A data-derived reference mixture representative of European wastewater treatment plant effluents to complement mixture assessment.

Aquatic environments are polluted with a multitude of organic micropollutants, which challenges risk assessment due the complexity and diversity of pollutant mixtures. The recognition that certain source-specific background pollution occurs ubiquitously in the aquatic environment might be one way forward to approach mixture risk assessment. To investigate this hypothesis, we prepared one typical and representative WWTP effluent mixture of organic micropollutants (EWERBmix) comprised of 81 compounds selected according to their high frequency of occurrence and toxic potential. Toxicological relevant effects of this reference mixture were measured in eight organism- and cell-based bioassays and compared with predicted mixture effects, which were calculated based on effect data of single chemicals retrieved from literature or different databases, and via quantitative structure-activity relationships (QSARs). The results show that the EWERBmix supports the identification of substances which should be considered in future monitoring efforts. It provides measures to estimate wastewater background concentrations in rivers under consideration of respective dilution factors, and to assess the extent of mixture risks to be expected from European WWTP effluents. The EWERBmix presents a reasonable proxy for regulatory authorities to develop and implement assessment approaches and regulatory measures to address mixture risks. The highlighted data gaps should be considered for prioritization of effect testing of most prevalent and relevant individual organic micropollutants of WWTP effluent background pollution. The here provided approach and EWERBmix are available for authorities and scientists for further investigations. The approach presented can furthermore serve as a roadmap guiding the development of archetypic background mixtures for other sources, geographical settings and chemical compounds, e.g. inorganic pollutants.

How does a Social and Behavioral Change Communication Intervention Predict Menstrual Health and Hygiene Management: A Cross-Sectional Study.

BACKGROUND: Interventions in India to improve menstrual health and hygiene management (MHHM) have been implemented at the national, state, district and school level. However, evaluations of these interventions have been scarce. The objective of the study was to determine if a social and behavioral change communication (SBCC) intervention (GARIMA) had a relationship with knowledge, attitudes, interpersonal communication, restrictions and MHHM using a comparison group post-test only design among 2206 adolescent girls. METHODS: Intervention villages and adolescent girls were selected through stratified random sampling based on where GARIMA was implemented. Villages and adolescent girls in comparison villages were matched socio-demographically to intervention villages and adolescent girls. Multi-level logistic regressions assessed the relationship between the encoded exposure, mediators and MHHM. RESULTS: The results showed that the encoded exposure predicted all behaviors corresponding to MHHM. Additionally, adolescent girls in the high encoded exposure group had significantly higher knowledge about puberty and reproductive parts (AOR: 2.03 (95% CI: 1.31 - 3.15)), positive attitudes towards gender (AOR: 1.48 (95% CI: 1.02 - 2.16)) and higher levels of some discussion and dialogue (AOR: 1.41 (95% CI: 1.04 - 1.92)). CONCLUSIONS: Future programs should use SBCC to improve MHHM behavior but involve families, peers and community members to a greater extent in order to improve attitudes towards menstruation, attitudes towards restrictions, attitudes towards absorbent use and reduce restrictions within the community.

Practice variation in the use of tests in UK primary care: a retrospective analysis of 16 million tests performed over 3.3 million patient years in 2015/16.

BACKGROUND: The UK's National Health Service (NHS) is currently subject to unprecedented financial strain. The identification of unnecessary healthcare resource use has been suggested to reduce spending. However, there is little very research quantifying wasteful test use, despite the £3 billion annual expenditure. Geographical variation has been suggested as one metric in which to quantify inappropriate use. We set out to identify tests ordered from UK primary care that are subject to the greatest between-practice variation in their use. METHODS: We used data from 444 general practices within the Clinical Practice Research Datalink to calculate a coefficient of variation (CoV) for the ordering of 44 specific tests from UK general practices. The coefficient of variation was calculated after adjusting for differences between practice populations. We also determined the tests that had both a higher-than-average CoV and a higher-than-average rate of use. RESULTS: In total, 16,496,218 tests were ordered for 4,078,091 patients over 3,311,050 person-years from April 1, 2015, to March 31, 2016. The tests subject to the greatest variation were drug monitoring 158% (95%CI 153 to 163%), urine microalbumin (52% (95%CI 49.9 to 53.2%)), pelvic CT (51% (95%CI 50 to 53%)) and Pap smear (49% (95%CI 48 to 51%). Seven tests were classified as high variability and high rate (clotting, vitamin D, urine albumin, prostate-specific antigen (PSA), bone profile, urine MCS and C-reactive protein (CRP)). CONCLUSIONS: There are wide variations in the use of common tests, which is unlikely to be explained by clinical indications. Since £3 billion annually are spent on tests, this represents considerable variation in the use of resources and inefficient management in the NHS. Our results can be of value to policy makers, researchers, patients and clinicians as the NHS strives towards identifying overuse and underuse of tests.

