To assist hospitals in reducing Clostridioides difficile infections (CDI), the Centers for Disease Control and Prevention (CDC) implemented a collaborative using the CDC CDI prevention strategies and the Targeted Assessment for Prevention (TAP) Strategy as foundational frameworks.

Acute-care hospitals.

We invited 400 hospitals with the highest cumulative attributable differences (CADs) to the 12-month collaborative, with monthly webinars, coaching calls, and deployment of the CDC CDI TAP facility assessments. Infection prevention barriers, gaps identified, and interventions implemented were qualitatively coded by categorizing them to respective CDI prevention strategies. Standardized infection ratios (SIRs) were reviewed to measure outcomes.

Overall, 76 hospitals participated, most often reporting CDI testing as their greatest barrier to achieving reduction (61%). In total, 5,673 TAP assessments were collected across 46 (61%) hospitals. Most hospitals (98%) identified at least 1 gap related to testing and at least 1 gap related to infrastructure to support prevention. Among 14 follow-up hospitals, 64% implemented interventions related to infrastructure to support prevention (eg, establishing champions, reviewing individual CDIs) and 86% implemented testing interventions (eg, 2-step testing, testing algorithms). The SIR decrease between the pre-collaborative and post-collaborative periods was significant among participants (16.7%; P < .001) but less than that among nonparticipants (25.1%; P < .001).

This article describes gaps identified and interventions implemented during a comprehensive CDI prevention collaborative in targeted hospitals, highlighting potential future areas of focus for CDI prevention efforts as well as reported challenges and barriers to prevention of one of the most common healthcare-associated infections affecting hospitals and patients nationwide.

Causes of childhood behavior problems remain poorly understood. Enriched family environments and corresponding brain development may reduce the risk of their onset, but research investigating white matter neurodevelopmental pathways explaining associations between the family environment and behavior remains limited. We hypothesized that more positive prenatal and mid-childhood family functioning – a measure of a family's problem solving and supportive capacity – would be associated with two markers of preadolescent white matter neurodevelopment related to reduced behavior problems: higher global fractional anisotropy (FA) and lower global mean diffusivity (MD).

Data are from 2727 families in the Generation R Study, the Netherlands. Mothers reported family functioning (McMaster Family Assessment Device, range 1–4, higher scores indicate healthier functioning) prenatally and in mid-childhood (mean age 6.1 years). In preadolescence (mean age 10.1), the study collected diffusion-weighted scans. We computed standardized global MD and FA values by averaging metrics from 27 white matter tracts, and we fit linear models adjusting for possible confounders to examine global and tract-specific outcomes.

Prenatal and mid-childhood family functioning scores were moderately correlated, r = 0.38. However, only prenatal family functioning – and not mid-childhood functioning – was associated with higher global FA and lower global MD in preadolescence in fully adjusted models: βglobal FA = 0.11 (95% CI 0.00, 0.21) and βglobal MD = −0.15 (95% CI −0.28, −0.03) per one-unit increase in functioning score. Sensitivity and tract-specific analyses supported these global findings.

These results suggest high-functioning prenatal or perinatal family environments may confer lasting white matter neurodevelopmental benefits into preadolescence.

The endogenous opioid system affects metabolism, including weight regulation. Evidence from preclinical and clinical studies provides a rationale for targeting this system to mitigate weight-related side effects of antipsychotics. This review describes the role of the opioid system in regulating weight and metabolism, examines the effects of opioid receptor antagonism on those functions, and explores the use of opioid antagonists to mitigate antipsychotic-associated weight gain and/or metabolic effects.

A PubMed literature search was conducted to identify representative opioid antagonists and associated preclinical and clinical studies examining their potential for the regulation of weight and metabolism.

The mu opioid receptor (MOR), delta opioid receptor (DOR), and kappa opioid receptor (KOR) types have overlapping but distinct patterns of central and peripheral expression, and each contributes to the regulation of body weight and metabolism. Three representative opioid antagonists (eg, naltrexone, samidorphan, and LY255582) were identified for illustration. These opioid antagonists differed in their receptor binding and pharmacokinetic profiles, including oral bioavailability, systemic clearance, and half-life, and were associated with varying effects on food intake, energy utilization, and metabolic dysregulation.

