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Dengue is the most common arbovirus infection globally, but its burden is poorly quantified. We estimated dengue mortality, incidence, and burden for the Global Burden of Disease Study 2013. We modelled mortality from vital registration, verbal autopsy, and surveillance data using the Cause of Death Ensemble Modelling tool. We modelled incidence from officially reported cases, and adjusted our raw estimates for under-reporting based on published estimates of expansion factors. In total, we had 1780 country-years of mortality data from 130 countries, 1636 country-years of dengue case reports from 76 countries, and expansion factor estimates for 14 countries. We estimated an average of 9221 dengue deaths per year between 1990 and 2013, increasing from a low of 8277 (95% uncertainty estimate 5353–10 649) in 1992, to a peak of 11 302 (6790–13 722) in 2010. This yielded a total of 576 900 (330 000–701 200) years of life lost to premature mortality attributable to dengue in 2013. The incidence of dengue increased greatly between 1990 and 2013, with the number of cases more than doubling every decade, from 8·3 million (3·3 million–17·2 million) apparent cases in 1990, to 58·4 million (23·6 million–121·9 million) apparent cases in 2013. When accounting for disability from moderate and severe acute dengue, and post-dengue chronic fatigue, 566 000 (186 000–1 415 000) years lived with disability were attributable to dengue in 2013. Considering fatal and non-fatal outcomes together, dengue was responsible for 1·14 million (0·73 million–1·98 million) disability-adjusted life-years in 2013. Although lower than other estimates, our results offer more evidence that the true symptomatic incidence of dengue probably falls within the commonly cited range of 50 million to 100 million cases per year. Our mortality estimates are lower than those presented elsewhere and should be considered in light of the totality of evidence suggesting that dengue mortality might, in fact, be substantially higher. Bill & Melinda Gates Foundation.

Atrial fibrillation (AF) is a major risk factor for stroke. To enable improvements to AF diagnosis and follow-up care, understanding current patient pathways and barriers to optimal care are essential. We investigated the patient care pathways and their drivers, and the impact of the COVID-19 pandemic on patient pathways in a middle-income country setting, Brazil. This mixed-methods study in São Paulo, included adults ([greater than or equal to]18y) with AF from 13 primary/secondary healthcare facilities. Surveys using baseline, follow-up (administered [greater than or equal to]two months after baseline) and COVID-19 questionnaires (quantitative), and three focus group discussions (FGDs) were conducted. Minimum sample size for the quantitative component was 236 and we aimed to reach saturation with at least three FGDs for the qualitative component. Descriptive statistics were used for quantitative data and a content analysis was used for qualitative data to identify themes related to AF diagnosis and follow-up care. 267 participants completed the baseline questionnaire: 25% were diagnosed in primary care, 65% in an emergency or inpatient department. At follow-up (n = 259), 31% visited more than one facility for AF care, and 7% had no follow-up. Intervals between international normalised ratio (INR) tests were increased during the pandemic, and the number of healthcare visits and availability of medication were reduced. Seventeen patients participated in three FGDs and revealed that AF diagnosis often occurred following a medical emergency and patients often delay care-seeking due to misconceptions about AF symptoms. Long waiting times, doctor/patient interactions and health system factors, such as doctor availability and the referral system, influence where participants visited for follow-up care. Lack of public awareness and underdeveloped primary healthcare lead to delayed diagnosis, which impacts clinical outcomes and excess patient and healthcare system costs. Health system, care-provider, and pandemic factors disrupt timely and effective continuity of care.

Hypothyroidism is the common clinical condition of thyroid hormone deficiency and, if left untreated, can lead to serious adverse health effects on multiple organ systems, with the cardiovascular system as the most robustly studied target. Overt primary hypothyroidism is defined as elevated thyroid-stimulating hormone (TSH) concentration in combination with free thyroxine (fT4) concentration below the reference range. Subclinical hypothyroidism, commonly considered an early sign of thyroid failure, is defined by elevated TSH concentrations but fT4 concentrations within the reference range. Hypothyroidism is classified as primary, central or peripheral based on pathology in the thyroid, the pituitary or hypothalamus, or peripheral tissue, respectively. Acquired primary hypothyroidism is the most prevalent form and can be caused by severe iodine deficiency but is more frequently caused by chronic autoimmune thyroiditis in iodine-replete areas. The onset of hypothyroidism is insidious in most cases and symptoms may present relatively late in the disease process. There is a large variation in clinical presentation and the presence of hypothyroid symptoms, especially in pregnancy and in children. Levothyroxine (LT4) is the mainstay of treatment and is one of the most commonly prescribed drugs worldwide. After normalization of TSH and fT4 concentrations, a considerable proportion of patients treated with LT4 continue to have persistent complaints, compromising quality of life. Further research is needed regarding the appropriateness of currently applied reference ranges and treatment thresholds, particularly in pregnancy, and the potential benefit of LT4/liothyronine combination therapy for thyroid-related symptom relief, patient satisfaction and long-term adverse effects.Hypothyroidism is a common condition of insufficient thyroid hormone production or metabolism, which can be life-threatening if untreated. This Primer reviews hypothyroidism epidemiology, pathogenesis, diagnosis, screening and prevention programmes, current treatment approaches, and areas for additional research.

