Treatment of type B periprosthetic femur fractures with curved non-locking plate with eccentric holes: Retrospective study of 43 patients with minimum 1-year follow-up.

INTRODUCTION: Periprosthetic femur fracture (PFF) is a serious complication after total hip arthroplasty that can be treated using different internal fixation devices. However, the outcomes with curved non-locking plates with eccentric holes in this indication have not been reported previously. The objectives of this study were to determine: (1) the union rate; (2) the complication rate; (3) autonomy in a group of patients with a Vancouver type B PFF who were treated with this plate. HYPOTHESIS: Use of this plate results in a high union rate with minimal mechanical complications. MATERIALS AND METHODS: Forty-three patients with a mean age of 79 years±13 (41-98) who had undergone fixation of Vancouver type B PFF with this plate between 2002 and 2007 were included in the study. The time to union and Parker Mobility Score were evaluated. The revision-free survival (all causes) was calculated using Kaplan-Meier analysis. The average follow-up was 42 months±20 (16-90). RESULTS: Union was obtained in all patients in a mean of 2.4 months±0.6 (2-4). One patient had varus malunion of the femur. The Parker Mobility Score decreased from 5.93±1.94 (2-9) to 4.93±1.8 (1-9) (P=0.01). Two patients required a surgical revision: one for an infection after 4.5 years and one for stem loosening. The survival of the femoral stem 5 years after fracture fixation was 83.3%±12.6%. CONCLUSION: Use of a curved plate with eccentric holes for treating type B PFF led to a high union rate and a low number of fixation-related complications. However, PFF remains a serious complication of hip arthroplasty that is accompanied by high morbidity and mortality rates. LEVEL OF EVIDENCE: Retrospective study, level IV.

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.

Signs of a vector's adaptive choice: on the evasion of infectious hosts and parasite-induced mortality

Laboratory and field experiments have demonstrated in many cases that malaria vectors do not feed randomly, but show important preferences either for infected or non-infected hosts. These preferences are likely in part shaped by the costs imposed by the parasites on both their vertebrate and dipteran hosts. However, the effect of changes in vector behaviour on actual parasite transmission remains a debated issue. We used the natural associations between a malaria-like parasite Polychromophilus murinus, the bat fly Nycteribia kolenatii and a vertebrate host the Daubenton's bat Myotis daubentonii to test the vector's feeding preference based on the host's infection status using two different approaches: 1) controlled behavioural assays in the laboratory where bat flies could choose between a pair of hosts; 2) natural bat fly abundance data from wild-caught bats, serving as an approximation of realised feeding preference of the bat flies. Hosts with the fewest infectious stages of the parasite were most attractive to the bat flies that did switch in the behavioural assay. In line with the hypothesis of costs imposed by parasites on their vectors, bat flies carrying parasites had higher mortality. However, in wild populations, bat flies were found feeding more based on the bat's body condition, rather than its infection level. Though the absolute frequency of host switches performed by the bat flies during the assays was low, in the context of potential parasite transmission they were extremely high. The decreased survival of infected bat flies suggests that the preference for less infected hosts is an adaptive trait. Nonetheless, other ecological processes ultimately determine the vector's biting rate and thus transmission. Inherent vector preferences therefore play only a marginal role in parasite transmission in the field. The ecological processes rather than preferences per se need to be identified for successful epidemiological predictions.

Self-reported nonadherence to antiretroviral therapy as a predictor of viral failure and mortality

OBJECTIVE: To determine the effect of nonadherence to antiretroviral therapy (ART) on virologic failure and mortality in naive individuals starting ART. DESIGN: Prospective observational cohort study. METHODS: Eligible individuals enrolled in the Swiss HIV Cohort Study, started ART between 2003 and 2012, and provided adherence data on at least one biannual clinical visit. Adherence was defined as missed doses (none, one, two, or more than two) and percentage adherence (>95, 90-95, and <90) in the previous 4 weeks. Inverse probability weighting of marginal structural models was used to estimate the effect of nonadherence on viral failure (HIV-1 viral load >500 copies/ml) and mortality. RESULTS: Of 3150 individuals followed for a median 4.7 years, 480 (15.2%) experienced viral failure and 104 (3.3%) died, 1155 (36.6%) reported missing one dose, 414 (13.1%) two doses and, 333 (10.6%) more than two doses of ART. The risk of viral failure increased with each missed dose (one dose: hazard ratio [HR] 1.15, 95% confidence interval 0.79-1.67; two doses: 2.15, 1.31-3.53; more than two doses: 5.21, 2.96-9.18). The risk of death increased with more than two missed doses (HR 4.87, 2.21-10.73). Missing one to two doses of ART increased the risk of viral failure in those starting once-daily (HR 1.67, 1.11-2.50) compared with those starting twice-daily regimens (HR 0.99, 0.64-1.54, interaction P = 0.09). Consistent results were found for percentage adherence. CONCLUSION: Self-report of two or more missed doses of ART is associated with an increased risk of both viral failure and death. A simple adherence question helps identify patients at risk for negative clinical outcomes and offers opportunities for intervention.

