Baseline brain function in the preadolescents of the ABCD Study.

The Adolescent Brain Cognitive Development (ABCD) Study® is a 10-year longitudinal study of children recruited at ages 9 and 10. A battery of neuroimaging tasks are administered biennially to track neurodevelopment and identify individual differences in brain function. This study reports activation patterns from functional MRI (fMRI) tasks completed at baseline, which were designed to measure cognitive impulse control with a stop signal task (SST; N = 5,547), reward anticipation and receipt with a monetary incentive delay (MID) task (N = 6,657) and working memory and emotion reactivity with an emotional N-back (EN-back) task (N = 6,009). Further, we report the spatial reproducibility of activation patterns by assessing between-group vertex/voxelwise correlations of blood oxygen level-dependent (BOLD) activation. Analyses reveal robust brain activations that are consistent with the published literature, vary across fMRI tasks/contrasts and slightly correlate with individual behavioral performance on the tasks. These results establish the preadolescent brain function baseline, guide interpretation of cross-sectional analyses and will enable the investigation of longitudinal changes during adolescent development.

Cognitive ageing is premature among a community sample of optimally treated people living with HIV.

OBJECTIVES: Evidence of premature cognitive ageing amongst people living with HIV (PLHIV) remains controversial due to previous research limitations including underpowered studies, samples with suboptimal antiretroviral access, varying rate of virological control, high rate of AIDS, over-representation of non-community samples, and inclusion of inappropriate controls. The current study addresses these limitations, while also considering mental health and non-HIV comorbidity burden to determine whether PLHIV showed premature cognitive ageing compared with closely comparable HIV-negative controls. METHODS: This study enrolled 254 PLHIV [92% on antiretroviral therapy; 84% with HIV RNA < 50 copies/mL; 15% with AIDS) and 72 HIV-negative gay and bisexual men [mean (SD) age = 49 (10.2) years] from a single primary care clinic in Sydney, Australia. Neurocognitive function was evaluated with the Cogstate Computerized Battery (CCB) at baseline and 6 months after. Linear mixed-effects (LME) models examined main and interaction effects of HIV status and chronological age on the CCB demographically uncorrected global neurocognitive z-score (GZS), adjusting for repeated testing, and then adjusting sequentially for HIV disease markers, mental health and comorbidities. RESULTS: HIV status and age interacted with a lower GZS (ß = -0.43, P < 0.05). Higher level of anxiety symptoms (ß = -0.11, P < 0.01), historical AIDS (ß = -0.12, P < 0.05) and historical HIV brain involvement (ß = -0.12, P < 0.05) were associated with lower GZS. CONCLUSIONS: We found a robust medium-sized premature ageing effect on cognition in a community sample with optimal HIV care. Our study supports routine screening of cognitive and mental health among PLHIV aged ≥ 50 years.

Managing HIV-associated inflammation and ageing in the era of modern ART.

OBJECTIVES: This paper aims to address the concerns around ongoing immune activation, inflammation, and resistance in those ageing with HIV that represent current challenges for clinicians. METHODS: Presentations at a symposium addressing issues of ageing with HIV infection were reviewed and synthesised. RESULTS: The changing natural history and demographics of human immunodeficiency virus (HIV)-infected individuals means new challenges in contemporary management. In the early years of the epidemic,management was focussed on acute, potentially life-threatening AIDS-related complications. From initial monotherapy with first-generation antiretroviral therapy (ART), the development of combination highly active ART (HAART) allowed HIV control but ART toxicities, treatment adherence and drug resistance emerged as major issues. Today, the availability of potent and tolerable ART has made viral suppression achievable in most people living with HIV (PLHIV), and clinicians are confronted with managing a chronic condition among an ageing population. The combination of diseases of ageing and the co-morbidities associated with HIV-infection, even when well controlled, results in a complex set of challenges for many older PLHIV. There is a growing appreciation that many non-AIDS-related co-morbidities are caused, at least in part, by persistent, low-grade immune activation, inflammation, and hypercoagulability, despite suppressive ART. CONCLUSIONS: In order to further improve HIV management, it is important to understand the enduring effects of chronically suppressed HIV infection, the potential contribution of these factors to the ageing process, the possibility of drug resistance, and the impact of different treatment strategies, including early ART initiation.