Thyroid disorders are highly prevalent, occurring most frequently in aging women. Thyroid-associated symptoms are very similar to symptoms of the aging process; thus, improved methods for diagnosing overt and subclinical hypothyroidism in elderly people are crucial. Thyrotropin measurement is considered to be the main test for detecting hypothyroidism. Combined evaluations of thyroid stimulating hormone (TSH) and free-thyroxine can detect overt hypothyroidism (high TSH with low free-thyroxine levels) and subclinical hypothyroidism (high TSH with normal free-thyroxine levels). It is difficult to confirm the diagnosis of thyroid diseases based only on symptoms, but presence of symptoms could be an indicator of who should be evaluated for thyroid function. The most important reasons to treat overt hypothyroidism are to relieve symptoms and avoid progression to myxedema. Overt hypothyroidism is classically treated using L-thyroxine; elderly patients require a low initial dose that is increased every 4 to 6 weeks until normalization of TSH levels. After stabilization, TSH levels are monitored yearly. There is no doubt about the indication for treatment of overt hypothyroidism, but indications for treatment of subclinical disease are controversial. Although treatment of subclinical hypothyroidism may result in lipid profile improvement, there is no evidence that this improvement is associated with decreased cardiovascular or all-cause mortality in elderly patients. In patients with a high risk of progression from subclinical to overt disease, close monitoring of thyroid function could be the best option.

Our goal was to evaluate cross-sectionally the association between ideal risk factor (IRF) profile and the presence and severity of subclinical atherosclerosis measured as coronary artery calcium (CAC) in the Brazilian Longitudinal Study of Adult Health. We included 4,077 participants with no prior history of cardiovascular disease aged 35 to 74 years who underwent CAC measurement. The 2010 Task Force of the American Heart Association cutoffs were used to define the ideal level of smoking, physical activity, diet, blood pressure, glucose/cholesterol levels, and body mass index. Participants were categorized according the number of IRF: 0 to 1 (n = 1,025, 25.1%), 2 (n = 1,200, 29.4%), 3 to 4 (n = 1,551, 38.1%), or 5 to 7 (n = 301, 7.4%). Compared to individuals with 0 to 1 IRF, the odds ratio of participants with 2 IRFs presenting with CAC >0 (compared to 0), ≥100 (compared to <100), and ≥400 (compared to <400) was 0.75 (95% CI 0.62-0.91), 0.64 (0.49-0.84), and 0.75 (0.49-1.15), respectively. Similarly, the odds ratios of CACs >0, ≥100, and ≥400 in individuals with 3 to 4 IRFs were 0.59 (95% CI 0.48-0.71), 0.46 (0.34-0.62), and 0.50 (0.30-0.83), respectively, and, for individuals with 5 to 7 IRFs, were 0.36 (95% CI 0.24-0.56), 0.22 (0.09-0.55), and 0.20 (0.03-1.45), respectively. Subjects with an IRF profile have lower CAC when compared to subjects with fewer controlled risk factors. However, even among individuals with 5 to 7 IRFs, it is possible to find a CAC higher than zero reflecting that measures of IRF do not fully account for all factors that resulted in coronary artery disease.

Few studies have evaluated the association between diet and mental disorders, and it has been established that ω-3 (n-3) fatty acids may have a beneficial effect for sufferers of anxiety disorders. This study is part of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)—a population-based cohort study on diet and mental health—and searched for associations between anxiety disorders and consumption of n-3 polyunsaturated fatty acids (PUFA). The study had a cross-sectional design, with a total sample of 12,268 adults. Dietary exposure was measured by a quantitative food-frequency questionnaire, and mental diagnoses were assessed by the Clinical Interview Schedule—Revised Version and diagnosed according to the International Classification of Diseases (ICD-10). Logistic regression models were built using quintiles of n-3, ω 6 (n-6), n-6/n-3 ratio, and PUFA, using the 1st quintile as reference. Anxiety disorders were identified in 15.4% of the sample. After adjusting for sociodemographic variables, cardiovascular risk factors, diet variables, and depression, intakes in the 5th quintile were inversely associated with anxiety disorders for EPA (OR = 0.82, 95% CI = 0.69–0.98), DHA (OR = 0.83, 95% CI = 0.69–0.98), and DPA (OR = 0.82, 95% CI = 0.69–0.98). Participants in the fifth quintile of n-6/n-3 ratio had a positive association with anxiety disorders. Although results suggest a possible protective effect of n-3 fatty acids against anxiety, all associations lost significance after adjustment for multiple comparisons.