Weather and cardiovascular mortality.

Already in ancient Greece, Hippocrates postulated that disease showed a seasonal pattern characterised by excess winter mortality. Since then, several studies have confirmed this finding, and it was generally accepted that the increase in winter mortality was mostly due to respiratory infections and seasonal influenza. More recently, it was shown that cardiovascular disease (CVD) mortality also displayed such seasonality, and that the magnitude of the seasonal effect increased from the poles to the equator. The recent study by Yang et al assessed CVD mortality attributable to ambient temperature using daily data from 15 cities in China for years 2007-2013, including nearly two million CVD deaths. A high temperature variability between and within cities can be observed (figure 1). They used sophisticated statistical methodology to account for the complex temperature-mortality relationship; first, distributed lag non-linear models combined with quasi-Poisson regression to obtain city-specific estimates, taking into account temperature, relative humidity and atmospheric pressure; then, a meta-analysis to obtain the pooled estimates. The results confirm the winter excess mortality as reported by the Eurowinter3 and other4 groups, but they show that the magnitude of ambient temperature.

Reasons for late presentation to HIV care in Switzerland.

INTRODUCTION: Late presentation to HIV care leads to increased morbidity and mortality. We explored risk factors and reasons for late HIV testing and presentation to care in the nationally representative Swiss HIV Cohort Study (SHCS). METHODS: Adult patients enrolled in the SHCS between July 2009 and June 2012 were included. An initial CD4 count <350 cells/µl or an AIDS-defining illness defined late presentation. Demographic and behavioural characteristics of late presenters (LPs) were compared with those of non-late presenters (NLPs). Information on self-reported, individual barriers to HIV testing and care were obtained during face-to-face interviews. RESULTS: Of 1366 patients included, 680 (49.8%) were LPs. Seventy-two percent of eligible patients took part in the survey. LPs were more likely to be female (p<0.001) or from sub-Saharan Africa (p<0.001) and less likely to be highly educated (p=0.002) or men who have sex with men (p<0.001). LPs were more likely to have their first HIV test following a doctor's suggestion (p=0.01), and NLPs in the context of a regular check-up (p=0.02) or after a specific risk situation (p<0.001). The main reasons for late HIV testing were "did not feel at risk" (72%), "did not feel ill" (65%) and "did not know the symptoms of HIV" (51%). Seventy-one percent of the participants were symptomatic during the year preceding HIV diagnosis and the majority consulted a physician for these symptoms. CONCLUSIONS: In Switzerland, late presentation to care is driven by late HIV testing due to low risk perception and lack of awareness about HIV. Tailored HIV testing strategies and enhanced provider-initiated testing are urgently needed.

Final results of the SAKK 16/00 trial: a randomized phase III trial comparing neoadjuvant chemoradiation to chemotherapy alone in stage IIIA/N2 non-small cell lung cancer (NSCLC).