Cardiovascular disease and diabetes in HIV-positive and HIV-negative gay and bisexual men over the age of 55 years in Australia: insights from the Australian Positive & Peers Longevity Evaluation Study.

OBJECTIVES: As HIV-positive people age, diagnosis and management of comorbidities associated with ageing are of increasing concern. In this study, we aimed to compare the self-reported prevalences of heart disease, stroke, thrombosis and diabetes in older Australian HIV-positive and HIV-negative gay and bisexual men (GBM). METHODS: We analysed data from the Australian Positive & Peers Longevity Evaluation Study (APPLES), a study of a prospectively recruited cross-sectional sample of 228 (51.1%) HIV-positive and 218 (48.9%) HIV-negative GBM, aged ≥ 55 years. Regression methods were used to assess the association of HIV status with self-reported comorbidities. RESULTS: Of 446 patients, 389 [200 (51.4%) HIV-positive] reported their disease history. The reported prevalence of comorbidities was higher in the HIV-positive group than in the HIV-negative group: heart disease, 19.5 versus 12.2%; stroke, 7.5 versus 4.2%; thrombosis, 10.5 versus 4.2%; and diabetes, 15.0 versus 9.0%, respectively. In adjusted analyses, HIV-positive GBM had significantly increased odds of reporting heart disease [adjusted odds ratio (aOR) 1.99; P = 0.03] and thrombosis (aOR 2.87; P = 0.01). In our analysis, HIV status was not significantly associated with either age at diagnosis of heart disease (median 53 years for HIV-positive GBM versus 55 years for HIV-negative GBM; P = 0.64) or 5-year cardiovascular disease (CVD) risk estimated using the Framingham risk score. CONCLUSIONS: HIV-positive GBM more commonly reported heart disease and thrombosis compared with their HIV-negative peers. These results further highlight the need to understand the impact of HIV on age-related comorbidities in GBM, to guide optimal screening and treatment strategies to reduce the risk of these comorbidities among the HIV-positive population.

[From guinea pig to man: Tinea outbreak due to Trichophyton mentagrophytes var. porcellae in pet shops in Nancy (France)]. / Du cochon d'Inde à l'Homme : épidémie de teigne à Trichophyton mentagrophytes var. porcellae dans les animaleries nancéiennes.

Dermatophytes are responsible for widespread superficial fungal infections, currently representing a real public health problem. Some of the fungi involved in these mycoses are transmitted by pets, illustrating great host specificity within this fungal group. Thus, a new variety of zoophilic dermatophyte has been described in recent years by the Mycology Laboratory of the University Hospital of Nancy, within the complex T. mentagrophytes. This variant was named T. mentagrophytes var. porcellae, following the observation of a significant number of patients with dermatomycoses of exposed parts of the body and having had contact with a guinea pig. The current work follows this first description and aims to assess the frequency of T. mentagrophytes var. porcellae in guinea pigs within three pet shops in the region of Nancy (France). In total, almost two thirds of collected guinea pigs were carriers of this new dermatophyte. This study highlights the risks associated with the adaptation of dermatophytes to potential new hosts that may spread to new species. Thus, in this context, sanitary measures could be proposed to the pet shops, usually not informed of the risks facing the growing enthusiasm of the population for new pets, in order to limit contamination.

Protocol for an open-label, single-arm trial of HIV pre-exposure prophylaxis (PrEP) among people at high risk of HIV infection: the NSW Demonstration Project PRELUDE.

