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Meningeal sporotrichosis is rare and occurs predominantly in immunosuppressed individuals. This retrospective study explored clinical and laboratory characteristics, treatment, and prognosis of patients with disseminated sporotrichosis who underwent lumbar puncture (LP) at a Brazilian reference center from 1999 to 2020. Kaplan-Meier and Cox regression models were used to estimate overall survival and hazard ratios. Among 57 enrolled patients, 17 had meningitis. Fifteen (88.2%) had HIV infection, and in 6 of them, neurological manifestations occurred because of the immune reconstitution inflammatory syndrome (IRIS). The most frequent symptom was headache (88.2%). Meningeal symptoms at first LP were absent in 7/17 (41.2%) patients. Sporothrix was diagnosed in cerebrospinal fluid either by culture or by polymerase chain reaction in seven and four patients, respectively. All but one patient received prolonged courses of amphotericin B formulations, and seven received posaconazole, but relapses were frequent. Lethality among patients with meningitis was 64.7%, with a higher chance of death compared to those without meningitis (HR = 3.87; IC95% = 1.23;12.17). Meningeal sporotrichosis occurs mostly in people with HIV and can be associated with IRIS. Screening LP is indicated in patients with disseminated disease despite the absence of neurological complaints. Meningitis is associated with poor prognosis, and better treatment strategies are needed.

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OBJECTIVE: Some patients with dengue fever tend to develop thrombocytopenia during the course of infection and are thus vulnerable to haemorrhagic manifestations and other complications. However, the factors associated with the development of thrombocytopenia are unknown. We aimed to identify factors associated with an increased risk of thrombocytopenia and haematological changes in patients with confirmed dengue fever. DESIGN: Retrospective cohort study. SETTING: Brazilian multicentre primary care databases. PARTICIPANTS: 387 patients had positive laboratory serological confirmation of dengue infection during 2014. The data were identified from two databases: Notification of Injury Information System (SINAN) and Municipal Laboratory. MAIN OUTCOME MEASURE: The presence of thrombocytopenia (platelet count <1 50×109/L). The associations of factors that predisposed patients to thrombocytopenia and haematological changes were analysed using logistic regression. ORs and 95% CIs were calculated. RESULTS: Among 387 patients, 156 had both dengue and thrombocytopenia. The risk factors associated with thrombocytopenia included male sex (OR: 1.77, 95% CI: 1.16 to 2.71, p=0.007), age of 46-64 years (OR: 2.20, 95% CI: 1.15 to 4.21, p=0.009) or ≥65 years (OR: 3.02, 95% CI: 1.40 to 6.50, p=0.002), presence of leucopenia (OR: 6.85, 95% CI: 4.27 to 10.99, p<0.001) and high mean corpuscular haemoglobin (MCH) levels (OR: 2.00, 95% CI: 1.29 to 3.12, p=0.005). CONCLUSION: Older age, male sex, presence of leucopenia and high MCH levels were identified as risk factors associated with the development of thrombocytopenia in this population.

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The effects of dose reduction or spacing of all types of biologics in rheumatoid arthritis has not been consistently assessed in systematic reviews. We aimed to assess the effects of biologics reduction compared with dose maintenance in patients with rheumatoid arthritis in low disease activity or remission. We performed a systematic review with meta-analysis according to a previously registered protocol (PROSPERO registration: CRD42017069080); and searched MEDLINE, Embase, Scopus, Cochrane Library and trial registers up to July, 2020. Two researchers selected, extracted and assessed the risk of bias of controlled trials that randomized patients to reduction/spacing or dose maintenance of biologics. Low disease activity, disability and other clinically important outcomes were summarized in random effect meta-analyses. We rated the certainty of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation approach. We included ten studies (n = 1331 patients), which assessed reduction or spacing of abatacept, adalimumab, certolizumab pegol, etanercept, or tocilizumab. Risk of bias was high in over half of trials, mainly due to lack of blinding. No statistically significant difference was found in low disease activity (RR = 0.90; 95% CI 0.78-1.04; I2 = 60%, very low certainty), and other outcomes. Subgroup analysis of blinded studies led to homogeneous results, which remained heterogeneous in open-label studies. Reduction or spacing biologics did not affect disease activity and other important outcome. Changes in the doses regimen should consider patient preferences, considering the low certainty of evidence.