Preclinical and clinical data suggest that antagonism of the endogenous opioid system is a mechanism to address antipsychotic-associated weight gain and metabolic dysregulation. However, evidence suggests that the differing roles of MOR, DOR, and KOR in metabolism, together with the differences in receptor binding, pharmacokinetic, and functional activity profiles of the opioid receptor antagonists discussed in this review, likely contribute to their differential pharmacodynamic effects and clinical outcomes observed regarding antipsychotic-associated weight gain.

To examine awareness and recall of healthy eating public education campaigns in five countries.

Data were cross-sectional and collected as part of the 2018 International Food Policy Study. Respondents were asked whether they had seen government healthy eating campaigns in the past year; if yes (awareness), they were asked to describe the campaign. Open-ended descriptions were coded to indicate recall of specific campaigns. Logistic models regressed awareness of healthy eating campaigns on participant country, age, sex, ethnicity, education, income adequacy and BMI. Analyses were also stratified by country.

Online surveys.

Participants were Nielsen panelists aged ≥18 years in Australia, Canada, Mexico, UK and the USA (n 22 463).

Odds of campaign awareness were higher in Mexico (50·9 %) than UK (18·2 %), Australia (17·9 %), the USA (13·0 %) and Canada (10·2 %) (P < 0·001). Awareness was also higher in UK and Australia v. Canada and the USA, and the USA v. Canada (P < 0·001). Overall, awareness was higher among males v. females and respondents with medium or high v. low education (P < 0·001 for all). Similar results were found in stratified models, although no sex difference was observed in Australia or UK (P > 0·05), and age was associated with campaign awareness in UK (P < 0·001). Common keywords in all countries included sugar/sugary drinks, fruits and vegetables, and physical activity. The top five campaigns recalled were Chécate, mídete, muévete (Mexico), PrevenIMSS (Mexico), Change4Life (UK), LiveLighter® (Australia), and Actívate, Vive Mejor (Mexico).

In Mexico, UK and Australia, comprehensive campaigns to promote healthy lifestyles appear to have achieved broad, population-level reach.

To compare differences in clozapine doses and plasma levels between Bangladeshi and White British patients. Following ethical approval we identified all current Bangladeshi and White British patients on clozapine maintenance in an east London clinic. We carried out univariate and multivariate regression analyses to examine associations between clozapine doses and ethnicity, age, gender, smoking status and weight. We also compared plasma clozapine levels of the two groups.

On univariate analysis White British patients had on average 85 mg higher doses than Bangladeshi patients (P = 0.004). Older age, male gender and smoking were also associated with higher dose. On multivariate analysis only age and smoking status remained significant. A greater proportion of Bangladeshi patients had high plasma clozapine levels compared with White British (30.76% v. 20.75%), although the difference was not statistically significant.

Our findings point to the need for the broadening of data collection on ethnic differences in clozapine prescribing within big data-sets such as Prescribing Observatory for Mental Health (POM-UK). Ethnopharmacological variations can inform more person-centred guidance on prescribing.

Observational studies have linked elevated homocysteine to vascular conditions. Folate intake has been associated with lower homocysteine concentration, although randomised controlled trials of folic acid supplementation to decrease the incidence of vascular conditions have been inconclusive. We investigated determinants of maternal homocysteine during pregnancy, particularly in a folic acid-fortified population.

Data were from the Ottawa and Kingston Birth Cohort of 8085 participants. We used multivariable regression analyses to identify factors associated with maternal homocysteine, adjusted for gestational age at bloodwork. Continuous factors were modelled using restricted cubic splines. A subgroup analysis examined the modifying effect of MTHFR 677C>T genotype on folate, in determining homocysteine concentration.

Participants were recruited in Ottawa and Kingston, Canada, from 2002 to 2009.

Women were recruited when presenting for prenatal care in the early second trimester.

In 7587 participants, factors significantly associated with higher homocysteine concentration were nulliparous, smoking and chronic hypertension, while factors significantly associated with lower homocysteine concentration were non-Caucasian race, history of a placenta-mediated complication and folic acid supplementation. Maternal age and BMI demonstrated U-shaped associations. Folic acid supplementation of >1 mg/d during pregnancy did not substantially increase folate concentration. In the subgroup analysis, MTHFR 677C>T modified the effect of folate status on homocysteine concentration.

We identified determinants of maternal homocysteine relevant to the lowering of homocysteine in the post-folic acid fortification era, characterised by folate-replete populations. A focus on periconceptional folic acid supplementation and improving health status may form an effective approach to lower homocysteine.