INTRODUCTION: Despite a number of HIV prevention strategies, the number of new HIV infections remains high. In Australia, over three-quarters of new HIV diagnoses are in gay and bisexual men (GBM). Pre-exposure prophylaxis (PrEP) has been shown to be effective at preventing new HIV infections in several randomised trials. The PRELUDE study aims to evaluate the implementation of PrEP in healthcare settings in New South Wales (NSW), Australia, among a sample of high-risk adults. METHODS AND ANALYSIS: PRELUDE is an ongoing open-label, single-arm demonstration project, conducted in public and private clinics across NSW, Australia. Enrolment began in November 2014. The study is designed for 300 high-risk participants-mainly GBM and heterosexual women. Participants receive daily oral PrEP, composed of emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF), for up to 2.5 years. Quarterly study visits include testing for HIV and sexually transmitted infections (STIs), assessment of ongoing eligibility and side effects, and self-reported adherence. Following each study visit, online behavioural surveys are administered to collect information on medication adherence, risk behaviours and attitudes. Blood samples will be collected in a subset of patients 1, 6 and 12 months after PrEP initiation to measure FTC/TDF concentrations. Analyses using longitudinal regression models will focus on feasibility, adherence, safety, tolerability and effects of PrEP on behaviour. This study will inform PrEP policy and guide the implementation of PrEP in Australia in people at high risk of HIV. ETHICS AND DISSEMINATION: The study will be conducted in accordance with the Declaration of Helsinki. All patients will provide written informed consent prior to participation in the study. Publications relating to each of the primary end points will be gradually released after 12 months of follow-up is complete. TRIAL REGISTRATION NUMBER: NCT02206555; Pre-results.

Rosuvastatin vs. protease inhibitor switching for hypercholesterolaemia: a randomized trial.

OBJECTIVES: The aim of the study was to compare the efficacy and safety of rosuvastatin initiation with those of switching of ritonavir-boosted protease inhibitors (PI/rs) in HIV-1-infected adults with hypercholesterolaemia and increased cardiovascular risk scores. METHODS: In this open-label, multicentre study, HIV-1-infected adults on PI/r-based therapy with viral load < 50 HIV-1 RNA copies/mL, fasting total cholesterol ≥ 5.5 mmol/L (both for ≥ 6 months) and elevated cardiovascular risk (Framingham score ≥ 8% or diabetes or family history), and not on lipid-lowering therapy, were randomized to open-label rosuvastatin 10 mg/day or to PI/r switching, both with standardized diet/exercise advice. The primary endpoint was change in total cholesterol at week 12 (intention to treat). RESULTS: There were 43 participants (23 on rosuvastatin). Baseline characteristics were: mean [± standard deviation (SD)] age 55 (8.5) years, 42 (98%) male, 41 (95%) white race, and mean (± SD) total cholesterol 6.2 (1.2) mmol/L. At enrolment, PI/rs were lopinavir/ritonavir (n = 22; 51%), atazanavir/ritonavir (n = 12; 28%) and darunavir/ritonavir (n = 9; 21%). The commonest PI/r substitutes were raltegravir (n = 9; 45%) and rilpivirine (n = 4; 20%). All participants were adherent through to week 12. Rosuvastatin yielded greater declines than PI/r switching in total (- 21.4% vs. - 8.7%, respectively; P = 0.003) and low-density lipoprotein (- 29.9% vs. - 1.0%, respectively; P < 0.001) cholesterol, but smaller declines in very low-density lipoprotein cholesterol and triglycerides (P < 0.01). Cholesterol lowering was greater in participants on atazanavir/ritonavir or once-daily darunavir/ritonavir (vs. lopinavir/ritonavir). More study drug-related adverse events (mostly grade 1 nausea/diarrhoea; 10 vs. one, respectively; P = 0.001) occurred with PI/r switching than with rosuvastatin. CONCLUSIONS: In adults receiving a PI/r, rosuvastatin 10 mg/day for 12 weeks yielded larger decreases in total and low-density lipoprotein cholesterol than PI/r switching, and was better tolerated.

Dolutegravir: clinical and laboratory safety in integrase inhibitor-naive patients.