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OBJECTIVES: To estimate the prevalence of multimorbidity and to identify factors associated with it in the adult population from the metropolitan region of Manaus. DESIGN: Cross-sectional population-based study. SETTING: Interviews conducted between May and August of 2015 in eight cities that compose the metropolitan region of Manaus, Amazonas, Brazil. PARTICIPANTS: 4001 adults aged ≥18 years. PRIMARY OUTCOME MEASURES: Multimorbidity, measured by the occurrence of ≥2 and ≥3 chronic diseases, was the primary outcome. The associated factors were investigated by calculating the prevalence ratio (PR) obtained by Poisson regression, with robust adjustment of the variance in a hierarchical model. A factor analysis was conducted to investigate multimorbidity clusters. RESULTS: Half of the interviewees were women. The presence of a chronic disease was reported by 57.2% (95% CI 56.6% to 59.7%) of the interviewees, and the mean morbidity was 1.2 (1.1-1.2); 29.0% (95% CI 27.6% to 30.5%) reported ≥2 morbidities and 15.2% (95% CI 14.1% to 16.4%) reported ≥3 chronic conditions. Back pain was reported by one-third of the interviewees. Multimorbidity was highest in women, PR=1.66 (95% CI 1.50 to 1.83); the elderly, PR=5.68 (95% CI 4.51 to 7.15) and individuals with worse health perception, PR=3.70 (95% CI 2.73 to 5.00). Associated factors also included undergoing medical consultations, hospitalisation in the last year, suffering from dengue in the last year and seeking the same healthcare service. Factor analysis revealed a pattern of multimorbidity in women. The factor loading the most strength of association in women was heart disease. In men, an association was identified in two groups, and lung disease was the disease with the highest factorial loading. CONCLUSION: Multimorbidity was frequent in the metropolitan region of Manaus. It occurred most often in women, in the elderly and in those with worse health perception.

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BACKGROUND: The purpose of this study was to assess the prevalence and associated factors of generalized anxiety disorder (GAD) in adults using the seven-item GAD scale (GAD-7) and to evaluate the properties of the two-item (GAD-2) as a population screening tool. METHODS: We carried out a cross-sectional population-based study in the Manaus Metropolitan Region in 2015, Brazil. Adults aged 18 years or more were eligible to participate. We performed probabilistic three-phase sampling and collected sociodemographic and clinical variables. Descriptive statistics and a Poisson regression with robust variance with corrections for complex sampling were used. The accuracy of GAD-2 was assessed using GAD-7 as the gold standard. RESULTS: We included 4001 participants. The prevalence of GAD was 8.4% (95% confidence interval 7.6-9.4%) and was significantly associated with self-reported poor health status and presenting depressive symptoms (p < 0.01). GAD-2 sensitivity was 63.9%, and its specificity was 97.4%. LIMITATIONS: Because of the cross-sectional design of the study, the results are prone to reverse causality and recall bias. The surveyed people were not questioned about their medical diagnosis of anxiety, access to mental health services, or alcohol, tobacco or other drug use. The screening tools were not validated in the Brazilian or Amazon population. CONCLUSION: About eight in 100 adults living in Manaus presented GAD, and it is more prevalent among people with a poorer health status and depression. Because of its low sensitivity, GAD-2 is not useful as a screening tool.

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Given the high prevalence of hypertension in adolescents, it is important to investigate alternatives for estimating the magnitude of the disease. Our objective was to investigate the accuracy of self-reported hypertension. The study assessed participants of the Study of Cardiovascular Risk in Adolescents (ERICA). The following were calculated: sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The associations between inaccurate self-reporting and socioeconomic factors were investigated. The accuracy of self-reported hypertension had a sensitivity of 7.5% (95% CI, 6.9-8.2), a specificity of 96.6% (95% CI, 96.5-96.7), a PPV of 18.9% (95% CI, 17.4-20.5), and a NPV of 90.8% (95% CI, 90.6-91.0). The prevalence of inaccurate self-reported hypertension was smaller among girls (PR 0.68; 95% CI, 0.55-0.83) and younger boys (PR 0.68; 95% CI, 0.54-0.86) who were attending private schools. The use of self-reported hypertension was not a good strategy for investigating the hypertension in adolescents.

