Antioxidant enzymes, inflammatory indices and lifestyle factors in older men: a cohort analysis

We examined the relationship between blood antioxidant enzyme activities, indices of inflammatory status and a number of lifestyle factors in the Caerphilly prospective cohort study of ischaemic heart disease. The study began in 1979 and is based on a representative male population sample. Initially 2512 men were seen in phase I, and followed-up every 5 years in phases II and III; they have recently been seen in phase IV. Data on social class, smoking habit, alcohol consumption were obtained by questionnaire, and body mass index was measured. Antioxidant enzyme activities and indices of inflammatory status were estimated by standard techniques. Significant associations were observed for: age with α-1-antichymotrypsin (p<0.0001) and with caeruloplasmin, both protein and oxidase (p<0.0001); smoking habit with α-1-antichymotrypsin (p<0.0001), with caeruloplasmin, both protein and oxidase (p<0.0001) and with glutathione peroxidose (GPX) (p<0.0001); social class with α-1-antichymotrypsin (p<0.0001), with caeruloplasmin both protein (p<0.001) and oxidase (p<0.01) and with GPX (p<0.0001); body mass index with α-1-antichymotrypsin (p<0.0001) and with caeruloplasmin protein (p<0.001). There was no significant association between alcohol consumption and any of the blood enzymes measured. Factor analysis produced a three-factor model (explaining 65.9% of the variation in the data set) which appeared to indicate close inter-relationships among antioxidants.

Glargine vs. NPH insulin therapy in pregnancies complicated by diabetes: An observational cohort study

Aims: The effects of glargine insulin therapy in pregnancies are not well established. We compared maternal and neonatal outcomes of women with pregestational and gestational diabetes treated with glargine or NPH insulin.Methods: A prospective cohort study was conducted analyzing outcomes from 56 women with pregestational and 82 with gestational diabetes treated with either insulin regimen.Results: Comparisons were performed among 138 women: 56 with pregestational and 82 with gestational diabetes. In relation to maternal complications, worsening of retinopathy and nephropathy, preeclampsia, micro and macroalbuminuria, and all kinds of hypoglycemia were found higher in women with pregestational diabetes NPH-treated vs. glargine-treated. In women with gestational diabetes NPH-treated, it was observed increased incidence of prepregnancy and new-onset pregnancy hypertension, micro and macroalbuminuria, as well as mild and frequent hypoglycemia, compared to glargine-treated. Among the neonatal outcomes, 1-min Apgar score <7, necessity of intensive care unit and fetal death in pregestational, while jaundice and congenital malformations in gestational diabetes, respectively, were more frequently observed in infants born to NPH-treated, compared to glargine-treated.Conclusions: Glargine use during pregnancy from preconception through delivery, showed to be safe since it is associated with decreased maternal and neonatal adverse outcomes compared with NPH insulin-treated patients. (C) 2010 Elsevier B.V. All rights reserved.

Nursing Workload as a Risk Factor for Healthcare Associated Infections in ICU: A Prospective Study

Introduction: Nurse understaffing is frequently hypothesized as a potential risk factor for healthcare-associated infections (HAI). This study aimed to evaluate the role of nursing workload in the occurrence of HAI, using Nursing Activities Score (NAS). Methods: This prospective cohort study enrolled all patients admitted to 3 Medical ICUs and one step-down unit during 3 months (2009). Patients were followed-up until HAI, discharge or death. Information was obtained from direct daily observation of medical and nursing rounds, chart review and monitoring of laboratory system. Nursing workload was determined using NAS. Non-compliance to the nurses' patient care plans (NPC) was identified. Demographic data, clinical severity, invasive procedures, hospital interventions, and the occurrence of other adverse events were also recorded. Patients who developed HAI were compared with those who did not. Results: 195 patients were included and 43 (22%) developed HAI: 16 pneumonia, 12 urinary-tract, 8 bloodstream, 2 surgical site, 2 other respiratory infections and 3 other. Average NAS and average proportion of non compliance with NPC were significantly higher in HAI patients. They were also more likely to suffer other adverse events. Only excessive nursing workload (OR: 11.41; p: 0.019) and severity of patient's clinical condition (OR: 1.13; p: 0.015) remained as risk factors to HAI. Conclusions: Excessive nursing workload was the main risk factor for HAI, when evaluated together with other invasive devices except mechanical ventilation. To our knowledge, this study is the first to evaluate prospectively the nursing workload as a potential risk factor for HAI, using NAS.

