Evidence Of Difference In Effect Research Articles

Comparative cardiometabolic safety and effectiveness of aripiprazole in people with severe mental illness: A target trial emulation.

There is limited and conflicting evidence on the comparative cardiometabolic safety and effectiveness of aripiprazole in the management of severe mental illness. We investigated the hypothesis that aripiprazole has a favourable cardiometabolic profile, but similar effectiveness when compared to olanzapine, quetiapine, and risperidone. We conducted an observational emulation of a head-to-head trial of aripiprazole versus olanzapine, quetiapine, and risperidone in UK primary care using data from the Clinical Practice Research Datalink. We included adults diagnosed with severe mental illness (i.e., bipolar disorder, schizophrenia, and other non-organic psychoses) who were prescribed a new antipsychotic between 2005 and 2017, with a 2-year follow-up to 2019. The primary outcome was total cholesterol at 1 year (cardiometabolic safety). The main secondary outcome was psychiatric hospitalisation (effectiveness). Other outcomes included body weight, blood pressure, all-cause discontinuation, and mortality. Analyses adjusted for baseline confounders, including sociodemographics, diagnoses, concomitant medications, and cardiometabolic parameters. We included 26,537 patients (aripiprazole, n = 3,573, olanzapine, n = 8,554, quetiapine, n = 8,289, risperidone, n = 6,121). Median (IQR) age was 53 (42-67) years, 55.4% were female, 82.3% White, and 18.0% were diagnosed with schizophrenia. Patients prescribed aripiprazole had similar total cholesterol levels after 1 year to those prescribed olanzapine (adjusted mean difference [aMD], -0.03, 95% CI, -0.09 to 0.02, p = 0.261), quetiapine (aMD, -0.03, 95% CI, -0.09 to 0.03, p = 0.324), and risperidone (aMD, -0.01, 95% CI, -0.08 to 0.05, p = 0.707). However, there was evidence that patients prescribed aripiprazole had better outcomes on other cardiometabolic parameters, such as body weight and blood pressure, especially compared to olanzapine. After additional adjustment for prior hospitalisation, patients prescribed aripiprazole had similar rates of psychiatric hospitalisation as those prescribed olanzapine (adjusted hazard ratio [aHR], 0.91, 95% CI, 0.82-1.01, p = 0.078), quetiapine (aHR, 0.94, 95% CI, 0.85-1.04, p = 0.230), or risperidone (aHR, 1.01, 95% CI, 0.91-1.12, p = 0.854). Data from our large, powered, diverse, real-world target trial emulation sample, followed over 2 years, suggest that adults diagnosed with severe mental illness prescribed aripiprazole have similar total cholesterol 1 year after first prescription compared to those prescribed olanzapine, quetiapine, and risperidone. However, patients prescribed aripiprazole had better outcomes on some other cardiometabolic parameters, and there was little evidence of differences in effectiveness. Our findings inform a common clinical dilemma and contribute to the evidence base for real-world clinical decision-making on antipsychotic choice for patients diagnosed with severe mental illness.

Evaluating the impact on physical inactivity of Together an Active Future, a partnership approach to physical activity promotion. A difference-in-differences study

BackgroundLow physical activity is one of the leading causes of ill health in the UK and an important determinant of health inequalities. Little is known about the effectiveness of community-wide...

Which patients with metastatic hormone-sensitive prostate cancer benefit from docetaxel: a systematic review and meta-analysis of individual participant data from randomised trials

