information. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risk of bias for each study. We used GRADE to assess the quality of the included studies. We reassessed previously excluded studies following our decision to define logins to EHI as a measure of professional behavior. We reported results in natural units. When possible, we calculated and reported median effect size (odds ratio (OR), interquartile ranges (IQR)). Due to high heterogeneity across studies, meta-analysis was not feasible. MAIN RESULTS: We included two RCTs and four CRCTs involving 352 physicians, 48 residents, and 135 allied health practitioners. Overall risk of bias was low as was quality of the evidence. One comparison was supported by three studies and three comparisons were supported by single studies, but outcomes across the three studies were highly heterogeneous. We found no studies to support EHI versus no alternative. Given these factors, it was not possible to determine the relative effectiveness of interventions. All studies reported practitioner use of EHI, two reported on compliance with electronic practice guidelines, and none reported on patient outcomes.One trial (139 participants) measured guideline adherence for an electronic versus printed guideline, but reported no difference between groups (median OR 0.85, IQR 0.74 to 1.08). One small cross-over trial (10 participants) reported increased use of clinical guidelines when provided with a mobile versus stationary, desktop computer (mean use per shift: intervention group (IG) 3.6, standard deviation (SD) 1.7 vs. control group (CG) 2.0 (SD 1.9), P value = 0.033). One cross-over trial (203 participants) reported that using a customized versus a generic interface had little impact on practitioners' use of EHI (mean difference in adjusted end-of-study rate: 0.77 logins/month/user, 95% confidence interval (CI) CI 0.43 to 1.11). Three trials included education or training and reported increased use of EHI by practitioners following training. AUTHORS' CONCLUSIONS: This review provided no evidence that the use of EHI translates into improved clinical practice or patient outcomes, though it does suggest that when practitioners are provided with EHI and education or training, the use of EHI increases. We have defined use as the activity of logging into an EHI resource, but based on our findings use does not automatically translate to the application of EHI in practice. While using EHI may be an important component of evidence-based medicine, alone it is insufficient to improve patient care or clinical practices. For EHI to be applied in patient care, it will be necessary to understand why practitioners' are reluctant to apply EHI when treating people, and to determine the most effective way(s) to reduce this reluctance.

Diagnostic accuracy of point-of-care tests for detecting albuminuria: a systematic review and meta-analysis.

BACKGROUND: Experts recommend screening for albuminuria in patients at risk for kidney disease. PURPOSE: To systematically review evidence about the diagnostic accuracy of point-of-care (POC) tests for detecting albuminuria in individuals for whom guidelines recommend such detection. DATA SOURCES: Cochrane Library, EMBASE, Medion database, MEDLINE, and Science Citation Index from 1963 through 5 December 2013; hand searches of other relevant journals; and reference lists. STUDY SELECTION: Cross-sectional studies, published in any language, that compared the accuracy of machine-read POC tests of urinary albumin-creatinine ratio with that of laboratory measurement. DATA EXTRACTION: Two independent reviewers extracted study data and assessed study quality using the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) tool. DATA SYNTHESIS: Sixteen studies (n = 3356 patients) that evaluated semiquantitative or quantitative POC tests and used random urine samples collected in primary or secondary ambulatory care settings met inclusion criteria. Pooling results from a bivariate random-effects model gave sensitivity and specificity estimates of 76% (95% CI, 63% to 86%) and 93% (CI, 84% to 97%), respectively, for the semiquantitative test. Sensitivity and specificity estimates for the quantitative test were 96% (CI, 78% to 99%) and 98% (CI, 93% to 99%), respectively. The negative likelihood ratios for the semiquantitative and quantitative tests were 0.26 (CI, 0.16 to 0.40) and 0.04 (CI, 0.01 to 0.25), respectively. LIMITATION: Accuracy estimates were based on data from single-sample urine measurement, but guidelines require that diagnosis of albuminuria be based on at least 2 of 3 samples collected in a 6-month period. CONCLUSION: A negative semiquantitative POC test result does not rule out albuminuria, whereas quantitative POC testing meets required performance standards and can be used to rule out albuminuria. PRIMARY FUNDING SOURCE: None.

Vitamin K for improved anticoagulation control in patients receiving warfarin.

