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This is the first cross-national study of intermittent explosive disorder (IED). A total of 17 face-to-face cross-sectional household surveys of adults were conducted in 16 countries (n = 88 063) as part of the World Mental Health Surveys initiative. The World Health Organization Composite International Diagnostic Interview (CIDI 3.0) assessed DSM-IV IED, using a conservative definition. Lifetime prevalence of IED ranged across countries from 0.1 to 2.7% with a weighted average of 0.8%; 0.4 and 0.3% met criteria for 12-month and 30-day prevalence, respectively. Sociodemographic correlates of lifetime risk of IED were being male, young, unemployed, divorced or separated, and having less education. The median age of onset of IED was 17 years with an interquartile range across countries of 13-23 years. The vast majority (81.7%) of those with lifetime IED met criteria for at least one other lifetime disorder; co-morbidity was highest with alcohol abuse and depression. Of those with 12-month IED, 39% reported severe impairment in at least one domain, most commonly social or relationship functioning. Prior traumatic experiences involving physical (non-combat) or sexual violence were associated with increased risk of IED onset. Conservatively defined, IED is a low prevalence disorder but this belies the true societal costs of IED in terms of the effects of explosive anger attacks on families and relationships. IED is more common among males, the young, the socially disadvantaged and among those with prior exposure to violence, especially in childhood.

•MD epidemiology and vaccination strategies in Latin America were reviewed.•Routine infant MCC vaccination program was implemented in Brazil in 2010.•Brazil: a dramatic reduction in MD incidence rates was observed in those <2 years.•Emergence of serogroup W disease was identified in Chile and Argentina.•Chile: reactive MenACWY vaccination implemented in children aged 9 months to 5 years has impacted only in this age group. The Global Meningococcal Initiative (GMI) was established in 2009 and comprises an international team of scientists, clinicians, and public health officials with expertise in meningococcal disease (MD). Its primary goal is to promote global prevention of MD through education, research, international cooperation, and developing recommendations that include decreasing the burden of severe disease. The group held its first roundtable meeting with experts from Latin American countries in 2011, and subsequently proposed several recommendations to reduce the regional burden of MD. A second roundtable meeting was convened with Latin American representatives in June 2013 to reassess MD epidemiology, vaccination strategies, and unmet needs in the region, as well as to update the earlier recommendations. Special emphasis was placed on the emergence and spread of serogroup W disease in Argentina and Chile, and the control measures put in place in Chile were a particular focus of discussions. The impact of routine meningococcal vaccination programs, notably in Brazil, was also evaluated. There have been considerable improvements in MD surveillance systems and diagnostic techniques in some countries (e.g., Brazil and Chile), but the lack of adequate infrastructure, trained personnel, and equipment/reagents remains a major barrier to progress in resource-poor countries. The Pan American Health Organization's Revolving Fund is likely to play an important role in improving access to meningococcal vaccines in Latin America. Additional innovative approaches are needed to redress the imbalance in expertise and resources between countries, and thereby improve the control of MD. In Latin America, the GMI recommends establishment of a detailed and comprehensive national/regional surveillance system, standardization of laboratory procedures, adoption of a uniform MD case definition, maintaining laboratory-based surveillance, replacement of polysaccharide vaccines with conjugate formulations (wherever possible), monitoring and evaluating implemented vaccination strategies, conducting cost-effectiveness studies, and developing specific recommendations for vaccination of high-risk groups.