Adding docetaxel to androgen deprivation therapy (ADT) improves survival in patients with metastatic, hormone-sensitive prostate cancer, but uncertainty remains about who benefits most. We therefore aimed to obtain up-to-date estimates of the overall effects of docetaxel and to assess whether these effects varied according to prespecified characteristics of the patients or their tumours. The STOPCAP M1 collaboration conducted a systematic review and meta-analysis of individual participant data. We searched MEDLINE (from database inception to March 31, 2022), Embase (from database inception to March 31, 2022), the Cochrane Central Register of Controlled Trials (from database inception to March 31, 2022), proceedings of relevant conferences (from Jan 1, 1990, to Dec 31, 2022), and ClinicalTrials.gov (from database inception to March 28, 2023) to identify eligible randomised trials that assessed docetaxel plus ADT compared with ADT alone in patients with metastatic, hormone-sensitive prostate cancer. Detailed and updated individual participant data were requested directly from study investigators or through relevant repositories. The primary outcome was overall survival. Secondary outcomes were progression-free survival and failure-free survival. Overall pooled effects were estimated using an adjusted, intention-to-treat, two-stage, fixed-effect meta-analysis, with one-stage and random-effects sensitivity analyses. Missing covariate values were imputed. Differences in effect by participant characteristics were estimated using adjusted two-stage, fixed-effect meta-analysis of within-trial interactions on the basis of progression-free survival to maximise power. Identified effect modifiers were also assessed on the basis of overall survival. To explore multiple subgroup interactions and derive subgroup-specific absolute treatment effects we used one-stage flexible parametric modelling and regression standardisation. We assessed the risk of bias using the Cochrane Risk of Bias 2 tool. This study is registered with PROSPERO, CRD42019140591. We obtained individual participant data from 2261 patients (98% of those randomised) from three eligible trials (GETUG-AFU15, CHAARTED, and STAMPEDE trials), with a median follow-up of 72 months (IQR 55-85). Individual participant data were not obtained from two additional small trials. Based on all included trials and patients, there were clear benefits of docetaxel on overall survival (hazard ratio [HR] 0·79, 95% CI 0·70 to 0·88; p<0·0001), progression-free survival (0·70, 0·63 to 0·77; p<0·0001), and failure-free survival (0·64, 0·58 to 0·71; p<0·0001), representing 5-year absolute improvements of around 9-11%. The overall risk of bias was assessed to be low, and there was no strong evidence of differences in effect between trials for all three main outcomes. The relative effect of docetaxel on progression-free survival appeared to be greater with increasing clinical T stage (pinteraction=0·0019), higher volume of metastases (pinteraction=0·020), and, to a lesser extent, synchronous diagnosis of metastatic disease (pinteraction=0·077). Taking into account the other interactions, the effect of docetaxel was independently modified by volume and clinical T stage, but not timing. There was no strong evidence that docetaxel improved absolute effects at 5 years for patients with low-volume, metachronous disease (-1%, 95% CI -15 to 12, for progression-free survival; 0%, -10 to 12, for overall survival). The largest absolute improvement at 5 years was observed for those with high-volume, clinical T stage 4 disease (27%, 95% CI 17 to 37, for progression-free survival; 35%, 24 to 47, for overall survival). The addition of docetaxel to hormone therapy is best suited to patients with poorer prognosis for metastatic, hormone-sensitive prostate cancer based on a high volume of disease and potentially the bulkiness of the primary tumour. There is no evidence of meaningful benefit for patients with metachronous, low-volume disease who should therefore be managed differently. These results will better characterise patients most and, importantly, least likely to gain benefit from docetaxel, potentially changing international practice, guiding clinical decision making, better informing treatment policy, and improving patient outcomes. UK Medical Research Council and Prostate Cancer UK.

Effects of environmental impact and nutrition labelling on food purchasing: An experimental online supermarket study

Nutrition labels and ecolabels can support consumers to make healthier and more sustainable choices, and the former is now widespread. But there is no information on the impact of ecolabels in the presence of nutrition labels. The aims of this study were primarily to examine whether (1) ecolabels are effective at promoting sustainable purchasing behaviour if presented alongside nutrition labels; (2) and secondarily, whether nutrition labels are effective at promoting healthier purchasing if presented alongside ecolabels. Participants (N = 2730) visited an experimental online supermarket platform, and were randomised to see products with (1) environmental impact labels only; (2) nutrition (NutriScore) labels only; (3) both environmental and nutrition labels; (4) no labels. Linear regressions compared the mean environmental impact scores (EIS; primary outcome) and health scores of products in participants’ shopping baskets across each condition. Compared to control (no labels) there were significant reductions in the EIS when environmental impact labels were presented: Alone (−1.3, 95%CI: −2.3 to −0.4) or With nutrition labels (−2.0, 95%CI: −2.9 to −1.0), with no evidence of differences in effectiveness between these two conditions. There was no evidence of an impact of nutrition labels on either the EIS or the healthiness of purchases, both when nutrition labels were shown alone and when ecolabels were also present. Environmental impact labels may be effective at encouraging more sustainable purchases alone or when used alongside nutrition labels. This adds to the evidence base on the feasibility and effectiveness of environmental impact labelling as an important measure to change dietary behaviour to improve planetary health.

Early (&lt; 7 days) systemic postnatal corticosteroids for prevention of bronchopulmonary dysplasia in preterm infants.

Early (&lt; 7 days) systemic postnatal corticosteroids for prevention of bronchopulmonary dysplasia in preterm infants.

