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The first episode of psychosis is a critical period in the emergence of cardiometabolic risk.
We set out to explore the influence of individual and lifestyle factors on cardiometabolic outcomes in early psychosis.
This was a prospective cohort study of 293 UK adults presenting with first-episode psychosis investigating the influence of sociodemographics, lifestyle (physical activity, sedentary behaviour, nutrition, smoking, alcohol, substance use) and medication on cardiometabolic outcomes over the following 12 months.
Rates of obesity and glucose dysregulation rose from 17.8% and 12%, respectively, at baseline to 23.7% and 23.7% at 1 year. Little change was seen over time in the 76.8% tobacco smoking rate or the quarter who were sedentary for over 10 h daily. We found no association between lifestyle at baseline or type of antipsychotic medication prescribed with either baseline or 1-year cardiometabolic outcomes. Median haemoglobin A1c (HbA1c) rose by 3.3 mmol/mol in participants from Black and minority ethnic (BME) groups, with little change observed in their White counterparts. At 12 months, one-third of those with BME heritage exceeded the threshold for prediabetes (HbA1c >39 mmol/mol).
Unhealthy lifestyle choices are prevalent in early psychosis and cardiometabolic risk worsens over the next year, creating an important window for prevention. We found no evidence, however, that preventative strategies should be preferentially directed based on lifestyle habits. Further work is needed to determine whether clinical strategies should allow for differential patterns of emergence of cardiometabolic risk in people of different ethnicities.
Declaration of interest
F.G. has received honoraria for advisory work and lectures or CME activity support from Roche, BMS, Lundbeck, Otsuka, Janssen and Sunovion, is a collaborator on an NHS Innovations project co-funded by Janssen and has a family member with professional links to Lilly and GSK, including shares. R.M.M. has received honoraria for lectures from Lundbeck, Otsuka, Janssen and Sunovian. M.D.F. has received honoraria for lectures from Janssen and Sunovian. Z.A. has received honoraria for advisory work and lectures from Roche, Sanofi, Lilly and Otsuka. O.H. has received investigator-initiated research funding from and/or participated in advisory/speaker meetings organised by Astra-Zeneca, Autifony, Biogen, BMS, Eli Lilly, Heptares, Jansenn, Lundbeck, Lyden-Delta, Otsuka, Servier, Sunovion, Rand and Roche. D.T. has received funding for lectures and research from Janssen, Otsuka, Servier, Lundbeck, Sunovion.
We apply two methods to estimate the 21-cm bispectrum from data taken within the Epoch of Reionisation (EoR) project of the Murchison Widefield Array (MWA). Using data acquired with the Phase II compact array allows a direct bispectrum estimate to be undertaken on the multiple redundantly spaced triangles of antenna tiles, as well as an estimate based on data gridded to the uv-plane. The direct and gridded bispectrum estimators are applied to 21 h of high-band (167–197 MHz; z = 6.2–7.5) data from the 2016 and 2017 observing seasons. Analytic predictions for the bispectrum bias and variance for point-source foregrounds are derived. We compare the output of these approaches, the foreground contribution to the signal, and future prospects for measuring the bispectra with redundant and non-redundant arrays. We find that some triangle configurations yield bispectrum estimates that are consistent with the expected noise level after 10 h, while equilateral configurations are strongly foreground-dominated. Careful choice of triangle configurations may be made to reduce foreground bias that hinders power spectrum estimators, and the 21-cm bispectrum may be accessible in less time than the 21-cm power spectrum for some wave modes, with detections in hundreds of hours.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Background: The classic ketogenic diet is the main non-pharmacological treatment for refractory epilepsy; however, adherence is often challenging. The low glycemic index diet (LGID) is less strict, almost equally effective, and associated with improved adherence. Little is known about the quality of life of children treated with LGID. The objective of this study was to explore changes in the quality of life of children with epilepsy transitioning to the LGID. Methods: Patients on LGID and their parents filled out Pediatric Quality of Life Epilepsy Module questionnaires; one while being on the LGID, and one retrospectively for the time prior to starting the LGID. Results: Data was collected from five children ages 3-13 and their parents. Complete seizure control was seen in two children, >50% seizure reduction in one, and no change in two children. Parental reported quality of life while on the LGID increased with two participants but decreased in all child self reports. Conclusions: Although the LGID led to improved seizure control in three out of five patients, the child-reported quality of life decreased in all children. Larger prospective studies are warranted to reliably assess the impact of the LGID on the quality of life in children with epilepsy.
