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 13 years 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.

General Practitioners' vitamin K antagonist monitoring is associated with better blood pressure control in patients with hypertension - a cross-sectional database study.

BACKGROUND Patients requiring anticoagulation suffer from comorbidities such as hypertension. On the occasion of INR monitoring, general practitioners (GPs) have the opportunity to control for blood pressure (BP). We aimed to evaluate the impact of Vitamin-K Antagonist (VKA) monitoring by GPs on BP control in patients with hypertension. METHODS We cross-sectionally analyzed the database of the Swiss Family Medicine ICPC Research using Electronic Medical Records (FIRE) of 60 general practices in a primary care setting in Switzerland. This database includes 113,335 patients who visited their GP between 2009 and 2013. We identified patients with hypertension based on antihypertensive medication prescribed for ≥6 months. We compared patients with VKA for ≥3 months and patients without such treatment regarding BP control. We adjusted for age, sex, observation period, number of consultations and comorbidity. RESULTS We identified 4,412 patients with hypertension and blood pressure recordings in the FIRE database. Among these, 569 (12.9 %) were on Phenprocoumon (VKA) and 3,843 (87.1 %) had no anticoagulation. Mean systolic and diastolic BP was significantly lower in the VKA group (130.6 ± 14.9 vs 139.8 ± 15.8 and 76.6 ± 7.9 vs 81.3 ± 9.3 mm Hg) (p < 0.001 for both). The difference remained after adjusting for possible confounders. Systolic and diastolic BP were significantly lower in the VKA group, reaching a mean difference of -8.4 mm Hg (95 % CI -9.8 to -7.0 mm Hg) and -1.5 mm Hg (95 % CI -2.3 to -0.7 mm Hg), respectively (p < 0.001 for both). CONCLUSIONS In a large sample of hypertensive patients in Switzerland, VKA treatment was independently associated with better systolic and diastolic BP control. The observed effect could be due to better compliance with antihypertensive medication in patients treated with VKA. Therefore, we conclude to be aware of this possible benefit especially in patients with lower expected compliance and with multimorbidity.

Patients with community acquired pneumonia admitted to European intensive care units: an epidemiological survey of the GenOSept cohort.

INTRODUCTION Community acquired pneumonia (CAP) is the most common infectious reason for admission to the Intensive Care Unit (ICU). The GenOSept study was designed to determine genetic influences on sepsis outcome. Phenotypic data was recorded using a robust clinical database allowing a contemporary analysis of the clinical characteristics, microbiology, outcomes and independent risk factors in patients with severe CAP admitted to ICUs across Europe. METHODS Kaplan-Meier analysis was used to determine mortality rates. A Cox Proportional Hazards (PH) model was used to identify variables independently associated with 28-day and six-month mortality. RESULTS Data from 1166 patients admitted to 102 centres across 17 countries was extracted. Median age was 64 years, 62% were male. Mortality rate at 28 days was 17%, rising to 27% at six months. Streptococcus pneumoniae was the commonest organism isolated (28% of cases) with no organism identified in 36%. Independent risk factors associated with an increased risk of death at six months included APACHE II score (hazard ratio, HR, 1.03; confidence interval, CI, 1.01-1.05), bilateral pulmonary infiltrates (HR1.44; CI 1.11-1.87) and ventilator support (HR 3.04; CI 1.64-5.62). Haematocrit, pH and urine volume on day one were all associated with a worse outcome. CONCLUSIONS The mortality rate in patients with severe CAP admitted to European ICUs was 27% at six months. Streptococcus pneumoniae was the commonest organism isolated. In many cases the infecting organism was not identified. Ventilator support, the presence of diffuse pulmonary infiltrates, lower haematocrit, urine volume and pH on admission were independent predictors of a worse outcome.

Patients with faecal peritonitis admitted to European intensive care units: an epidemiological survey of the GenOSept cohort.

