Treatment outcomes of integrase inhibitors, boosted protease inhibitors and nonnucleoside reverse transcriptase inhibitors in antiretroviral-naïve persons starting treatment.

OBJECTIVES: Although outcomes of antiretroviral therapy (ART) have been evaluated in randomized controlled trials, experiences from subpopulations defined by age, CD4 count or viral load (VL) in heterogeneous real-world settings are limited. METHODS: The study design was an international multicohort collaboration. Logistic regression was used to compare virological and immunological outcomes at 12 ± 3 months after starting ART with an integrase strand transfer inhibitor (INSTI), contemporary nonnucleoside reverse transcriptase inhibitor (NNRTI) or boosted protease inhibitor (PI/b) with two nucleos(t)ides after 1 January 2012. The composite treatment outcome (cTO) defined success as VL < 200 HIV-1 RNA copies/mL with no regimen change and no AIDS/death events. Immunological success was defined as a CD4 count > 750 cells/µL or a 33% increase where the baseline CD4 count was ≥ 500 cells/µL. Poisson regression compared clinical failures (AIDS/death ≥ 14 days after starting ART). Interactions between ART class and age, CD4 count, and VL were determined for each endpoint. RESULTS: Of 5198 ART-naïve persons in the International Cohort Consortium of Infectious Diseases (RESPOND), 45.4% started INSTIs, 26.0% PI/b and 28.7% NNRTIs; 880 (17.4%) were aged > 50 years, 2539 (49.4%) had CD4 counts < 350 cells/µL and 1891 (36.8%) had VL > 100 000 copies/mL. Differences in virological and immunological success and clinical failure among ART classes were similar across age groups (≤ 40, 40-50 and > 50 years), CD4 count categories (≤ 350 vs. > 350 cells/µL) and VL categories at ART initiation (≤ 100 000 vs. > 100 000 copies/mL), with all investigated interactions being nonsignificant (P > 0.05). CONCLUSIONS: Differences among ART classes in virological, immunological and clinical outcomes in ART-naïve participants were consistent irrespective of age, immune suppression or VL at ART initiation. While confounding by indication cannot be excluded, this provides reassuring evidence that such subpopulations will equally benefit from contemporary ART.

High inter-observer reliability in standardized ultrasound measurements of subcutaneous adipose tissue in children aged three to six years.

BACKGROUND: A procedure to measure subcutaneous adipose (SAT) using brightness-mode ultrasound has recently been standardized and applied to various groups of adults including underweight, overweight and obese adults. High reliability of this procedure was found in each of the examined groups. The purpose of this study was to determine inter-observer reliability of the standardized brightness-mode ultrasound measurement of uncompressed SAT in three to six-year-old children. METHODS: Three experienced observers independently captured the ultrasound images at the eight standardized measurement sites in each of the 20 children and evaluated their images using an interactive software that detects the SAT contour and automatically measures multiple thicknesses in each image; the mean of these represents SAT thickness at a given site. The children were aged 4.9 ± 1.0 years; their body mass index ranged from 13.6-17.7 kgm- 2. Sound speed was set to 1450 ms- 1 for SAT. RESULTS: SAT thickness sums with fibrous structures included (DI) ranged from 25.7-86.4 mm, mean DI was 48.1 ± 15.5 mm. For DI, resulting from 160 measurements by each observer, the intra-class correlation coefficient was 0.998 (95% confidence interval 0.980-0.999), standard error of the estimate was 1.1 mm, and 95% limits of agreement were within ±2.1 mm. The median difference in DI was 0.8 mm, i.e. about 1.9% of mean DI. CONCLUSIONS: Inter-observer results in children are comparable to previously described high reliability in adults. This method, which provides a technical thickness measurement accuracy of about 0.1 to 0.2 mm, enables monitoring of subcutaneous adipose tissue in children with a similarly high reliability as was obtained in adults previously. TRIAL REGISTRATION: German Institute of Medical Documentation and Information, German Clinical Trials Register (DRKS) ID: DRKS00010089; Date 24/02/2016.

Short communication: Design and validation of a hygiene score for calves.

The objective of this study was the establishment and validation of a scoring system for calf dirtiness. Defined areas of the belly, side, and rear of the calves were scored according to the percentage of dirtiness: score 1 ranges from 0 to 10% of the area (no or little soiling), score 2 from over 10 to 30% (medium soiling), and score 3 applies to soiling of more than 30% of the area (heavy soiling). The scores of the individual regions were summed up to yield the calf hygiene score (CHS) ranging from 3 to 9. The validation of the CHS was performed by 5 veterinarians on 42 calves. It was validated for its inter- and intra-observer-reliability and against a standard method created by image processing of photographs of calves. The agreement between the observers and the standard method was weak to moderate with kappa values from 0.58 to 0.67. Inter- and intra-observer reliability resulted in a moderate to strong agreement with 29 of 36 kappa values between 0.60 and 0.89. The CHS was thus successfully validated as reliable and could be a useful tool for herd health management.

