Parasite load and risk factors for poor outcome among children with visceral leishmaniasis. A cohort study in Belo Horizonte, Brazil, 2010-2011

Clinical and laboratory risk factors for death from visceral leishmaniasis (VL) are relatively known, but quantitative real-time polymerase chain reaction (qPCR) might assess the role of parasite load in determining clinical outcome. The aim of this study was to identify risk factors, including parasite load in peripheral blood, for VL poor outcome among children. This prospective cohort study evaluated children aged ≤ 12 years old with VL diagnosis at three times: pre-treatment (T0), during treatment (T1) and post-treatment (T2). Forty-eight patients were included and 16 (33.3%) met the criteria for poor outcome. Age ≤ 12 months [relative risk (RR) 3.51; 95% confidence interval (CI) 1.89-6.52], tachydyspnoea (RR 3.46; 95% CI 2.19-5.47), bacterial infection (RR 3.08; 95% CI 1.27-7.48), liver enlargement (RR 3.00; 95% CI 1.44-6.23) and low serum albumin (RR 7.00; 95% CI 1.80-27.24) were identified as risk factors. qPCR was positive in all patients at T0 and the parasite DNA was undetectable in 76.1% of them at T1 and in 90.7% at T2. There was no statistical association between parasite load at T0 and poor outcome.

Association of alcohol consumption and HIV surrogate markers in participants of the swiss HIV cohort study.

BACKGROUND: Alcohol consumption may affect the course of HIV infection and/or antiretroviral therapy (ART). The authors investigated the association between self-reported alcohol consumption and HIV surrogate markers in both treated and untreated individuals. DESIGN: Prospective cohort study. METHODS: Over a 7-year period, the authors analyzed 2 groups of individuals in the Swiss HIV Cohort Study: (1) ART-naïve individuals remaining off ART and (2) individuals initiating first ART. For individuals initiating first ART, time-dependent Cox proportional hazards models were used to assess the association between alcohol consumption, virological failure, and ART interruption. For both groups, trajectories of log-transformed CD4 cell counts were analyzed using linear mixed models with repeated measures. RESULTS: The authors included 2982 individuals initiating first ART and 2085 ART naives. In individuals initiating first ART, 241 (8%) experienced virological failure. Alcohol consumption was not associated with virological failure. ART interruption was noted in 449 (15%) individuals and was more prevalent in severe compared with none/light health risk drinkers [hazard ratio: 2.24, 95% confidence interval: 1.42 to 3.52]. The association remained significant even after adjusting for nonadherence. The authors did not find an association between alcohol consumption and change in CD4 cell count over time in either group. CONCLUSIONS: No effect of alcohol consumption on either virological failure or CD4 cell count in both groups of ART-initiating and ART-naive individuals was found. However, severe drinkers were more likely to interrupt ART. Efforts on ART continuation should be especially implemented in individuals reporting high alcohol consumption.

Age-related differences in the use of guideline-recommended medical and interventional therapies for acute coronary syndromes: a cohort study.

OBJECTIVES: To compare the use of guideline-recommended medical and interventional therapies in older and younger patients with acute coronary syndromes (ACSs). DESIGN: Prospective cohort study. SETTING: Fifty-five hospitals in Switzerland. PARTICIPANTS: Eleven thousand nine hundred thirty-two patients with ACS enrolled between March 1, 2001, and June 30, 2006. ACS definition included ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI), and unstable angina pectoris (UA). MEASUREMENTS: Use of medical and interventional therapies was determined after exclusion of patients with contraindications and after adjustment for comorbidities. Multivariate logistic regression models were used to calculate odds ratios (ORs) per year increase in age. RESULTS: Elderly patients were less likely to receive acetylsalicylic acid (OR=0.976, 95% confidence interval (CI)=0.969-0.980) or beta-blockers (OR=0.985, 95% CI=0.981-0.989). No age-dependent difference was found for heparin use. Elderly patients with STEMI were less likely to receive percutaneous coronary intervention (PCI) or thrombolysis (OR=0.955, 95% CI=0.949-0.961). Elderly patients with NSTEMI or UA less often underwent PCI (OR=0.943, 95% CI=0.937-0.949). CONCLUSION: Elderly patients across the whole spectrum of ACS were less likely to receive guideline-recommended therapies, even after adequate adjustment for comorbidities. Prognosis of elderly patients with ACS may be improved by increasing adherence to guideline-recommended medical and interventional therapies.

