High hepatic and extrahepatic mortality and low treatment uptake in HCV-coinfected persons in the Swiss HIV cohort study between 2001 and 2013.

BACKGROUND & AIMS: The landscape of HCV treatments is changing dramatically. At the beginning of this new era, we highlight the challenges for HCV therapy by assessing the long-term epidemiological trends in treatment uptake, efficacy and mortality among HIV/HCV-coinfected people since the availability of HCV therapy. METHODS: We included all SHCS participants with detectable HCV RNA between 2001 and 2013. To identify predictors for treatment uptake uni- and multivariable Poisson regression models were applied. We further used survival analyses with Kaplan-Meier curves and Cox regression with drop-out as competing risk. RESULTS: Of 12,401 participants 2107 (17%) were HCV RNA positive. Of those, 636 (30%) started treatment with an incidence of 5.8/100 person years (PY) (95% CI 5.3-6.2). Sustained virological response (SVR) with pegylated interferon/ribavirin was achieved in 50% of treated patients, representing 15% of all participants with replicating HCV-infection. 344 of 2107 (16%) HCV RNA positive persons died, 59% from extrahepatic causes. Mortality/100 PY was 2.9 (95% CI 2.6-3.2) in untreated patients, 1.3 (1.0-1.8) in those treated with failure, and 0.6 (0.4-1.0) in patients with SVR. In 2013, 869/2107 (41%) participants remained HCV RNA positive. CONCLUSIONS: Over the last 13years HCV treatment uptake was low and by the end of 2013, a large number of persons remain to be treated. Mortality was high, particularly in untreated patients, and mainly due to non-liver-related causes. Accordingly, in HIV/HCV-coinfected patients, integrative care including the diagnosis and therapy of somatic and psychiatric disorders is important to achieve mortality rates similar to HIV-monoinfected patients.

TBS reflects trabecular microarchitecture in premenopausal women and men with idiopathic osteoporosis and low-traumatic fractures.

Transiliac bone biopsies, while widely considered to be the standard for the analysis of bone microstructure, are typically restricted to specialized centers. The benefit of Trabecular Bone Score (TBS) in addition to areal bone mineral density (aBMD) for fracture risk assessment has been documented in cross-sectional and prospective studies. The aim of this study was to test if TBS may be useful as a surrogate to histomorphometric trabecular parameters of transiliac bone biopsies. Transiliac bone biopsies from 80 female patients (median age 39.9years-interquartile range, IQR 34.7; 44.3) and 43 male patients (median age 42.7years-IQR 38.9; 49.0) with idiopathic osteoporosis and low traumatic fractures were included. Micro-computed tomography values of bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), structural model index (SMI) as well as serum bone turnover markers (BTMs) sclerostin, intact N-terminal type 1 procollagen propeptide (P1NP) and cross-linked C-telopeptide (CTX) were investigated. TBS values were higher in females (1.282 vs 1.169, p< 0.0001) with no differences in spine aBMD, whereas sclerostin levels (45.5 vs 33.4pmol/L) and aBMD values at the total hip (0.989 vs 0.971g/cm(2), p<0.001 for all) were higher in males. Multiple regression models including: gender, aBMD and BTMs revealed TBS as an independent, discriminative variable with adjusted multiple R(2) values of 69.1% for SMI, 79.5% for Tb.N, 68.4% for Tb.Sp, and 83.3% for BV/TV. In univariate regression models, BTMs showed statistically significant results, whereas in the multiple models only P1NP and CTX were significant for Tb.N. TBS is a practical, non-invasive, surrogate technique for the assessment of cancellous bone microarchitecture and should be implemented as an additional tool for the determination of trabecular bone properties.

Swiss medical centres vary significantly when it comes to outcomes of neonates with a very low gestational age.