BACKGROUND: Effective use of warfarin involves keeping the international normalised ratio (INR) within a relatively narrow therapeutic range. However, patients respond widely to their dose of warfarin. Overcoagulation can lead to an increased risk of excessive bleeding, while undercoagulation can lead to increased clot formation. There is some evidence that patients with a variable response to warfarin may benefit from a concomitant low dose of vitamin K. OBJECTIVES: To assess the effects of concomitant supplementation of low-dose oral vitamin K for anticoagulation control in patients being initiated on or taking a maintenance dose of warfarin. SEARCH METHODS: To identify previous reviews, we searched the Database of Abstracts of Reviews of Effects (DARE via The Cochrane Library, Wiley) (Issue 2, 2011). To identify primary studies, we searched the Cochrane Central Register of Controlled Trials (CENTRAL via The Cochrane Library, Wiley) (Issue 2, 2014), Ovid MEDLINE (R) In-Process & Other Non-Indexed Citations database and Ovid MEDLINE (R) (OvidSP) (1946 to 25 February 2014), Embase (OvidSP) (1974 to week 8 of 2014), Science Citation Index Expanded™ & Conference Proceedings Citation Index - Science (Web of Science™) (1945 to 27 February 2014), and the NHS Economics Evaluations Database (NHS EED) (via The Cochrane Library, Wiley) (Issue 2, 2014). We did not apply any language or date restrictions. We used additional methods to identify grey literature and ongoing studies. SELECTION CRITERIA: Randomised controlled trials comparing the addition of vitamin K versus placebo in patients initiating warfarin or already taking warfarin. DATA COLLECTION AND ANALYSIS: Two review authors independently selected and extracted data from included studies. When disagreement arose, a third author helped reached a consensus. We also assessed risk of bias. MAIN RESULTS: We identified two studies with a total of 100 participants for inclusion in the review. We found the overall risk of bias to be unclear in a number of domains. Neither study reported the time taken to the first INR in range. Only one study (70 participants) reported the mean time in therapeutic range as a percentage. This study found that in the group of participants deemed to have poor INR control, the addition of 150 micrograms (mcg) oral vitamin K significantly improved anticoagulation control in those with unexplained instability of response to warfarin. The second study (30 participants) reported the effect of 175 mcg oral vitamin K versus placebo on participants with high variability in their INR levels. The study concluded that vitamin K supplementation did not significantly improve the stability of anticoagulation for participants on chronic anticoagulation therapy. However, the study was only available in abstract form, and communication with the lead author confirmed that there were no further publications. Therefore, we interpreted this conclusion with caution. Neither study reported any thromboembolic events, haemorrhage, or death from the addition of vitamin K supplementation. AUTHORS' CONCLUSIONS: Two included studies in this review compared whether the addition of a low dose (150 to 175 mcg) of vitamin K given to participants with a high-variability response to warfarin improved their INR control. One study demonstrated a significant improvement, while another smaller study (published in abstract only) suggested no overall benefit. Currently, there are insufficient data to suggest an overall benefit. Larger, higher quality trials are needed to examine if low-dose vitamin K improves INR control in those starting or already taking warfarin.

Symptomatic treatment of the cough in whooping cough.