HACEK infective endocarditis: characteristics and outcomes from a large, multi-national cohort.

The HACEK organisms (Haemophilus species, Aggregatibacter species, Cardiobacterium hominis, Eikenella corrodens, and Kingella species) are rare causes of infective endocarditis (IE). The objective of this study is to describe the clinical characteristics and outcomes of patients with HACEK endocarditis (HE) in a large multi-national cohort. Patients hospitalized with definite or possible infective endocarditis by the International Collaboration on Endocarditis Prospective Cohort Study in 64 hospitals from 28 countries were included and characteristics of HE patients compared with IE due to other pathogens. Of 5591 patients enrolled, 77 (1.4%) had HE. HE was associated with a younger age (47 vs. 61 years; p<0.001), a higher prevalence of immunologic/vascular manifestations (32% vs. 20%; p<0.008) and stroke (25% vs. 17% p = 0.05) but a lower prevalence of congestive heart failure (15% vs. 30%; p = 0.004), death in-hospital (4% vs. 18%; p = 0.001) or after 1 year follow-up (6% vs. 20%; p = 0.01) than IE due to other pathogens (n = 5514). On multivariable analysis, stroke was associated with mitral valve vegetations (OR 3.60; CI 1.34-9.65; p<0.01) and younger age (OR 0.62; CI 0.49-0.90; p<0.01). The overall outcome of HE was excellent with the in-hospital mortality (4%) significantly better than for non-HE (18%; p<0.001). Prosthetic valve endocarditis was more common in HE (35%) than non-HE (24%). The outcome of prosthetic valve and native valve HE was excellent whether treated medically or with surgery. Current treatment is very successful for the management of both native valve prosthetic valve HE but further studies are needed to determine why HE has a predilection for younger people and to cause stroke. The small number of patients and observational design limit inferences on treatment strategies. Self selection of study sites limits epidemiological inferences.

Virtual autopsy with multiphase postmortem computed tomographic angiography versus traditional medical autopsy to investigate unexpected deaths of hospitalized patients: a cohort study.

BACKGROUND: "Virtual" autopsy by postmortem computed tomography (PMCT) can replace medical autopsy to a certain extent but has limitations for cardiovascular diseases. These limitations might be overcome by adding multiphase PMCT angiography. OBJECTIVE: To compare virtual autopsy by multiphase PMCT angiography with medical autopsy. DESIGN: Prospective cohort study. (ClinicalTrials.gov: NCT01541995) SETTING: Single-center study at the University Medical Center Hamburg-Eppendorf, Hamburg, Germany, between 1 April 2012 and 31 March 2013. PATIENTS: Hospitalized patients who died unexpectedly or within 48 hours of an event necessitating cardiopulmonary resuscitation. MEASUREMENTS: Diagnoses from clinical records were compared with findings from both types of autopsy. New diagnoses identified by autopsy were classified as major or minor, depending on whether they would have altered clinical management. RESULTS: Of 143 eligible patients, 50 (35%) had virtual and medical autopsy. Virtual autopsy confirmed 93% of all 336 diagnoses identified from antemortem medical records, and medical autopsy confirmed 80%. In addition, virtual and medical autopsy identified 16 new major and 238 new minor diagnoses. Seventy-three of the virtual autopsy diagnoses, including 32 cases of coronary artery stenosis, were identified solely by multiphase PMCT angiography. Of the 114 clinical diagnoses classified as cardiovascular, 110 were confirmed by virtual autopsy and 107 by medical autopsy. In 11 cases, multiphase PMCT angiography showed "unspecific filling defects," which were not reported by medical autopsy. LIMITATION: These results come from a single center with concerted interest and expertise in postmortem imaging; further studies are thus needed for generalization. CONCLUSION: In cases of unexpected death, the addition of multiphase PMCT angiography increases the value of virtual autopsy, making it a feasible alternative for quality control and identification of diagnoses traditionally made by medical autopsy. PRIMARY FUNDING SOURCE: University Medical Center Hamburg-Eppendorf.