BACKGROUND: The efficacy of dolutegravir (DTG) has been demonstrated in 5 randomized studies in integrase inhibitor (INI)-naive adult populations. To date, a detailed safety review of DTG has not been provided in the literature. OBJECTIVE: To describe the safety and tolerability profile of DTG in adults based on 5 randomized, controlled trials and comparison with drugs in 3 major antiretroviral (ARV) classes. METHODS: Safety data from phase IIb/III/IIIb trials in ART-naive and ART-experienced, INI-naive adults were integrated. RESULTS: In 4 ART-naive (SPRING-1, SPRING-2, SINGLE, FLAMINGO) and 1 ART-experienced, INI-naive study (SAILING), 1,579 individuals received a DTG-containing regimen. The proportion of individuals from DTG treatment arms who withdrew due to adverse events (AEs) was low (≤2%) compared to raltegravir (RAL; 2% SPRING-2, 4% SAILING), efavirenz (EFV)-containing comparator arm (10% SINGLE), and darunavir + ritonavir (DRV/r; 4% FLAMINGO). The most frequently observed AEs (diarrhea, nausea, headache), typically grade 1 or 2 in severity, did not lead to study discontinuation. Psychiatric and nervous system disorders with DTG were comparable to RAL- and DRV/r-containing regimens and favorable to EFV-containing regimens. In hepatitis B and/or C coinfected ART-naive individuals, the incidence of transaminase elevations was lower with DTG versus RAL and EFV comparators, but was similar to DRV/r. In SAILING, transaminase elevations were more commonly observed with DTG, particularly in the setting of inadequate hepatitis B therapy or immune reconstitution. On DTG treatment, mild creatinine elevations occurred and stabilized early. Few cases of hypersensitivity reaction and/or severe rash were seen. Rates of these events were comparable to or lower than with RAL-, EFV-, and DRV/r-containing regimens. CONCLUSIONS: The safety profile for DTG 50 mg once daily in INI-naive individuals was comparable to RAL- and DRV/r-containing regimens and generally favorable compared with EFV-containing regimens.

[Intravesical therapy for non-muscle invasive bladder tumours with doxorubicin. An update of the standard of care in urological practices]. / Intravesikale Instillationstherapie mit Doxorubicin beim nicht-muskelinvasiven Urothelkarzinom der Harnblase. Ein Update der Versorgungssituation.

INTRODUCTION: The aim of this study was to evaluate the current quality-of-care in newly diagnosed non-muscle invasive bladder cancer patients with regard to immediate postoperative and adjuvant intravesical instillation therapy. METHODS: Using a standardised questionnaire, we collected clinical and follow-up data from 250 patients with newly diagnosed urothelial carcinoma of the bladder (UCB) between February 2008 and October 2012 from urological health-care practitioners. Since diagnostic and therapeutic decisions were not influenced by a specific protocol, these findings are representative of current practice patterns. RESULTS: 250 patients were available for analysis. Immediate postoperative instillation chemotherapy was performed in 82 (44.8%) of 183 evaluable patients. Only seldom did clinics give therapeutic advice on adjuvant therapy. Patients -received in the mean 10.5 instillations. Administration of adjuvant intravesical therapy was associated no side effects in 95%, and was completed according to protocol in 87% of the patients. CONCLUSION: Our descriptive study presents current findings and practice patterns in patients with newly diagnosed UCB. Rates of immediate postoperative instillation chemotherapy were lower than expected. Bladder instillation therapy was well tolerated. In most of the patients therapy was completed according to the protocol. There are still differences in urological practice patterns as compared to the relevant guidelines.

Meta-analysis: hoarding symptoms associated with poor treatment outcome in obsessive-compulsive disorder.

DSM-5 recognizes hoarding disorder as distinct from obsessive-compulsive disorder (OCD), codifying a new consensus. Hoarding disorder was previously classified as a symptom of OCD and patients received treatments designed for OCD. We conducted a meta-analysis to determine whether OCD patients with hoarding symptoms responded differently to traditional OCD treatments compared with OCD patients without hoarding symptoms. An electronic search was conducted for eligible studies in PubMed. A trial was eligible for inclusion if it (1) was a randomized controlled trial, cohort or case-control study; (2) compared treatment response between OCD patients with and those without hoarding symptoms, or examined response to treatment between OCD symptom dimensions (which typically include hoarding) and (3) examined treatment response to pharmacotherapy, behavioral therapy or their combination. Our primary outcome was differential treatment response between OCD patients with and those without hoarding symptoms, expressed as an odds ratio (OR). Twenty-one studies involving 3039 total participants including 304 with hoarding symptoms were included. Patients with OCD and hoarding symptoms were significantly less likely to respond to traditional OCD treatments than OCD patients without hoarding symptoms (OR=0.50 (95% confidence interval 0.42-0.60), z=-7.5, P<0.0001). This finding was consistent across treatment modalities. OCD patients with hoarding symptoms represent a population in need of further treatment research. OCD patients with hoarding symptoms may benefit more from interventions specifically targeting their hoarding symptoms.

