Immunogenicity and seroefficacy of 10-valent and 13-valent pneumococcal conjugate vaccines: a systematic review and network meta-analysis of individual participant data.

Background: Vaccination of infants with pneumococcal conjugate vaccines (PCV) is recommended by the World Health Organization. Evidence is mixed regarding the differences in immunogenicity and efficacy of the different pneumococcal vaccines. Methods: In this systematic-review and network meta-analysis, we searched the Cochrane Library, Embase, Global Health, Medline, clinicaltrials.gov and trialsearch.who.int up to February 17, 2023 with no language restrictions. Studies were eligible if they presented data comparing the immunogenicity of either PCV7, PCV10 or PCV13 in head-to-head randomised trials of young children under 2 years of age, and provided immunogenicity data for at least one time point after the primary vaccination series or the booster dose. Publication bias was assessed via Cochrane's Risk Of Bias due to Missing Evidence tool and comparison-adjusted funnel plots with Egger's test. Individual participant level data were requested from publication authors and/or relevant vaccine manufacturers. Outcomes included the geometric mean ratio (GMR) of serotype-specific IgG and the relative risk (RR) of seroinfection. Seroinfection was defined for each individual as a rise in antibody between the post-primary vaccination series time point and the booster dose, evidence of presumed subclinical infection. Seroefficacy was defined as the RR of seroinfection. We also estimated the relationship between the GMR of IgG one month after priming and the RR of seroinfection by the time of the booster dose. The protocol is registered with PROSPERO, ID CRD42019124580. Findings: 47 studies were eligible from 38 countries across six continents. 28 and 12 studies with data available were included in immunogenicity and seroefficacy analyses, respectively. GMRs comparing PCV13 vs PCV10 favoured PCV13 for serotypes 4, 9V, and 23F at 1 month after primary vaccination series, with 1.14- to 1.54- fold significantly higher IgG responses with PCV13. Risk of seroinfection prior to the time of booster dose was lower for PCV13 for serotype 4, 6B, 9V, 18C and 23F than for PCV10. Significant heterogeneity and inconsistency were present for most serotypes and for both outcomes. Two-fold higher antibody after primary vaccination was associated with a 54% decrease in risk of seroinfection (RR 0.46, 95% CI 0.23-0.96). Interpretation: Serotype-specific differences were found in immunogenicity and seroefficacy between PCV13 and PCV10. Higher antibody response after vaccination was associated with a lower risk of subsequent infection. These findings could be used to compare PCVs and optimise vaccination strategies. Funding: The NIHR Health Technology Assessment Programme.

Accuracy of self-diagnosis in conditions commonly managed in primary care: diagnostic accuracy systematic review and meta-analysis.

OBJECTIVES: To assess the diagnostic accuracy of self-diagnosis compared with a clinical diagnosis for common conditions in primary care. DESIGN: Systematic review. DATA SOURCES: Medline, Embase, Cochrane CENTRAL, Cochrane Database of Systematic Reviews and CINAHL from inception to 25 January 2021. STUDY SELECTION: Eligible studies were prospective or retrospective studies comparing the results of self-diagnosis of common conditions in primary care to a relevant clinical diagnosis or laboratory reference standard test performed by a healthcare service provider. Studies that considered self-testing only were excluded. DATA EXTRACTION: Two authors independently extracted data using a predefined data extraction form and assessed risk of bias using Quality Assessment of Diagnostic Accuracy Studies-2. METHODS AND RESULTS: 5047 records identified 18 studies for inclusion covering the self-diagnosis of three common conditions: vaginal infection (five studies), common skin conditions (four studies) and HIV (nine studies). No studies were found for any other condition. For self-diagnosis of vaginal infection and common skin conditions, meta-analysis was not appropriate and data were reported narratively. Nine studies, using point-of-care oral fluid tests, reported on the accuracy of self-diagnosis of HIV and data were pooled using bivariate meta-analysis methods. For these nine studies, the pooled sensitivity was 92.8% (95% CI, 86% to 96.5%) and specificity was 99.8% (95% CI, 99.1% to 99.9%). Post hoc, the robustness of the pooled findings was tested in a sensitivity analysis only including four studies using laboratory testing as the reference standard. The pooled sensitivity reduced to 87.7% (95% CI, 81.4% to 92.2%) and the specificity remained the same. The quality of all 18 included studies was assessed as mixed and overall study methodology was not always well described. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Overall, there was a paucity of evidence. The current evidence does not support routine self-diagnosis for vaginal infections, common skin conditions and HIV in primary care. PROSPERO REGISTRATION NUMBER: CRD42018110288.