Prognostic relevance of pre- and postoperative plasma l-lactate measurements in calves with acute abdominal emergencies.

In both human and veterinary medicine, l-lactate is a well-established prognostic biomarker of disease severity and mortality and has also attracted increasing attention in bovine medicine due to the availability and validation of cheap and portable l-lactate analyzers. The aim of the present study was to evaluate the prognostic accuracy of plasma L-lactate measurements in calves with acute abdominal emergencies before and during the initial therapeutic period after surgical intervention. A prospective observational study was carried out involving 83 hospitalized calves up to an age of 7 mo, which required surgical intervention for reasons of an acute abdominal emergency such as gastrointestinal ileus or peritonitis. Plasma l-lactate (L-LAC) concentrations were determined immediately before initiation of surgery and 6, 12, 24, 48, and 72 h later. The outcome of calves was evaluated 3 mo after discharge by a phone call to the farmer, and a positive outcome was defined if the calf was still alive and the owner was satisfied with the animal's postsurgical progress. A total of 29% of calves were discharged from the hospital and the proportion of calves with a positive outcome after the 3-mo period was 24%. At all sampling times during the first 48 h after initiation of surgical intervention, calves with a negative outcome had significantly higher L-LAC than calves with a positive outcome. A binary logistic regression analysis indicated that the odds for a negative outcome during the 3-mo observation period increased by a factor of 1.23 [95% confidence interval (CI): 1.04-1.44] for every mmol/L increase of L-LAC before initiation of surgical intervention, but by a factor of 5.29 (95% CI: 1.69-16.6) and 5.92 (95% CI: 1.29-27.3) at 12 and 24 h, respectively. The largest area under the receiver operating characteristic curve for L-LAC was observed at 12 h (0.91; 95% CI: 0.83-0.99), and a cut-point of 2.75 mmol/L was identified that had a sensitivity and specificity for predicting a negative outcome of 68 and 100%, respectively. In conclusion, persistent hyper-l-lactatemia during the early postoperative period is a more reliable indicator for a negative outcome in calves with acute surgical abdominal emergencies than hyper-l-lactatemia before initiation of surgical intervention. Postoperative measurements of L-LAC are therefore a clinically useful tool to identify patients with an increased risk for a negative outcome at an early stage after surgical intervention was carried out.

Prognostic value of preoperative plasma l-lactate concentrations in calves with acute abdominal emergencies.

Acute abdominal emergencies in calves due to abomasal disorders, gastrointestinal ileus, or peritonitis are characterized by a rapid disease progression and usually require immediate surgical intervention. Those conditions are associated with a guarded prognosis, and the aim of the present study was to assess the prognostic relevance of preoperatively measured plasma l-lactate concentrations (l-LAC) in a large study population of calves with a broad spectrum of acute abdominal emergencies. For the purpose of this study, the medical records of 587 calves admitted to a veterinary teaching hospital over a 10-yr period were analyzed retrospectively. Plasma l-LAC was measured as part of a routinely performed biochemistry panel before initiation of surgical intervention. Hyper-l-lactatemia (plasma l-LAC >2.2 mmol/L) was evident in 75% of calves, and the overall survival rate until hospital discharge was 31%. Calves with a negative outcome were younger (median: 3.4 vs. 6 wk) and had higher plasma l-LAC (median: 4.96 vs. 3.09 mmol/L) than calves with a positive outcome. At the individual diagnosis level, l-LAC was associated with mortality in calves with a diagnosis of mesenteric torsion, right-sided dilated abomasum, small intestinal volvulus, or paralytic ileus, but not in calves suffering from peritonitis, malformations, abomasal volvulus, bloat, or small intestinal intussusceptions. Considering the whole study population, the area under the receiver operating characteristic (ROC) curve for plasma l-LAC was 0.66 [95% confidence interval (CI): 0.61-0.70]. A classification tree analysis indicated that l-LAC >8.84 mmol/L and age categories of <3 wk and <1 wk were independent predictors of mortality. The area under the ROC curve of this model was 0.75 (95% CI: 0.71-0.79) and the resulting sensitivity and specificity for the prediction of nonsurvival at the optimal probability cut-point of 0.62 were 67.7 and 76.6%, respectively. In conclusion, hyper-l-lactatemia is common in calves suffering from acute abdominal emergencies. Markedly increased plasma l-LAC is associated with an increased mortality risk, but it is not possible to reliably predict the outcome of affected calves based on a single, preoperative measurement. However, a clinically important finding of this study was that the ability to predict a negative outcome is improved when the age of the calf is considered in addition to plasma l-LAC.