Background: Spinal muscular atrophy (SMA) is a children’s neuromuscular disorder. Although motor neuron loss is a major feature of the disease, we have identified fatty acid abnormalities in SMA patients and in preclinical animal models, suggesting metabolic perturbation is also an important component of SMA. Methods: Biochemical, histological, proteomic, and high resolution respirometry were used. Results: SMA patients are more susceptible to dyslipidemia than the average population as determined by a standard lipid profile in a cohort of 72 pediatric patients. As well, we observed a non-alcoholic liver disease phenotype in apreclinical mouse model. Denervation alone was not sufficient to induce liver steatosis, as a mouse model of ALS, did not develop fatty liver. Hyperglucagonemia in Smn2B/-mice could explain the hepatic steatosis by increasing plasma substrate availability via glycogen depletion and peripheral lipolysis. Proteomic analysis identified mitochondrion and lipid metabolism as major clusters. Alterations in mitochondrial function were revealed by high-resolution respirometry. Finally, low-fat diets led to increased survival in Smn2B/-mice. Conclusions: These results provide strong evidence for lipid metabolism defects in SMA. Further investigation will be required to establish the primary mechanism of these alterations and understand how they lead to additional co-morbidities in SMA patients.
Reducing hospitalisation and length of stay (LOS) in hospital following first episode psychosis (FEP) is important, yet reliable measures of these outcomes and their moderators are lacking. We conducted a systematic review and meta-analysis to investigate the proportion of FEP cases who were hospitalised after their first contact with services and the LOS in a hospital during follow-up.
Studies were identified from a systematic search across major electronic databases from inception to October 2017. Random effects meta-analyses and meta-regression analyses were conducted.
81 longitudinal studies encompassing data for 23 280 FEP patients with an average follow-up length of 7 years were included. 55% (95% CI 50.3–60.5%) of FEP cases were hospitalised at least once during follow-up with the pooled average LOS of 116.7 days (95% CI 95.1–138.3). Older age of illness onset and being in a stable relationship were associated with a lower proportion of people who were hospitalised. While the proportion of hospitalised patients has not decreased over time, LOS has, with the sharpest reduction in the latest time period. The proportion of patients hospitalised during follow-up was highest in Australia and New Zealand (78.4%) compared to Europe (58.1%) and North America (48.0%); and lowest in Asia (32.5%). Black ethnicity and longer duration of untreated psychosis were associated with longer LOS; while less severe psychotic symptoms at baseline were associated with shorter LOS.
One in two FEP cases required hospitalisation at least once during a 7-year follow-up with an average length of hospitalisation of 4 months during this period. LOS has declined over time, particularly in those countries in which it was previously longest.
Introduction: Accurate forecasting of emergency department (ED) patient visits can inform better resource matching. Calendar variables such as day of week and time of day are routinely used as predictors of ED volume. Further improvement in forecasting will likely come from dynamic variables. The effect of snowfall on ED volumes in colder climates remains poorly understood. We sought to determine whether accounting for snowfall improves ED patient volume forecasting. Our secondary objective was to characterize the magnitude of effect of snowfall on ED volume. Methods: This was a retrospective observational study using historical patient volume data and local snowfall records from April 1st, 2011 to March 31st, 2018 (2,542 days) at a single urban ED. We fit a series of four generalized linear models: a baseline model which included calendar variables and three different snowfall models which contained the variables in the baseline model plus an indicator variable for modelling snowfall. Each snowfall model had a different daily threshold for its indicator variable: any snowfall ( >0cm), moderate snowfall ( > = 1 cm), or high snowfall ( > = 5 cm). We modeled daily ED volume as the dependent variable using a Poisson distribution. To evaluate model fit, we examined the Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC) in each of the four models. In both cases, a lower number indicates better model fit. Incident rate ratios were calculated to determine the effect of snowfall. We used the delta method to calculate confidence intervals. Results: A total of 2542 days were used to develop the model. All three snowfall models demonstrated improved model fit compared to the baseline model with lower AIC and BIC values. The best fitting model included a binary variable for moderate snowfall ( > = 1cm/day). This model showed a statistically significant decrease in ED volume of 2.65% (95% CI: 1.23% -4.00%) on snowfall days, representing 5.4 (95% CI: 2.5 -8.2) patients per day at our hospital with an average daily volume of 205 patients. Conclusion: The addition of a snowfall variable results in improved forecasting model performance in ED volume forecasting with optimal threshold set at 1 cm of snow in our setting. Snowfall is associated with a modest, but statistically significant reduction in ED volume.