Measured weight loss as a precursor to cancer diagnosis: retrospective cohort analysis of 43 302 primary care patients.

BACKGROUND: Unexpected weight loss is a presenting feature of cancer in primary care. Data from primary care are lacking to quantify how much weight loss over what period should trigger further investigation for cancer. This research aimed to quantify cancer diagnosis rates associated with measured weight change in people attending primary care. METHODS: Retrospective cohort study of primary care electronic health records data linked to the Surveillance, Epidemiology, and End Results cancer registry (Integrated healthcare delivery system in Washington State, United States). Multivariable Cox regression incorporating time varying covariates using splines to model non-linear associations (age, percentage weight change, and weight change interval). Fifty thousand randomly selected patients aged 40 years and over followed for up to 9 years (1 January 2006 to 31 December 2014). Outcome measures are hazard ratios (95% confidence intervals) to quantify the association between percentage weight change and cancer diagnosis for all cancers combined, individual cancer sites and stages; percentage risk of cancer diagnosis within 6 months of the end of each weight change episode; and the positive predictive value for cancer diagnosis. RESULTS: There were 43 302 included in the analysis after exclusions. Over 287 858 patient-years of follow-up, including 24 272 (56.1%) females, 23 980 (55.4%) aged 40 to 59 years, 15 113 (34.9%) 60 to 79 years, and 4209 (9.7%) aged 80 years and over. Adjusted hazard ratios (95% confidence interval) for cancer diagnosis in a 60 years old ranged from 1.04 (1.02 to 1.05, P < 0.001) for 1% weight loss to 1.44 (1.23 to 1.68, P < 0.001) for 10%. An independent linear association was observed between percentage weight loss and increasing cancer risk. The absolute risk of cancer diagnosis increased with increasing age (up to 85 years) and as the weight change measurement interval decreased (<1 year). The positive predictive value for a cancer diagnosis within 1 year of ≥5% measured weight loss in a 60 to 69 years old was 3.41% (1.57% to 6.37%) in men and 3.47% (1.68% to 6.29%) in women. The risk of cancer diagnosis was significantly increased for pancreatic, myeloma, gastro-oesophageal, colorectal, breast, stage II and IV cancers. CONCLUSIONS: Weight loss is a sign of undiagnosed cancer regardless of the interval over which it occurs. Guidelines should resist giving an arbitrary cut-off for the interval of weight loss and focus on the percentage of weight loss and the patient's age. Future studies should focus on the association between diagnostic evaluation of weight change and risk of cancer mortality.

Point-of-care NT-proBNP monitoring for heart failure: observational feasibility study in primary care.

BACKGROUND: Around one million individuals in the UK have heart failure (HF), a chronic disease that causes significant morbidity and mortality. N-terminal pro-B-type natriuretic peptide (NT-proBNP) monitoring could help improve the care of patients with HF in the community. AIM: The aim of this study is to provide evidence to support the routine use of point-of-care (POC) NT-proBNP monitoring in primary care. DESIGN & SETTING: In this observational cohort study, the Roche Cobas h 232 POC device was used to measure NT-proBNP in 27 patients with HF at 0, 6, and 12 months, with a subset reanalysed in the laboratory for comparison. METHOD: Data were analysed for within-person and between-person variability and concordance with laboratory readings using Passing-Bablok regression. GPs reported whether POC results impacted clinical decisionmaking, and patients indicated their willingness to participate in long-term cohort studies using the Likert acceptability scale. RESULTS: Within-person variability in POC NT-proBNP over 12 months was 881 pg/mL (95% confidence interval [CI] = 380 to 1382 pg/mL). Between-person variability was 1972 pg/mL (95% CI = 1,525 to 2791 pg/mL). Passing-Bablok regression showed no significant systematic difference between POC and laboratory measurements. Patients indicated a high level of acceptability, and GP decisionmaking was affected for at least one visit in a third of patients. CONCLUSION: Within-person variability in POC NT-proBNP is around half of between-person variability, so detecting changes could be of use in HF management. High patient acceptability and impact on clinical decisionmaking warrant further investigation in a larger long-term cohort study.

Natriuretic peptide-guided treatment for heart failure: a systematic review and meta-analysis.