Two approaches for ultrafast random bit generation based on the chaotic dynamics of a semiconductor laser.

This paper reports the experimental investigation of two different approaches to random bit generation based on the chaotic dynamics of a semiconductor laser with optical feedback. By computing high-order finite differences of the chaotic laser intensity time series, we obtain time series with symmetric statistical distributions that are more conducive to ultrafast random bit generation. The first approach is guided by information-theoretic considerations and could potentially reach random bit generation rates as high as 160 Gb/s by extracting 4 bits per sample. The second approach is based on pragmatic considerations and could lead to rates of 2.2 Tb/s by extracting 55 bits per sample. The randomness of the bit sequences obtained from the two approaches is tested against three standard randomness tests (ENT, Diehard, and NIST tests), as well as by calculating the statistical bias and the serial correlation coefficients on longer sequences of random bits than those used in the standard tests.

Lung transplantation as rescue therapy in patients too sick to be discharged from acute care.

BACKGROUND: There is an increasing demand for lung transplantation in patients in advanced respiratory failure. Although many of these patients do not require mechanical ventilation or extracorporeal membrane oxygenation, an increasing number are critically ill. In this single-center study, we have analyzed our experience with lung transplantation in subjects who were inpatients at the time of their transplant and not expected to survive to discharge. METHODS: Between July 2006 and March 2012, we performed 274 bilateral sequential lung transplants and 34 single-lung transplants. Twenty-six patients who were inpatients at the time of their transplant, and were not expected to survive to hospital discharge, formed the inpatient group in this retrospective review. The remaining 281 outpatient lung transplant patients formed the comparison group. RESULTS: The inpatient group spent significantly fewer days on the waiting list compared to the outpatient group. Postoperative survival was significantly poorer in the inpatient group compared to the outpatient group (P = .001), and this was most noticeable in the first 90 days. There was no significant difference in survival between the inpatient transplant cohort and a historically comparable wait list cohort (P = .614). CONCLUSION: Lung transplantation in critically ill inpatients, although associated with a survival advantage compared to not transplanting them, does give poorer survival results compared to postoperative survival in outpatient patients.

Switch from tenofovir to raltegravir increases low bone mineral density and decreases markers of bone turnover over 48 weeks.

BACKGROUND: Tenofovir, particularly when given with a ritonavir-boosted protease inhibitor (rPI), reduces bone mineral density (BMD) and increases bone turnover markers (BTMs), both of which are associated with increased fracture risk. Raltegravir has not been associated with bone loss. METHODS: In an open-label, nonrandomized, pilot study, tenofovir was switched to raltegravir in adults also receiving a rPI for at least 6 months with a spine or hip T-score ≤ -1.0 and plasma HIV RNA < 50 HIV-1 RNA copies/mL for at least 3 months. The primary endpoint was BMD change by dual-energy X-ray absorptiometry. Student's paired t-test was used to compare continuous variables. Factors associated with BMD increase were assessed using linear regression. RESULTS: Thirty-seven patients were enrolled in the study: 97% were male, the mean age was 49 years, the mean T-scores were -1.4 (spine) and -1.3 (total left hip), and the mean tenofovir treatment duration was 3.1 years. BMD increases were significant at weeks 24 and 48. At week 48, spine BMD increased by 3.0% [95% confidence interval (CI) 1.9, 4.0%; P < 0.0001] and left total hip BMD increased by 2.5% (95% CI 1.6, 3.3%; P < 0.0001). BTMs (N-telopeptide, osteocalcin and bone alkaline phosphatase) all decreased significantly at week 24 (P ≤ 0.0017). There were no raltegravir-related serious or grade 3-4 adverse events. HIV viral load remained <50 copies/mL plasma on raltegravir/rPI therapy. CONCLUSIONS: Switching virologically suppressed HIV-infected adults with low BMD taking an rPI from tenofovir to raltegravir was safe and significantly improved hip and spine BMD and reduced markers of bone turnover over 48 weeks.