AIM: This study quantified the impact of perinatal predictors and medical centre on the outcome of very low-gestational-age neonates (VLGANs) born at <32 completed weeks in Switzerland. METHODS: Using prospectively collected data from a 10-year cohort of VLGANs, we developed logistic regression models for three different time points: delivery, NICU admission and seven days of age. The data predicted survival to discharge without severe neonatal morbidity, such as major brain injury, moderate or severe bronchopulmonary dysplasia, retinopathy of prematurity (≥stage three) or necrotising enterocolitis (≥stage three). RESULTS: From 2002 to 2011, 6892 VLGANs were identified: 5854 (85%) of the live-born infants survived and 84% of the survivors did not have severe neonatal complications. Predictors for adverse outcome at delivery and on NICU admission were low gestational age, low birthweight, male sex, multiple birth, birth defects and lack of antenatal corticosteroids. Proven sepsis was an additional risk factor on day seven of life. The medical centre remained a statistically significant factor at all three time points after adjusting for perinatal predictors. CONCLUSION: After adjusting for perinatal factors, the survival of Swiss VLGANs without severe neonatal morbidity was strongly influenced by the medical centre that treated them.

Social factors related to the clinical severity of influenza cases in Spain during the A(H1N1)2009 virus pandemic

Background During the 2009 influenza pandemic, a change in the type of patients most often affected by influenza was observed. The objective of this study was to assess the role of individual and social determinants in hospitalizations due to influenza A (H1N1) 2009 infection. Methods We studied hospitalized patients (cases) and outpatients (controls) with confirmed influenza A (H1N1) 2009 infection. A standardized questionnaire was used to collect data. Variables that might be related to the hospitalization of influenza cases were compared by estimation of the odds ratio (OR) and 95% confidence intervals (CI) and the variables entered into binomial logistic regression models. Results Hospitalization due to pandemic A (H1N1) 2009 influenza virus infections was associated with non-Caucasian ethnicity (OR: 2.18, 95% CI 1.17 − 4.08), overcrowding (OR: 2.84, 95% CI 1.20 − 6.72), comorbidity and the lack of previous preventive information (OR: 2.69, 95% CI: 1.50 − 4.83). Secondary or higher education was associated with a lower risk of hospitalization (OR 0.56, 95% CI: 0.36 − 0.87) Conclusions In addition to individual factors such as comorbidity, other factors such as educational level, ethnicity or overcrowding were associated with hospitalization due to A (H1N1) 2009 influenza virus infections.

Multi-institutional validation of the prognostic value of Ki-67 labeling index in patients treated with radical prostatectomy.

OBJECTIVE: Several smaller single-center studies have reported a prognostic role for Ki-67 labeling index in prostate cancer. Our aim was to test whether Ki-67 is an independent prognostic marker of biochemical recurrence (BCR) in a large international cohort of patients treated with radical prostatectomy (RP). METHODS: Ki-67 immunohistochemical staining on prostatectomy specimens from 3,123 patients who underwent RP for prostate cancer was retrospectively performed. Univariable and multivariable Cox regression models were used to assess the association of Ki-67 status with BCR. RESULTS: Ki-67 positive status was observed in 762 (24.4 %) patients and was associated with lymph node involvement (LNI) (p = 0.039). Six hundred and twenty-one (19.9 %) patients experienced BCR. The estimated 3-year biochemical-free survivals were 85 % for patients with negative Ki-67 status and 82.1 % for patients with positive Ki-67 status (log-rank test, p = 0.014). In multivariable analysis that adjusted for the effects of age, preoperative PSA, RP Gleason sum, seminal vesicle invasion, extracapsular extension, positive surgical margins, lymphovascular invasion, and LNI, Ki-67 was significantly associated with BCR (HR = 1.19; p = 0.019). Subgroup analysis revealed that Ki-67 is associated with BCR in patients without LNI (p = 0.004), those with RP Gleason sum 7 (p = 0.015), and those with negative surgical margins (p = 0.047). CONCLUSION: We confirmed Ki-67 as an independent predictor of BCR after RP. Ki-67 could be particularly informative in patients with favorable pathologic characteristics to help in the clinical decision-making regarding adjuvant therapy and optimized follow-up scheduling.