BACKGROUND: GUIDE-IT, the largest trial to date, published in August 2017, evaluating the effectiveness of natriuretic peptide (NP)-guided treatment of heart failure (HF), was stopped early for futility on a composite outcome. However, the reported effect sizes on individual outcomes of all-cause mortality and HF admissions are potentially clinically relevant. OBJECTIVE: This systematic review and meta-analysis aims to combine all available trial level evidence to determine if NP-guided treatment of HF reduces all-cause mortality and HF admissions in patients with HF. STUDY SELECTION: Eight databases, no language restrictions, up to November 2017 were searched for all randomised controlled trials comparing NP-guided treatment versus clinical assessment alone in adult patients with HF. No language restrictions were applied. Publications were independently double screened and extracted. Fixed-effect meta-analyses were conducted. FINDINGS: 89 papers were included, reporting 19 trials (4554 participants), average ages 62-80 years. Pooled risk ratio estimates for all-cause mortality (16 trials, 4063 participants) were 0.87, 95% CI 0.77 to 0.99 and 0.80, 95% CI 0.72 to 0.89 for HF admissions (11 trials, 2822 participants). Sensitivity analyses, restricted to low risk of bias, produced similar estimates, but were no longer statistically significant. CONCLUSIONS: Considering all the evidence to date, the pooled effects suggest that NP-guided treatment is beneficial in reducing HF admissions and all-cause mortality. However, there is still insufficient high-quality evidence to make definitive recommendations on the use of NP-guided treatment in clinical practice. TRIAL REGISTRATION NUMBER: Systematic Review Cochrane Database Number: CD008966.

Effects of antihypertensives, lipid-modifying drugs, glycaemic control drugs and sodium bicarbonate on the progression of stages 3 and 4 chronic kidney disease in adults: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the effects of drug interventions that may modify the progression of chronic kidney disease (CKD) in adults with CKD stages 3 and 4. DESIGN: Systematic review and meta-analysis. METHODS: Searching MEDLINE, EMBASE, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, International Clinical Trials Registry Platform, Health Technology Assessment, Science Citation Index, Social Sciences Citation Index, Conference Proceedings Citation Index and Clinical Trials Register, from March 1999 to July 2018, we identified randomised controlled trials (RCTs) of drugs for hypertension, lipid modification, glycaemic control and sodium bicarbonate, compared with placebo, no drug or a drug from another class, in ≥40 adults with CKD stages 3 and/or 4, with at least 2 years of follow-up and reporting renal function (primary outcome), proteinuria, adverse events, maintenance dialysis, transplantation, cardiovascular events, cardiovascular mortality or all-cause mortality. Two reviewers independently screened citations and extracted data. For continuous outcomes, we used the ratio of means (ROM) at the end of the trial in random-effects meta-analyses. We assessed methodological quality with the Cochrane Risk of Bias Tool and confidence in the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. RESULTS: We included 35 RCTs and over 51 000 patients. Data were limited, and heterogeneity varied. Final renal function (estimated glomerular filtration rate) was 6% higher in those taking glycaemic control drugs (ROM 1.06, 95% CI 1.02 to 1.10, I2=0%, low GRADE confidence) and 4% higher in those taking lipid-modifying drugs (ROM 1.04, 95% CI 1.00 to 1.08, I2=88%, very low GRADE confidence). For RCTs of antihypertensive drugs, there were no significant differences in renal function. Treatment with lipid-modifying drugs led to a 36% reduction in cardiovascular disease and 26% reduction in all-cause mortality. CONCLUSIONS: Glycaemic control and lipid-modifying drugs may slow the progression of CKD, but we found no pooled evidence of benefit nor harm from antihypertensive drugs. However, given the data limitations, further research is needed to confirm these findings. PROSPERO REGISTRATION NUMBER: CRD42015017501.

Investigating midwives' barriers and facilitators to multiple health promotion practice behaviours: a qualitative study using the theoretical domains framework.