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OBJECTIVES: To estimate the prevalence of healthcare use and associated factors in the Manaus metropolitan region and to describe the reasons for lack of access. DESIGN: Cross-sectional population-based study. SETTING: A survey conducted between May and August of 2015 in eight cities from Manaus metropolitan region, Amazonas, Brazil. PARTICIPANTS: 4001 adults ≥18 years of age. PRIMARY OUTCOMES MEASURES: Physician visits, dentist visits and hospitalisations in the last 12 months were the primary outcomes. Associated factors were investigated through the calculation of prevalence ratio (PR) obtained by hierarchical Poisson regression modelling. RESULTS: 4001 adults were included in the study, 53% of whom were women. The self-reported prevalence of medical visits was 77% (95% CI 75% to 77%); dentist visits, 36% (95% CI 34% to 37%) and hospital admission, 7% (95% CI 6% to 7%). Physician visits were higher in women PR=1.18 (95% CI 1.14 to 1.23), the elderly PR=1.18 (95% CI 1.10 to 1.26) and people with health insurance PR=1.14 (95% CI 1.10 to 1.19). Dentist visits declined with older age PR=0.38 (95% CI 0.30 to 0.49), lower education level PR=0.62 (95% CI 0.51 to 0.74) and lower economic class PR=0.65 (95% CI 0.57 to 0.75). Hospitalisations were found to be twice as frequent for women than for men and three times as frequent among those who reported very poor health status. Among the individuals who did not receive medical attention in the previous 2 weeks, 58% reported lack of facilities or appointment unavailable and 14% reported lack of doctors. CONCLUSION: While more than half visited the doctor in the last year, a lower proportion of people with socioeconomic inequities visited the dentist. Organisational and service policies are needed to increase equity in health services in the region.

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BACKGROUND: Depression is an affective disorder and one of the main contributors to the burden of disease worldwide. Our purpose is to estimate the prevalence of depressive symptoms and associated factors in the population of the Manaus Metropolitan Region. METHODS: We conducted a population-based, cross-sectional study with a probabilistic three-phase sampling in 2015, based on a previously calculated sample size. Adults living in Manaus and seven inner cities of the metropolitan region were surveyed for depressive symptoms using the Patient Health Questionnaire (PHQ-9) and a cutoff score of ≥ 9. We performed a Poisson regression with robust variance using a hierarchical approach to calculate the prevalence ratio (PR) of depression and 95% confidence intervals (CIs). RESULTS: Among 4001 participants (response rate 76%), the prevalence of current depressive symptoms was 7% (95% CI: 6-8%). Depressive symptoms were more frequent in inhabitants of Manaus than in those from the countryside (PR = 6.13, 95% CI: 2.91-12.91); in women than in men (PR = 2.55, 95% CI: 1.96-3.33); in indigenous than in white people (PR = 2.56, 95% CI: 1.24-5.30); and in those with hypertension (PR = 1.47, 95% CI: 1.13-1.92), cardiac disease (PR = 1.62, 95% CI: 1.12-2.33), and poor health status (fair: PR = 5.10, 95% CI: 2.50-10.37; bad: PR = 10.27, 95% CI: 4.92-21.44 very bad: PR = 21.14, CI 95%: 10.16-43.99). High school education (PR = 0.55, 95% CI: 0.32-0.95) and middle class economic status (PR = 0.33, 95% CI: 0.12-0.89) were protective factors. LIMITATIONS: Limitations include the lack of measurement of physical activity, religious beliefs, leisure time, and use of alcohol and other drugs since these factors can affect depression and health status. CONCLUSION: Seven out of every 100 adults from the Manaus Metropolitan Region have depressive symptoms. This rate is higher in women, individuals living in Manaus, indigenous people, people with hypertension or chronic cardiac disease, and those with a poor health status.

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Objective: To estimate and compare the effect of self-reported long-term health conditions and sociodemographic factors on perceived health-related quality of life (HRQoL). Methods: A population-based survey of adults (18 to 65 years) living in Brasilia, Brazil, was conducted in 2012. Descriptive and multivariate analyses using a Tobit model were performed with data on sociodemographic variables, self-reported conditions, and the European Quality of Life-5 Dimensions (EQ-5D) health states, providing utility scores (preferred health state) between 0 and 1 for HRQoL estimates. Results: The mean utility of 1,820 adults interviewed (mean age: 38.4±12.6 years) was 0.883 (95% confidence interval [95%CI] 0.874-0.892), with 76.2% in the highest utility range (0.8 to 1.0). EQ-5D dimensions with moderate problems were pain/discomfort (33.8%) and anxiety/depression (20.5%). Serious problems were reported by only 0.3% of the sample in the mobility and self-care domain and by 3.1% in the pain/discomfort domain. Multivariate analysis revealed reduced HRQoL in individuals with depression, diabetes, and hypertension. Living in satellite towns (outside the city core), belonging to a lower economic class, or not being formally employed were also associated with decreased HRQoL. Beta coefficients for these impacts ranged from -0.033 (not formally employed) to -0.141 (depression), reflecting the strongest impact. Conclusion: Of the long-term health conditions studied, depression had the greatest impact on HRQoL. Social class, employment status, and place of residence also affected HRQoL.