INTRODUCTION Faecal peritonitis (FP) is a common cause of sepsis and admission to the intensive care unit (ICU). The Genetics of Sepsis and Septic Shock in Europe (GenOSept) project is investigating the influence of genetic variation on the host response and outcomes in a large cohort of patients with sepsis admitted to ICUs across Europe. Here we report an epidemiological survey of the subset of patients with FP. OBJECTIVES To define the clinical characteristics, outcomes and risk factors for mortality in patients with FP admitted to ICUs across Europe. METHODS Data was extracted from electronic case report forms. Phenotypic data was recorded using a detailed, quality-assured clinical database. The primary outcome measure was 6-month mortality. Patients were followed for 6 months. Kaplan-Meier analysis was used to determine mortality rates. Cox proportional hazards regression analysis was employed to identify independent risk factors for mortality. RESULTS Data for 977 FP patients admitted to 102 centres across 16 countries between 29 September 2005 and 5 January 2011 was extracted. The median age was 69.2 years (IQR 58.3-77.1), with a male preponderance (54.3%). The most common causes of FP were perforated diverticular disease (32.1%) and surgical anastomotic breakdown (31.1%). The ICU mortality rate at 28 days was 19.1%, increasing to 31.6% at 6 months. The cause of FP, pre-existing co-morbidities and time from estimated onset of symptoms to surgery did not impact on survival. The strongest independent risk factors associated with an increased rate of death at 6 months included age, higher APACHE II score, acute renal and cardiovascular dysfunction within 1 week of admission to ICU, hypothermia, lower haematocrit and bradycardia on day 1 of ICU stay. CONCLUSIONS In this large cohort of patients admitted to European ICUs with FP the 6 month mortality was 31.6%. The most consistent predictors of mortality across all time points were increased age, development of acute renal dysfunction during the first week of admission, lower haematocrit and hypothermia on day 1 of ICU admission.

Prognostic factors and outcomes in primary urethral cancer: results from the international collaboration on primary urethral carcinoma.

PURPOSE To evaluate risk factors for survival in a large international cohort of patients with primary urethral cancer (PUC). METHODS A series of 154 patients (109 men, 45 women) were diagnosed with PUC in ten referral centers between 1993 and 2012. Kaplan-Meier analysis with log-rank test was used to investigate various potential prognostic factors for recurrence-free (RFS) and overall survival (OS). Multivariate models were constructed to evaluate independent risk factors for recurrence and death. RESULTS Median age at definitive treatment was 66 years (IQR 58-76). Histology was urothelial carcinoma in 72 (47 %), squamous cell carcinoma in 46 (30 %), adenocarcinoma in 17 (11 %), and mixed and other histology in 11 (7 %) and nine (6 %), respectively. A high degree of concordance between clinical and pathologic nodal staging (cN+/cN0 vs. pN+/pN0; p < 0.001) was noted. For clinical nodal staging, the corresponding sensitivity, specificity, and overall accuracy for predicting pathologic nodal stage were 92.8, 92.3, and 92.4 %, respectively. In multivariable Cox-regression analysis for patients staged cM0 at initial diagnosis, RFS was significantly associated with clinical nodal stage (p < 0.001), tumor location (p < 0.001), and age (p = 0.001), whereas clinical nodal stage was the only independent predictor for OS (p = 0.026). CONCLUSIONS These data suggest that clinical nodal stage is a critical parameter for outcomes in PUC.

Impact of perioperative chemotherapy on survival in patients with advanced primary urethral cancer: results of the international collaboration on primary urethral carcinoma.