Technical note: Automatic evaluation of infrared thermal images by computerized active shape modeling of bovine udders challenged with Escherichia coli.

Mastitis causes substantial economic losses and animal suffering in the dairy industry. The trend toward larger herd sizes complicates the monitoring of udder health in individual animals. Infrared thermography has successfully been used for early mastitis detection. However, manual thermogram analysis is time consuming and requires a skilled examiner, and automated image processing has not been tested. The aim of this study was to determine whether automatic evaluation of thermograms showed results comparable to those of manual evaluation of thermograms. Five healthy cows underwent an intramammary challenge with Escherichia coli to induce clinical mastitis. Multiple udder thermograms were taken every 2 h for 24 h before and after the challenge, resulting in 4,143 images in total. All images were evaluated using image recognition software (automatically) and a polygon tool (manually) to calculate the average and maximum surface temperatures. Because of the slightly different regions of interest, temperatures ascertained from the thermograms using the automatic method were consistently lower than those ascertained using the manual method. However, average udder surface temperatures evaluated using both methods were strongly correlated (r = 0.98 in the left hindquarter, and r = 0.99 in the right hindquarter) and showed maximum temperature peaks at the same time, 13 and 15 h after intramammary challenge. In the receiver operating characteristic analysis, both methods provided good results for sensitivity and specificity in detecting clinical E. coli-induced mastitis at different threshold values. For automatically evaluated maximum right hindquarter temperature, sensitivity was 93.75% and specificity was 94.96%, and for manually evaluated maximum right hindquarter temperature, sensitivity was 93.75% and specificity was 96.40%. Thus, automatic thermogram evaluation is a promising tool for automated mastitis detection.

Predictors for and coverage of influenza vaccination among HIV-positive patients: a cross-sectional survey.

OBJECTIVES: Influenza vaccination is recommended for HIV-infected patients, but limited data about vaccination rates are available. The aim of this study was to evaluate the coverage of and predictors for influenza vaccination among HIV-positive patients. METHODS: All HIV-positive patients who visited the HIV out-patient department of the University Hospital of Vienna, Austria, between June and August 2015 were asked to participate in this survey by completing a questionnaire. RESULTS: A total of 455 HIV-positive patients completed a questionnaire, with 359 male and 96 female participants with a mean age of 46 years. The influenza vaccination rate for the previous season (2014/2015) was 11.9% [n = 54/455; 95% confidence interval (CI) 9.2-15.2%]. Older age was significantly associated with a positive influenza vaccination status. Obtaining information through a medical consultation or receiving a direct recommendation for vaccination by a physician had a significant impact on vaccination behaviour. The probability of being vaccinated against influenza was about 13 times higher among patients who received a recommendation for vaccination by their family physician or by their HIV specialist (P < 0.001). Important reasons for declining vaccination were fear of side effects (39%), not considering influenza as a severe disease (36%) and reasons related to HIV: 17% were worried that the vaccine could worsen the course of HIV infection and 16% believed vaccination would fail because of their compromised immune system. CONCLUSIONS: A low influenza vaccination rate of 11.9% was detected in this HIV-positive cohort. The most effective impact for a positive vaccination status was direct recommendation of the influenza vaccine by the attending physician.

[Individualization of exercise load control for inpatient cardiac rehabilitation. Development and evaluation of a HRV-based intervention program for patients with ischemic heart failure]. / Individualisierung der Belastungssteuerung in der kardiologischen stationären Rehabilitation. Entwicklung und Evaluation eines HRV-gesteuerten Interventionsprogramms für Patienten mit ischämisch bedingter Herzinsuffizienz.