Childbearing in adolescence: intergenerational dejà-vu? Evidence from a Brazilian birth cohort

Abstract Background Pregnancy in adolescence tends to repeat over generations. This event has been little studied in middle and low-income societies undergoing a rapid epidemiological transition. To assess this association it is important to adjust for socioeconomic conditions at different points in lifetime. Therefore, the aim of this study is to analyze the independent effect of adolescent childbearing in a generation on its recurrence in the subsequent generation, after adjusting for socioeconomic status at different points in life. Methods The study was conducted on a prospective cohort of singleton liveborn females from the city of Ribeirão Preto, Brazil, evaluated in 1978/79, and their daughters assessed in 2002/04. A total of 1059 mother-daughter pairs were evaluated. The women who had their first childbirth before 20 years of age were considered to be adolescent mothers. The risk of childbearing in adolescence for the daughter was modeled as a function of the occurrence of teenage childbearing in her mother, after adjustment for socio-demographic variables in a Poisson regression model. Results The rate of childbearing during adolescence was 31.4% in 1978/79 and 17.1% in 2002/04. Among the daughters of the 1st generation adolescent mothers, this rate was 26.7%, as opposed to 12.7% among the daughters of non adolescent mothers. After adjustments the risk of adolescent childbearing for the 2nd generation was 35% higher for women whose mothers had been pregnant during adolescence – RR = 1.35 (95% CI 1.04-1.74). Conclusion Adolescent childbearing in the 1st generation was a predictor of adolescent childbearing in the 2nd, regardless of socioeconomic factors determined at different points in lifetime.

Anti-infective surgical therapy of peri-implantitis. A 12-month prospective clinical study

The aim of this prospective cohort study was to evaluate an anti-infective surgical protocol for the treatment of peri-implantitis.

Invasive findings in patients with angina equivalent symptoms but no coronary artery disease; Results from the heart quest cohort study

The cause of angina in patients presenting at coronary angiography without significant coronary artery disease (CAD) has not been systematically assessed in a large prospective cohort. This study is aimed to identify the cause of angina in these patients.

The common G-allele of interleukin-18 single-nucleotide polymorphism is a genetic risk factor for atopic asthma. The SAPALDIA Cohort Study

BACKGROUND: IL-18 is a pleiotrophic cytokine involved in both, T-helper type 1 (Th1) and Th2 differentiation. Recently genetic variants in the IL-18 gene have been associated with increased risk of atopy and asthma. OBJECTIVE: To examine the relationship of a genetic, haplotype-tagging promotor variant -137G/C in the IL-18 gene with atopic asthma in a large, well-characterized and population-based study of adults. METHODS: Prospective cohort study design was used to collect interview and biological measurement data at two examination time-points 11 years apart. Multivariate logistic regression analysis was used to assess the association of genotype with asthma and atopy. RESULTS: The G-allele of the IL-18 promotor variant (-137G/C) was associated with a markedly increased risk for the prevalence of physician-diagnosed asthma with concomitant skin reactivity to common allergens. Stratification of the asthma cases by skin reactivity to common allergens revealed an exclusive association of IL-18 -137 G-allele with an increased prevalence of atopic asthma (adjusted odds ratio (OR): 3.63; 95% confidence interval: (1.64-8.02) for GC or GG carriers vs. CC carriers), and no according association with asthma and concomitant negative skin reactivity (adjusted OR: 1.13; 0.66-1.94). The interaction between IL-18 -137G/C genotype and positive skin prick test was statistically significant (P=0.029). None of 74 incident asthma cases with atopy at baseline exhibited the CC genotype. CONCLUSION: Our results strongly suggest that this variant of the IL-18 gene is an important genetic determinant involved in the development of atopic asthma.