A Systematic Switch From Originator Infliximab to Biosimilar Infliximab in Patients With Non-Infectious Uveitis

To investigate the efficacy of biosimilar infliximab compared to that of the originator infliximab for the treatment of chronic non-infectious uveitis. Before-and-after study. All patients in the Central Norway Health Region between 2007 and 2018 were included. They were switched from originator to biosimilar infliximab therapy from 2014 to 2017. The primary outcome was quiescence of uveitis before and after the switch. All patients were seen every 1-3months. Visits were binned into 3-month long periods for each patient takingboth medications. Poisson regression analysis was used to estimate the incidence rate ratio (IRR) of quiescence between the 2 treatments. Twenty-nine patients were treated with infliximab. Twenty-three of those patients were switched from originator to biosimilar infliximab. The majority were white (87%), female (92%), and had chronic anterior uveitis (65%). For patients taking the originator and biosimilar drugs, the median treatment duration was38months (range: 8-131months) and 15months (range: 5-55months), respectively. Concomitant immunosuppressive medications and topical and oral steroids were used similarly during treatment with both originator and biosimilar infliximab. The IRR for quiescence was 0.91 (95% confidence intervals [CI]: 0.7-1.1; P= 0.38), which indicated no statistically significant differences in achieving quiescence after the switch. Also, there were no differences in the incidence rate of flare events with the switch (IRR: 1.04; 95% CI: 0.36-2.98; P= 0.95). IRR adjusted for intraocular surgery was 0.90 (95% CI: 0.7-1.1; P= 0.37). No evidence of differences in effectiveness were found in comparing biosimilar to originator infliximab in patients with chronic non-infectious uveitis.

All-Cause Mortality Risks Associated with Long-Term Exposure to Ambient Fine Particulate Matter in the Chinese Healthy Longevity Cohort

There is extensive evidence from cohort studies in North America and Europe for increased mortality risk from long-term exposure to fine particulate matter (PM2.5). However, this association has rarely been quantified at higher ambient concentrations. We sought to estimate the hazard ratio (HR) for all-cause mortality from long-term exposures to PM2.5 exposure in a well-defined Chinese cohort of older adults. The Chinese Longitudinal Healthy Longevity Survey (CLHLS) study is a prospective cohort study of elderly men and women enrolled in 2008 and followed through 2014 for mortality events. We studied 13,344 subjects for whom residential locations during the follow-up period were available for linkage to 1 km gridded PM2.5 concentrations, derived from ground-based measurements and satellite remote sensing. The outcome measure was all-cause mortality. Cox proportional hazards models were used to estimate the effect of long-term PM2.5 concentrations on all-cause mortality, controlling for age, sex, smoking status, drinking status, physical activity, BMI, household income, marital status, education. We then applied our results to estimate PM2.5-related premature mortality for persons older than 65 years-of-age in all of China in 2010. The overall HR for a 10 mg/m3 increase in 3-year average PM2.5 concentration was 1.08 (95% CI: 1.06&amp;#8211;1.09). There was strong evidence for differences in effects by urban/rural, north/south and high/low PM2.5 exposure. The HR was higher in rural and southern regions, and at lower PM2.5 exposure levels. The estimated total PM2.5 related all-cause mortality of Chinese elderly was 1,765,820 in 2010. Long-term exposure to PM2.5 was associated with an increased risk of all-cause mortality among elderly adults in China, but the magnitude of the risk declined as concentrations increased.

Couple therapy for depression.

Couple therapy for depression.

Family and carer smoking control programmes for reducing children's exposure to environmental tobacco smoke.

Children's exposure to other people's tobacco smoke (environmental tobacco smoke, or ETS) is associated with a range of adverse health outcomes for children. Parental smoking is a common source of children's exposure to ETS. Older children in child care or educational settings are also at risk of exposure to ETS. Preventing exposure to ETS during infancy and childhood has significant potential to improve children's health worldwide. To determine the effectiveness of interventions designed to reduce exposure of children to environmental tobacco smoke, or ETS. We searched the Cochrane Tobacco Addiction Group Specialised Register and conducted additional searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PsycINFO, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Education Resource Information Center (ERIC), and the Social Science Citation Index & Science Citation Index (Web of Knowledge). We conducted the most recent search in February 2017. We included controlled trials, with or without random allocation, that enrolled participants (parents and other family members, child care workers, and teachers) involved in the care and education of infants and young children (from birth to 12 years of age). All mechanisms for reducing children's ETS exposure were eligible, including smoking prevention, cessation, and control programmes. These include health promotion, social-behavioural therapies, technology, education, and clinical interventions. Two review authors independently assessed studies and extracted data. Due to heterogeneity of methods and outcome measures, we did not pool results but instead synthesised study findings narratively. Seventy-eight studies met the inclusion criteria, and we assessed all evidence to be of low or very low quality based on GRADE assessment. We judged nine studies to be at low risk of bias, 35 to have unclear overall risk of bias, and 34 to have high risk of bias. Twenty-one interventions targeted populations or community settings, 27 studies were conducted in the well-child healthcare setting and 26 in the ill-child healthcare setting. Two further studies conducted in paediatric clinics did not make clear whether visits were made to well- or ill-children, and another included visits to both well- and ill-children. Forty-five studies were reported from North America, 22 from other high-income countries, and 11 from low- or middle-income countries. Only 26 of the 78 studies reported a beneficial intervention effect for reduction of child ETS exposure, 24 of which were statistically significant. Of these 24 studies, 13 used objective measures of children's ETS exposure. We were unable to pinpoint what made these programmes effective. Studies showing a significant effect used a range of interventions: nine used in-person counselling or motivational interviewing; another study used telephone counselling, and one used a combination of in-person and telephone counselling; three used multi-component counselling-based interventions; two used multi-component education-based interventions; one used a school-based strategy; four used educational interventions, including one that used picture books; one used a smoking cessation intervention; one used a brief intervention; and another did not describe the intervention. Of the 52 studies that did not show a significant reduction in child ETS exposure, 19 used more intensive counselling approaches, including motivational interviewing, education, coaching, and smoking cessation brief advice. Other interventions consisted of brief advice or counselling (10 studies), feedback of a biological measure of children's ETS exposure (six studies), nicotine replacement therapy (two studies), feedback of maternal cotinine (one study), computerised risk assessment (one study), telephone smoking cessation support (two studies), educational home visits (eight studies), group sessions (one study), educational materials (three studies), and school-based policy and health promotion (one study). Some studies employed more than one intervention. 35 of the 78 studies reported a reduction in ETS exposure for children, irrespective of assignment to intervention and comparison groups. One study did not aim to reduce children's tobacco smoke exposure but rather sought to reduce symptoms of asthma, and found a significant reduction in symptoms among the group exposed to motivational interviewing. We found little evidence of difference in effectiveness of interventions between the well infant, child respiratory illness, and other child illness settings as contexts for parental smoking cessation interventions. A minority of interventions have been shown to reduce children's exposure to environmental tobacco smoke and improve children's health, but the features that differentiate the effective interventions from those without clear evidence of effectiveness remain unclear. The evidence was judged to be of low or very low quality, as many of the trials are at a high risk of bias, are small and inadequately powered, with heterogeneous interventions and populations.