BACKGROUND To investigate the impact of perioperative chemo(radio)therapy in advanced primary urethral carcinoma (PUC). PATIENTS AND METHODS A series of 124 patients (86 men, 38 women) were diagnosed with and underwent surgery for PUC in 10 referral centers between 1993 and 2012. Kaplan-Meier analysis with log-rank testing was used to investigate the impact of perioperative chemo(radio)therapy on overall survival (OS). The median follow-up was 21 months (mean: 32 months; interquartile range: 5-48). RESULTS Neoadjuvant chemotherapy (NAC), neoadjuvant chemoradiotherapy (N-CRT) plus adjuvant chemotherapy (ACH), and ACH was delivered in 12 (31%), 6 (15%) and 21 (54%) of these patients, respectively. Receipt of NAC/N-CRT was associated with clinically node-positive disease (cN+; P = 0.033) and lower utilization of cystectomy at surgery (P = 0.015). The objective response rate to NAC and N-CRT was 25% and 33%, respectively. The 3-year OS for patients with objective response to neoadjuvant treatment (complete/partial response) was 100% and 58.3% for those with stable or progressive disease (P = 0.30). Of the 26 patients staged ≥cT3 and/or cN+ disease, 16 (62%) received perioperative chemo(radio)therapy and 10 upfront surgery without perioperative chemotherapy (38%). The 3-year OS for this locally advanced subset of patients (≥cT3 and/or cN+) who received NAC (N = 5), N-CRT (N = 3), surgery-only (N = 10) and surgery plus ACH (N = 8) was 100%, 100%, 50% and 20%, respectively (P = 0.016). Among these 26 patients, receipt of neoadjuvant treatment was significantly associated with improved 3-year relapse-free survival (RFS) (P = 0.022) and OS (P = 0.022). Proximal tumor location correlated with inferior 3-year RFS and OS (P = 0.056/0.005). CONCLUSION In this series, patients who received NAC/N-CRT for cT3 and/or cN+ PUC appeared to demonstrate improved survival compared with those who underwent upfront surgery with or without ACH.

Long distance root–shoot signalling in plant–insect community interactions

Plants mediate interactions between insects, including leaf- and root-feeders; yet the underlying mechanisms and connection with ecological theory remain unresolved. In this review, based on novel insights into long-distance (i.e., leaf–leaf, root–shoot) defence signalling, we explore the role of phytohormones in driving broad-scale patterns of aboveground–belowground interactions that can be extrapolated to general plant–insect relationships. We propose that the outcome of intra-feeding guild interactions is generally negative due to induction of similar phytohormonal pathways, whereas between-guild interactions are often positive due to negative signal crosstalk. However, not all outcomes could be explained by feeding guild; we argue that future studies should target ecologically representative plant–insect systems, distinguish subguilds, and include plant growth hormones to improve our understanding of plant-mediated interactions.

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.

Impact of the Ebola epidemic on general and HIV care in Macenta, Forest Guinea, 2014.

OBJECTIVE The current Ebola epidemic massively affected the Macenta district in Forest Guinea. We aimed at investigating its impact on general and HIV care at the only HIV care facility in the district. DESIGN Prospective observational single-facility study. METHODS Routinely collected data on use of general hospital services and HIV care were linked to Ebola surveillance data published by the Guinea Ministry of Health. In addition, we compared retention among HIV-infected patients enrolled into care in the first semesters of 2013 and 2014. RESULTS Throughout 2014, service offer was continuous and unaltered at the facility. During the main epidemic period (August-December 2014), compared with the same period of 2013, there were important reductions in attendance at the primary care outpatient clinic (-40%), in HIV tests done (-46%), in new diagnoses of tuberculosis (-53%) and in patients enrolled into HIV care (-47%). There was a smaller reduction in attendance at the HIV follow-up clinic (-11%). Kaplan-Meier estimates of retention were similar among the patients enrolled into care in 2014 and 2013. In a multivariable Cox regression analysis, the year of enrolment was not associated with attrition (hazard ratio 1.02; 95% confidence interval: 0.72-1.43). CONCLUSION The Ebola epidemic resulted in an important decrease in utilization of the facility despite unaltered service offer. Effects on care of HIV-positive patients enrolled prior to the epidemic were limited. HIV care in such circumstances is challenging, but not impossible.