BACKGROUND: In addition to their more traditional clinical role, midwives are expected to perform various health promotion practice behaviours (HePPBes) such as informing pregnant women about the benefits of physical activity during pregnancy and asking women about their alcohol consumption. There is evidence to suggest several barriers exist to performing HePPBes. The aim of the study was to investigate the barriers and facilitators midwives perceive to undertaking HePPBes. METHODS: The research compromised of two studies. Study 1: midwives based in a community setting (N = 11) took part in semi-structured interviews underpinned by the theoretical domains framework (TDF). Interviews were analysed using a direct content analysis approach to identify important barriers or facilitators to undertaking HePPBes. Study 2: midwives (N = 505) completed an online questionnaire assessing views on their HePPBes including free text responses (n = 61) which were coded into TDF domains. Study 2 confirmed and supplemented the barriers and facilitators identified in study 1. RESULTS: Midwives' perceived a multitude of barriers and facilitators to carrying out HePPBes. Key barriers were requirements to perform an increasing amount of HePPBes on top of existing clinical work load, midwives' cognitive resources, the quality of relationships with pregnant women, a lack of continuity of care and difficulty accessing appropriate training. Key facilitators included midwives' motivation to support pregnant women to address their health. Study 1 highlighted strategies that midwives use to overcome the barriers they face in carrying out their HePPBes. CONCLUSIONS: Despite high levels of motivation to carry out their health promotion practice, midwives perceive numerous barriers to carrying out these tasks in a timely and effective manner. Interventions that support midwives by addressing key barriers and facilitators to help pregnant women address their health behaviours are urgently needed.

Essential components in natriuretic peptide-guided management of heart failure: an intervention synthesis.

Aim: To identify the key components of natriuretic peptide (NP)-guided treatment interventions which reduced hospitalisation in patients with heart failure (HF). Methods and results: We extracted detailed information on the components of interventions from studies of NP-guided treatment of HF identified in a previous systematic review. We used meta-regression techniques to assess univariate associations between components and the strength of the reduction in HF hospitalisations and all-cause mortality. A Bayesian meta-analysis approach was used to re-estimate study-level effects in order to identify the study with the most effective NP-guided monitoring intervention. Finally, we examined the intervention options common to the studies in which the 95% credible interval excluded no effect. We identified eight components of NP-guided treatment from ten studies. Univariate comparisons produced mainly equivocal results, but single trial choice and common components analysis led to similar conclusions. Using a predefined treatment protocol, setting a stringent NP target (N-terminal pro-B-type natriuretic peptide of 1000 pg/mL or B-type natriuretic peptide 100 pg/mL) and including a relative targetwere potential key components to reducing HF hospitalisations using NP-guided therapy. Conclusion: This analysis provides a description of the key components of NP-guided treatment which could help policy makers develop specific recommendations for HF management. Our research suggests that NP-guided interventions could be simplified, but more research in relevant health settings, such as primary care, is required.

Systematic Review and Metaanalysis Comparing the Bias and Accuracy of the Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration Equations in Community-Based Populations.

BACKGROUND: The majority of patients with chronic kidney disease are diagnosed and monitored in primary care. Glomerular filtration rate (GFR) is a key marker of renal function, but direct measurement is invasive; in routine practice, equations are used for estimated GFR (eGFR) from serum creatinine. We systematically assessed bias and accuracy of commonly used eGFR equations in populations relevant to primary care. CONTENT: MEDLINE, EMBASE, and the Cochrane Library were searched for studies comparing measured GFR (mGFR) with eGFR in adult populations comparable to primary care and reporting both the Modification of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations based on standardized creatinine measurements. We pooled data on mean bias (difference between eGFR and mGFR) and on mean accuracy (proportion of eGFR within 30% of mGFR) using a random-effects inverse-variance weighted metaanalysis. We included 48 studies of 26875 patients that reported data on bias and/or accuracy. Metaanalysis of within-study comparisons in which both formulae were tested on the same patient cohorts using isotope dilution-mass spectrometry-traceable creatinine showed a lower mean bias in eGFR using CKD-EPI of 2.2 mL/min/1.73 m2 (95% CI, 1.1-3.2; 30 studies; I2 = 74.4%) and a higher mean accuracy of CKD-EPI of 2.7% (1.6-3.8; 47 studies; I2 = 55.5%). Metaregression showed that in both equations bias and accuracy favored the CKD-EPI equation at higher mGFR values. SUMMARY: Both equations underestimated mGFR, but CKD-EPI gave more accurate estimates of GFR.

Performance of point-of-care HbA1c test devices: implications for use in clinical practice - a systematic review and meta-analysis.