Association Between Lead Time and Prostate Cancer Grade: Evidence of Grade Progression from Long-term Follow-up of Large Population-based Cohorts Not Subject to Prostate-specific Antigen Screening

BackgroundLead time (LT) is of key importance in early detection of cancer, but cannot be directly measured. We have previously provided LT estimates for prostate cancer (PCa) using archived blood samples from cohorts followed for many years without screening. ObjectiveTo determine the association between LT and PCa grade at diagnosis to provide an insight into whether grade progresses or is stable over time. Design, setting, and participantsThe setting was three long-term epidemiologic studies in Sweden including men not subject to prostate-specific antigen (PSA) screening. The cohort included 1041 men with PSA of 3–10 ng/ml at blood draw and subsequently diagnosed with PCa with grade data available. Outcome measurements and statistical analysisMultivariable logistic regression was used to predict high-grade (Gleason grade group ≥2 or World Health Organization grade 3) versus low-grade PCa at diagnosis in terms of LT, defined as the time between the date of elevated PSA and the date of PCa diagnosis with adjustment for cohort and age. Results and limitationsThe probability that PCa would be high grade at diagnosis increased with LT. Among all men combined, the risk of high-grade disease increased with LT (odds ratio 1.13, 95% confidence interval [CI] 1.10–1.16; p<0.0001), with no evidence of differences in effect by age group or cohort. Higher PSA predicted shorter LT by 0.46 yr (95% CI 0.28–0.64; p<0.0001) per 1 ng/ml increase in PSA. However, there was no interaction between PSA and grade, suggesting that the longer LT for high-grade tumors is not simply related to age. Limitations include the assumption that men with elevated PSA and subsequently diagnosed with PCa would have had biopsy-detectable PCa at the time of PSA elevation. ConclusionsOur data support grade progression, whereby following a prostate over time would reveal transitions from benign to low-grade and then high-grade PCa. Patient summaryMen with a longer lead time between elevated prostate-specific antigen and subsequent prostate cancer diagnosis were more likely to have high-grade cancers at diagnosis.

Inhaled versus systemic corticosteroids for the treatment of bronchopulmonary dysplasia in ventilated very low birth weight preterm infants.