BACKGROUND: The effective use of rehabilitation programs is of primary importance in order to improve the physical performance of cardiac disease patients. A modular program has been developed which is intended to structure and individualize conventional, exercise-based rehabilitation programs according to the individual needs and physical condition of each patient. The individualization of the program is based on detailed diagnostics before patients enter the program and daily measurements of heart rate variability (HRV) during cardiac rehabilitation. METHODS: A total of 30 patients with ischemic heart disease were randomly assigned either to the intervention group (IG), completing the modular individualized rehabilitation program [n=15, mean age 54.4±4.2 years and mean left ventricular ejection fraction (LVEF) 28.53±6.25%) or to the control group (CG) taking part in the conventional rehabilitation program (n=15, mean age 56.4±4.4 years and mean LVEF 27.63±5.62). Before and after the intervention, cardiorespiratory fitness was assessed by measurement of maximal oxygen consumption (relative VO2max) during bicycle ergometry and the 6-minute walk test (6-MWT). Pre-post comparisons of cardiorespiratory fitness indicators were used to evaluate the effectiveness of the rehabilitation program. In addition to the results of the basic clinical investigations and the cardiorespiratory testing, results of standardized HRV measurements of 10 min at morning rest served as criteria for program individualization. RESULTS: The relative VO2max increased significantly (p<0.05) in the IG whereas no change was found in the CG. Similar results were found for maximum power output during bicycle ergometry (p<0.01) and for 6-MWT distance (p<0.001). Although patients in the IG completed less aerobic exercise sessions than those in the CG (p<0.001) the physical performance of the IG improved significantly. DISCUSSION: The results prove the effectiveness and efficacy of the modular individualized rehabilitation program. They further suggest the need for an individual program matrix instead of a maximum performance matrix in cardiac rehabilitation. Individualization should be based on clinical and performance diagnostics before and accompanying assessments of training condition, e.g. by HRV measurements, during rehabilitation programs. Each patient should only perform those intervention programs which match the results of the basic clinical investigation and additional analyses during rehabilitation.

[Work-Related Setting Approach with Health Counselling Supports a Healthy Lifestyle of Long-Term Unemployed Persons]. / Arbeitsmarktintegratives Setting mit Gesundheitsberatung unterstützt gesundheitsförderlichen Lebensstil bei Langzeiterwerbslosen.

Unemployment is a major reason for health inequalties. In a pilot study (N=119), the acceptance and effectiveness of a low threshold health promotion intervention for older long-term unemployed persons were evaluated. Health counselling supported the participants in the development of a healthy lifestyle.

Revisiting predictors of virologic response to PEGIFN + RBV therapy in HIV-/HCV-coinfected patients: the role of metabolic factors and elevated GGT levels.

Evaluation of metabolic factors and elevated γ-glutamyltransferase (GGT) levels as independent predictors of treatment failure in a thoroughly documented cohort of HIV-/HCV-coinfected patients (HIV/HCV). Sixty-four HIV/HCV patients treated with pegylated interferon-α-2a plus ribavirin (PEGIFN + RBV) at the Medical University of Vienna within a prospective trial were included in this study. In addition, 124 patients with HIV/HCV from the AIFA-HIV and AHIVCOS cohorts were included as a validation cohort. Advanced liver fibrosis, GGT elevation, insulin resistance (IR) and low CD4+ nadir were defined as METAVIR F3/F4, GGT levels >1.5× sex-specific upper limit of normal, homoeostasis model assessment of insulin resistance >2 and CD4+ nadir <350 cells/µL, respectively. HCV-genotype 1/4 (OR26.3; P = 0.006), advanced liver fibrosis (OR20.2; P = 0.009), interleukin 28B rs12979860 non-C/C SNP (OR8.27; P = 0.02) and GGT elevation (OR7.97; P = 0.012) were independent predictors of treatment failure, while both IR (OR3.51; P = 0.106) and low CD4 + nadir (OR2.64; P = 0.263) were not independently associated with treatment failure. A statistically significant correlation between GGT elevation and prior alcohol abuse (r = 0.259; P = 0.039), liver steatosis (r = 0.301; P = 0.034) and low-density lipoprotein-cholesterol (r = -0.256; P = 0.041) was observed. The importance of GGT elevation as an independent predictor of treatment failure was confirmed in a validation cohort (OR2.76; P = 0.026). While GGT elevation emerged as an independent predictor of treatment failure in both the derivation and the validation cohort, no independent associations between metabolic factors and treatment failure were observed. Thus, our findings suggest that GGT elevation is an independent predictor of treatment failure in HIV/HCV that can easily be incorporated into predictive algorithms.

Viral determinants predicting hepatitis B surface antigen (HBsAg) seroclearance in HIV-/HBV-coinfected patients.

The aim of this retrospective study was the identification of clinically useful viral determinants for the prediction of hepatitis B surface antigen (HBsAg) seroclearance and sustained virological response in hepatitis B virus/human immunodeficiency virus (HBV-/HIV)-coinfected patients receiving HBV-active combined antiretroviral therapy (cART). Quantification of HBsAg, HBeAg and HBV DNA before and after initiation of HBV-active cART in a cohort of 59 HIV-/HBV-coinfected patients was performed. Calculations of receiver operating characteristics (ROC) and Kaplan-Meier analysis were used for the identification of predictors of HBsAg seroclearance for HBeAg-positive [HBeAg(+); n = 36] and HBeAg-negative [HBeAg(-);n = 23] patients. HBeAg(+) patients with an HBsAg on-treatment decline ≥ 1 log IU/mL per year achieved higher HBsAg loss rates (P = 0.0294), whereas the quantification of HBeAg had no predictive value for HBsAg seroclearance. Among HBeAg(-) patients, a pretreatment baseline cut-off level of HBsAg ≤ 100 IU/mL was highly predictive for HBsAg seroclearance. No significant influence of the HBV genotype on HBsAg seroclearance was observed among the entire cohort. Quantitative determination of HBsAg provides a clinically useful viral parameter for the prediction of HBsAg seroclearance both in HBeAg(+) and HBeAg(-) HIV-/HBV-coinfected patients receiving HBV-active cART.