BACKGROUND: Point-of-care (POC) devices could be used to measure hemoglobin A1c (HbA1c) in the doctors' office, allowing immediate feedback of results to patients. Reports have raised concerns about the analytical performance of some of these devices. We carried out a systematic review and meta-analysis using a novel approach to compare the accuracy and precision of POC HbA1c devices. METHODS: Medline, Embase and Web of Science databases were searched in June 2015 for published reports comparing POC HbA1c devices with laboratory methods. Two reviewers screened articles and extracted data on bias, precision and diagnostic accuracy. Mean bias and variability between the POC and laboratory test were combined in a meta-analysis. Study quality was assessed using the QUADAS2 tool. RESULTS: Two researchers independently reviewed 1739 records for eligibility. Sixty-one studies were included in the meta-analysis of mean bias. Devices evaluated were A1cgear, A1cNow, Afinion, B-analyst, Clover, Cobas b101, DCA 2000/Vantage, HemoCue, Innovastar, Nycocard, Quo-Lab, Quo-Test and SDA1cCare. Nine devices had a negative mean bias which was significant for three devices. There was substantial variability in bias within devices. There was no difference in bias between clinical or laboratory operators in two devices. CONCLUSIONS: This is the first meta-analysis to directly compare performance of POC HbA1c devices. Use of a device with a mean negative bias compared to a laboratory method may lead to higher levels of glycemia and a lower risk of hypoglycaemia. The implications of this on clinical decision-making and patient outcomes now need to be tested in a randomized trial.

Interventions for sustained healthcare professional behaviour change: a protocol for an overview of reviews.

BACKGROUND: Failure to successfully implement and sustain change over the long term continues to be a major problem in health and social care. Translating evidence into routine clinical practice is notoriously complex, and it is recognised that to implement new evidence-based interventions and sustain them over time, professional behaviour needs to change accordingly. A number of theories and frameworks have been developed to support behaviour change among health and social care professionals, and models of sustainability are emerging, but few have translated into valid and reliable interventions. The long-term success of healthcare professional behavioural change interventions is variable, and the characteristics of successful interventions unclear. Previous reviews have synthesised the evidence for behaviour change, but none have focused on sustainability. In addition, multiple overlapping reviews have reported inconsistent results, which do not aid translation of evidence into practice. Overviews of reviews can provide accessible succinct summaries of evidence and address barriers to evidence-based practice. We aim to compile an overview of reviews, identifying, appraising and synthesising evidence relating to sustained social and healthcare professional behaviour change. METHODS: We will conduct a systematic review of Cochrane reviews (an Overview). We plan to systematically search the Cochrane Database of Systematic Reviews. We will include all systematic reviews of randomised controlled trials comparing a healthcare professional targeted behaviour change intervention to a standard care or no intervention control group. Two reviewers will independently assess the eligibility of the reviews and the methodological quality of included reviews using the ROBIS tool. The quality of evidence within each comparison in each review will be judged based on the GRADE criteria. Disagreements will be resolved through discussion. Effects of interventions will be systematically tabulated and the quality of evidence used to determine implications for clinical practice and make recommendations for future research. DISCUSSION: This overview will bring together the best available evidence relating to the sustainability of health professional behaviour change, thus supporting policy makers with decision-making in this field.

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.

Optimal strategies for monitoring lipid levels in patients at risk or with cardiovascular disease: a systematic review with statistical and cost-effectiveness modelling.