[Physical and psychological status of 60-70-year-old citizens of Bern with neurotic symptoms in childhood--a study over more than 50 years (Emmental cohort)]

The present study was undertaken to assess the influence of childhood variables (physical and emotional) to later well-being in a group of rural Swiss (Emmental Cohort). Our study is the first prospective cohort over a time period of more than 50 years. It includes 1537 children who were listed and assessed in 1942 (T1) because they had difficulties in school or were otherwise behaviorally disturbed. In 1995 (T2) more than 60% of the initial population could be reassessed by our study group. We found more subjects at T2 who had been rated as intelligent at T1. More subjects responding to T2 belonged to a higher social class, were more anxious, and had more psychosocial problems at T1. Social income at T2 is correlated to the social class at T1. More subjects have died since who were rated at T1 as being less intelligent, less neurotical, and having higher psychosocial problems. Twice as many men died than women. The emotional situation at T2 is significantly correlated to psychological well-being at T1. The somatic complaints at T2 correlate significantly to neurotic symptoms in childhood (T1). The more intelligent the children were rated at T1, the less emotional and somatic complaints were voiced at T2 and the better the psychic well-being was rated (T2). In addition, the former social milieu (T1) significantly determined somatic and psychological complaints at T2. Our data discern a significant correlation between actual status and former childhood variables more than 50 years later in a rural Swiss cohort (Emmental Cohort).

Timing of initiation of antiretroviral therapy in AIDS-free HIV-1-infected patients: a collaborative analysis of 18 HIV cohort studies

BACKGROUND: The CD4 cell count at which combination antiretroviral therapy should be started is a central, unresolved issue in the care of HIV-1-infected patients. In the absence of randomised trials, we examined this question in prospective cohort studies. METHODS: We analysed data from 18 cohort studies of patients with HIV. Antiretroviral-naive patients from 15 of these studies were eligible for inclusion if they had started combination antiretroviral therapy (while AIDS-free, with a CD4 cell count less than 550 cells per microL, and with no history of injecting drug use) on or after Jan 1, 1998. We used data from patients followed up in seven of the cohorts in the era before the introduction of combination therapy (1989-95) to estimate distributions of lead times (from the first CD4 cell count measurement in an upper range to the upper threshold of a lower range) and unseen AIDS and death events (occurring before the upper threshold of a lower CD4 cell count range is reached) in the absence of treatment. These estimations were used to impute completed datasets in which lead times and unseen AIDS and death events were added to data for treated patients in deferred therapy groups. We compared the effect of deferred initiation of combination therapy with immediate initiation on rates of AIDS and death, and on death alone, in adjacent CD4 cell count ranges of width 100 cells per microL. FINDINGS: Data were obtained for 21 247 patients who were followed up during the era before the introduction of combination therapy and 24 444 patients who were followed up from the start of treatment. Deferring combination therapy until a CD4 cell count of 251-350 cells per microL was associated with higher rates of AIDS and death than starting therapy in the range 351-450 cells per microL (hazard ratio [HR] 1.28, 95% CI 1.04-1.57). The adverse effect of deferring treatment increased with decreasing CD4 cell count threshold. Deferred initiation of combination therapy was also associated with higher mortality rates, although effects on mortality were less marked than effects on AIDS and death (HR 1.13, 0.80-1.60, for deferred initiation of treatment at CD4 cell count 251-350 cells per microL compared with initiation at 351-450 cells per microL). INTERPRETATION: Our results suggest that 350 cells per microL should be the minimum threshold for initiation of antiretroviral therapy, and should help to guide physicians and patients in deciding when to start treatment.