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OBJECTIVE:: To estimate and compare the effect of self-reported long-term health conditions and sociodemographic factors on perceived health-related quality of life (HRQoL). METHODS:: A population-based survey of adults (18 to 65 years) living in Brasilia, Brazil, was conducted in 2012. Descriptive and multivariate analyses using a Tobit model were performed with data on sociodemographic variables, self-reported conditions, and the European Quality of Life-5 Dimensions (EQ-5D) health states, providing utility scores (preferred health state) between 0 and 1 for HRQoL estimates. RESULTS:: The mean utility of 1,820 adults interviewed (mean age: 38.4±12.6 years) was 0.883 (95% confidence interval [95%CI] 0.874-0.892), with 76.2% in the highest utility range (0.8 to 1.0). EQ-5D dimensions with moderate problems were pain/discomfort (33.8%) and anxiety/depression (20.5%). Serious problems were reported by only 0.3% of the sample in the mobility and self-care domain and by 3.1% in the pain/discomfort domain. Multivariate analysis revealed reduced HRQoL in individuals with depression, diabetes, and hypertension. Living in satellite towns (outside the city core), belonging to a lower economic class, or not being formally employed were also associated with decreased HRQoL. Beta coefficients for these impacts ranged from -0.033 (not formally employed) to -0.141 (depression), reflecting the strongest impact. CONCLUSION:: Of the long-term health conditions studied, depression had the greatest impact on HRQoL. Social class, employment status, and place of residence also affected HRQoL.

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The aim of this study was to identify the factors associated with the combined use of antidepressants and benzodiazepines (BDZs) in patients with major depression. We conducted a case-control study in the public health service of the city of São Paulo, Brazil. The participants were all patients being treated with antidepressants, who were diagnosed with major depression. Patients who received a combination of antidepressants and BDZs were classified as cases, and those who used only antidepressants, as controls. Data were obtained from a pharmacy database, medical records and interviews with the healthcare team. The association of predisposing factors for combined therapy was analysed using logistic regression analysis, and the odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Of the 1355 users of antidepressants, 265 had major depression, of whom 138 were cases and 127 were controls. The factors associated with combined use were age older than 35 years (OR 2.2, 95% CI 1.0-4.7), absence of comorbidities (OR 2.3, 95% CI 1.4-4.1) and no use of other drugs (OR 1.9, 95% CI 1.1-3.3). Patients with combined use were more likely to exhibit inadequate prescribing, including inappropriate antidepressants (OR 4.7, 95% CI 2.2-9.9), inadequate dosages (OR 3.62, 95% CI 1.4-9.6) and/or a non-recommended duration (OR 66.6, 95% CI 18.4-240.7). The factors identified showed the groups most susceptible to combined use in this population, who in turn are more likely to receive inappropriate prescriptions.

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OBJECTIVE: To estimate the prevalence of obesity and overweight and associated factors in indigenous people of the Jaguapiru village in Central Brazil. METHODS: We conducted a population-based cross-sectional study between January 2009 and July 2011 in the adult native population of the Jaguapiru village, Central Brazil. Sociodemographic and lifestyle data were obtained; anthropometric measures, arterial blood pressure, and blood glucose were measured. The independent variables were tested by Poisson regression, and the interactions between them were analyzed. RESULTS: 1,608 indigenous people (982 females, mean age 37.7 ± 15.1 years) were included. The prevalence of obesity was 23.2% (95% CI 20.9-25.1%). Obesity was more prevalent among 40- to 49-year-old and overweight among 50- to 59-year-old persons. Obesity was positively associated with female sex, higher income, and hypertension. Among indigenous people, interactions were found with hypertension and sedentary lifestyle - hypertension in males and sedentary lifestyle in females. CONCLUSIONS: The prevalence of obesity and overweight in indigenous people of the Jaguapiru village is high. Males as well as hypertensive and higher family income individuals have higher rates. Sedentary lifestyle and hypertension leverage the rates of obesity. Prevention and adequate public health policies can be critical for the control of excess weight and its comorbidities among Brazilian indigenous people.