BACKGROUND: Various lipid measurements in monitoring/screening programmes can be used, alone or in cardiovascular risk scores, to guide treatment for prevention of cardiovascular disease (CVD). Because some changes in lipids are due to variability rather than true change, the value of lipid-monitoring strategies needs evaluation. OBJECTIVE: To determine clinical value and cost-effectiveness of different monitoring intervals and different lipid measures for primary and secondary prevention of CVD. DATA SOURCES: We searched databases and clinical trials registers from 2007 (including the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, the Clinical Trials Register, the Current Controlled Trials register, and the Cumulative Index to Nursing and Allied Health Literature) to update and extend previous systematic reviews. Patient-level data from the Clinical Practice Research Datalink and St Luke's Hospital, Japan, were used in statistical modelling. Utilities and health-care costs were drawn from the literature. METHODS: In two meta-analyses, we used prospective studies to examine associations of lipids with CVD and mortality, and randomised controlled trials to estimate lipid-lowering effects of atorvastatin doses. Patient-level data were used to estimate progression and variability of lipid measurements over time, and hence to model lipid-monitoring strategies. Results are expressed as rates of true-/false-positive and true-/false-negative tests for high lipid or high CVD risk. We estimated incremental costs per quality-adjusted life-year. RESULTS: A total of 115 publications reported strength of association between different lipid measures and CVD events in 138 data sets. The summary adjusted hazard ratio per standard deviation of total cholesterol (TC) to high-density lipoprotein (HDL) cholesterol ratio was 1.25 (95% confidence interval 1.15 to 1.35) for CVD in a primary prevention population but heterogeneity was high (I(2) = 98%); similar results were observed for non-HDL cholesterol, apolipoprotein B and other ratio measures. Associations were smaller for other single lipid measures. Across 10 trials, low-dose atorvastatin (10 and 20 mg) effects ranged from a TC reduction of 0.92 mmol/l to 2.07 mmol/l, and low-density lipoprotein reduction of between 0.88 mmol/l and 1.86 mmol/l. Effects of 40 mg and 80 mg were reported by one trial each. For primary prevention, over a 3-year period, we estimate annual monitoring would unnecessarily treat 9 per 1000 more men (28 vs. 19 per 1000) and 5 per 1000 more women (17 vs. 12 per 1000) than monitoring every 3 years. However, annual monitoring would also undertreat 9 per 1000 fewer men (7 vs. 16 per 1000) and 4 per 1000 fewer women (7 vs. 11 per 1000) than monitoring at 3-year intervals. For secondary prevention, over a 3-year period, annual monitoring would increase unnecessary treatment changes by 66 per 1000 men and 31 per 1000 women, and decrease undertreatment by 29 per 1000 men and 28 per 1000 men, compared with monitoring every 3 years. In cost-effectiveness, strategies with increased screening/monitoring dominate. Exploratory analyses found that any unknown harms of statins would need utility decrements as large as 0.08 (men) to 0.11 (women) per statin user to reverse this finding in primary prevention. LIMITATION: Heterogeneity in meta-analyses. CONCLUSIONS: While acknowledging known and potential unknown harms of statins, we find that more frequent monitoring strategies are cost-effective compared with others. Regular lipid monitoring in those with and without CVD is likely to be beneficial to patients and to the health service. Future research should include trials of the benefits and harms of atorvastatin 40 and 80 mg, large-scale surveillance of statin safety, and investigation of the effect of monitoring on medication adherence. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013003727. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Effectiveness of school-based smoking prevention curricula: systematic review and meta-analysis.

OBJECTIVE: To assess effectiveness of school-based smoking prevention curricula keeping children never-smokers. DESIGN: Systematic review, meta-analysis. DATA: MEDLINE (1966+), EMBASE (1974+), Cinahl, PsycINFO (1967+), ERIC (1982+), Cochrane CENTRAL, Health Star, Dissertation Abstracts, conference proceedings. DATA SYNTHESIS: pooled analyses, fixed-effects models, adjusted ORs. Risk of bias assessed with Cochrane Risk of Bias tool. SETTING: 50 randomised controlled trials (RCTs) of school-based smoking curricula. PARTICIPANTS: Never-smokers age 5-18 (n=143,495); follow-up ≥6 months; all countries; no date/language limitations. INTERVENTIONS: Information, social influences, social competence, combined social influences/competence and multimodal curricula. OUTCOME MEASURE: Remaining a never-smoker at follow-up. RESULTS: Pooling all curricula, trials with follow-up ≤1 year showed no statistically significant differences compared with controls (OR 0.91 (0.82 to 1.01)), though trials of combined social competence/social influences curricula had a significant effect on smoking prevention (7 trials, OR 0.59 (95% CI 0.41 to 0.85)). Pooling all trials with longest follow-up showed an overall significant effect in favour of the interventions (OR 0.88 (0.82 to 0.95)), as did the social competence (OR 0.65 (0.43 to 0.96)) and combined social competence/social influences curricula (OR 0.60 (0.43 to 0.83)). No effect for information, social influences or multimodal curricula. Principal findings were not sensitive to inclusion of booster sessions in curricula or to whether they were peer-led or adult-led. Differentiation into tobacco-only or multifocal curricula had a similar effect on the primary findings. Few trials assessed outcomes by gender: there were significant effects for females at both follow-up periods, but not for males. CONCLUSIONS: RCTs of baseline never-smokers at longest follow-up found an overall significant effect with average 12% reduction in starting smoking compared with controls, but no effect for all trials pooled at ≤1 year. However, combined social competence/social influences curricula showed a significant effect at both follow-up periods. SYSTEMATIC REVIEW REGISTRATION: Cochrane Tobacco Review Group CD001293.