Objectives: We assessed trends in the incidence, prevalence, and post-diagnosis mortality of parkinsonism in Ontario, Canada over 18 years. We also explored the influence of a range of risk factors for brain health on the trend of incident parkinsonism. Methods: We established an open cohort by linking population-based health administrative databases from 1996 to 2014 in Ontario. The study population comprised residents aged 20–100 years with an incident diagnosis of parkinsonism ascertained using a validated algorithm. We calculated age- and sex-standardized incidence, prevalence, and mortality of parkinsonism, stratified by young onset (20–39 years) and mid/late onset (≥40 years). We assessed trends in incidence using Poisson regression, mortality using negative binomial regression, and prevalence of parkinsonism and pre-existing conditions (e.g., head injury) using the Cochran–Armitage trend test. To better understand trends in the incidence of mid/late-onset parkinsonism, we adjusted for various pre-existing conditions in the Poisson regression model. Results: From 1996 to 2014, we identified 73,129 incident cases of parkinsonism (source population of ∼10.5 million), of whom 56% were male, mean age at diagnosis was 72.6 years, and 99% had mid/late-onset parkinsonism. Over 18 years, the age- and sex-standardized incidence decreased by 13.0% for mid/late-onset parkinsonism but remained unchanged for young-onset parkinsonism. The age- and sex-standardized prevalence increased by 22.8%, while post-diagnosis mortality decreased by 5.5%. Adjustment for pre-existing conditions did not appreciably explain the declining incidence of mid/late-onset parkinsonism. Conclusion: Young-onset and mid/late-onset parkinsonism exhibited differing trends in incidence over 18 years in Ontario. Further research to identify other factors that may appreciably explain trends in incident parkinsonism is warranted.
At Risk Mental State (ARMS) clinics are specialised mental health services for young, help-seeking people, thought to be at ultra-high risk of developing psychosis. Their stated purpose is to reduce transitions from the ARMS state to clinical psychotic disorder. Reports of ARMS clinics provide ‘evidence-based recommendations’ or ‘guidance’ for the treatment of such individuals, and claim that such clinics prevent the development of psychosis. However, we note that in an area with a very well-developed ARMS clinic (South London), only a very small proportion (4%) of patients with first episode psychosis had previously been seen at this clinic with symptoms of the ARMS. We conclude that the task of reaching sufficient people to make a major contribution to the prevention of psychosis is beyond the power of ARMS clinics. Following the preventative approaches used for many medical disorders (e.g. lung cancer, coronary artery disease), we consider that a more effective way of preventing psychosis will be to adopt a public health approach; this should attempt to decrease exposure to environmental factors such as cannabis use which are known to increase risk of the disorder.
Jumping to conclusions (JTC), which is the proneness to require less information before forming beliefs or making a decision, has been related to formation and maintenance of delusions. Using data from the National Institute of Health Research Biomedical Research Centre Genetics and Psychosis (GAP) case–control study of first-episode psychosis (FEP), we set out to test whether the presence of JTC would predict poor clinical outcome at 4 years.
One-hundred and twenty-three FEP patients were assessed with the Positive and Negative Syndrome Scale (PANSS), Global Assessment of Functioning (GAF) and the probabilistic reasoning ‘Beads’ Task at the time of recruitment. The sample was split into two groups based on the presence of JTC bias. Follow-up data over an average of 4 years were obtained concerning clinical course and outcomes (remission, intervention of police, use of involuntary treatment – the Mental Health Act (MHA) – and inpatient days).