BACKGROUND: Around 16 million cases of whooping cough (pertussis) occur worldwide each year, mostly in low-income countries. Much of the morbidity of whooping cough in children and adults is due to the effects of the paroxysmal cough. Cough treatments proposed include corticosteroids, beta2-adrenergic agonists, pertussis-specific immunoglobulin, antihistamines and possibly leukotriene receptor antagonists (LTRAs). OBJECTIVES: To assess the effectiveness and safety of interventions to reduce the severity of paroxysmal cough in whooping cough in children and adults. SEARCH METHODS: We updated our searches of the Cochrane Central Register of Controlled Trials (CENTRAL, 2014, Issue 1), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, the Database of Abstracts of Reviews of Effects (DARE 2014, Issue 2), accessed from The Cochrane Library, MEDLINE (1950 to 30 January 2014), EMBASE (1980 to 30 January 2014), AMED (1985 to 30 January 2014), CINAHL (1980 to 30 January 2014) and LILACS (30 January 2014). We searched Current Controlled Trials to identify trials in progress. SELECTION CRITERIA: We selected randomised controlled trials (RCTs) and quasi-RCTs of any intervention (excluding antibiotics and vaccines) to suppress the cough in whooping cough. DATA COLLECTION AND ANALYSIS: Two review authors (SB, MT) independently selected trials, extracted data and assessed the quality of each trial for this review in 2009. Two review authors (SB, KW) independently reviewed additional studies identified by the updated searches in 2012 and 2014. The primary outcome was frequency of paroxysms of coughing. Secondary outcomes were frequency of vomiting, frequency of whoop, frequency of cyanosis (turning blue), development of serious complications, mortality from any cause, side effects due to medication, admission to hospital and duration of hospital stay.  MAIN RESULTS: We included 12 trials of varying sample sizes (N = 9 to 135), mainly from high-income countries, including a total of 578 participants. Ten trials recruited children (N = 448 participants). Two trials recruited adolescents and adults (N = 130 participants). We considered only three trials to be of high methodological quality (one trial each of diphenhydramine, pertussis immunoglobulin and montelukast). Included studies did not show a statistically significant benefit for any of the interventions. Only six trials, including a total of 196 participants, reported data in sufficient detail for analysis. Diphenhydramine did not change coughing episodes; the mean difference (MD) of coughing spells per 24 hours was 1.9; 95% confidence interval (CI) -4.7 to 8.5 (N = 49 participants from one trial). One trial on pertussis immunoglobulin reported a possible mean reduction of -3.1 whoops per 24 hours (95% CI -6.2 to 0.02, N = 47 participants) but no change in hospital stay (MD -0.7 days; 95% CI -3.8 to 2.4, N = 46 participants). Dexamethasone did not show a clear decrease in length of hospital stay (MD -3.5 days; 95% CI -15.3 to 8.4, N = 11 participants from one trial) and salbutamol showed no change in coughing paroxysms per day (MD -0.2; 95% CI -4.1 to 3.7, N = 42 participants from two trials). Only one trial comparing pertussis immunoglobulin versus placebo (N = 47 participants) reported data on adverse events: 4.3% in the treatment group (rash) versus 5.3% in the placebo group (loose stools, pain and swelling at injection site). AUTHORS' CONCLUSIONS: There is insufficient evidence to draw conclusions about the effectiveness of interventions for the cough in whooping cough. More high-quality trials are needed to assess the effectiveness of potential antitussive treatments in patients with whooping cough.

Development of a search filter for identifying studies completed in primary care.

BACKGROUND: Identifying articles relevant to primary care is challenging for busy clinicians. Setting specific search strategies can be used to help clinicians find pertinent studies in a timely fashion. OBJECTIVES: To develop search filters for identifying research studies of relevance to primary care in MEDLINE (OvidSP). METHODS: We conducted a search of MEDLINE (OvidSP) for articles published in five core medical journals at five yearly intervals. We identified a gold standard set of primary care relevant articles which was divided into two subsets. The first subset was used to identify frequently occurring words and phrases through textual analysis. Search filters were developed from these words and phrases and internally validated against records in the second subset. We evaluated the filters performance in a search for articles on two common primary care conditions in MEDLINE (OvidSP). RESULTS: Of the 12 045 articles retrieved, 9028 records were reviewed, of which 371 articles were relevant to primary care (gold standard). When the search filters generated from textual analysis were internally validated, filter specificity peaked at 99% with 60% sensitivity, 67% precision and 97% accuracy. When evaluated against a set of articles on two common primary care conditions, the best performing combination search filter specificity maximized at 99.7% with sensitivity reaching 15% (precision 90%; accuracy 89%). CONCLUSION: The best performing combination search filter works well in reducing the number of irrelevant papers retrieved in a MEDLINE (OvidSP) search if a busy clinician needs to focus on research relevant to primary care.

Accuracy of prenatal and postnatal biomarkers for estimating gestational age: a systematic review and meta-analysis.