This is an update of a review published in 2012. A related review "Inhaled versus systemic corticosteroids for preventing bronchopulmonary dysplasia in ventilated very low birth weight preterm neonates" has been updated as well. Bronchopulmonary dysplasia (BPD) is a serious and common problem among very low birth weight infants, despite the use of antenatal steroids and postnatal surfactant therapy to decrease the incidence and severity of respiratory distress syndrome. Due to their anti-inflammatory properties, corticosteroids have been widely used to treat or prevent BPD. However, the use of systemic steroids has been associated with serious short- and long-term adverse effects. Administration of corticosteroids topically through the respiratory tract may result in beneficial effects on the pulmonary system with fewer undesirable systemic side effects. To compare the effectiveness of inhaled versus systemic corticosteroids administered to ventilator-dependent preterm neonates with birth weight ≤ 1500 g or gestational age ≤ 32 weeks after 7 days of life on the incidence of death or BPD at 36 weeks' postmenstrual age. We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2017, Issue 1), MEDLINE via PubMed (1966 to 23 February 2017), Embase (1980 to 23 February 2017), and CINAHL (1982 to 23 February 2017). We also searched clinical trials registers, conference proceedings and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. Randomised or quasi-randomised controlled trials comparing inhaled versus systemic corticosteroid therapy (irrespective of dose and duration) starting after the first week of life in ventilator-dependent very low birth weight infants. We used standard methodological procedures expected by the Cochrane Collaboration. We included three trials that involved a total of 431 participants which compared inhaled versus systemic corticosteroids to treat BPD. No new trials were included for the 2017 update.Although one study randomised infants at < 72 hours (N = 292), treatment started when infants were aged > 15 days. In this larger study, deaths were included from the point of randomisation and before treatment started. Two studies (N = 139) randomised and started treatment at 12 to 21 days.Two trials reported non-significant differences between groups for the primary outcome: incidence of death or BPD at 36 weeks' postmenstrual age among all randomised infants. Estimates for the largest trial were Relative risk (RR) 1.04 (95% Confidence interval (CI) 0.86 to 1.26), Risk difference (RD) 0.03 (95% CI -0.09 to 0.15); (moderate-quality evidence). Estimates for the other trial reporting the primary outcome were RR 0.94 (95% CI 0.83 to 1.05), RD -0.06 (95% CI -0.17 to 0.05); (low-quality evidence).Secondary outcomes that included data from all three trials showed no significant differences in the duration of mechanical ventilation or supplemental oxygen, length of hospital stay, or the incidence of hyperglycaemia, hypertension, necrotising enterocolitis, gastrointestinal bleed, retinopathy of prematurity or culture-proven sepsis moderate- to low-quality evidence).In a subset of 75 surviving infants who were enrolled from the United Kingdom and Ireland, there were no significant differences in developmental outcomes at seven years of age between groups (moderate-quality evidence). One study received grant support and the industry provided aerochambers and metered dose inhalers of budesonide and placebo for the same study. No conflict of interest was identified. We found no evidence that inhaled corticosteroids confer net advantages over systemic corticosteroids in the management of ventilator-dependent preterm infants. There was no evidence of difference in effectiveness or adverse event profiles for inhaled versus systemic steroids.A better delivery system guaranteeing selective delivery of inhaled steroids to the alveoli might result in beneficial clinical effects without increasing adverse events.To resolve this issue, studies are needed to identify the risk/benefit ratio of different delivery techniques and dosing schedules for administration of these medications. The long-term effects of inhaled steroids, with particular attention to neurodevelopmental outcomes, should be addressed in future studies.

Long-acting FSH versus daily FSH for women undergoing assisted reproduction.

Assisted reproduction techniques (ART), such as in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI), can help subfertile couples to create a family. It is necessary to induce multiple follicles, which is achieved by follicle stimulating hormone (FSH) injections. Current treatment regimens prescribe daily injections of FSH (urinary FSH either with or without luteinizing hormone (LH) injections or recombinant FSH (rFSH)).Recombinant DNA technologies have produced a new recombinant molecule which is a long-acting FSH, named corifollitropin alfa (Elonva) or FSH-CTP. A single dose of long-acting FSH is able to keep the circulating FSH level above the threshold necessary to support multi-follicular growth for an entire week. The optimal dose of long-acting FSH is still being determined. A single injection of long-acting FSH can replace seven daily FSH injections during the first week of controlled ovarian stimulation (COS) and can make assisted reproduction more patient friendly. To compare the effectiveness of long-acting FSH versus daily FSH in terms of pregnancy and safety outcomes in women undergoing IVF or ICSI treatment cycles. We searched the following electronic databases, trial registers and websites from inception to June 2015: the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Menstrual Disorders and Subfertility Group (MDSG) Specialized Register, MEDLINE, EMBASE, PsycINFO, CINAHL, electronic trial registers for ongoing and registered trials, citation indexes, conference abstracts in the ISI Web of Knowledge, LILACS, Clinical Study Results (for clinical trial results of marketed pharmaceuticals), PubMed and OpenSIGLE. We also carried out handsearches. We included all randomised controlled trials (RCTs) comparing long-acting FSH versus daily FSH in women who were part of a couple with subfertility and undertaking IVF or ICSI treatment cycles with a GnRH antagonist or agonist protocol. Two review authors independently performed study selection, data extraction and assessment of risk of bias. We contacted trial authors in cases of missing data. We calculated risk ratios for each outcome, and our primary outcomes were live birth rate and ovarian hyperstimulation syndrome (OHSS) rate. Our secondary outcomes were ongoing pregnancy rate, clinical pregnancy rate, multiple pregnancy rate, miscarriage rate, any other adverse event (including ectopic pregnancy, congenital malformations, drug side effects and infection) and patient satisfaction with the treatment. Trials reported all outcomes, except patient satisfaction with the treatment. We included six RCTs with a total of 3753 participants and we graded the quality of the included studies as moderate. All studies included women with an indication for COS as part of an IVF/ICSI cycle with age ranging from 18 to 41 years. A comparison of long-acting FSH versus daily FSH did not show evidence of difference in effect on overall live birth rate (Risk ratio (RR) 0.95, 95% confidence interval (CI) 0.84 to 1.07; 2363 participants, eight studies; I² statistic = 44%) or OHSS (RR 1.00, 95% CI 0.74 to 1.37; 3753 participants, nine studies; I² statistic = 0%). We compared subgroups by dose of long-acting FSH. There was evidence of reduced live birth rate in women who received lower doses (60 to 120 μg) of long-acting FSH compared to daily FSH (RR 0.70, 95% CI 0.52 to 0.93; 645 participants, three studies; I² statistic = 0%). There was no evidence a difference between the groups in live births in the medium dose (150 to 180 μg) subgroup (RR 1.03, 95% CI 0.90 to 1.18; 1685 participants, four studies; I² statistic = 6%). There was no evidence of a difference between the groups in the clinical pregnancy rate (any dose), ongoing pregnancy rate (any dose), multiple pregnancy rate (any dose), miscarriage rate (low or medium dose), ectopic pregnancy rate (any dose), congenital malformation rate, congenital malformation rate; major or minor (low or medium dose). The use of a medium dose (150 to 180 μg) of long-acting FSH is a safe treatment option and equally effective compared to daily FSH in women with unexplained subfertility. There was evidence of reduced live birth rate in women receiving a low dose (60 to 120 μg) of long-acting FSH compared to daily FSH. Further research is needed to determine whether long-acting FSH is safe and effective for use in hyper- or poor responders and in women with all causes of subfertility.