Accuracy of four cardiovascular risk scores in a Swiss population-based cohort

Purpose: To assess the global cardiovascular (CV) risk of an individual, several scores have been developed. However, their accuracy and comparability need to be evaluated in populations others from which they were derived. The aim of this study was to compare the predictive accuracy of 4 CV risk scores using data of a large population-based cohort. Methods: Prospective cohort study including 4980 participants (2698 women, mean age± SD: 52.7±10.8 years) in Lausanne, Switzerland followed for an average of 5.5 years (range 0.2 - 8.5). Two end points were assessed: 1) coronary heart disease (CHD), and 2) CV diseases (CVD). Four risk scores were compared: original and recalibrated Framingham coronary heart disease scores (1998 and 2001); original PROCAM score (2002) and its recalibrated version for Switzerland (IAS-AGLA); Reynolds risk score. Discrimination was assessed using Harrell's C statistics, model fitness using Akaike's information criterion (AIC) and calibration using pseudo Hosmer-Lemeshow test. The sensitivity, specificity and corresponding 95% confidence intervals were assessed for each risk score using the highest risk category ([20+ % at 10 years) as the "positive" test. Results: Recalibrated and original 1998 and original 2001 Framingham scores show better discrimination (>0.720) and model fitness (low AIC) for CHD and CVD. All 4 scores are correctly calibrated (Chi2<20). The recalibrated Framingham 1998 score has the best sensitivities, 37.8% and 40.4%, for CHD and CVD, respectively. All scores present specificities >90%. Framingham 1998, PROCAM and IAS-AGLA scores include the greatest proportion of subjects (>200) in the high risk category whereas recalibrated Framingham 2001 and Reynolds include <=44 subjects. Conclusion: In this cohort, we see variations of accuracy between risk scores, the original Framingham 2001 score demonstrating the best compromise between its accuracy and its limited selection of subjects in the highest risk category. We advocate that national guidelines, based on independently validated data, take into account calibrated CV risk scores for their respective countries.

Respiratory viruses in bronchoalveolar lavage: a hospital-based cohort study in adults.

BACKGROUND: The epidemiology of respiratory viruses and their potential clinical impact when recovered in lower respiratory specimens has not been established in the hospital setting. A study was performed to investigate the association between positive viral detection and respiratory infection in an at-risk population. METHODS: 299 adult patients who underwent bronchoalveolar lavage (BAL) procedures were enrolled in a hospital-based prospective cohort study. Descriptive epidemiology is presented of 17 different respiratory viruses detected by reverse transcription-polymerase chain reaction assays in BAL fluid specimens. Multivariate analysis was conducted to identify the clinical characteristics independently associated with the presence of virus. RESULTS: Of 522 BAL fluid specimens analysed, 81% were collected in adult transplant recipients or other immunocompromised patients. Overall, PCR assays identified viral nucleic acid in 91 BAL fluid samples (17.4%). Similar rates of virus-positive BAL fluid were found in the different subpopulations studied (p = 0.113). Coronaviruses were the most frequent (32.3%), followed by rhinovirus (22.6%), parainfluenza (19.5%), influenza (9.7%), respiratory synctial virus (8.6%), human metapneumovirus (4.2%) and bocavirus (3.1%). Multivariate analysis using mixed models showed that respiratory viral infections were associated with a lack of antibiotic treatment response (OR 2.2, 95% CI 1.2 to 4.1) and the absence of radiological infiltrate (OR 0.3, 95% CI 0.2 to 0.8). In lung transplant recipients in whom a respiratory infection was suspected, the respiratory viral detection rate was 24.4% compared with 13.8% overall in other patients (p = 0.02). CONCLUSIONS: In this cohort of hospitalised adults, respiratory viruses detected in BAL fluid specimens were associated with respiratory symptoms, absence of radiological infiltrates and a poor response to antibiotic therapy.

Defining risk thresholds for a 10-year probability of hip fracture model that combines clinical risk factors and quantitative ultrasound: results using the EPISEM cohort.