Treatment of cannabis dependence using escitalopram in combination with cognitive-behavior therapy: a double-blind placebo-controlled study.

BACKGROUND: Cannabis is the most frequently used illegal substance in the United States and Europe. There is a dramatic increase in the demand for treatment for cannabis dependence. Cannabis users frequently have co-morbid mood symptoms, especially depression and anxiety, and regular cannabis users may self-medicate for such symptoms. OBJECTIVES: We report a double-blind, placebo-controlled treatment study, for the prevention of cannabis use in cannabis-dependent individuals. METHOD: Regular cannabis-dependent users (n = 52) were treated for 9 weeks with weekly cognitive-behavior and motivation-enhancement therapy sessions together with escitalopram 10 mg/day. Urine samples were collected to monitor delta-9 tetrahydrocannabinol (THC) during treatment and questionnaires were administered to assess anxiety and depression. RESULTS: We observed a high rate of dropout (50%) during the 9-week treatment program. Fifty-two patients were included in the intention-to-treat analysis. Of these, ten (19%) remained abstinent after 9 weeks of treatment as indicated by negative urine samples for THC. Escitalopram provided no advantage over placebo in either abstinence rates from cannabis or anxiety and depression scores during the withdrawal and abstinent periods. CONCLUSIONS: Escitalopram treatment does not provide an additional benefit either for achieving abstinence, or for the treatment of the cannabis withdrawal syndrome. Due to limitations of our study, namely, a high dropout rate and effects of low abstinence rates on measures of anxiety, depression and withdrawal, it is premature to conclude that selective serotonin reuptake inhibitors are not effective for treatment of the cannabis withdrawal syndrome.

Pre-hospital spinal immobilisation: an initial consensus statement.

This paper reviews the current evidence available on the practice of spinal immobilisation in the prehospital environment. Following this, initial conclusions from a consensus meeting held by the Faculty of Pre-hospital Care, Royal College of Surgeons of Edinburgh in March 2012 are presented.

Peritoneal dialysis versus hemodialysis in patients with delayed graft function.

Delayed graft function (DGF) in kidney transplantation affects adverse outcomes. It remains unclear whether the post-transplant dialysis modality alters perioperative or long-term graft outcomes. We performed a retrospective observational quality initiative at two Canadian renal transplant centers, in which DGF occurred in the recipient, necessitating one of peritoneal dialysis (PD) or hemodialysis (HD). There was no difference in baseline factors between patients with post-transplant PD (n = 14) or HD (n = 63). The use of PD was associated with an increased risk of wound infection/leakage (PD 5/14 vs. HD 6/63, p = 0.024), shorter length of hospitalization (13.7 vs. 18.7 d, p = 0.009) and time requiring dialysis post-operatively (6.5 vs 11.0 d, p = 0.043). There were no differences in readmission to hospital within 6 months (4/14 vs. 23/63, p = 0.759), graft loss (0/14 vs. 2/63, p = 1.000) or acute rejection episodes (1/14 vs. 4/63, p = 1.000) at one yr, and GFR did not differ between the PD or HD groups at 30 d (35.7 vs. 33.8 mL/min/m(2), p = 0.731), six months (46.9 vs. 45.5 mL/min/m(2), p = 0.835) or one yr (46.6 vs. 44.5 mL/min/m(2), p = 0.746). Further research is needed to determine which transplant patients are most appropriate to undergo PD catheter removal at the time of transplantation.

Rilpivirine versus efavirenz in HIV-1-infected subjects receiving emtricitabine/tenofovir DF: pooled 96-week data from ECHO and THRIVE Studies.