The Effect of Regular Hazelnut Consumption on Cardiovascular Risk Factors and Acceptance in Māori and European

Aims Studies reporting reductions in heart disease risk with regular nut consumption comprise populations largely of European descent. Whether the healthful effects of nuts extend to other ethnic groups is largely unknown. This study compared the effects of consuming 30 g/d of hazelnuts on risk factors for cardiovascular disease (CVD) and acceptance amongst Māori and Europeans. Methods Twenty Māori and 19 European participants consumed 30 g/d of hazelnuts for 28 days. Plasma lipids and lipoproteins, apolipoproteins (apo), high sensitivity C-reactive protein (hs-CRP), blood pressure, dietary intake, and body weight were measured at baseline and at the end of the intervention. ‘Desire to consume’ and ‘overall liking’ for hazelnuts were assessed daily. Results There were no significant differences in the changes of any of the outcome measurements between Māori and Europeans (P≥0.145). Further, there were no significant changes among participants overall in biochemical indices, blood pressure, body weight, BMI, or body composition (P≥0.114) aside from systolic blood pressure which decreased by 3% (P=0.031) and hs-CRP which increased by 0.21 mg/dl (P=0.047) during the study. However, the hazelnut-enriched diet significantly increased energy, total fat, monounsaturated and polyunsaturated fat intake in study participants (all P≤0.006), with no changes for other nutrients (all P≥0.116) or difference between groups (all P≥0.513). ‘Desire to consume’ and ‘overall liking’ remained relatively stable over the 28-day intervention period. Conclusions There was no evidence of difference in effects on CVD risk factors between Māori and European following regular consumption of nuts. It appears both ethnic groups continued to like nuts and wished to consume them daily after consuming nuts for 28-days, suggesting adherence to guidelines to consume nuts regularly is achievable in both populations.

Exercise for reducing fear of falling in older people living in the community.

Exercise for reducing fear of falling in older people living in the community.

PARTNERSHIP TRANSITIONS AND ANTISOCIAL BEHAVIOR IN YOUNG ADULTHOOD: A WITHIN-PERSON, MULTI-COHORT ANALYSIS.

This study examines the effects of young adult transitions into marriage and cohabitation on criminal offending and substance use, and whether those effects changed since the 1970s as marriage rates declined and cohabitation rates rose dramatically. It also examines whether any beneficial effects of cohabitation depend on marriage intentions. Using multi-cohort national panel data from Monitoring the Future (N = 15,875), the authors estimated fixed effects models relating within-person changes in marriage and cohabitation to changes in criminal offending and substance use. Marriage predicts lower levels of criminal offending and substance use, but the effects of cohabitation are limited to substance use outcomes and to engaged cohabiters. There are no cohort differences in the associations of marriage and cohabitation with criminal offending, and no consistent cohort differences in their associations with substance use. There is little evidence of differences in effects by gender or parenthood. Young adults are increasingly likely to enter romantic partnership statuses that do not appear as effective in reducing antisocial behavior. Although cohabitation itself does not reduce antisocial behavior, engagement might. Future research should examine the mechanisms behind these effects, and why non-marital partnerships reduce substance use and not crime.