Aim: One standard option in the treatment of stage IIIA/N2 NSCLC is neoadjuvant chemotherapy followed by surgery. We investigated in a randomized trial whether the addition of neoadjuvant radiotherapy would improve the outcome. Here we present the final results of this study. Methods: Patients (pts.) with pathologically proven, resectable stage IIIA/N2 NSCLC, performance status 0-1, and adequate organ function were randomized 1:1 to chemoradiation (CRT) with 3 cycles of neoadjuvant chemotherapy (cisplatin 100 mg/m2 and docetaxel 85 mg/m2 d1, q3weeks) followed by accelerated concomitant boost radiotherapy (RT) with 44 Gy in 22 fractions in 3 weeks, or neoadjuvant chemotherapy alone (CT), with subsequent surgery for all pts. The primary endpoint was event-free survival (EFS). Results: 232 pts. were randomized in 23 centers, the median follow-up was 53 months. Two thirds were men, median age was 60 years (range 37-76). Histology was squamous cell in 33%, adenocarcinoma in 43%. Response rate to CRT was 61% vs. 44% with CT. 85% of all pts. underwent surgery, 30-day postoperative mortality was 1%. The rate of complete resection was 91% (CRT) vs. 81% (CT) and the pathological complete remission (pCR) rate was 16% vs. 12%. The median EFS was 13.1 months (95% CI 9.9 - 23.5) for the CRT group vs. 11.8 months (95% CI 8.4 - 15.2) in the CT arm (p 0.665). The median overall survival (OS) with CRT was 37.1 months (95% CI 22.6 -50), with CT 26.1 months ( 95% CI 26.1 - 52.1, p 0.938). The local failure rate was 23% in both arms. In the CT arm 12 pts. were given postoperative radiotherapy (PORT) for R1 resection, 6 pts. received PORT in violation of the protocol. Pts. with a pCR, mediastinal downstaging to ypN0/1 and complete resection had a better outcome. Toxicity of chemotherapy was substantial, especially febrile neutropenia was common, whereas RT was well tolerated. Conclusions: This is the first completed phase III trial to evaluate the role of induction chemoradiotherapy and surgery, in comparison to neoadjuvant CT alone followed by surgery. RT was active, it increased response, complete resection and pCR rates. However, this failed to translate into an improvement of local control, EFS or OS. Notably, surgery after induction treatment was safe, including pneumonectomy. The overall survival rates of our neoadjuvant regimen are very encouraging, especially for a multicenter setting. Disclosure: M. Pless: Advisory Board for Sanofi; R. Cathomas: Advisory Board Sanofi D.C. Betticher: Advisory Board Sanofi. All other authors have declared no conflicts of interest.

Risk of All-Cause Mortality in Alcohol-Dependent Individuals: A Systematic Literature Review and Meta-Analysis.

BACKGROUND: Alcohol dependence (AD) carries a high mortality burden, which may be mitigated by reduced alcohol consumption. We conducted a systematic literature review and meta-analysis investigating the risk of all-cause mortality in alcohol-dependent subjects. METHODS: MEDLINE, MEDLINE In-Process, Embase and PsycINFO were searched from database conception through 26th June 2014. Eligible studies reported all-cause mortality in both alcohol-dependent subjects and a comparator population of interest. Two individuals independently reviewed studies. Of 4540 records identified, 39 observational studies were included in meta-analyses. FINDINGS: We identified a significant increase in mortality for alcohol-dependent subjects compared with the general population (27 studies; relative risk [RR] = 3.45; 95% CI [2.96, 4.02]; p < 0.0001). The mortality increase was also significant compared to subjects qualifying for a diagnosis of alcohol abuse or subjects without alcohol use disorders (AUDs). Alcohol-dependent subjects continuing to drink heavily had significantly greater mortality than alcohol-dependent subjects who reduced alcohol intake, even if abstainers were excluded (p < 0.05). INTERPRETATION: AD was found to significantly increase an individual's risk of all-cause mortality. While abstinence in alcohol-dependent subjects led to greater mortality reduction than non-abstinence, this study suggests that alcohol-dependent subjects can significantly reduce their mortality risk by reducing alcohol consumption.

Future development of gastrointestinal cancer incidence and mortality rates in Switzerland: a tumour registry- and population-based projection up to 2030.

QUESTIONS UNDER STUDY: Since tumour burden consumes substantial healthcare resources, precise cancer incidence estimations are pivotal to define future needs of national healthcare. This study aimed to estimate incidence and mortality rates of oesophageal, gastric, pancreatic, hepatic and colorectal cancers up to 2030 in Switzerland. METHODS: Swiss Statistics provides national incidences and mortality rates of various cancers, and models of future developments of the Swiss population. Cancer incidences and mortality rates from 1985 to 2009 were analysed to estimate trends and to predict incidence and mortality rates up to 2029. Linear regressions and Joinpoint analyses were performed to estimate the future trends of incidences and mortality rates. RESULTS: Crude incidences of oesophageal, pancreas, liver and colorectal cancers have steadily increased since 1985, and will continue to increase. Gastric cancer incidence and mortality rates reveal an ongoing decrease. Pancreatic and liver cancer crude mortality rates will keep increasing, whereas colorectal cancer mortality on the contrary will fall. Mortality from oesophageal cancer will plateau or minimally increase. If we consider European population-standardised incidence rates, oesophageal, pancreatic and colorectal cancer incidences are steady. Gastric cancers are diminishing and liver cancers will follow an increasing trend. Standardised mortality rates show a diminution for all but liver cancer. CONCLUSIONS: The oncological burden of gastrointestinal cancer will significantly increase in Switzerland during the next two decades. The crude mortality rates globally show an ongoing increase except for gastric and colorectal cancers. Enlarged healthcare resources to take care of these complex patient groups properly will be needed.