[Management of patients with the cardinal symptom dizziness or vertigo]. / Versorgungssituation von Patienten mit dem Leitsymptom Schwindel.

BACKGROUND: Vertigo and dizziness are common symptoms leading patients to consult a physician. The nationally representative "2003 Health Survey" depicts the epidemiology of the symptoms vertigo and dizziness across all of Germany. A breakdown of the data by region is not available. METHODS: Routine data of the Bavarian Association of Statutory Health Insurance Physicians accounting centre ("Kassenärztliche Vereinigung Bayerns", KVB) from 2008 were analysed using multilevel models to investigate individual and regional factors and the relevance of nonspecific regional heterogeneity. RESULTS: Altogether, 866,086 of 9,269,729 (9.34%) inhabitants received an ambulatory diagnosis of vertigo or dizziness, including 1.77 times as many women as men. Visits to the doctor because of vertigo or dizziness increased with age. After adjustments for age and sex, a North-South divide and a higher prevalence in the urban centres were apparent within Bavaria. The majority of patients were seen by their GP and nearby doctors. This held especially true for women. Also older patients were less likely to go to specialists further afield. CONCLUSION: This analysis of the KVB data of patients with vertigo or dizziness underlines the central role that is played by GPs in diagnosis and treatment. In order to correctly diagnose the underlying causes, treat patients or send them to specialists effectively, all doctors need to be trained about this relevant clinical symptom. The insufficient representation of clinically established vertigo disorders by the ICD-10 was problematic. The most frequently coded diagnosis was N95.1 "postmenopausal dizziness".

Therapy and prophylaxis of opportunistic infections in HIV-infected patients: a guideline by the German and Austrian AIDS societies (DAIG/ÖAG) (AWMF 055/066).

INTRODUCTION: There was a growing need for practical guidelines for the most common OIs in Germany and Austria under consideration of the local epidemiological conditions. MATERIALS AND METHODS: The German and Austrian AIDS societies developed these guidelines between March 2010 and November 2011. A structured Medline research was performed for 12 diseases, namely Immune reconstitution inflammatory syndrome, Pneumocystis jiroveci pneumonia, cerebral toxoplasmosis, cytomegalovirus manifestations, candidiasis, herpes simplex virus infections, varizella zoster virus infections, progressive multifocal leucencephalopathy, cryptosporidiosis, cryptococcosis, nontuberculosis mycobacteria infections and tuberculosis. Due to the lack of evidence by randomized controlled trials, part of the guidelines reflects expert opinions. The German version was accepted by the German and Austrian AIDS Societies and was previously published by the Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF; German Association of the Scientific Medical Societies). CONCLUSION: The review presented here is a translation of a short version of the German-Austrian Guidelines of opportunistic infections in HIV patients. These guidelines are well-accepted in a clinical setting in both Germany and Austria. They lead to a similar treatment of a heterogeneous group of patients in these countries.

Lipid profiles for etravirine versus efavirenz in treatment-naive patients in the randomized, double-blind SENSE trial.

BACKGROUND: Etravirine is approved for use in treatment-experienced patients at a dose of 200 mg twice daily. Efavirenz has been associated with greater increases in serum lipids compared with other non-nucleosides in randomized trials of first-line treatment. METHODS: In this double-blind, placebo-controlled trial, 157 treatment-naive patients with HIV RNA >5000 copies/mL were randomized 1:1 to either 400 mg of etravirine once daily (n=79) or 600 mg of efavirenz once daily (n=78) plus two nucleoside analogues (either abacavir/lamivudine, zidovudine/lamivudine or tenofovir/emtricitabine) for 48 weeks. Lipids were measured under fasting conditions at baseline and all visits to Week 48. Clinicaltrials.gov identifier: NCT00903682. RESULTS: Overall, the patients had a median baseline CD4 count of 302 cells/mm(3) (range 74-722) and a median HIV RNA of 4.8 log(10) copies/mL (range 3.5-6.6). Both the non-nucleosides and the nucleoside analogues used caused changes in serum lipids. In the efavirenz arm, patients showed significantly larger increases in high-density lipoprotein (HDL) (+0.15 mmol/L, P=0.004), low-density lipoprotein (LDL) (+0.35 mmol/L, P=0.005), total cholesterol (+0.61 mmol/L, P<0.0001) and triglycerides (+0.33 mmol/L, P=0.03) at Week 48 compared with the etravirine arm. Across the two arms, patients taking abacavir/lamivudine showed greater increases in total cholesterol (+0.47 mmol/L, P=0.005) compared with patients taking tenofovir/emtricitabine. There were fewer grade 3/4 elevations in total cholesterol, LDL and triglycerides in the etravirine arm (2 patients, 1 patient and 0 patients, respectively) versus the efavirenz arm (8 patients, 6 patients and 2 patients, respectively). CONCLUSIONS: In the SENSE trial, first-line treatment with 400 mg of etravirine once daily plus two nucleoside analogues led to fewer grade 3 or 4 lipid elevations compared with efavirenz plus two nucleoside analogues.