Using a large prospective cohort of over 12,000 women, we determined 2 thresholds (high risk and low risk of hip fracture) to use in a 10-yr hip fracture probability model that we had previously described, a model combining the heel stiffness index measured by quantitative ultrasound (QUS) and a set of easily determined clinical risk factors (CRFs). The model identified a higher percentage of women with fractures as high risk than a previously reported risk score that combined QUS and CRF. In addition, it categorized women in a way that was quite consistent with the categorization that occurred using dual X-ray absorptiometry (DXA) and the World Health Organization (WHO) classification system; the 2 methods identified similar percentages of women with and without fractures in each of their 3 categories, but the 2 identified only in part the same women. Nevertheless, combining our composite probability model with DXA in a case findings strategy will likely further improve the detection of women at high risk of fragility hip fracture. We conclude that the currently proposed model may be of some use as an alternative to the WHO classification criteria for osteoporosis, at least when access to DXA is limited.

Longer term clinical and virological outcome of sub-Saharan African participants on antiretroviral treatment in the Swiss HIV Cohort Study.

OBJECTIVES: Persons from sub-Saharan Africa (SSA) are increasingly enrolled in the Swiss HIV Cohort Study (SHCS). Cohorts from other European countries showed higher rates of viral failure among their SSA participants. We analyzed long-term outcomes of SSA versus North Western European participants. DESIGN: We analyzed data of the SHCS, a nation-wide prospective cohort study of HIV-infected adults at 7 sites in Switzerland. METHODS: SSA and North Western European participants were included if their first treatment combination consisted of at least 3 antiretroviral drugs (cART), if they had at least 1 follow-up visit, did not report active injecting drug use, and did not start cART with CD4 counts >200 cells per microliter during pregnancy. Early viral response, CD4 cell recovery, viral failure, adherence, discontinuation from SHCS, new AIDS-defining events, and survival were analyzed using linear regression and Cox proportional hazard models. RESULTS: The proportion of participants from SSA within the SHCS increased from 2.6% (<1995) to 20.8% (2005-2009). Of 4656 included participants, 808 (17.4%) were from SSA. Early viral response (6 months) and rate of viral failure in an intent-to-stay-on-cART approach were similar. However, SSA participants had a higher risk of viral failure on cART (adjusted hazard ratio: 2.03, 95% confidence interval: 1.50 to 2.75). Self-reported adherence was inferior for SSA. There was no increase of AIDS-defining events or mortality in SSA participants. CONCLUSIONS: Increased attention must be given to factors negatively influencing adherence to cART in participants from SSA to guarantee equal longer-term results on cART.

Pregnancy outcome following maternal exposure to mirtazapine: a multicenter, prospective study.

This multicenter, observational prospective cohort study addresses the risk associated with exposure to mirtazapine during pregnancy. Pregnancy outcomes after exposure to mirtazapine were compared with 2 matched control groups: (1) exposure to any selective serotonin reuptake inhibitor (SSRI, control subjects with a psychiatric condition) and (2) no exposure to medication known to be teratogenic or any antidepressant (general control subjects). Data were collected by members of the European Network of Teratology Information Services between 1995 and 2011. Observations from 357 exposed pregnancies were compared with 357 pregnancies from each control group. The rate of major birth defects between the mirtazapine and the SSRI group did not differ significantly (4.5% vs 4.2%; odds ratio [OR], 1.1; 95% confidence interval [95% CI], 0.5-2.3; P = 0.9). A trend toward a higher rate of birth defects in the mirtazapine group compared with general control subjects (4.5% vs 1.9%; OR, 2.4; 95% CI, 0.9-6.3; P = 0.08) reached statistical significance after exclusion of chromosomal or genetic anomalies (4.1% vs 1.3%; OR, 3.3; 95% CI, 1.04-10.3; P = 0.03), but this difference became again nonsignificant if cases of exposure not comprising the first trimester were excluded from the analysis (3.4% vs 1.9%; OR, 1.8; 95% CI, 0.6-5.0; P = 0.26). The crude miscarriage rate did not differ significantly between the mirtazapine, the SSRI, and the general control groups (12.1% vs 12.0% vs 9.3%; P = 0.44). However, a higher rate of elective pregnancy termination was observed in the mirtazapine group compared with SSRI and general control subjects (7.8% vs 3.4% vs 5.6%; P = 0.03). This study did not observe a statistically significant difference in the rate of major birth defects after first-trimester exposure between mirtazapine, SSRI-exposed, and nonexposed pregnancies. A marginally higher rate of birth defects was, however, observed in the mirtazapine and SSRI groups compared with the low rate of birth defects in our general control subjects. Overall pregnancy outcome after mirtazapine exposure was similar to that of the SSRI-exposed control group.