Evidence synthesis (ES) is often required for economic evaluation (EE) of pharmaceuticals. Commonly used methods are based on the assumption of proportional hazards in trial data, using the hazard ratio (HR). Alternative methods for ES are increasingly used in EE, in situations where the pattern of hazards in the trial data indicates that the proportional hazards assumption may be violated. The impact of these methodological choices on model outcomes is explored.

A network of trials of BRAF-targeted treatments for advanced melanoma, derived using a systematic review of the literature, is chosen for the study. Guyot's method is used to create individual-patient Kaplan-Meier (K-M) data from published survival curves. Log-cumulative hazard plots and Schoenfeld residuals are derived to examine patterns in hazards within the trial data. All analyses are conducted in R version 3.5.0©. Three alternative methods for ES are tested: 1) Network meta-analysis (NMA) based on published HRs and the assumption of proportional hazards. 2) NMA using fractional polynomials (FP) based on digitised K-M data, allowing the relaxation of the proportional hazards assumption. 3) NMA using an accelerated failure time (AFT) model based on digitised K-M data, allowing the relaxation of the proportional hazards assumption. The derived estimates of relative efficacy from each method are applied in a partitioned survival cost-effectiveness model programmed in Microsoft Excel™.

The model outcomes predicted by each method (HR, FP and AFT) are presented and compared. Both deterministic and probabilistic results are presented, alongside a discussion around how the uncertainty in these structural assumptions may be captured in EE.

Structural assumptions in ES may lead to differences in model outcomes. The impact of these differences may be important in situations where decision uncertainty is high. Methods should be chosen and justified based on patterns of hazard present in the trial data.

To estimate the prevalence and sociodemographic characteristics of youth and young adults in major Canadian cities with self-reported vegetarian dietary practices and examine efforts to alter their diets.

Data were collected in autumn 2016 via web-based surveys. Respondents reported vegetarian dietary practices (vegan, vegetarian or pescatarian) and efforts in the preceding year to consume more or less of several nutrients, food groups and/or foods with particular attributes. Logistic regression models examined sociodemographic correlates of each vegetarian dietary practice and differences in other eating practices by diet type.

Participants were recruited from five major Canadian cities.

Youth and young adults, aged 16–30 years (n 2566).

Overall, 13·6 % of respondents reported vegetarian dietary practices: 6·6 % vegetarian, 4·5 % pescatarian and 2·5 % vegan. Sex, race/ethnicity, self-reported frequency of using the Nutrition Facts table and health literacy were significantly correlated with self-reported vegetarian dietary practice (P < 0·01 for all). Efforts to consume more fruits and vegetables (66·8 %) and protein (54·8 %), and less sugar (61·3 %) and processed foods (54·7 %), were prevalent overall. Respondents with vegetarian dietary practices were more likely to report efforts to consume fewer carbohydrates and animal products, and more organic, locally produced, ethically sourced/sustainably sourced/fair trade and non-GM foods (P < 0·01 for all), compared with those without these reported dietary practices.

Nearly 14 % of the sampled youth and young adults in major Canadian cities reported vegetarian dietary practices and may be especially likely to value and engage in behaviours related to health-conscious diets and sustainable food production.

Adolescence is a critical period for development of depression and understanding of behavioural risk factors is needed to support appropriate preventive strategies. We examined associations between adolescent diet quality and depressive symptoms, cross-sectionally and prospectively, in a large community cohort, adjusting for behavioural and psychosocial covariates.

Prospective community-based cohort study (ROOTS).

Secondary schools in Cambridgeshire and Suffolk, UK.

Study participants (n 603) who completed 4 d diet diaries at age 14 years and reported depressive symptoms (Moods and Feelings Questionnaire (MFQ)) at 14 and 17 years of age.

Diet data were processed to derive a Mediterranean diet score (MDS) and daily servings of fruit and vegetables, and fish. At age 14 years, a negative association between fruit and vegetable intake and MFQ score was seen in the unadjusted cross-sectional regression model (β=−0·40; 95 % CI −0·71,−0·10), but adjustment for behavioural covariates, including smoking and alcohol consumption, attenuated this association. Fish intake and MDS were not cross-sectionally associated with MFQ score. No prospective associations were found between MDS, fruit and vegetable intake or fish intake and later MFQ score.

Diet quality was not associated with depressive symptoms in mid-adolescence. Previously reported associations in this age range may be due to confounding. Further longitudinal studies are needed that investigate associations between adolescent diet and depression across different time frames and populations, ensuring appropriate adjustment for covariates.

Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.

To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.

Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.

A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).

The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.

Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.