The role of adjuvant chemotherapy for lymph node-positive upper tract urothelial carcinoma following radical nephroureterectomy: a retrospective study.

OBJECTIVE: To evaluate the effect of adjuvant chemotherapy (AC) on mortality after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) with positive lymph nodes (LNs) and to identify patient subgroups that are most likely to benefit from AC. PATIENTS AND METHODS: We retrospectively analysed data of 263 patients with LN-positive UTUC, who underwent full surgical resection. In all, 107 patients (41%) received three to six cycles of AC, while 156 (59.3%) were treated with RNU alone. UTUC-related mortality was evaluated using competing-risks regression models. RESULTS: In all patients (Tall N+), administration of AC had no significant impact on UTUC-related mortality on univariable (P = 0.49) and multivariable (P = 0.11) analysis. Further stratified analyses showed that only N+ patients with pT3-4 disease benefited from AC. In this subgroup, AC reduced UTUC-related mortality by 34% (P = 0.019). The absolute difference in mortality was 10% after the first year and increased to 23% after 5 years. On multivariable analysis, administration of AC was associated with significantly reduced UTUC-related mortality (subhazard ratio 0.67, P = 0.022). Limitations of this study are the retrospective non-randomised design, selection bias, absence of a central pathological review and different AC protocols. CONCLUSIONS: AC seems to reduce mortality in patients with pT3-4 LN-positive UTUC after RNU. This subgroup of LN-positive patients could serve as target population for an AC prospective randomised trial.

The Effect of Cigarette Smoking on Diabetic Peripheral Neuropathy: A Systematic Review and Meta-Analysis.

OBJECTIVE: Studies suggest that smoking may be a risk factor for the development of microvascular complications such as diabetic peripheral neuropathy (DPN). The objective of this study was to assess the relationship between smoking and DPN in persons with type 1 or type 2 diabetes. RESEARCH DESIGN AND METHODS: A systematic review of the PubMed, Embase, and Cochrane clinical trials databases was conducted for the period from January 1966 to November 2014 for cohort, cross-sectional and case-control studies that assessed the relationship between smoking and DPN. Separate meta-analyses for prospective cohort studies and case-control or cross-sectional studies were performed using random effects models. RESULTS: Thirty-eight studies (10 prospective cohort and 28 cross-sectional) were included. The prospective cohort studies included 5558 participants without DPN at baseline. During follow-up ranging from 2 to 10 years, 1550 cases of DPN occurred. The pooled unadjusted odds ratio (OR) of developing DPN associated with smoking was 1.26 (95% CI 0.86-1.85; I(2) = 74%; evidence grade: low strength). Stratified analyses of the prospective studies revealed that studies of higher quality and with better levels of adjustment and longer follow-up showed a significant positive association between smoking and DPN, with less heterogeneity. The cross-sectional studies included 27,594 participants. The pooled OR of DPN associated with smoking was 1.42 (95% CI 1.21-1.65; I(2) = 65%; evidence grade: low strength). There was no evidence of publication bias. CONCLUSIONS: Smoking may be associated with an increased risk of DPN in persons with diabetes. Further studies are needed to test whether this association is causal and whether smoking cessation reduces the risk of DPN in adults with diabetes.

Strong impact of smoking on multimorbidity and cardiovascular risk among human immunodeficiency virus-infected individuals in comparison with the general population.