Background: Knowledge of gestational age (GA) is key in clinical management of individual obstetric patients, and critical to be able to calculate rates of preterm birth and small for GA at a population level. Currently, the gold standard for pregnancy dating is measurement of the fetal crown rump length at 11-14 weeks of gestation. However, this is not possible for women first presenting in later pregnancy, or in settings where routine ultrasound is not available. A reliable, cheap and easy to measure GA-dependent biomarker would provide an important breakthrough in estimating the age of pregnancy. Therefore, the aim of this study was to determine the accuracy of prenatal and postnatal biomarkers for estimating gestational age (GA). Methods: Systematic review prospectively registered with PROSPERO (CRD42020167727) and reported in accordance with the PRISMA-DTA. Medline, Embase, CINAHL, LILACS, and other databases were searched from inception until September 2023 for cohort or cross-sectional studies that reported on the accuracy of prenatal and postnatal biomarkers for estimating GA. In addition, we searched Google Scholar and screened proceedings of relevant conferences and reference lists of identified studies and relevant reviews. There were no language or date restrictions. Pooled coefficients of correlation and root mean square error (RMSE, average deviation in weeks between the GA estimated by the biomarker and that estimated by the gold standard method) were calculated. The risk of bias in each included study was also assessed. Findings: Thirty-nine studies fulfilled the inclusion criteria: 20 studies (2,050 women) assessed prenatal biomarkers (placental hormones, metabolomic profiles, proteomics, cell-free RNA transcripts, and exon-level gene expression), and 19 (1,738,652 newborns) assessed postnatal biomarkers (metabolomic profiles, DNA methylation profiles, and fetal haematological components). Among the prenatal biomarkers assessed, human chorionic gonadotrophin measured in maternal serum between 4 and 9 weeks of gestation showed the highest correlation with the reference standard GA, with a pooled coefficient of correlation of 0.88. Among the postnatal biomarkers assessed, metabolomic profiling from newborn blood spots provided the most accurate estimate of GA, with a pooled RMSE of 1.03 weeks across all GAs. It performed best for term infants with a slightly reduced accuracy for preterm or small for GA infants. The pooled RMSEs for metabolomic profiling and DNA methylation profile from cord blood samples were 1.57 and 1.60 weeks, respectively. Interpretation: We identified no antenatal biomarkers that accurately predict GA over a wide window of pregnancy. Postnatally, metabolomic profiling from newborn blood spot provides an accurate estimate of GA, however, as this is known only after birth it is not useful to guide antenatal care. Further prenatal studies are needed to identify biomarkers that can be used in isolation, as part of a biomarker panel, or in combination with other clinical methods to narrow prediction intervals of GA estimation. Funding: The research was funded by the Bill and Melinda Gates Foundation (INV-000368). ATP is supported by the Oxford Partnership Comprehensive Biomedical Research Centre with funding from the NIHR Biomedical Research Centre funding scheme. The views expressed are those of the authors and not necessarily those of the UK National Health Service, the NIHR, the Department of Health, or the Department of Biotechnology. The funders of this study had no role in study design, data collection, analysis or interpretation of the data, in writing the paper or the decision to submit for publication.

Primary care clinicians' attitudes towards point-of-care blood testing: a systematic review of qualitative studies.

BACKGROUND: Point-of-care blood tests are becoming increasingly available and could replace current venipuncture and laboratory testing for many commonly used tests. However, at present very few have been implemented in most primary care settings. Understanding the attitudes of primary care clinicians towards these tests may help to identify the barriers and facilitators to their wider adoption. We aimed to systematically review qualitative studies of primary care clinicians' attitudes to point-of-care blood tests. METHODS: We systematically searched Medline, Embase, ISI Web of Knowledge, PsycINFO and CINAHL for qualitative studies of primary care clinicians' attitudes towards point-of-care blood tests in high income countries. We conducted a thematic synthesis of included studies. RESULTS: Our search identified seven studies, including around two hundred participants from Europe and Australia. The synthesis generated three main themes: the impact of point-of-care testing on decision-making, diagnosis and treatment; impact on clinical practice more broadly; and impact on patient-clinician relationships and perceived patient experience. Primary care clinicians believed point-of-care testing improved diagnostic certainty, targeting of treatment, self-management of chronic conditions, and clinician-patient communication and relationships. There were concerns about test accuracy, over-reliance on tests, undermining of clinical skills, cost, and limited usefulness. CONCLUSIONS: We identified several perceived benefits and barriers regarding point-of-care tests in primary care. These imply that if point-of-care tests are to become more widely adopted, primary care clinicians require evidence of their accuracy, rigorous testing of the impact of introduction on patient pathways and clinical practice, and consideration of test funding.

The impact of renin-angiotensin-aldosterone system inhibitors on Type 1 and Type 2 diabetic patients with and without early diabetic nephropathy.