Five-year on-treatment efficacy of lamivudine-, tenofovir- and tenofovir + emtricitabine-based HAART in HBV-HIV-coinfected patients.

Data on the efficacy of lamivudine (LAM)-, tenofovir (TDF)- and emtricitabine (FTC)-based antiretroviral therapy (HAART) in HBV-HIV coinfection are limited. We completed a retrospective analysis of HBV-HIV-coinfected patients treated at the Medical University of Vienna. One-hundred and ten coinfected patients were included, with 57% being initially HBV e-Antigen (HBeAg) positive. Baseline HBV load was significantly higher in HBeAg+ than in HBeAg- patients (5962 ± 3663 vs 20 ± 19 × 10(6) IU/mL; P < 0.0001). Over a median observation period of 83 month (range: 26-183), 87% received HAART and 91% showed a suppression of HBV replication. After 5 years of continuous treatment, HBeAg seroconversion was achieved in 21% of LAM-, 50% of TDF- (P = 0.042 vs LAM) and in 57% of TDF + FTC (P = 0.008 vs LAM)-treated patients, respectively. HBsAg loss after 5 years was found in 8% (LAM), 25% (TDF; P = 0.085 vs LAM) and 29% (TDF + FTC; P = 0.037 vs LAM) of HBeAg+ patients. In HBeAg- patients, HBsAg loss was achieved in 11% (LAM), 27% (TDF; P = 0.263 vs LAM) and 36% (TDF + FTC; P = 0.05 vs LAM), respectively. Pretreatment CD4+ counts did not influence rates of HBeAg seroconversion and of HBsAg loss. Patients with HBsAg loss had lower baseline HBV-DNA levels and higher AST/ALT levels than patients without HBsAg loss. Transient HAART-related hepatotoxicity was found in 32% (Grade I: 21%; II:7%; III:2%; IV:0%). Most HBV-HIV-coinfected patients achieve complete suppression of HBV replication despite high baseline viremia. TDF-based HAART leads to high rates of HBeAg seroconversion and HBsAg loss after 5 years of continuous exposure. One-third of HBV-HIV-coinfected patients may experience transient HAART-related hepatotoxicity.

Concomitant highly active antiretroviral therapy leads to smaller decline and faster recovery of CD4+ cell counts during and after pegylated interferon plus ribavirin therapy in HIV-hepatitis C virus coinfected patients.

INTRODUCTION: The impact of highly active antiretroviral therapy (HAART) on CD4+ cell course during treatment with pegylated interferon plus ribavirin (PegIFN-RBV) in patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is unknown. METHODS: We determined CD4(+) cell count in 94 HIV-HCV coinfected patients undergoing treatment with pegylated interferon plus RBV at baseline, treatment weeks 4-48 (W4-W48), and months 1, 3, and 6 of follow-up. Of the 94 patients, 70 underwent concomitant HAART (group A) and 24 did not (group B). RESULTS: Group A showed smaller CD4(+) cell decreases from W24-W48 (P = .027) and greater CD4(+) cell increases after cessation of pegylated interferon plus ribavirin therapy (P = .002) than group B showed. CONCLUSIONS: Concomitant HAART leads to smaller decreases and faster recovery of CD4(+) cells during and after pegylated interferon plus RBV therapy.

Gene expression analysis of MAOA and the clock gene ARNTL in individuals with bipolar disorder compared to healthy controls.