Background.  Although acquired immune deficiency syndrome-associated morbidity has diminished due to excellent viral control, multimorbidity may be increasing among human immunodeficiency virus (HIV)-infected persons compared with the general population. Methods.  We assessed the prevalence of comorbidities and multimorbidity in participants of the Swiss HIV Cohort Study (SHCS) compared with the population-based CoLaus study and the primary care-based FIRE (Family Medicine ICPC-Research using Electronic Medical Records) records. The incidence of the respective endpoints were assessed among SHCS and CoLaus participants. Poisson regression models were adjusted for age, sex, body mass index, and smoking. Results.  Overall, 74 291 participants contributed data to prevalence analyses (3230 HIV-infected; 71 061 controls). In CoLaus, FIRE, and SHCS, multimorbidity was present among 26%, 13%, and 27% of participants. Compared with nonsmoking individuals from CoLaus, the incidence of cardiovascular disease was elevated among smoking individuals but independent of HIV status (HIV-negative smoking: incidence rate ratio [IRR] = 1.7, 95% confidence interval [CI] = 1.2-2.5; HIV-positive smoking: IRR = 1.7, 95% CI = 1.1-2.6; HIV-positive nonsmoking: IRR = 0.79, 95% CI = 0.44-1.4). Compared with nonsmoking HIV-negative persons, multivariable Poisson regression identified associations of HIV infection with hypertension (nonsmoking: IRR = 1.9, 95% CI = 1.5-2.4; smoking: IRR = 2.0, 95% CI = 1.6-2.4), kidney (nonsmoking: IRR = 2.7, 95% CI = 1.9-3.8; smoking: IRR = 2.6, 95% CI = 1.9-3.6), and liver disease (nonsmoking: IRR = 1.8, 95% CI = 1.4-2.4; smoking: IRR = 1.7, 95% CI = 1.4-2.2). No evidence was found for an association of HIV-infection or smoking with diabetes mellitus. Conclusions.  Multimorbidity is more prevalent and incident in HIV-positive compared with HIV-negative individuals. Smoking, but not HIV status, has a strong impact on cardiovascular risk and multimorbidity.

Respiratory health effects of fifteen years of improved collective protection in a wheat-processing worker population.

INTRODUCTION: Occupational exposure to grain dust causes respiratory symptoms and pathologies. To decrease these effects, major changes have occurred in the grain processing industry in the last twenty years. However, there are no data on the effects of these changes on workers' respiratory health. OBJECTIVES: The aim of this study was to evaluate the respiratory health of grain workers and farmers involved in different steps of the processing industry of wheat, the most frequently used cereal in Europe, fifteen years after major improvements in collective protective equipment due to mechanisation. MATERIALS AND METHOD: Information on estimated personal exposure to wheat dust was collected from 87 workers exposed to wheat dust and from 62 controls. Lung function (FEV1, FVC, and PEF), exhaled nitrogen monoxide (FENO) and respiratory symptoms were assessed after the period of highest exposure to wheat during the year. Linear regression models were used to explore the associations between exposure indices and respiratory effects. RESULTS: Acute symptoms - cough, sneezing, runny nose, scratchy throat - were significantly more frequent in exposed workers than in controls. Increased mean exposure level, increased cumulative exposure and chronic exposure to more than 6 mg.m (-3) of inhaled wheat dust were significantly associated with decreased spirometric parameters, including FEV1 and PEF (40 ml and 123 ml.s (-1) ), FEV1 and FVC (0.4 ml and 0.5 ml per 100 h.mg.m (-3) ), FEV1 and FVC (20 ml and 20 ml per 100 h at >6 mg.m (-3) ). However, no increase in FENO was associated with increased exposure indices. CONCLUSIONS: The lung functions of wheat-related workers are still affected by their cumulative exposure to wheat dust, despite improvements in the use of collective protective equipment.

Bayesian Networks for the Age Classification of Living Individuals: a Study on Transition Analysis

Over the past few decades, age estimation of living persons has represented a challenging task for many forensic services worldwide. In general, the process for age estimation includes the observation of the degree of maturity reached by some physical attributes, such as dentition or several ossification centers. The estimated chronological age or the probability that an individual belongs to a meaningful class of ages is then obtained from the observed degree of maturity by means of various statistical methods. Among these methods, those developed in a Bayesian framework offer to users the possibility of coherently dealing with the uncertainty associated with age estimation and of assessing in a transparent and logical way the probability that an examined individual is younger or older than a given age threshold. Recently, a Bayesian network for age estimation has been presented in scientific literature; this kind of probabilistic graphical tool may facilitate the use of the probabilistic approach. Probabilities of interest in the network are assigned by means of transition analysis, a statistical parametric model, which links the chronological age and the degree of maturity by means of specific regression models, such as logit or probit models. Since different regression models can be employed in transition analysis, the aim of this paper is to study the influence of the model in the classification of individuals. The analysis was performed using a dataset related to the ossifications status of the medial clavicular epiphysis and results support that the classification of individuals is not dependent on the choice of the regression model.