Family and carer smoking control programmes for reducing children's exposure to environmental tobacco smoke

Children's exposure to other people's cigarette smoke (environmental tobacco smoke, or ETS) is associated with a range of adverse health outcomes for children. Parental smoking is a common source of children's exposure to ETS. Older children are also at risk of exposure to ETS in child care or educational settings. Preventing exposure to cigarette smoke in infancy and childhood has significant potential to improve children's health worldwide. To determine the effectiveness of interventions aiming to reduce exposure of children to ETS. We searched the Cochrane Tobacco Addiction Group Specialized Register and conducted additional searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PsycINFO, EMBASE, CINAHL, ERIC, and The Social Science Citation Index & Science Citation Index (Web of Knowledge). Date of the most recent search: September 2013. Controlled trials with or without random allocation. Interventions must have addressed participants (parents and other family members, child care workers and teachers) involved with the care and education of infants and young children (aged 0 to 12 years). All mechanisms for reduction of children's ETS exposure, and smoking prevention, cessation, and control programmes were included. These include health promotion, social-behavioural therapies, technology, education, and clinical interventions. Two authors independently assessed studies and extracted data. Due to heterogeneity of methodologies and outcome measures, no summary measures were possible and results were synthesised narratively. Fifty-seven studies met the inclusion criteria. Seven studies were judged to be at low risk of bias, 27 studies were judged to have unclear overall risk of bias and 23 studies were judged to have high risk of bias. Seven interventions were targeted at populations or community settings, 23 studies were conducted in the 'well child' healthcare setting and 24 in the 'ill child' healthcare setting. Two further studies conducted in paediatric clinics did not make clear whether the visits were to well or ill children, and another included both well and ill child visits. Thirty-six studies were from North America, 14 were in other high income countries and seven studies were from low- or middle-income countries. In only 14 of the 57 studies was there a statistically significant intervention effect for child ETS exposure reduction. Of these 14 studies, six used objective measures of children's ETS exposure. Eight of the studies had a high risk of bias, four had unclear risk of bias and two had a low risk of bias. The studies showing a significant effect used a range of interventions: seven used intensive counselling or motivational interviewing; a further study used telephone counselling; one used a school-based strategy; one used picture books; two used educational home visits; one used brief intervention and one study did not describe the intervention. Of the 42 studies that did not show a significant reduction in child ETS exposure, 14 used more intensive counselling or motivational interviewing, nine used brief advice or counselling, six used feedback of a biological measure of children's ETS exposure, one used feedback of maternal cotinine, two used telephone smoking cessation advice or support, eight used educational home visits, one used group sessions, one used an information kit and letter, one used a booklet and no smoking sign, and one used a school-based policy and health promotion. In 32 of the 57 studies, there was reduction of ETS exposure for children in the study irrespective of assignment to intervention and comparison groups. One study did not aim to reduce children's tobacco smoke exposure, but rather aimed to reduce symptoms of asthma, and found a significant reduction in symptoms in the group exposed to motivational interviewing. We found little evidence of difference in effectiveness of interventions between the well infant, child respiratory illness, and other child illness settings as contexts for parental smoking cessation interventions. While brief counselling interventions have been identified as successful for adults when delivered by physicians, this cannot be extrapolated to adults as parents in child health settings. Although several interventions, including parental education and counselling programmes, have been used to try to reduce children's tobacco smoke exposure, their effectiveness has not been clearly demonstrated. The review was unable to determine if any one intervention reduced parental smoking and child exposure more effectively than others, although seven studies were identified that reported motivational interviewing or intensive counselling provided in clinical settings was effective.

Benefits and risks of benzodiazepines and Z-drugs: comparison of perceptions of GPs and community pharmacists in Germany.

Objective: Newer non-benzodiazepines zolpidem and zopiclone (“Z-drugs”) are often prescribed instead of benzodiazepine hypnotics, although there is no evidence of differences in effectiveness and safety. Aim was to compare perceptions on benefits and harms of benzodiazepines and Z-drugs between general practitioners (GPs) and community pharmacists (CPs).Methods: A questionnaire was mailed to a random sample of 1,350 GPs and 600 CPs in 2012. They were asked to rate perceptions on a five-point Likert scale used for both benzodiazepines and Z-drugs. Wilcoxon signed rank test was performed for the comparison of perceptions between GPs and CPs. Due to multiple testing, only p-values ≤0.01 were considered statistically significant.Results: 458 GPs and 202 CPs returned questionnaires (response 33.9% and 33.7%). Mean age of GPs was 53.3 years (40.6% female) and 48.8 years for CPs (59.2% females). Perceptions on benefits of benzodiazepines (and Z-drugs) between GPs and CPs were not different for 3 (and 2) of 5 items. Concerning side effects of benzodiazepines, there were no statistically significant differences for 3 of 5 comparisons. CPs perceived that 4 of 5 studied side effects of Z-drugs occur significantly more often than GPs (p=0.003 or less). For instance, whereas 45.2% of CPs answered that withdrawal effects on stopping happen often or very often/always on Z-drugs, these were only 28.3% of the GPs. Conclusions: Although it is difficult to draw unambiguous conclusions from these findings, pharmacists might have a somewhat more critical view on Z-drugs, especially concerning side effects.