PurposeWe aimed to test the effects of providing municipal support and training to primary health care providers compared to both training alone and to care as usual on the proportion of adult patients having their alcohol consumption measured.MethodsWe undertook a quasi-experimental study reporting on a 5-month implementation period in 58 primary health care centres from municipal areas within Bogotá (Colombia), Mexico City (Mexico), and Lima (Peru). Within the municipal areas, units were randomized to four arms: (1) care as usual (control); (2) training alone; (3) training and municipal support, designed specifically for the study, using a less intensive clinical and training package; and (4) training and municipal support, designed specifically for the study, using a more intense clinical and training package. The primary outcome was the cumulative proportion of consulting adult patients out of the population registered within the centre whose alcohol consumption was measured (coverage).ResultsThe combination of municipal support and training did not result in higher coverage than training alone (incidence rate ratio (IRR) = 1.0, 95% CI = 0.6 to 0.8). Training alone resulted in higher coverage than no training (IRR = 9.8, 95% CI = 4.1 to 24.7). Coverage did not differ by intensity of the clinical and training package (coefficient = 0.8, 95% CI 0.4 to 1.5).ConclusionsTraining of providers is key to increasing coverage of alcohol measurement amongst primary health care patients. Although municipal support provided no added value, it is too early to conclude this finding, since full implementation was shortened due to COVID-19 restrictions.Trial RegistrationClinical Trials.gov ID: NCT03524599; Registered 15 May 2018; https://clinicaltrials.gov/ct2/show/NCT03524599

Background. Asymptomatic dengue virus-infected individuals are thought to play a major role in dengue virus transmission. The efficacy of the recently approved quadrivalent CYD-TDV dengue vaccine against asymptomatic dengue virus infection has not been previously assessed. Methods. We pooled data for 3 736 individuals who received either CYD-TDV or placebo at 0, 6, and 12 months in the immunogenicity subsets of 2 phase 3 trials (clinical trials registration NCT01373281 and NCTO1374516). We defined a seroconversion algorithm (ie, a ≥4-fold increase in the neutralizing antibody titer and a titer of ≥40 from month 13 to month 25) as a surrogate of asymptomatic infection in the vaccine and placebo groups. Results. The algorithm detected seroconversion in 94% of individuals with a diagnosis of virologically confirmed dengue between months 13 and 25, validating its discriminatory power. Among those without virologically confirmed dengue (n = 3 669), 219 of 2 485 in the vaccine group and 157 of 1 184 in the placebo group seroconverted between months 13 and 25, giving a vaccine efficacy of 33.5% (95% confidence interval [CI], 17.9%-46.1%) against asymptomatic infection. Vaccine efficacy was marginally higher in subjects aged 9-16 years (38.6%; 95% CI, 22.1%-51.5%). The annual incidence of asymptomatic dengue virus infection in this age group was 14.8%, which was 4.4 times higher than the incidence for symptomatic dengue (3.4%). Conclusions. The observed vaccine efficacy against asymptomatic dengue virus infections is expected to translate into reduced dengue virus transmission if sufficient individuals are vaccinated in dengue-endemic areas.

In trials, dengue vaccine efficacy evaluation relies on participants presenting with febrile illness/clinically suspected dengue contacting the study site for sample collection and clinical assessment within a short timeframe. Here, we present key considerations to maintain high compliance with the febrile surveillance procedures in a trial that assessed TAK-003 efficacy. DEN-301 (NCT02747927) is a randomized phase 3 trial in children/adolescents from eight dengue-endemic countries in Latin America (LATAM) and Asia-Pacific (APAC). Febrile surveillance consisted of weekly contact with the participant to identify cases of fever (≥38 °C; two of three consecutive days). Blood samples were collected for molecular testing, preferably ≤5 days of fever onset, together with thorough clinical assessment by the investigators. The data are presented descriptively. Of the 20,071 (LATAM, 11,080; APAC, 8991) participants who received TAK-003/placebo, 18,260 (91.0 %) completed 4.5 years of follow-up. The overall incidence of febrile illness was 30 (LATAM, 26.0; APAC, 35.1) cases per 100 person-years. The rate samples collected during the acute phase was 98.1 %. The overall rate of samples collected after 5 days of fever onset (missed/out-of-window) was 6 % (LATAM, 10 %; APAC, 2 %). A trend toward reduced missed/out-of-window samples was observed after implementing measures, such as transportation, engagement, and healthcare aid tailored per study site in 2017, which appeared to increase during the COVID-19 pandemic. The design of the febrile surveillance protocol ensured high compliance in the trial. Maintaining engagement and access to healthcare beyond the protocol was important in improving febrile case evaluation ≤5 days of fever onset. •Efficient febrile surveillance is key for evaluating efficacy of a dengue vaccine.•Compliance with the protocol was high across all sites in the DEN-301 trial.•Despite the low level of out-of-window samples collected, variations were observed.•Measures for better access to healthcare improved compliance with the protocol.•Understanding noncompliance causes and prompt feedback to the site are important.