Low Risk of Death, but Substantial Program Attrition, in Pediatric HIV Treatment Cohorts in Sub-Saharan Africa

BACKGROUND: To date, an estimated 10% of children eligible for antiretroviral treatment (ART) receive it, and the frequency of retention in programs is unknown. We evaluated the 2-year risks of death and loss to follow-up (LTFU) of children after ART initiation in a multicenter study in sub-Saharan Africa. METHODS: Pooled analysis of routine individual data from 16 participating clinics produced overall Kaplan-Meier estimates of the probabilities of death or LTFU after ART initiation. Risk factors analysis used Weibull regression, accounting for between-cohort heterogeneity. RESULTS: The median age of 2405 children at ART initiation was 4.9 years (12%, younger than 12 months), 52% were male, 70% had severe immunodeficiency, and 59% started ART with a nonnucleoside reverse transcriptase inhibitor. The 2-year risk of death after ART initiation was 6.9% (95% confidence interval [CI]: 5.9 to 8.1), independently associated with baseline severe anemia (adjusted hazard ratio [aHR]: 4.10 [CI: 2.36 to 7.13]), immunodeficiency (adjusted aHR: 2.95 [CI: 1.49 to 5.82]), and severe clinical status (adjusted aHR: 3.64 [CI: 1.95 to 6.81]); the 2-year risk of LTFU was 10.3% (CI: 8.9 to 11.9), higher in children with severe clinical status. CONCLUSIONS: Once on treatment, the 2-year risk of death is low but the LTFU risk is substantial. ART is still mainly initiated at advanced disease stage in African children, reinforcing the need for early HIV diagnosis, early initiation of ART, and procedures to increase program retention.

Einige Worte zur Einsegnung der in der Nacht vom 18. zum 19. März 1848 gefallenen Bürger: Auch der katholische Geistliche grüßt in Namen seiner Kirche die sterblichen Ueberreste derer ...

Welsch (Projektbearbeiter): Veröffentlichung der anläßlich der Einsegnung der Märzgefallenen von dem katholischen Geistlichen Ruland, dem Kaplan der Berliner St.-Hedwigs-Gemeinde gesprochenen Trauerworte

Completeness of Follow-Up Determines Validity of Study Findings: Results of a Prospective Repeated Measures Cohort Study.

BACKGROUND Current reporting guidelines do not call for standardised declaration of follow-up completeness, although study validity depends on the representativeness of measured outcomes. The Follow-Up Index (FUI) describes follow-up completeness at a given study end date as ratio between the investigated and the potential follow-up period. The association between FUI and the accuracy of survival-estimates was investigated. METHODS FUI and Kaplan-Meier estimates were calculated twice for 1207 consecutive patients undergoing aortic repair during an 11-year period: in a scenario A the population's clinical routine follow-up data (available from a prospective registry) was analysed conventionally. For the control scenario B, an independent survey was completed at the predefined study end. To determine the relation between FUI and the accuracy of study findings, discrepancies between scenarios regarding FUI, follow-up duration and cumulative survival-estimates were evaluated using multivariate analyses. RESULTS Scenario A noted 89 deaths (7.4%) during a mean considered follow-up of 30±28months. Scenario B, although analysing the same study period, detected 304 deaths (25.2%, P<0.001) as it scrutinized the complete follow-up period (49±32months). FUI (0.57±0.35 versus 1.00±0, P<0.001) and cumulative survival estimates (78.7% versus 50.7%, P<0.001) differed significantly between scenarios, suggesting that incomplete follow-up information led to underestimation of mortality. Degree of follow-up completeness (i.e. FUI-quartiles and FUI-intervals) correlated directly with accuracy of study findings: underestimation of long-term mortality increased almost linearly by 30% with every 0.1 drop in FUI (adjusted HR 1.30; 95%-CI 1.24;1.36, P<0.001). CONCLUSION Follow-up completeness is a pre-requisite for reliable outcome assessment and should be declared systematically. FUI represents a simple measure suited as reporting standard. Evidence lacking such information must be challenged as potentially flawed by selection bias.