Kaposi sarcoma-associated herpes virus and response to antiretroviral therapy: a prospective study of HIV-infected adults

BACKGROUND The possible impact of coinfection with the Kaposi sarcoma-associated herpes virus (KSHV) on the response to antiretroviral therapy (ART) is unknown. Prospective studies are rare, particularly in Africa. METHODS We enrolled a prospective cohort of HIV-infected adults initiating ART in Johannesburg, South Africa. The subjects were defined as seropositive to KSHV if they were reactive to either KSHV lytic K8.1 or latent Orf73 antigen or to both. The subjects were followed from ART initiation until 18 months of treatment. HIV viral load and CD4 counts were tested 6 monthly. Linear generalized estimating and log-binomial regression models were used to estimate the effect of KSHV infection on immunologic recovery and response and HIV viral load suppression within 18 months after ART initiation. RESULTS Three hundred eighty-five subjects initiating ART from November 2008 to March 2009 were considered to be eligible including 184 (48%) KSHV+. The KSHV+ group was similar to the KSHV- in terms of age, gender, initiating CD4 count, body mass index, tuberculosis, and hemoglobin levels. The KSHV+ group gained a similar number of cells at 6 [difference of 10 cells per cubic millimeter, 95% confidence interval (CI): -11 to 31], 12 (3 cells per cubic millimeter, 95% CI: -19 to 25), and 18 months (24 cells per cubic millimeter, 95% CI: -13 to 61) compared with that gained by the KSHV- group. Adjusted relative risk of failure to suppress viral load to <400 copies per milliliter (1.03; 95% CI: 0.90 to 1.17) were similar for KSHV+ and KSHV- by 6 months on treatment. CONCLUSIONS In a population with a high KSHV prevalence, HIV-positive adults coinfected with KSHV achieved similar immunologic and virologic responses to ART early after treatment initiation compared with those with KSHV-.

Dynamics of the nasal microbiota in infancy: A prospective cohort study.

BACKGROUND Understanding the composition and dynamics of the upper respiratory tract microbiota in healthy infants is a prerequisite to investigate the role of the microbiota in patients with respiratory diseases. This is especially true in early life, when the immune system is in development. OBJECTIVE We sought to describe the dynamics of the upper respiratory tract microbiota in healthy infants within the first year of life. METHODS After exclusion of low-quality samples, microbiota characterization was performed by using 16S rDNA pyrosequencing of 872 nasal swabs collected biweekly from 47 unselected infants. RESULTS Bacterial density increased and diversity decreased within the first year of life (R(2) = 0.95 and 0.73, respectively). A distinct profile for the first 3 months of life was found with increased relative abundances of Staphlyococcaceae and Corynebacteriaceae (exponential decay: R(2) = 0.94 and 0.96, respectively). In addition, relative bacterial abundance and composition differed significantly from summer to winter months. The individual composition of the microbiota changed with increasing time intervals between samples and was best modeled by an exponential function (R(2) = 0.97). Within-subject dissimilarity in a 2-week time interval was consistently lower than that between subjects, indicating a personalized microbiota. CONCLUSION This study reveals age and seasonality as major factors driving the composition of the nasal microbiota within the first year of life. A subject's microbiota is personalized but dynamic throughout the first year. These data are indispensable to interpretation of cross-sectional studies and investigation of the role of the microbiota in both healthy subjects and patients with respiratory diseases. They might also serve as a baseline for future intervention studies.

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.