Identifying Primary Care Pathways from Quality of Care to Outcomes and Satisfaction Using Structural Equation Modeling.

OBJECTIVE: To study the relationships between the different domains of quality of primary health care for the evaluation of health system performance and for informing policy decision making. DATA SOURCES: A total of 137 quality indicators collected from 7,607 English practices between 2011 and 2012. STUDY DESIGN: Cross-sectional study at the practice level. Indicators were allocated to subdomains of processes of care ("quality assurance," "education and training," "medicine management," "access," "clinical management," and "patient-centered care"), health outcomes ("intermediate outcomes" and "patient-reported health status"), and patient satisfaction. The relationships between the subdomains were hypothesized in a conceptual model and subsequently tested using structural equation modeling. PRINCIPAL FINDINGS: The model supported two independent paths. In the first path, "access" was associated with "patient-centered care" (ß = 0.63), which in turn was strongly associated with "patient satisfaction" (ß = 0.88). In the second path, "education and training" was associated with "clinical management" (ß = 0.32), which in turn was associated with "intermediate outcomes" (ß = 0.69). "Patient-reported health status" was weakly associated with "patient-centered care" (ß = -0.05) and "patient satisfaction" (ß = 0.09), and not associated with "clinical management" or "intermediate outcomes." CONCLUSIONS: This is the first empirical model to simultaneously provide evidence on the independence of intermediate health care outcomes, patient satisfaction, and health status. The explanatory paths via technical quality clinical management and patient centeredness offer specific opportunities for the development of quality improvement initiatives.

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.

Cost effective interventions for the prevention of cardiovascular disease in low and middle income countries: a systematic review.

BACKGROUND: While there is good evidence to show that behavioural and lifestyle interventions can reduce cardiovascular disease risk factors in affluent settings, less evidence exists in lower income settings.This study systematically assesses the evidence on cost-effectiveness for preventive cardiovascular interventions in low and middle-income settings. DESIGN: Systematic review of economic evaluations on interventions for prevention of cardiovascular disease. DATA SOURCES: PubMed, Web of Knowledge, Scopus and Embase, Opensigle, the Cochrane database, Business Source Complete, the NHS Economic Evaluations Database, reference lists and email contact with experts. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: we included economic evaluations conducted in adults, reporting the effect of interventions to prevent cardiovascular disease in low and middle income countries as defined by the World Bank. The primary outcome was a change in cardiovascular disease occurrence including coronary heart disease, heart failure and stroke. DATA EXTRACTION: After selection of the studies, data were extracted by two independent investigators using a previously constructed tool and quality was evaluated using Drummond's quality assessment score. RESULTS: From 9731 search results we found 16 studies, which presented economic outcomes for interventions to prevent cardiovascular disease in low and middle income settings, with most of these reporting positive cost effectiveness results.When the same interventions were evaluated across settings, within and between papers, the likelihood of an intervention being judged cost effective was generally lower in regions with lowest gross national income. While population based interventions were in most cases more cost effective, cost effectiveness estimates for individual pharmacological interventions were overall based upon a stronger evidence base. CONCLUSIONS: While more studies of cardiovascular preventive interventions are needed in low and mid income settings, the available high-level of evidence supports a wide range of interventions for the prevention of cardiovascular disease as being cost effective across all world regions.

Participant- and study-related characteristics predicting treatment completion and study retention in an adolescent smoking cessation trial.

PURPOSE: To determine which factors predict smoking cessation treatment completion and retention among adolescents. METHODS: In a multisite, randomized, controlled trial, the efficacy of motivational interviewing was compared with structured brief advice for smoking cessation and reduction in adolescents (n = 355) aged 14-18 years (55% female, 45% black, 12% Hispanic). Treatment spanned 12 weeks, with follow-up assessments at 24 weeks. Treatment completion was defined as completion of all five counseling sessions. Study retention was defined as completing the 24-week assessment. Participant and study variables served as predictors of treatment completion and retention. RESULTS: In all, 79% of participants completed all five counseling sessions and the same percent completed the 24-week assessment. Black race, precontemplation stage to cut back, and shorter length of time between the baseline assessment and the first counseling session were significantly associated with treatment completion. For every 7.5-day delay in starting treatment after the baseline visit, there was a 50% decrease in the odds of completing all five treatment sessions. Retention at 24 weeks was predicted by black race, younger age, greater maternal education, expectations of graduating college, and structured brief advice intervention. CONCLUSIONS: High rates of treatment completion and study retention can be achieved in a multisession, behavioral intervention for adolescent smoking cessation. Findings suggest that treatment should begin soon after the intake session to maximize treatment completion. Enhanced efforts to retain older adolescents and youth with lower academic goals and lower family income will be important in future studies.