Being Small for Gestational Age: Does it Matter for the Neurodevelopment of Premature Infants? A Cohort Study.

BACKGROUND: Whether being small for gestational age (SGA) increases the risk of adverse neurodevelopmental outcome in premature infants remains controversial. OBJECTIVE: to study the impact of SGA (birthweight < percentile 10) on cognition, behavior, neurodevelopmental impairment and use of therapy at 5 years old. METHODS: This population-based prospective cohort included infants born before 32 weeks of gestation. Cognition was evaluated with the K-ABC, and behavior with the Strengths and Difficulties Questionnaire (SDQ). Primary outcomes were cognitive and behavioral scores, as well as neurodevelopmental impairment (cognitive score < 2SD, hearing loss, blindness, or cerebral palsy). The need of therapy, an indirect indicator of neurodevelopmental impairment, was a secondary outcome. Linear and logistic regression models were used to analyze the association of SGA with neurodevelopment. RESULTS: 342/515 (76%) premature infants were assessed. SGA was significantly associated with hyperactivity scores of the SDQ (coefficient 0.81, p < 0.04), but not with cognitive scores, neurodevelopmental impairment or the need of therapy. Gestational age, socio-economic status, and major brain lesions were associated with cognitive outcome in the univariate and multivariate model, whereas asphyxia, sepsis and bronchopulmonary dysplasia were associated in the univariate model only. Severe impairment was associated with fetal tobacco exposition, asphyxia, gestational age and major brain lesions. Different neonatal factors were associated with the use of single or multiple therapies: children with one therapy were more likely to have suffered birth asphyxia or necrotizing enterocolitis, whereas the need for several therapies was predicted by major brain lesions. DISCUSSION: In this large cohort of premature infants, assessed at 5 years old with a complete panel of tests, SGA was associated with hyperactive behavior, but not with cognition, neurodevelopmental impairment or use of therapy. Birthweight <10th percentile alone does not appear to be an independent risk factor of neurodevelopmental adverse outcome in preterm children.

The swiss transplant cohort study: lessons from the first 6 years.

Prospective cohort studies significantly contribute to answering specific research questions in a defined population. Since 2008, the Swiss Transplant Cohort Study (STCS) systematically enrolled >95 % of all transplant recipients in Switzerland, collecting predefined data at determined time points. Designed as an open cohort, the STCS has included >3900 patients to date, with a median follow-up of 2.96 years (IQR 1.44-4.73). This review highlights some relevant findings in the field of transplant-associated infections gained by the STCS so far. Three key general aspects have crystallized: (i) Well-run cohort studies are a powerful tool to conduct genetic studies, which are crucially dependent on a meticulously described phenotype. (ii) Long-term real-life observations are adding a distinct layer of information that cannot be obtained during randomized studies. (iii) The systemic collection of data, close interdisciplinary collaboration, and continuous analysis of some key outcome data such as infectious diseases endpoints can improve patient care.

Epidemiology and outcome of fungemia in a cancer Cohort of the Infectious Diseases Group (IDG) of the European Organization for Research and Treatment of Cancer (EORTC 65031).