Tuberculosis-related mortality in people living with HIV in Europe and Latin America: an international cohort study

BACKGROUND Management of tuberculosis in patients with HIV in eastern Europe is complicated by the high prevalence of multidrug-resistant tuberculosis, low rates of drug susceptibility testing, and poor access to antiretroviral therapy (ART). We report 1 year mortality estimates from a multiregional (eastern Europe, western Europe, and Latin America) prospective cohort study: the TB:HIV study. METHODS Consecutive HIV-positive patients aged 16 years or older with a diagnosis of tuberculosis between Jan 1, 2011, and Dec 31, 2013, were enrolled from 62 HIV and tuberculosis clinics in 19 countries in eastern Europe, western Europe, and Latin America. The primary endpoint was death within 12 months after starting tuberculosis treatment; all deaths were classified according to whether or not they were tuberculosis related. Follow-up was either until death, the final visit, or 12 months after baseline, whichever occurred first. Risk factors for all-cause and tuberculosis-related deaths were assessed using Kaplan-Meier estimates and Cox models. FINDINGS Of 1406 patients (834 in eastern Europe, 317 in western Europe, and 255 in Latin America), 264 (19%) died within 12 months. 188 (71%) of these deaths were tuberculosis related. The probability of all-cause death was 29% (95% CI 26-32) in eastern Europe, 4% (3-7) in western Europe, and 11% (8-16) in Latin America (p<0·0001) and the corresponding probabilities of tuberculosis-related death were 23% (20-26), 1% (0-3), and 4% (2-8), respectively (p<0·0001). Patients receiving care outside eastern Europe had a 77% decreased risk of death: adjusted hazard ratio (aHR) 0·23 (95% CI 0·16-0·31). In eastern Europe, compared with patients who started a regimen with at least three active antituberculosis drugs, those who started fewer than three active antituberculosis drugs were at a higher risk of tuberculosis-related death (aHR 3·17; 95% CI 1·83-5·49) as were those who did not have baseline drug-susceptibility tests (2·24; 1·31-3·83). Other prognostic factors for increased tuberculosis-related mortality were disseminated tuberculosis and a low CD4 cell count. 18% of patients were receiving ART at tuberculosis diagnosis in eastern Europe compared with 44% in western Europe and 39% in Latin America (p<0·0001); 12 months later the proportions were 67% in eastern Europe, 92% in western Europe, and 85% in Latin America (p<0·0001). INTERPRETATION Patients with HIV and tuberculosis in eastern Europe have a risk of death nearly four-times higher than that in patients from western Europe and Latin America. This increased mortality rate is associated with modifiable risk factors such as lack of drug susceptibility testing and suboptimal initial antituberculosis treatment in settings with a high prevalence of drug resistance. Urgent action is needed to improve tuberculosis care for patients living with HIV in eastern Europe. FUNDING EU Seventh Framework Programme.

Injury risk from popular childhood physical activities: results from an Australian primary school cohort

Background: Children engage in various physical activities that pose different injury risks. However, the lack of adequate data on exposure has meant that these risks have not been quantified or compared in young children aged 5-12 years. Objectives: To measure exposure to popular activities among Australian primary school children and to quantify the associated injury risks. Method: The Childhood Injury Prevention Study prospectively followed up a cohort of randomly selected Australian primary and preschool children aged 5-12 years. Time (min) engaged in various physical activities was measured using a parent-completed 7-day diary. All injuries over 12 months were reported to the study. All data on exposure and injuries were coded using the International classification of external causes of injury. Injury rates per 1000 h of exposure were calculated for the most popular activities. Results: Complete diaries and data on injuries were available for 744 children. Over 12 months, 314 injuries relating to physical activity outside of school were reported. The highest injury risks per exposure time occurred for tackle-style football (2.18/1000 h), wheeled activities (1.72/1000 h) and tennis (1.19/1000 h). Overall, boys were injured more often than girls; however, the differences were non-significant or reversed for some activities including soccer, trampolining and team ball sports. Conclusion: Although the overall injury rate was low in this prospective cohort, the safety of some popular childhood activities can be improved so that the benefits may be enjoyed with fewer negative consequences.