Patients hospitalized for acute decompensated heart failure (ADHF) are at high risk for early mortality and rehospitalization. Risk stratification of ADHF using clinically available data on admission is increasingly important to integrate with clinical pathways. Our goal was to create a simple method of screening patients upon admission to identify those with increased risk of future adverse events. Using ASCEND-HF, a pragmatic clinical trial conducted in 398 sites globally, we developed and validated logistic regression risk models for (a) 30-day mortality/HF rehospitalization, (b) 30-day mortality/all-cause rehospitalization, (c) 30-day all-cause mortality, and (d) 180-day all-cause mortality. Fifty-one candidate variables were evaluated based on prior publications and clinical review. Final models were selected based on stepwise selection with entry and a staying criterion of P < .01. The 30-day mortality model was externally validated, and coefficients were converted to an additive risk score. Among 7,141 patients, the median age was 67 years, 34% were female, and 80% had a left ventricular ejection fraction <40%. The models had between 5 and 12 risk factors with c-indices ranging from 0.68 to 0.75. A simplified score, including age, systolic blood pressure, sodium, blood urea nitrogen, and dyspnea at rest, discriminated 30-day mortality risk from 0.5% (score 0) to 53% (score 10). Commonly available clinical variables provide simple risk stratification for clinical outcomes among patients with ADHF, and these models may be considered for integration into routine clinical care.

To evaluate the association of rainy season with overall dengue disease incidence and with the efficacy of the Sanofi Pasteur recombinant, live, attenuated, tetravalent vaccine (CYD-TDV) in two randomized, controlled multicenter phase III clinical trials in Asia and Latin America. Rainy seasons were defined for each study site using climatological information from the World Meteorological Organization. The dengue attack rate in the placebo group for each study month was calculated as the number of symptomatic, virologically-confirmed dengue events in a given month divided by the number of participants at risk in the same month. Time-dependent Cox proportional hazard models were used to test whether rainy season was associated with dengue disease and whether it modified vaccine efficacy in each of the two trials and in both of the trials combined. Rainy season, country, and age were all significantly associated with dengue disease in both studies. Vaccine efficacy did not change during the rainy season in any of the analyses. Although dengue transmission and exposure are expected to increase during the rainy season, our results indicate that CYD-TDV vaccine efficacy remains constant throughout the year in endemic regions.

We explored for geographic variations in coronary atheroma progression rates in the United States compared to other world regions (Canada, Latin America, Western Europe, and Central–Eastern Europe) and sought to ascertain if this associated with regional differences in major adverse cardiovascular events (MACE; cardiovascular death, nonfatal myocardial infarction, coronary revascularization). Across 7 randomized trials with a global recruitment pattern, 5,451 participants with angiographic coronary disease underwent serial coronary intravascular ultrasonography during 18 or 24 months, with adjudicated MACE. Change in coronary percent atheroma volume (ΔPAV) and MACE in the United States versus other world regions were assessed. Despite similar baseline angiographic and plaque characteristics across participants and regions, following propensity-weighted and multivariate analysis, US (n = 3,706) versus non-US (n = 1,745) participants demonstrated marginal but significantly greater annualized ΔPAV (least-square means ± SE: 0.27 ± 0.14% vs 0.062 ± 0.14%, p = 0.005). However, MACE rates were disproportionately higher in US compared to non-US participants (23.5% vs 10.9%, p <0.001), driven by a doubling in crude rates of coronary revascularization procedures (16.1% vs 7.8%, p <0.001). The US participants hospitalized with unstable angina demonstrated more significant disease progression than their non-US counterparts (ΔPAV: 0.57 ± 0.19% vs −0.30 ± 0.36%, p = 0.033) and greater MACE (9.1% vs 4.8%, p <0.001). A US geographic disposition independently associated with MACE (hazard ratio 1.53, 95% confidence interval 1.22 to 1.92, p <0.001). In conclusion, in participants with stable coronary disease, coronary atheroma progression rates are modestly higher in US-based compared to non-US–based participants. Elective coronary revascularization rates however are disproportionately greater in US-based participants.