Renin-angiotensin-aldosterone system inhibitors prevent the progression of kidney disease in patients with diabetic nephropathy, and we studied how that benefit varies by the type of diabetes and baseline urinary albumin. We pooled data from 49 randomized controlled trials in a meta-analysis using the ratio of endpoint urinary albumin levels in those treated compared to those untreated with renin-angiotensin-aldosterone system inhibitors in both fixed- and random-effects models. The urinary albumin excretion for treated microalbuminuric patients with Type 1 diabetes was on average 60% lower at the end of the trial compared with patients not treated with renin-angiotensin-aldosterone system inhibitors using the fixed-effects model and 67% lower using the random-effects model. There was no significant effect of treatment in patients with normal albumin excretion. For normoalbuminuric patients with Type 2 diabetes, urinary albumin excretion was on average 12% lower after treatment using the fixed-effects model compared to 21% lower using the random-effects model. For microalbuminuric patients, urinary albumin excretion was on average 23% lower using the fixed-effects model and 27% lower using the random-effects model. Thus, renin-angiotensin-aldosterone system inhibition reduced urinary albumin excretion for Type 1 diabetic patients with micro-, but not those with normoalbuminuria. Treatment reduced urinary albumin excretion for Type 2 diabetic patients with and without microalbuminuria.

Symptomatic treatment of the cough in whooping cough.

BACKGROUND: The worldwide incidence of whooping cough (pertussis) has been estimated at 48.5 million cases and nearly 295,000 deaths per year. In low-income countries, the case-fatality rate among infants may be as high as 4%. Much of the morbidity of whooping cough in children and adults is due to the effects of the paroxysmal cough. Cough treatments proposed include corticosteroids, beta 2-adrenergic agonists, pertussis-specific immunoglobulin, antihistamines and possibly leukotriene receptor antagonists (LTRAs). OBJECTIVES: To assess the effectiveness and safety of interventions to reduce the severity of paroxysmal cough in whooping cough in children and adults. SEARCH METHODS: We updated searches of the Cochrane Central Register of Controlled Trials (CENTRAL Issue 2, 2012), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, the Database of Abstracts of Reviews of Effects (DARE Issue 2, 2012) accessed from The Cochrane Library, MEDLINE (1950 to January 2012), EMBASE (1980 to January 2012), AMED (1985 to January 2012), CINAHL (1980 to January 2012) and LILACS (January 2012). We searched Current Controlled Trials to identify trials in progress. SELECTION CRITERIA: We selected randomised controlled trials (RCTs) and quasi-RCTs of any intervention (excluding antibiotics and vaccines) to suppress the cough in whooping cough. DATA COLLECTION AND ANALYSIS: Two review authors (SB, MT) independently selected trials, extracted data and assessed the quality of each trial for this review in 2009. Two review authors (SB, KW) independently reviewed additional studies identified by the updated search in 2012. The primary outcome was frequency of paroxysms of coughing. Secondary outcomes were frequency of vomiting, frequency of whoop, frequency of cyanosis (turning blue), development of serious complications, mortality from any cause, side effects due to medication, admission to hospital and duration of hospital stay.  MAIN RESULTS: Ten trials were included of varying sample sizes (N = 9 to 135) from high-income countries. Study quality was generally poor. Included studies did not show a statistically significant benefit for any of the interventions. Only six trials including a total of 196 participants reported data in sufficient detail for analysis. Diphenhydramine did not change coughing episodes; the mean difference (MD) of coughing spells per 24 hours was 1.9; 95% confidence interval (CI) - 4.7 to 8.5. One study on pertussis immunoglobulin reported a possible mean reduction of -3.1 whoops per 24 hours (95% CI -6.2 to 0.02) but no change in hospital stay (MD -0.7 days; 95% CI -3.8 to 2.4). Dexamethasone did not show a clear decrease in length of hospital stay (MD -3.5 days; 95% CI -15.3 to 8.4) and salbutamol showed no change in coughing paroxysms per 24 hours (MD -0.2; 95% CI -4.1 to 3.7). Only one trial comparing pertussis immunoglobulin versus placebo reported data on adverse events: 4.3% in the treatment group (rash) versus 5.3% in the placebo group (loose stools, pain and swelling at injection site). AUTHORS' CONCLUSIONS: There is insufficient evidence to draw conclusions about the effectiveness of interventions for the cough in whooping cough.