Effets des contraintes psychosociales au travail sur la détresse psychologique et les absences médicalement certifiées pour problèmes de santé mentale: une étude prospective de 5 ans

Contexte : Les effets cumulés des contraintes psychosociales du modèle déséquilibre efforts-reconnaissance (DER) sur la santé mentale sont peu connus. Aussi, peu d’études ont évalué les effets du DER sur des indicateurs objectifs de problèmes de santé mentale (PSM). Enfin, aucune étude prospective antérieure n’a évalué l’effet combiné des contraintes psychosociales du DER et du modèle demande-latitude (DL) et sur les PSM médicalement certifiés. La présente thèse vise à combler ces limites. Objectifs : 1) Mesurer l’effet de l’exposition cumulée au déséquilibre efforts-reconnaissance sur la prévalence de la détresse psychologique sur une période de cinq ans; 2) Mesurer l’effet du déséquilibre efforts-reconnaissance sur l’incidence des absences médicalement certifiées pour PSM sur une période de cinq ans; 3) Évaluer l’effet indépendant et l’effet combiné des contraintes psychosociales des modèles Demande-Latitude et Déséquilibre Efforts-Reconnaissance sur l’incidence des absences médicalement certifiées pour PSM sur une période de cinq ans. Méthodes : La cohorte était constituée de plus de 2000 hommes et femmes occupant des emplois de cols blancs. La collecte des données a été réalisée à trois reprises avec une moyenne de suivi de cinq ans. À chaque temps, les contraintes psychosociales et la détresse psychologique ont été mesurées à l’aide d’instruments validés. Les absences médicalement certifiées pour PSM ont été récoltées à partir des fichiers administratifs des employeurs. Les PSM ont été modélisés à l’aide des régressions log-binomiale et de Cox. Les analyses ont été réalisées séparément chez les hommes et les femmes, en ajustant pour les principaux facteurs de confusion. Résultats : Chez les hommes et les femmes, une exposition chronique au DER sur trois ans était associée à une prévalence plus élevée de la détresse psychologique. Les effets observés à trois ans ont persisté à cinq ans chez les hommes (Rapport de prévalence (RP)=1,91 (1,20–3,04)) et les femmes (RP=2,48 (1,97–3,11)). Ces effets étaient de plus grande amplitude que ceux observés en utilisant l’exposition initiale à l’entrée dans l’étude (de +0,30 à +0,94). Par ailleurs, les hommes et les femmes exposés au DER présentaient un risque plus élevé d’absences médicalement certifiées pour PSM (Risque relatif (RR)=1,38 (1,08–1,76)), comparés aux travailleurs non-exposés. La faible reconnaissance au travail était associée à un risque important d’absences pour PSM chez les hommes (RR=3,04 (1,46–6,33)) mais pas chez les femmes (RR=1,24 (0,90–1,72)). Chez les femmes uniquement, un effet indépendant du « job strain » (RR=1,50 (1,12–2,07)) et du DER (RR=1,34 (0,98–1,84)), ainsi qu’un effet de l’exposition combinée au « job strain » (demande psychologique élevée et faible latitude décisionnelle) et au DER (RR=1,97 (1,40–2,78)) sur le risque d’absences médicalement certifiées pour PSM ont également été observés. Conclusion : Les résultats de cette thèse supportent l’effet délétère de l’exposition au DER sur la prévalence de la détresse psychologique et sur le risque d’absences médicalement certifiées pour PSM chez les hommes et les femmes. Chez les hommes et les femmes, l’exposition cumulée au DER était associée à une prévalence élevée de la détresse psychologique à trois ans et à cinq ans. De plus, les contraintes psychosociales du DER ont été associées aux absences médicalement certifiés pour PSM. Chez les femmes particulièrement, un effet combiné du « job strain » et du DER était associé à un risque plus élevé d’absences médicalement certifiées pour PSM, que l’exposition à un seul des deux facteurs. Ces résultats suggèrent que la réduction des contraintes psychosociales au travail pourrait contribuer à réduire l’incidence des PSM, incluant les absences médicalement certifiées pour PSM.