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Aim. The aim of this study was to estimate the prevalence of diabetes and its associated risk factors in adults from Brasilia, Brazil. Methods. The present cross-sectional population-based study consisted of interviews with individuals aged 18-65 years. Participants were selected through two-stage probability sampling by clusters and stratified by sex and age. Demographic and clinical data were collected directly with participants from February to May 2012. Self-reported diabetes prevalence was calculated at a 95% confidence interval (CI). Prevalence ratios (PR) were adjusted by Poisson regression with robust variance. Results. In all, 1,820 individuals were interviewed. Diabetes prevalence in the adult population of Brasilia was 10.1% (95% CI, 8.5%-11.6%). Variables associated with diabetes were an age between 35 and 49 years (PR = 1.83; 95% CI, 1.19-2.82) or 50 and 65 years (PR = 1.95; 95% CI, 1.17-3.23), hypertension (PR = 4.04; 95% CI, 2.66-6.13), respiratory disease (PR = 1.67; 95% CI, 1.11-2.50), cardiovascular disease (PR = 1.74; 95% CI, 1.15-2.63), and pain/discomfort (PR = 1.71; 95% CI, 1.21-2.41). Conclusion. Diabetes is a prevalent condition in adults living in Brasilia, and disease risk increases with age and comorbidities. Future health policies should focus on screening programs and prevention for the more vulnerable groups.

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Objective: To estimate the prevalence of depressive symptoms and major depressive disorder, as assessed in population-based cross-sectional studies of Brazilian adults. Methods: We performed a systematic review of the literature. The major databases were searched up through October 2013. Two researchers selected the studies, extracted the data, and assessed their methodological quality. Meta-analyses were performed using random effects. Results: Of the 2,971 records retrieved, we selected 27 studies that assessed the prevalence of depression morbidity in 464,734 individuals (66% women). Eleven different screening tools were used to assess depression morbidity. The prevalence of depressive symptoms was 14% (95% confidence interval [95%CI] 13-16; I2 = 99.5%), whereas the 1-year prevalence of major depressive disorder was 8% (95%CI 7-10; I2 = 86.7%), and the lifetime prevalence of major depressive disorder was 17% (95%CI 14-19; I2 = 91.6%). All rates were higher in women than in men. No causes of heterogeneity could be identified. Conclusion: Depression morbidity was common among Brazilian adults, and affects more women than men. Inconsistencies across studies highlight the need for standardization of future research. Clinicians should routinely investigate for the presence of depression morbidity in this population. .

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OBJECTIVE: To estimate the prevalence of depressive symptoms and major depressive disorder, as assessed in population-based cross-sectional studies of Brazilian adults. METHODS: We performed a systematic review of the literature. The major databases were searched up through October 2013. Two researchers selected the studies, extracted the data, and assessed their methodological quality. Meta-analyses were performed using random effects. RESULTS: Of the 2,971 records retrieved, we selected 27 studies that assessed the prevalence of depression morbidity in 464,734 individuals (66% women). Eleven different screening tools were used to assess depression morbidity. The prevalence of depressive symptoms was 14% (95% confidence interval [95%CI] 13-16; I2 = 99.5%), whereas the 1-year prevalence of major depressive disorder was 8% (95%CI 7-10; I2 = 86.7%), and the lifetime prevalence of major depressive disorder was 17% (95%CI 14-19; I2 = 91.6%). All rates were higher in women than in men. No causes of heterogeneity could be identified. CONCLUSION: Depression morbidity was common among Brazilian adults, and affects more women than men. Inconsistencies across studies highlight the need for standardization of future research. Clinicians should routinely investigate for the presence of depression morbidity in this population.

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OBJECTIVE: To assess the effects of problem-based learning (PBL) on the learning achievements of pharmacy students. METHODS: We searched for controlled studies that compared PBL to traditional learning in pharmacy courses (graduate and undergraduate) in the major literature databases up to January 2014. Two independent researchers selected the studies, extracted the data, and assessed the quality of the studies. Meta-analyses of the outcomes were performed using a random effects model. RESULTS: From 1,988 retrieved records, five were included in present review. The studies assessed students' impressions about the PBL method and compared student grades on the midterm and final examinations. PBL students performed better on midterm examinations (odds ratio [OR] = 1.46; confidence interval [IC] 95%: 1.16, 1.89) and final examinations (OR = 1.60; IC 95%: 1.06, 2.43) compared with students in the traditional learning groups. No difference was found between the groups in the subjective evaluations. CONCLUSION: pharmacy students' knowledge was improved by the PBL method. Pharmaceutical education courses should consider implementing PBL.