•Bivalent Oral Polio Vaccine (bOPV) without type 2 poliovirus has replaced trivalent OPV globally.•Inactivated polio vaccine is now the only elective source of protection against type 2 poliovirus.•We examined the relationship of humoral and intestinal type 2 immunity from new IPV-bOPV schedules.•High neutralizing antibody titers were weakly associated with lower type 2 shedding. Inactivated polio vaccine (IPV) is now the only source of routine type 2 protection. The relationship, if any, between vaccine-induced type 2 humoral and intestinal immunity is poorly understood. Two clinical trials in five Latin American countries of mixed or sequential bOPV-IPV schedules in 1640 infants provided data on serum neutralizing antibodies (NAb) and intestinal immunity, assessed as viral shedding following oral mOPV2 challenge. Analyses with generalized additive and quantile regression models examined the relationships between prechallenge NAb titers and proportion, duration and titers (magnitude) of viral shedding. We found a statistically significant (p < .0001) but weak relationship between NAb titer at the time of mOPV2 challenge and the Shedding Index Endpoint, the mean log10 stool viral titer over 4 post-challenge assessments. Day 28 post-challenge shedding was 13.4% (8.1%, 18.8%) lower and the Day 21 post-challenge median titer of shed virus was 3.10 log10 (2.21, 3.98) lower for subjects with NAb titers at the ULOQ as compared with LLOQ on day of challenge. Overall, there was a weak but significant negative relationship, with high NAb titers associated with lower rates of viral shedding, an effect supported by subset analysis to elucidate between-country differences. Taken alone, the weak association between pre-challenge NAb titers following IPV or mixed/sequential bOPV/IPV immunization and differences in intestinal immunity is insufficient to predict polio type 2 intestinal immunity; even very high titers may not preclude viral shedding. Further research is needed to identify predictive markers of intestinal immunity in the context of global OPV cessation and IPV-only immunization.

BackgroundLATITUDE was the first phase 3 trial examining the survival benefit of adding abiraterone acetate (AA) + prednisone (P) to androgen-deprivation therapy (ADT) in newly diagnosed metastatic, castration-sensitive prostate cancer (mCSPC). Due to significant improvement in overall survival after the first interim analysis, patients in the placebos + ADT arm could switch to AA + P + ADT during an open-label extension. As in other studies where switching is allowed, statistical adjustments are needed to assess the real benefit of new drugs.Patients and MethodsThis was a post hoc analysis to estimate the true survival benefit of AA + P + ADT in patients with newly diagnosed mCSPC by applying statistical adjustments commonly used to adjust for treatment switching.ResultsOf 112 patients still receiving placebos + ADT at the first interim analysis, 72 switched to AA + P + ADT during the open-label extension. Final analysis was conducted after median follow-up of 51.8 months. Compared to the placebos + ADT arm, the risk of death in the AA + P + ADT arm was 34% lower [hazard ratio (HR) = 0.663 (95% confidence interval 0.566–0.778)] by unadjusted intent-to-treat analysis, 37% lower [HR = 0.629 (95% confidence interval 0.526–0.753)] by rank preserving structure failure time modeling, and 38% lower [HR = 0.616 (95% confidence interval 0.524–0.724)] by inverse probability of censoring weights.ConclusionsAnalyses adjusting for treatment switching using two different statistical approaches confirm the improved survival benefit of adding AA + P to ADT in patients with newly diagnosed mCSPC.Trial RegistrationClinicalTrials.gov identifier NCT01715285.