FEP who presented JTC at baseline were more likely during the follow-up period to be detained under the MHA [adjusted OR 15.62, 95% confidence interval (CI) 2.92–83.54, p = 0.001], require intervention by the police (adjusted OR 14.95, 95% CI 2.68–83.34, p = 0.002) and have longer admissions (adjusted IRR = 5.03, 95% CI 1.91–13.24, p = 0.001). These associations were not accounted for by socio-demographic variables, IQ and symptom dimensions.
JTC in FEP is associated with poorer outcome as indicated and defined by more compulsion police intervention and longer periods of admission. Our findings raise the question of whether the implementation of specific interventions to reduce JTC, such as Metacognition Training, may be a useful addition in early psychosis intervention programmes.
To determine the impact of specialized treatments, relative to comparator treatments, upon the weight and psychological symptoms of anorexia nervosa (AN) at end-of-treatment (EOT) and follow-up.
Randomized controlled trials (RCTs) between January 1980 and December 2017 that reported the effects of at least two treatments on AN were screened. Weight and psychological symptoms were analyzed separately for each study. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed, and studies were assessed using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) criteria and Cochrane risk of bias tool.
We identified 35 eligible RCTs, comprising data from 2524 patients. Meta-analyses revealed a significant treatment effect on weight outcomes at EOT [g = 0.16, 95% CI (0.05–0.28), p = 0.006], but not at follow-up [g = 0.11, 95% CI (−0.04 to 0.27), p = 0.15]. There was no significant treatment effect on psychological outcomes at either EOT [g = −0.03, 95% CI (−0.14 to 0.08), p = 0.63], or follow-up [g = −0.001, 95% CI (−0.11 to 0.11), p = 0.98]. There was no strong evidence of publication bias or significant moderator effects for illness duration, mean age, year of publication, comparator group category, or risk of bias (all p values > 0.05).
Current specialized treatments are more adept than comparator interventions at imparting change in weight-based AN symptoms at EOT, but not at follow-up. Specialized treatments confer no advantage over comparator interventions in terms of psychological symptoms. Future precision treatment efforts require a specific focus on the psychological symptoms of AN.
Agriculture is one of the major sources of methane in the UK and the major contribution is that from the ruminant animal. Most current inventories include evaluations of emission rates determined from ammals in respiration chambers. Methodolgy has been developed at IGER, North Wyke which enables measurements to be made with grazing animals (tunnel system). Preliminary measurements have indicated that methane emissions from grazing sheep in the tunnel system were lower than reported values for zero-grazed grass determined in chambers. The objective was to determine if these observed differences were a result of methodological differences.
Alcohol use is commonly initiated during adolescence, with earlier onset known to increase the risk for alcohol use disorder (AUD). Altered function in neural reward circuitry is thought to increase the risk for AUD. To test the hypothesis that adolescent alcohol misuse primes the brain for alcohol-related psychopathology in early adulthood, we examined whether adolescent alcohol consumption rates predicted reward responsivity in the ventral striatum (VS), and in turn, AUD symptoms in adulthood.
A total of 139 low income, racially diverse urban males reported on their alcohol use at ages 11, 12, 15, and 17; completed self-reports of personality, psychiatric interviews, and a functional magnetic resonance imaging (fMRI) scan at age 20; and completed a psychiatric interview at age 22. We measured adolescent alcohol use trajectories using latent growth curve modeling and measured neural responses to monetary reward using a VS region of interest. We tested indirect effects of adolescent alcohol use on AUD symptoms at age 22 via VS reward-related reactivity at age 20.
Greater acceleration in adolescent alcohol use predicted increased VS response during reward anticipation at age 20. VS reactivity to reward anticipation at age 20 predicted AUD symptoms at age 22, over and above concurrent symptoms. Accelerated adolescent alcohol use predicted AUD symptoms in early adulthood via greater VS reactivity to reward anticipation.
Prospective findings support a pathway through which adolescent alcohol use increases the risk for AUD in early adulthood by impacting reward-related neural functioning. These results highlight increased VS reward-related reactivity as a biomarker for AUD vulnerability.