Perceptions of postnatal care: factors associated with primiparous mothers perceptions of postnatal communication and care.

BACKGROUND: The aim of this study was to determine whether personality and/or psychological functioning affect mothers' perceptions of postnatal communication and their level of satisfaction with their postnatal care. Mothers' perceptions of the communication with health professionals prenatally and during birth may be affected by their personality traits and psychological functioning and are linked to the level of satisfaction they have in their healthcare. Little is known about factors that are associated with perceptions of communication within postnatal care and the impact this may have on satisfaction with care. METHODS: A cross sectional survey recruited 71 first-time mothers, who had given birth vaginally in the U.K., within the previous 12 months. The questionnaire assessed personality traits using the Big 5 Mini Marker set, levels of anxiety and depression using HADS, perceptions of communication experienced with health professionals and overall levels of satisfaction with postnatal care via the Satisfaction with Care Scale. Covariates such as demographic factors were investigated. RESULTS: Higher ratings of communication were found to be directly correlated with higher satisfaction, as were the personality traits; agreeableness, conscientiousness and emotional stability. Depression significantly lowered participants' ratings of communication experienced with health visitors and total satisfaction. Mothers who breastfed had significantly lower communication and satisfaction ratings. Multiple regression analysis revealed communication ratings explained 71.8% of the variance in the level of satisfaction and none of the remaining predictors significantly directly affected satisfaction ratings. CONCLUSION: Future research should focus on the utility of these findings for improving care for primiparous mothers.

Autoinflation for hearing loss associated with otitis media with effusion.

BACKGROUND: This is an update of a Cochrane review first published in The Cochrane Library in Issue 4, 2006.Otitis media with effusion (OME) or 'glue ear' is an accumulation of fluid in the middle ear, in the absence of acute inflammation or infection. It is the commonest cause of acquired hearing loss in childhood and the usual reason for insertion of 'grommets'. Potential treatments include decongestants, mucolytics, steroids, antihistamines and antibiotics. Autoinflation devices have been proposed as a simple mechanical means of improving 'glue ear'. OBJECTIVES: To assess the effectiveness of autoinflation compared with no treatment in children and adults with otitis media with effusion. SEARCH METHODS: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the most recent search was 12 April 2013. SELECTION CRITERIA: We selected randomised controlled trials that compared any form of autoinflation to no autoinflation in individuals with 'glue ear'. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, assessed risk of bias and extracted data from included studies. MAIN RESULTS: Eight studies, with a total of 702 participants, met the inclusion criteria. Overall, the studies were predominantly assessed as being at low or unclear risk of bias; unclear risk was mainly due lack of information. There was no evidence of selective reporting.Pooled estimates favoured the intervention, but did not show a significant effect on tympanometry (type C2 and B) at less than one month, nor at more than one month. Similarly, there were no significant changes for discrete pure-tone audiometry and non-discrete audiometry. Pooled estimates favoured, but not significantly, the intervention for the composite measure of tympanogram or audiometry at less than one month; at more than one month the result became significant (RRI 1.74, 95% CI 1.22 to 2.50). Subgroup analysis based on the type of intervention showed a significant effect using a Politzer device under one month (RRI 7.07, 95% CI 3.70 to 13.51) and over one month (RRI 2.25, 95% CI 1.67 to 3.04).None of the studies demonstrated a significant difference in the incidence of side effects between interventions. AUTHORS' CONCLUSIONS: All of the studies were small, of limited treatment duration and had short follow-up. However, because of the low cost and absence of adverse effects it is reasonable to consider autoinflation whilst awaiting natural resolution of otitis media with effusion. Primary care could prove a beneficial place to evaluate such interventions and there is ongoing research in this area. Further research should also consider the duration of treatment, the long-term impact on developmental outcomes in children and additional quality of life outcome measures for children and families.

School-based programmes for preventing smoking.