INTRODUCTION: Circadian rhythms are associated with bipolar disorder (BD). This cross-sectional study aimed at investigating ARNTL and MAOA gene expression differences (1) between individuals with BD and controls, (2) between affective episodes, and (3) the relationship between ARNTL and MAOA expression. METHODS: ARNTL and MAOA gene expression in peripheral mononuclear blood cells were analysed from fasting blood samples (BD n = 81, controls n = 54) with quantitative real-time PCR operating on TaqMan® assays (normalised to 18S RNA expression). ANCOVAs corrected for age, sex, body mass index, and medication was used to evaluate expression differences and correlation analyses for the relation between ARNTL and MAOA expression. RESULTS: ARNTL gene expression differed between affective episodes (F(2,78) = 3.198, p = 0.047, Partial Eta2= 0.083), but not between BD and controls (n.s.). ARNTL and MAOA expression correlated positively in BD (r = 0.704, p < 0.001) and in controls (r = 0.932, p < 0.001). MAOA expression differed neither between BD and controls nor between affective episodes (n.s.). DISCUSSION: Clock gene expression changes were observed in different affective states of BD. More precisely, ARNTL gene expression was significantly higher in euthymia than in depression. ARNTL and MAOA gene expression correlated significantly in BD and in controls, which emphasises the strong concatenation between circadian rhythms and neurotransmitter breakdown.

[Meta-analysis to estimate the economic losses caused by reduced milk yield and reproductive performance associated with bovine paratuberculosis in Switzerland]. / Eine Meta-Analyse zur Schätzung der wirtschaftlichen Einbussen durch Milch- und Reproduktionsverluste infolge boviner Paratuberkulose in der Schweiz.

INTRODUCTION: Especially in regions with intensive cattle farming, paratuberculosis in ruminants can cause considerable economic losses for example through loss of sick animals, reduced milk yield and decreased reproduction performance. Although quantifying the actual economic losses is complex, this study attempts to quantify the losses caused by paratuberculosis in infected dairy farms in Switzerland by means of meta-analyses. For this purpose, in an elaborate selection process, data from 12 studies on milk yield and from three studies on the calving to conception interval were finally selected for further calculations. In addition, data from eight studies each on milk fat concentration and milk protein concentration were evaluated. For the meta-analyses, only studies in which «sick¼ (seropositive) and «healthy¼ (seronegative) animals based on the results of serum ELISA tests were compared at the individual animal level were considered. With a paratuberculosis prevalence of 5,99 % in cattle in Switzerland, a total loss of CHF 12 034 329,96 (95 % CI [CHF 8 625 406,02; CHF 16 409 276,30]; 11 095 652,20 € [7 952 624,35 €; 15 129 352,70 €]) per year was calculated for a population of 559 900 dairy cows. The main part of the losses is caused by an extended calving to conception interval: Seropositive animals need an average of 14,93 days longer (95 % CI [1,73; 28,13]) from calving to successful insemination as seronegative animals. This results in total costs for the extended calving to conception interval due to paratuberculosis of CHF 7 365 591,21 per year (95 % CI [CHF 900 394,95; CHF 14 838 087,61]; 6 791 075,10 € [830 164,14 €; 13 680 716,80 €]). Milk yield reduction based on a lactation period of 305 days results in an economic loss of CHF 4 668 738,75 per year (95 % CI [CHF 1 571 188,69; CHF 7 725 011,07]; 4 304 577,13 € [1 448 635,97 €; 7 122 460,21 €]). Milk fat and milk protein content were not found to be significantly changed. Despite a large number of studies in the screening phase, it was not possible to calculate all types of losses attributable to paratuberculosis due to lack of comparability between the studies, which is essential for meta-analyses. Nevertheless, it was possible to carry out four different meta-analyses, the results of which give a first impression of the economic importance of paratuberculosis in dairy cows in Switzerland.

INTRODUCTION: La paratuberculose des ruminants cause, particulièrement dans les régions ayant une industrie laitière intensive, des pertes économiques considérables, par exemple par la perte d'animaux malades, la réduction de la production laitière et une reproduction diminuée. Malgré la complexité de la quantification des pertes économiques effectives, on a essayé dans l'étude présentée ici de calculer les pertes causées par la paratuberculose dans les exploitations laitières en Suisse au moyen de méta-analyses. Dans ce but, des données extraites par un processus de sélection compliqué de 12 études sur la production laitière et de trois études sur la période de tarissement ont été utilisées pour calculer les pertes dues à la paratuberculose. De plus, huit études chacune sur la concentration de graisse et des protéines du lait ont été prises en compte. Seules des études où les animaux étaient classifiés comme «sains¼ (séronégatifs) et «malades¼ (séropositifs) sur la base d'un test ELISA sérique ont été prises en considération pour les méta-analyses. Pour une prévalence de la paratuberculose de 5,99 % chez les bovins en Suisse, on a pu calculer pour une population de 559 900 vaches laitières une perte totale de 12 034 329,96 CHF (IC 95 % [8 625 406,02 CHF; 16 409 276,30 CHF]; 11 095 652,20 € [7 952 624,35 €; 15 129 352,70 €]) par année. La plus grande partie de ces pertes sont dues à une période de tarissement prolongée: les vaches séropositifs ont besoin en moyenne de 14,93 jours de plus (IC 95 % [1,73; 28,13]) du vêlage à une insémination menant à une gestation que les animaux séronégatifs. Il en résulte des coûts dus à la paratuberculose en raison d'une période de tarissement prolongée de 7 365 591,21 CHF par année (IC 95 % [900 394,95 CHF; 14 838 087,61 CHF]; 6 791 075,10 € [830 164,14 €; 13 680 716,80 €]). La diminution de la production laitière cause pour une durée de lactation de 305 jours une perte économique de 4 668 738,75 CHF par année (IC 95 % [1 571 188,69 CHF; 7 725 011,07 CHF]; 4 304 577,13 € [1 448 635,97 €; 7 122 460,21 €]). Les pertes en valeurs de graisse et de protéines du lait n'étaient pas significatives. Malgré le nombre élevé d'études prises en compte dans la phase de recherche de publications pertinentes, il n'a pas été possible de calculer tous les types de pertes, car les études n'étaient pas suffisamment comparables entre elles, ce qui est une condition essentielle pour une méta-analyse. Il a cependant été possible de procéder à quatre méta-analyses différentes, dont les résultats donnent une idée de l'importance économique des pertes liées à la paratuberculose chez les vaches laitières en Suisse.