A genome-wide association meta-analysis of self-reported allergy identifies shared and allergy-specific susceptibility loci

Allergic disease is very common and carries substantial public-health burdens. We conducted a meta-analysis of genome-wide associations with self-reported cat, dust-mite and pollen allergies in 53,862 individuals. We used generalized estimating equations to model shared and allergy-specific genetic effects. We identified 16 shared susceptibility loci with association P<5×10(-8), including 8 loci previously associated with asthma, as well as 4p14 near TLR1, TLR6 and TLR10 (rs2101521, P=5.3×10(-21)); 6p21.33 near HLA-C and MICA (rs9266772, P=3.2×10(-12)); 5p13.1 near PTGER4 (rs7720838, P=8.2×10(-11)); 2q33.1 in PLCL1 (rs10497813, P=6.1×10(-10)), 3q28 in LPP (rs9860547, P=1.2×10(-9)); 20q13.2 in NFATC2 (rs6021270, P=6.9×10(-9)), 4q27 in ADAD1 (rs17388568, P=3.9×10(-8)); and 14q21.1 near FOXA1 and TTC6 (rs1998359, P=4.8×10(-8)). We identified one locus with substantial evidence of differences in effects across allergies at 6p21.32 in the class II human leukocyte antigen (HLA) region (rs17533090, P=1.7×10(-12)), which was strongly associated with cat allergy. Our study sheds new light on the shared etiology of immune and autoimmune disease.

Antibiotics for childhood urinary tract infection: can we be smarter?

Urinary tract infection (UTI) is a common bacterial infection of children, with a study published only 2 months ago showing the prevalence of UTI to be around 6% in preschool children presenting unwell to primary care.1 Accurate and timely diagnosis is important in children because appropriate treatment may alleviate suffering and help prevent long-term sequelae such as renal scarring, poor renal growth, recurrent pyelonephritis, impaired glomerular function, hypertension, end stage renal disease, and pre-eclampsia. There is evidence from NICE2 and our group3 regarding the children in whom UTI should be suspected, but much of the evidence was generated in secondary care. However, primary care generated evidence for the symptoms and signs of UTI in preschool children should be available by the end of 2013 from the Diagnosis of Urinary Tract infection in Young children (DUTY) study (see www.dutystudy.org.uk/). In terms of management, NICE recommends all children aged over 3 months with suspected cystitis/lower UTI receive 3 days of trimethoprim, nitrofurantoin, a cephalosporin, or amoxicillin (younger children, and any child with suspected pyelonephritis, should be immediately referred to secondary care).2 But which antibiotic should primary care clinicians use first? NICE says there is no evidence for differences in effectiveness and that the …

Efficacy and safety of intraarticular hylan or hyaluronic acids for osteoarthritis of the knee: A randomized controlled trial

To compare the efficacy and safety of intraarticular hylan and 2 hyaluronic acids (HAs) in osteoarthritis (OA) of the knee. This was a multicenter, patient-blind, randomized controlled trial in 660 patients with symptomatic knee OA. Patients were randomly assigned to receive 1 cycle of 3 intraarticular injections per knee of 1 of 3 preparations: a high molecular weight cross-linked hylan, a non-cross-linked medium molecular weight HA of avian origin, or a non-cross-linked low molecular weight HA of bacterial origin. The primary outcome measure was the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score at 6 months. Secondary outcome measures included local adverse events (effusions or flares) in injected knees. During months 7-12, patients were offered a second cycle of viscosupplementation. Pain relief was similar in all 3 groups. The difference in changes between baseline and 6 months between hylan and the combined HAs was 0.1 on the WOMAC pain score (95% confidence interval [95% CI] -0.2, 0.3). No relevant differences were observed in any of the secondary efficacy outcomes, and stratified analyses provided no evidence for differences in effects across different patient groups. There was a trend toward more local adverse events in the hylan group than in the HA groups during the first cycle (difference 2.2% [95% CI -2.4, 6.7]), and this trend became more pronounced during the second cycle (difference 6.4% [95% CI 0.6, 12.2]). We found no evidence for a difference in efficacy between hylan and HAs. In view of its higher costs and potential for more local adverse events, we see no rationale for the continued use of hylan in patients with knee OA.