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PURPOSE: To assess the prevalence of medicine use in adults of Brasilia and to elucidate the associated factors. METHODS: A cross-sectional study was conducted with adults (18 to 65 years) living in Brasilia, who were selected using a two-stage probabilistic sampling and interviewed in their home, from February to May 2012. The primary outcome was the use of medicines in the last 7 days. A Poisson regression with robust variance was employed to adjust for covariates following a hierarchical model. RESULTS: The study included 1820 individuals (11% losses), 60% of which were women, and the mean age was 37 ± 12.6 years. The prevalence of drug consumption was 35.7% (95% confidence interval [95%CI]: 33.5%-37.9%). Medicine consumption was significantly higher in women (prevalence ratio [PR] = 1.54; 95%CI: 1.28-1.85); unemployed or retired people (PR = 1.35; 95%CI: 1.15-1.59); people with hypertension (PR = 2.33; 95%CI: 2.00-2.71), diabetes (PR = 1.46; 95%CI: 1.22-1.74), depression (PR = 1.32; 95%CI: 1.13-1.53), or other chronic diseases (PR = 1.50; 95%CI: 1.26-1.79); and study participants who had a recent medical consultation (PR = 1.49; 95%CI: 1.29-1.71). Medication use was significantly higher at older ages. The participants obtained about half of the drugs from the Brazilian public health system, but this access was significantly different according to the economic class. CONCLUSIONS: Medication use was common among adults living in Brasilia and is associated with sex, age, health conditions, and access to healthcare.

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OBJECTIVE: The aim of the present study was to assess the prevalence of hypertension and cardiovascular risk factors among the native indigenous of Jaguapiru village in Dourados, Mato Grosso do Sul, Brazil. METHOD: A cross-sectional, population-based study was conducted with adult indigenous aged 18 years or more. The subjects' blood pressure was measured twice, and the mean of the two measurements was calculated. Body weight, height, capillary blood glucose and waist circumference were measured. Pregnant women, individuals using glucocorticoids, and non-indigenous villagers and their offspring were excluded. Multivariate regression analyses were conducted on the socio-demographic and clinical independent variables. Interactions between independent variables were also tested. RESULTS: We included 1,608 native indigenous eligible to the research. The prevalence of hypertension was 29.5% (95% CI: 27-31.5), with no significant difference between the genders. For both men and women, diastolic hypertension was more common than systolic hypertension. The prevalence of hypertension was higher among obese, diabetic, and older participants, as well as those who consumed alcohol, had a lower educational level, or had a family history of hypertension. There was no association between hypertension and tobacco smoking or family income. CONCLUSION: Hypertension among the indigenous from Jaguapiru village was similar to the prevalence in the Brazilians, but may have a more negative effect in such disadvantaged population. The associated factors we found can help drawing prevention policies.

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BACKGROUND: Because the incidence of depression increases after puberty, it is possible that pubertal timing in girls influences the onset of depression. Our objective was to assess the effect of early and late puberty in girls on the incidence of depression. METHODS: We systematically searched relevant databases for controlled studies that assessed the impact of pubertal timing in girls on the incidence of depression or depressive symptoms. The last search was completed in August 2013. Two authors selected the studies, extracted the data, and assessed the quality of the evidence. Meta-analyses of the adjusted and unadjusted results were calculated using random effects. RESULTS: Four cohort studies were included (n=8055 participants). Early puberty significantly increased the risk of new cases of depression in the unadjusted meta-analysis (RR=1.33; CI 95%: 1.02, 1.73) but not in the adjusted estimate of two of the included studies (RR=1.48; CI 95%: 0.69, 2.28). For late puberty, no significant associations were found (unadjusted RR=1.28; CI 95%: 0.87, 1.88). Two studies assessed the effect of early puberty on depressive symptoms and found positive associations. The quality of the available evidence was rated as very low. LIMITATIONS: The polled results had wide confidence intervals, and the available evidence was of very low quality. CONCLUSIONS: The available evidence supports little confidence regarding the impact of pubertal timing on the onset of depression in girls but suggests that early puberty in girls may increase the risk of depression. Further higher quality studies are needed to clarify the association between pubertal timing and the incidence of depression in girls and women.

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