Characterizing the vulnerability of frequent emergency department users by applying a conceptual framework: a controlled, cross-sectional study.

BACKGROUND: Frequent emergency department (ED) users meet several of the criteria of vulnerability, but this needs to be further examined taking into consideration all vulnerability's different dimensions. This study aimed to characterize frequent ED users and to define risk factors of frequent ED use within a universal health care coverage system, applying a conceptual framework of vulnerability. METHODS: A controlled, cross-sectional study comparing frequent ED users to a control group of non-frequent users was conducted at the Lausanne University Hospital, Switzerland. Frequent users were defined as patients with five or more visits to the ED in the previous 12 months. The two groups were compared using validated scales for each one of the five dimensions of an innovative conceptual framework: socio-demographic characteristics; somatic, mental, and risk-behavior indicators; and use of health care services. Independent t-tests, Wilcoxon rank-sum tests, Pearson's Chi-squared test and Fisher's exact test were used for the comparison. To examine the -related to vulnerability- risk factors for being a frequent ED user, univariate and multivariate logistic regression models were used. RESULTS: We compared 226 frequent users and 173 controls. Frequent users had more vulnerabilities in all five dimensions of the conceptual framework. They were younger, and more often immigrants from low/middle-income countries or unemployed, had more somatic and psychiatric comorbidities, were more often tobacco users, and had more primary care physician (PCP) visits. The most significant frequent ED use risk factors were a history of more than three hospital admissions in the previous 12 months (adj OR:23.2, 95%CI = 9.1-59.2), the absence of a PCP (adj OR:8.4, 95%CI = 2.1-32.7), living less than 5 km from an ED (adj OR:4.4, 95%CI = 2.1-9.0), and household income lower than USD 2,800/month (adj OR:4.3, 95%CI = 2.0-9.2). CONCLUSIONS: Frequent ED users within a universal health coverage system form a highly vulnerable population, when taking into account all five dimensions of a conceptual framework of vulnerability. The predictive factors identified could be useful in the early detection of future frequent users, in order to address their specific needs and decrease vulnerability, a key priority for health care policy makers. Application of the conceptual framework in future research is warranted.

Discrete distributions when modeling the disability severity score of motor victims

Many European states apply score systems to evaluate the disability severity of non-fatal motor victims under the law of third-party liability. The score is a non-negative integer with an upper bound at 100 that increases with severity. It may be automatically converted into financial terms and thus also reflects the compensation cost for disability. In this paper, discrete regression models are applied to analyze the factors that influence the disability severity score of victims. Standard and zero-altered regression models are compared from two perspectives: an interpretation of the data generating process and the level of statistical fit. The results have implications for traffic safety policy decisions aimed at reducing accident severity. An application using data from Spain is provided.

Regional differences of physical activity and sedentary behaviour in Swiss children are not explained by socio-demographics or the built environment.

OBJECTIVE: We evaluated whether regional differences in physical activity (PA) and sedentary behaviour (SB) existed along language boundaries within Switzerland and whether potential differences would be explained by socio-demographics or environmental characteristics. METHODS: We combined data of 611 children aged 4 to 7 years from four regional studies. PA and SB were assessed by accelerometers. Information about the socio-demographic background was obtained by questionnaires. Objective neighbourhood attributes could be linked to home addresses. Multivariate regression models were used to test associations between PA and SB and socio-demographic characteristics and neighbourhood attributes. RESULTS: Children from the German compared to the French-speaking region were more physically active and less sedentary (by 10-15 %, p < 0.01). Although German-speaking children lived in a more favourable environment and a higher socioeconomic neighbourhood (differences p < 0.001), these characteristics did not explain the differences in PA behaviour between French and German speaking. CONCLUSIONS: Factors related to the language region, which might be culturally rooted were among the strongest correlates of PA and SB among Swiss children, independent of individual, social and environmental factors.