OBJECTIVES: Week 96 efficacy and safety of the non-nucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine (RPV) was compared to efavirenz (EFV) in subset of 1,096 subjects who received emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) in pooled data from 2 phase 3 studies. METHODS: ECHO and THRIVE are double-blind, double-dummy, randomized, active-controlled, non-inferiority phase 3 studies of RPV versus EFV plus 2 NRTIs in antiretroviral-naïve adult subjects. The primary and secondary endpoints were the proportion of subjects with HIV-1 RNA <50 copies/ mL using an intent-to-treat, time to loss of virologic response (ITT-TLOVR) analysis at weeks 48 and 96, respectively. Safety, tolerability, immunologic response, adherence level, and other measures were also evaluated. RESULTS: At week 48, noninferior efficacy of RPV+FTC/TDF over EFV+FTC/TDF was established, and at week 96 RPV+FTC/TDF remained noninferior (77% overall response rate in both groups). Through week 96, rates of virologic failure were higher in the RPV+FTC/ TDF group, with low and similar rates of virologic failure and resistance mutations occurring during the second year of follow-up. Treatment with RPV+FTC/TDF was associated with a lower rate of discontinuation due to adverse events and grade 2-4 adverse events including dizziness, abnormal dreams/nightmares, rash, and lipid abnormalities. CONCLUSIONS: The pooled ECHO and THRIVE studies demonstrated noninferiority of RPV+FTC/TDF in achieving virologic response with safety and tolerability advantages over EFV+FTC/TDF through 96 weeks. Higher rates of virologic failure in the RPV+FTC/TDF group were balanced with higher rates of discontinuations due to adverse events in the EFV+FTC/TDF group.

[Quality of care in patients with newly diagnosed bladder cancer: a prospective assessment in northern Germany]. / Versorgungsstandard bei neu diagnostiziertem Blasenkarzinom : Eine prospektive Erhebung in Norddeutschland.

INTRODUCTION: The aim of this study was to evaluate the current quality of care in newly diagnosed bladder cancer patients in a regional representative sample of German urologists. MATERIAL AND METHODS: Using a standardized questionnaire clinical and pathological data from over 400 patients with newly diagnosed urothelial carcinoma of the bladder (UCB) between January and December 2010 were collected from urology health care practitioners in northern Germany. As diagnostic and therapeutic decisions were not influenced by a specific protocol these findings represent current regional practice patterns. RESULTS: Complete data of 359 patients were available for analysis. The median patient age at diagnosis was 72 years (range 29-98 years) with a male:female ratio of 3:1. The main reasons for transurethral resection of the bladder (TURB) were microhematuria (45.4 %), conspicuous ultrasound findings (12.8 %) and gross hematuria (11.7 %). Using photodynamic diagnosis (PDD) TURB was performed in 78 patients (21.7 %). The results of histopathology showed papillary urothelial neoplasm of low malignant potential (PUNLMP) in 8 patients (2.2 %), pTa in 202 (56.3 %), pTis in 7 (1.9 %), pT1 in 88 (24.5 %) and ≥pT2 bladder cancer in 54 (15 %) patients. Multiple tumors were recorded in 107 patients (29.8 %). A repeat TURB was performed in 130 patients (36.8 %) in a median of 45 days and residual tumor tissue was found in 79 of these patients (60.8 %). Immediate postoperative instillation chemotherapy was performed in 152 patients (42.3 %) and adjuvant intravesical maintenance therapy was performed in 142 patients (39.6 %, mitomycin 29.2 % vs. BCG 10.4 %). Patients treated with repeat TURB or adjuvant instillation therapy were more likely to have higher tumor stages and grades (p-values< 0.001). Overall 25 patients (7.7 %) experienced disease recurrence within 3 months. Lower tumor stage and grade, performance of repeat TURB and administration of adjuvant intravesical therapy were associated with reduced early disease recurrence (p-values ≤ 0.009). CONCLUSIONS: The current study presents contemporary findings and practice patterns in patients with newly diagnosed bladder cancer. Interestingly, the rates of immediate postoperative instillation chemotherapy and maintenance intravesical therapy were lower than expected. Utilization of PDD-TURB is still underrepresented. Remarkable is the high number of patients with residual tumor in the repeat TURB. Differences in patient counselling, hospital practice standards and compliance factors most likely contribute to variations in guideline adherence.