BACKGROUND: Anti-cancer treatment and the cancer population have evolved since the last European Organisation for Research and Treatment of Cancer (EORTC) fungemia survey, and there are few recent large epidemiological studies. METHODS: This was a prospective cohort study including 145 030 admissions of patients with cancer from 13 EORTC centers. Incidence, clinical characteristics, and outcome of fungemia were analyzed. RESULTS: Fungemia occurred in 333 (0.23%; 95% confidence interval [CI], .21-.26) patients, ranging from 0.15% in patients with solid tumors to 1.55% in hematopoietic stem cell transplantation recipients. In 297 evaluable patients age ranged from 17 to 88 years (median 56 years), 144 (48%) patients were female, 165 (56%) had solid tumors, and 140 (47%) had hematological malignancies. Fungemia including polymicrobial infection was due to: Candida spp. in 267 (90%), C. albicans in 128 (48%), and other Candida spp. in 145 (54%) patients. Favorable overall response was achieved in 113 (46.5%) patients by week 2. After 4 weeks, the survival rate was 64% (95% CI, 59%-70%) and was not significantly different between Candida spp. Multivariable logistic regression identified baseline septic shock (odds ratio [OR] 3.04, 95% CI, 1.22-7.58) and tachypnoea as poor prognostic factors (OR 2.95, 95% CI, 1.66-5.24), while antifungal prophylaxis prior to fungemia (OR 0.20, 95% CI, .06-.62) and remission of underlying cancer (OR, 0.18; 95% CI, .06-.50) were protective. CONCLUSIONS: Fungemia, mostly due to Candida spp., was rare in cancer patients from EORTC centers but was associated with substantial mortality. Antifungal prophylaxis and remission of cancer predicted better survival.

Clinical and course characteristics of depression and all-cause mortality: A prospective population-based study.

BACKGROUND: Given the large heterogeneity of depressive disorders (DD), studying depression characteristics according to clinical manifestations and course is a more promising approach than studying depression as a whole. The purpose of this study was to determine the association between clinical and course characteristics of DD and incident all-cause mortality. METHODS: CoLaus|PsyCoLaus is a prospective cohort study (mean follow-up duration=5.2 years) including 35-66 year-old randomly selected residents of an urban area in Switzerland. A total of 3668 subjects (mean age 50.9 years, 53.0% women) underwent physical and psychiatric baseline evaluations and had a known vital status at follow-up (98.8% of the baseline sample). Clinical (diagnostic severity, atypical features) and course characteristics (recency, recurrence, duration, onset) of DD according to the DSM-5 were elicited using a semi-structured interview. RESULTS: Compared to participants who had never experienced DD, participants with current but not remitted DD were more than three times as likely to die (Hazard Ratio: 3.2, 95% CI: 1.1-10.0) after adjustment for socio-demographic and lifestyle characteristics, comorbid anxiety disorders, antidepressant use, and cardiovascular risk factors and diseases. There was no evidence for associations between other depression characteristics and all-cause mortality. LIMITATIONS: The small proportion of deceased subjects impeded statistical analyses of cause-specific mortality. CONCLUSIONS: A current but not remitted DD is a strong predictor of all-cause mortality, independently of cardiovascular or lifestyle factors, which suggests that the effect of depression on mortality diminishes after remission and further emphasizes the need to adequately treat current depressive episodes.

The survival advantage of milk and dairy consumption: An overview of evidence from cohort studies of vascular diseases, diabetes and cancer

Objectives: To conduct it detailed evaluation, with meta-analyses, of the published evidence on milk and dairy consumption and the incidence of vascular diseases and diabetes. Also to summarise the evidence on milk and dairy consumption and cancer reported by the World Cancer Research Fund and then to consider the relevance of milk and dairy consumption to survival in the UK, a typical Western community. Finally, published evidence on relationships with whole milk and fat-reduced milks was examined. Methods: Prospective cohort studies of vascular disease and diabetes with baseline data on milk or dairy consumption and a relevant disease outcome were identified by searching MEDLINE, and reference lists in the relevant published reports. Meta-analyses of relationships in these reports were conducted. The likely effect of milk and dairy consumption on survival was then considered, taking into account the results of published overviews of relationships of these foods with cancer. Results: From meta-analysis of 15 studies the relative risk of stroke and/or heart disease in subjects with high milk or dairy consumption was 0.84 (95% CI 0.76, 0,93) and 0.79 (0.75, 0.82) respectively, relative to the risk in those with low consumption. Four studies reported incident diabetes as an outcome, and the relative risk in the Subjects with the highest intake of milk or diary foods was 0.92 (0.86, 0.97). Conclusions: Set against the proportion of total deaths attributable to the life-threatening diseases in the UK, vascular disease, diabetes and cancer, the results of meta-analyses provide evidence of an overall survival advantage from the consumption of milk and dairy foods.