BACKGROUND: Helping young people to avoid starting smoking is a widely endorsed public health goal, and schools provide a route to communicate with nearly all young people. School-based interventions have been delivered for close to 40 years. OBJECTIVES: The primary aim of this review was to determine whether school smoking interventions prevent youth from starting smoking. Our secondary objective was to determine which interventions were most effective. This included evaluating the effects of theoretical approaches; additional booster sessions; programme deliverers; gender effects; and multifocal interventions versus those focused solely on smoking. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Tobacco Addiction Group's Specialised Register, MEDLINE, EMBASE, PsycINFO, ERIC, CINAHL, Health Star, and Dissertation Abstracts for terms relating to school-based smoking cessation programmes. In addition, we screened the bibliographies of articles and ran individual MEDLINE searches for 133 authors who had undertaken randomised controlled trials in this area. The most recent searches were conducted in October 2012. SELECTION CRITERIA: We selected randomised controlled trials (RCTs) where students, classes, schools, or school districts were randomised to intervention arm(s) versus a control group, and followed for at least six months. Participants had to be youth (aged 5 to 18). Interventions could be any curricula used in a school setting to deter tobacco use, and outcome measures could be never smoking, frequency of smoking, number of cigarettes smoked, or smoking indices. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed studies for inclusion, extracted data and assessed risk of bias. Based on the type of outcome, we placed studies into three groups for analysis: Pure Prevention cohorts (Group 1), Change in Smoking Behaviour over time (Group 2) and Point Prevalence of Smoking (Group 3). MAIN RESULTS: One hundred and thirty-four studies involving 428,293 participants met the inclusion criteria. Some studies provided data for more than one group.Pure Prevention cohorts (Group 1) included 49 studies (N = 142,447). Pooled results at follow-up at one year or less found no overall effect of intervention curricula versus control (odds ratio (OR) 0.94, 95% confidence interval (CI) 0.85 to 1.05). In a subgroup analysis, the combined social competence and social influences curricula (six RCTs) showed a statistically significant effect in preventing the onset of smoking (OR 0.49, 95% CI 0.28 to 0.87; seven arms); whereas significant effects were not detected in programmes involving information only (OR 0.12, 95% CI 0.00 to 14.87; one study), social influences only (OR 1.00, 95% CI 0.88 to 1.13; 25 studies), or multimodal interventions (OR 0.89, 95% CI 0.73 to 1.08; five studies). In contrast, pooled results at longest follow-up showed an overall significant effect favouring the intervention (OR 0.88, 95% CI 0.82 to 0.96). Subgroup analyses detected significant effects in programmes with social competence curricula (OR 0.52, 95% CI 0.30 to 0.88), and the combined social competence and social influences curricula (OR 0.50, 95% CI 0.28 to 0.87), but not in those programmes with information only, social influence only, and multimodal programmes.Change in Smoking Behaviour over time (Group 2) included 15 studies (N = 45,555). At one year or less there was a small but statistically significant effect favouring controls (standardised mean difference (SMD) 0.04, 95% CI 0.02 to 0.06). For follow-up longer than one year there was a statistically nonsignificant effect (SMD 0.02, 95% CI -0.00 to 0.02).Twenty-five studies reported data on the Point Prevalence of Smoking (Group 3), though heterogeneity in this group was too high for data to be pooled.We were unable to analyse data for 49 studies (N = 152,544).Subgroup analyses (Pure Prevention cohorts only) demonstrated that at longest follow-up for all curricula combined, there was a significant effect favouring adult presenters (OR 0.88, 95% CI 0.81 to 0.96). There were no differences between tobacco-only and multifocal interventions. For curricula with booster sessions there was a significant effect only for combined social competence and social influences interventions with follow-up of one year or less (OR 0.50, 95% CI 0.26 to 0.96) and at longest follow-up (OR 0.51, 95% CI 0.27 to 0.96). Limited data on gender differences suggested no overall effect, although one study found an effect of multimodal intervention at one year for male students. Sensitivity analyses for Pure Prevention cohorts and Change in Smoking Behaviour over time outcomes suggested that neither selection nor attrition bias affected the results. AUTHORS' CONCLUSIONS: Pure Prevention cohorts showed a significant effect at longest follow-up, with an average 12% reduction in starting smoking compared to the control groups. However, no overall effect was detected at one year or less. The combined social competence and social influences interventions showed a significant effect at one year and at longest follow-up. Studies that deployed a social influences programme showed no overall effect at any time point; multimodal interventions and those with an information-only approach were similarly ineffective.Studies reporting Change in Smoking Behaviour over time did not show an overall effect, but at an intervention level there were positive findings for social competence and combined social competence and social influences interventions.