Background: Migraines are sub-optimally treated, affect millions of Canadians, and are underrepresented in medical training. A study was conducted to identify the needs of Canadian Healthcare Providers (HCPs) for migraine education, with the aim to inform the development of learning activities. Methods: This ethics-approved study was deployed in two consecutive phases using a mixed-methods approach. Phase 1 (qualitative) explored the causes of challenges to migraine care via a literature review, input from an expert working group, and semi-structured interviews with multiple stakeholders. Phase 2 (quantitative) validated these causes using an online survey. Results: The study included 103 participants (28 in phase 1; 75 in phase 2): general practitioners=37; neurologists=24; nurses=14; pharmacists=20; administrators, policy influencers and payers=8. Four areas of sub-optimal knowledge were identified: (1) Canadian guidelines, (2) diagnostic criteria, (3) preventive treatment, and (4) non-pharmacological therapies. Attitudinal issues related to the management of migraine patients were also identified. Detailed data including the frequencies of knowledge gaps among general practitioners and general neurologists will be presented along with qualitative findings. Conclusions: Educational activities for general practitioners and general neurologists who treat patients with migraines should be designed to address the four educational needs described in this study.
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.
Declaration of interest
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.
Introduction: With the increasing volume of medical literature published each year, it is difficult for clinicians to translate the latest research into practice. Awareness is the first step of knowledge translation and journals have begun using social media to increase the dissemination and awareness of their publications. Infographics can describe research findings visually, are shared broadly on social media, and may be a more effective way to convey information. We hypothesized that infographic abstracts would increase the social media dissemination and online readership of research articles relative to traditional abstracts. Methods: In this randomized controlled trial, 24 original research articles were chosen from the six issues of the Canadian Journal of Emergency Medicine (CJEM) published between July 2016 and May 2017 (4 articles per issue). Half were randomized to the infographic and control groups within each issue. Infographic articles were promoted using a visual infographic outlining the findings of the article. Control articles were promoted using a screen capture image of each articles abstract. Both were disseminated through the journals social media accounts (Twitter and Facebook) along with the link to the selected article. Infographics were also published on CanadiEM.org. Abstract views, full text views, and the change in Altmetric score were tracked for 30 days and compared between groups. Unpaired two-tailed t-tests were used to detect significant differences. Results: Abstract views (mean, SD) were significantly higher for infographic articles (378.9, 162.0) than control articles (175.5, 69.2, p<0.001). Mean Altmetric scores were significantly higher for infographic articles (26.4, 13.8) than control articles (3.4, 1.7, p<0.0001). There was no statistically significant difference in full-text views between infographic (49.7, 90.4) and control articles (25.3, 12.3). Conclusion: CJEM articles promoted on social media using infographics had higher abstract viewership and Altmetric scores than those promoted with traditional abstracts. Although there was no difference in full-text readership, our results suggest that infographic abstracts may have a role in increasing the dissemination of medical literature.
This paper reports on: (1) an evaluation of a common elements treatment approach (CETA) developed for comorbid presentations of depression, anxiety, traumatic stress, and/or externalizing symptoms among children in three Somali refugee camps on the Ethiopian/Somali border, and (2) an evaluation of implementation factors from the perspective of staff, lay providers, and families who engaged in the intervention.
This project was conducted in three refugee camps and utilized locally validated mental health instruments for internalizing, externalizing, and posttraumatic stress (PTS) symptoms. Participants were recruited from either a validity study or from referrals from social workers within International Rescue Committee Programs. Lay providers delivered CETA to youth (CETA-Youth) and families, and symptoms were re-assessed post-treatment. Providers and families responded to a semi-structured interview to assess implementation factors.
Children who participated in the CETA-Youth open trial reported significant decreases in symptoms of internalizing (d = 1.37), externalizing (d = 0.85), and posttraumatic stress (d = 1.71), and improvements in well-being (d = 0.75). Caregivers also reported significant decreases in child symptoms. Qualitative results were positive toward the acceptability and appropriateness of treatment, and its feasibility.
This project is the first to examine a common elements approach (CETA: defined as flexible delivery of elements, order, and dosing) with children and caregivers in a low-resource setting with delivery by lay providers. CETA-Youth may offer an effective treatment that is easier to implement and scale-up versus multiple focal interventions. A fullscale randomized clinical trial is warranted.