Prognostication of Mortality in Critically Ill Patients With Severe Infections.

BACKGROUND: The purpose of this study was to confirm the prognostic value of pancreatic stone protein (PSP) in patients with severe infections requiring ICU management and to develop and validate a model to enhance mortality prediction by combining severity scores with biomarkers. METHODS: We enrolled prospectively patients with severe sepsis or septic shock in mixed tertiary ICUs in Switzerland (derivation cohort) and Brazil (validation cohort). Severity scores (APACHE [Acute Physiology and Chronic Health Evaluation] II or Simplified Acute Physiology Score [SAPS] II) were combined with biomarkers obtained at the time of diagnosis of sepsis, including C-reactive-protein, procalcitonin (PCT), and PSP. Logistic regression models with the lowest prediction errors were selected to predict in-hospital mortality. RESULTS: Mortality rates of patients with septic shock enrolled in the derivation cohort (103 out of 158) and the validation cohort (53 out of 91) were 37% and 57%, respectively. APACHE II and PSP were significantly higher in dying patients. In the derivation cohort, the models combining either APACHE II, PCT, and PSP (area under the receiver operating characteristic curve [AUC], 0.721; 95% CI, 0.632-0.812) or SAPS II, PCT, and PSP (AUC, 0.710; 95% CI, 0.617-0.802) performed better than each individual biomarker (AUC PCT, 0.534; 95% CI, 0.433-0.636; AUC PSP, 0.665; 95% CI, 0.572-0.758) or severity score (AUC APACHE II, 0.638; 95% CI, 0.543-0.733; AUC SAPS II, 0.598; 95% CI, 0.499-0.698). These models were externally confirmed in the independent validation cohort. CONCLUSIONS: We confirmed the prognostic value of PSP in patients with severe sepsis and septic shock requiring ICU management. A model combining severity scores with PCT and PSP improves mortality prediction in these patients.

Modelling body mass index and endometrial cancer risk in a pooled-analysis of three case-control studies.

OBJECTIVE: To quantify the relation between body mass index (BMI) and endometrial cancer risk, and to describe the shape of such a relation. DESIGN: Pooled analysis of three hospital-based case-control studies. SETTING: Italy and Switzerland. POPULATION: A total of 1449 women with endometrial cancer and 3811 controls. METHODS: Multivariate odds ratios (OR) and 95% confidence intervals (95% CI) were obtained from logistic regression models. The shape of the relation was determined using a class of flexible regression models. MAIN OUTCOME MEASURE: The relation of BMI with endometrial cancer. RESULTS: Compared with women with BMI 18.5 to <25 kg/m(2) , the odds ratio was 5.73 (95% CI 4.28-7.68) for women with a BMI ≥35 kg/m(2) . The odds ratios were 1.10 (95% CI 1.09-1.12) and 1.63 (95% CI 1.52-1.75) respectively for an increment of BMI of 1 and 5 units. The relation was stronger in never-users of oral contraceptives (OR 3.35, 95% CI 2.78-4.03, for BMI ≥30 versus <25 kg/m(2) ) than in users (OR 1.22, 95% CI 0.56-2.67), and in women with diabetes (OR 8.10, 95% CI 4.10-16.01, for BMI ≥30 versus <25 kg/m(2) ) than in those without diabetes (OR 2.95, 95% CI 2.44-3.56). The relation was best fitted by a cubic model, although after the exclusion of the 5% upper and lower tails, it was best fitted by a linear model. CONCLUSIONS: The results of this study confirm a role of elevated BMI in the aetiology of endometrial cancer and suggest that the risk in obese women increases in a cubic nonlinear fashion. The relation was stronger in never-users of oral contraceptives and in women with diabetes. TWEETABLE ABSTRACT: Risk of endometrial cancer increases with elevated body weight in a cubic nonlinear fashion.