Comparison of four commercially available point-of-care tests to detect antibodies against canine distemper virus in dogs.

Pre-vaccination antibody testing to determine dogs' immunity against canine distemper virus (CDV) is increasingly used. Four point-of-care tests (POC A-D) are available in Europe, but their diagnostic accuracy has not been compared. The study evaluated the diagnostic accuracy and usability of these tests. Sera of client-owned dogs (n = 198; healthy n = 22; unhealthy dogs n = 176) and specific pathogen-free (SPF) dogs (n = 40) were included. Virus neutralisation (VN) was performed as the reference standard. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and overall accuracy (OA) were determined. McNemar's test was used to determine significant differences between specificity and sensitivity of the tests and Cohen's kappa was used to assess agreement. The prevalence of anti-CDV antibodies by VN was 80% in client-owned dogs overall, with 100% prevalence in healthy dogs, and 0% in SPF dogs. POC-C and POC-D were considered easiest to perform. Specificity of all tests was high using sera from SPF dogs (88-100%). In healthy dogs, sensitivity was variable (45-98%). Specificity was low in all four POC tests when using sera from acutely ill dogs (6-53%) and clinically healthy dogs with chronic disease (5-77%). In client-owned dogs, including healthy and unhealthy dogs, agreement was poor between tests. All POC tests had a low specificity when investigating sera from ill client-owned dogs and usefullness of these tests especially in dogs that are acutely ill or have chronic disease is not supported by this study.

Additive prognostic value of preoperative plasma glucose concentrations in calves undergoing abdominal surgery.

Surgical abdominal emergencies in calves are associated with a guarded prognosis, especially if neonates are affected. Because hypoglycemia has been associated with sepsis and endotoxemia, this study aimed to assess the prognostic relevance of preoperative plasma glucose concentrations (GLUC) in calves requiring surgery for an acute abdominal disorder. For this purpose, data from retrospective and prospective case series were analyzed, consisting of 586 and 83 hospitalized calves, respectively. The outcomes of calves were evaluated until hospital discharge (both study populations) and for 3 mo following discharge by a phone call to the farmer (prospective study population). For the retrospective study population, the overall survival rate was 31.2%. Calves with a negative outcome (NO) had significantly lower median GLUC (4.3 mmol/L) than calves with a positive outcome (PO; 5.0 mmol/L). The survival rates of calves with GLUC <2.4 mmol/L and 2.4 to 3.1 mmol/L were 3.6 and 8.3%, respectively. The inclusion of GLUC improved a previous prognostic model based on plasma l-lactate concentration and age. The resulting analyses indicated that NO was associated with low age (<7 d), hyper-l-lactatemia (>8.84 mmol/L), and GLUC <4.4 mmol/L (age 7-20 d) and <3.3 mmol/L (age ≥21 d), respectively. The area under the receiver operating characteristic curve of this model was 0.79 (95% confidence interval: 0.76-0.83) and the resulting sensitivity and specificity for NO at the optimal probability cut-point of 0.69 were 66.7 and 85.8%, respectively. For the prospective study population, the established model had sensitivity and specificity for predicting NO after 3 mo (proportion 24%) of 61.9 and 85%, respectively. In both study populations, hypoglycemia was significantly associated with intraoperative evidence of a septic process within the abdominal cavity. The present analyses show that hypoglycemia was highly indicative of a poor prognosis and serious intraoperative findings such as peritonitis. Determination of GLUC should therefore be part of the diagnostic work-up in calves suffering from an acute abdominal emergency.