Low-density lipoproteins (LDL) comprise a pool of particles with different densities that may have variable impact on atherogenesis. Studies suggest that obese individuals with elevated body mass index (BMI) and waist circumference (WC) have increased small and dense LDL subfractions (sdLDL-c). It is unclear if diabetes (T2D) and insulin resistance (IR) may modify this association. We included 4,111 (50.4 ± 8.6 years of age, 45.5% men) individuals with neither prior cardiovascular disease nor use of lipid-lowering medications. Total LDL-c and its subfractions (LDL 1 -c, LDL 2 -c, LDL 3 -c, and LDL 4 -c) were measured by vertical zonal ultracentrifugation. We considered the subfractions LDL 1 -c and LDL 2 -c as large buoyant LDL (lbLDL-c) and the subfractions LDL 3 -c and LDL 4 -c as sdLDL-c. We analyzed the association between LDL-c subclasses, BMI and WC using linear regression analysis and stratified by the presence of T2D and IR. For sdLDL-c, a direct association with hypertension, T2D, fasting plasma glucose, total cholesterol, LDL-c, and triglycerides was observed. In multivariate analysis, after adjustment for age, sex, race and triglycerides, the strong association of sdLDL-c with BMI (β 95% CI 0.16 (0,13–0,19)) and WC (β 95% CI 0.22 (0.19–0.26)) persisted. After stratification, the association of sdLDL-c and WC was present only in those with insulin resistance or diabetes. BMI showed a smaller impact than WC on this association. WC and BMI were strongly associated with sdLDL-c subfractions. Further, this association was modified by diabetes and insulin resistance status.

Identifying existing care pathways is the first step for understanding how services can be improved to enable early diagnosis and effective follow-up care for non-communicable diseases (NCDs); however, evidence on how care pathways can and should be identified in low- and middle-income countries (LMICs) is lacking. To describe generalisability and lessons learned from recruitment and data collection for the quantitative component of a mixed methods study designed to determine the care pathway for atrial fibrillation (AF) in Brazil, China and Sri Lanka. Adults (≥18 years) that spoke the local language and with an AF diagnosis were eligible. We excluded anyone with a hearing or cognitive impairment or ineligible address. Eligible participants were identified using electronic records in Brazil and China; in Sri Lanka, researchers attended the outpatient clinics to identify eligible participants. Data were collected using two quantitative questionnaires administered at least 2-months apart. A minimum sample size of 238 was required for each country. The required sample size was met in Brazil (n = 267) and China (n = 298), but a large proportion of AF patients could not be contacted (47% and 27%, respectively) or refused to participate (36% and 38%, respectively). In Sri Lanka, recruitment was challenging, resulting in a reduced sample (n = 151). Mean age of participants from Brazil, China and Sri Lanka was 69 (SD = 11.3), 65 (SD = 12.8) and 58 (SD = 11.7), respectively. Females accounted for 49% of the Brazil sample, 62% in China and 70% in Sri Lanka. Generalisability was an issue in Brazil and China, as was selection bias. Recruitment bias was highlighted in Sri Lanka. Additional or alternative recruitment methods may be required to ensure generalisability and reduce bias in future studies aimed at identifying NCD care pathways in LMICs.

We aimed to study the association between the American Heart Association cardiovascular health (CVH) score and job strain in the Brazilian Longitudinal Study of Adult Health baseline. We analyzed data from 11,351 active workers (aged 35 to 74 years) without overt cardiovascular disease and who had complete data. Job strain was assessed using the 17-item Brazilian version of the Swedish Job Demand-Control-Support Questionnaire. Clinical (fasting plasma glucose, total cholesterol, and blood pressure) and lifestyle (diet, physical activity, smoking, and body mass index) components of CVH score were assessed according to the American Heart Association criteria. We used quasi-Poisson and multinomial regression models, adjusted for age, gender, race, educational level and income, and positive relative predicted score differences (rPSDs) indicate greater predicted scores. Subjects with low skill discretion scores had lower global (rPSD: −1.8%; p = 0.021) and lifestyle (rPSD: −3.6%; p = 0.018) CVH scores. Participants with low decision authority (rPSD: −2.4%; p = 0.029) and low social support scores (rPSD: −3.3%; p = 0.001) also had lower lifestyle CVH scores. In conclusion, we found significant associations between job strain and CVH scores in this large multicenter sample.