IntroductionRenal safety is an important factor in selecting the most appropriate nucleos(t)ide analog (NA) treatment for patients with chronic hepatitis B (CHB). This systematic literature review and network meta-analysis aimed to assess renal function associated with telbivudine treatment compared to other NAs in patients with CHB.MethodsA systematic literature search via Medline, Medline In-Process, Embase, and the Cochrane library for publications of randomized controlled trials and observational studies was conducted. Network meta-analysis was performed to compare renal function with telbivudine treatment versus other NAs after 1 year of therapy.ResultsOverall, 40 (six randomized controlled and 34 observational) studies were included for review. Telbivudine consistently showed an improvement in renal function as measured by an estimated glomerular filtration rate (eGFR) over various time points regardless of the method of measurement. Changes in eGFR (mL/min) from baseline and corresponding 95% credible intervals with various NAs were as follows: monotherapies (telbivudine: 7.78 [6.91, 8.65], entecavir: −1.07 [−4.80, 2.62], lamivudine: −6.08 [−13.35, 1.15], tenofovir: −9.53 [−14.31, −4.89]) and combination therapies (telbivudine + adefovir: 8.37 [−34.00, 50.34], telbivudine + tenofovir: 8.29 [−0.05, 16.64], entecavir + adefovir: 4.15 [−38.55, 46.37], telbivudine + lamivudine: 0.51 [−11.77, 12.96], and lamivudine + adefovir: −0.39 [−42.48, 41.21]). At 1 year, the change in eGFR from baseline was significantly higher with telbivudine compared to other NAs.ConclusionThe systematic literature review and network meta-analysis provide evidence that telbivudine is associated with significant improvement in renal function in patients with CHB, either alone or in combination with other NAs.FundingNovartis Pharma AG.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-016-0337-2) contains supplementary material, which is available to authorized users.

IntroductionA comprehensive and up-to-date network meta-analysis (NMA) helps to determine the comparative efficacies of nucleos(t)ide analogs (NAs) in patients with chronic hepatitis B (CHB). The aim of this NMA was to assess the efficacy of telbivudine versus adefovir, entecavir, lamivudine, and tenofovir in nucleos(t)ide-naïve hepatitis B e antigen (HBeAg)-positive patients with CHB.MethodsA systematic review was conducted to search Medline, Medline-In Process, EMBASE, and the Cochrane Central Register of Controlled Trials databases for publications of randomized controlled trials (RCTs). NMA was performed to compare the efficacy outcomes of telbivudine versus other approved NAs at 1- and 2-year time points.ResultsA total of 75 RCTs were included in the systematic review. At the 1-year time point, telbivudine was associated with significantly higher rates of: (1) HBeAg seroconversion than adefovir [odds ratio (OR) 1.99 (95% credible interval (CrI): 1.05, 3.45)], entecavir [OR 2.00 (95% CrI: 1.44, 2.82)] and lamivudine [OR 1.49 (95% CrI: 1.10, 2.03)]; (2) HBeAg loss than entecavir [OR 1.85 (95% CrI: 1.28, 2.76)] and lamivudine [OR 1.62 (95% CrI: 1.20, 2.24)]; (3) alanine aminotransferase (ALT) normalization than lamivudine [OR 1.50 (95% CrI: 1.05, 2.21)]; and (4) hepatitis B virus (HBV) DNA suppression than adefovir [OR 2.77 (95% CrI: 1.28, 5.45)] and lamivudine [OR 2.97 (95% CrI: 1.99, 4.53)]. At the 2-year time point, the relative efficacy outcomes were not statistically significant.ConclusionAt 1 year, telbivudine was superior to adefovir, entecavir and lamivudine in HBeAg seroconversion, and to entecavir and lamivudine in HBeAg loss. Telbivudine was also superior to lamivudine in ALT normalization and to adefovir and lamivudine in suppressing HBV DNA levels.FundingNovartis Pharma AG.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-016-0305-x) contains supplementary material, which is available to authorized users.

The discovery of a series of thiophenephenyl­sulfonamides as positive allosteric modulators (PAM) of α7 nicotinic acetylcholine receptor (α7 nAChR) is described. Optimization of this series led to identification of compound 28, a novel PAM of α7 nicotinic acetylcholine receptor (α7 nAChR). Compound 28 showed good in vitro potency, with pharmacokinetic profile across species with excellent brain penetration and residence time. Compound 28 robustly reversed the cognitive deficits in episodic/working memory in both time-delay and scopolamine-induced amnesia paradigms in the novel object and social recognition tasks, at very low dose levels. Additionally, compound 28 has shown excellent safety profile in phase 1 clinical trials and is being evaluated for efficacy and safety as monotherapy in patients with mild to moderate Alzheimer’s disease.

Introduction: Inherited retinal dystrophies (IRDs) represent a genetically diverse group of progressive, visually debilitating diseases. Adult and paediatric patients with vision loss due to IRD caused by biallelic mutations in the 65-kDa retinal pigment epithelium (RPE65) gene are often clinically diagnosed as retinitis pigmentosa (RP), and Leber congenital amaurosis (LCA). This study aimed to understand the epidemiological landscape of RPE65 gene-mediated IRD through a systematic review of the literature, as the current evidence base for its epidemiology is very limited. Methods: Medline, Embase, and other databases were searched for articles on the epidemiology of RPE65 gene-mediated IRDs from inception until June 2021. Studies were included if they were original research articles reporting the epidemiology of RP and LCA and/or proportion of RPE65 gene mutations in these clinically diagnosed or molecularly confirmed IRDs patients. Results: A total of 100 studies with relevant data were included in this systematic review. The range for prevalence of LCA and RP in the literature was 1.20-2.37 and 11.09-26.43 per 100,000, respectively. The proportion of RPE65 mutations in clinically diagnosed patients with LCA was found to be between * 2-16% within the US and major European countries (France, Germany, Italy, Spain, and the UK). This range was also comparable to our findings in the Asian region for RPE65-LCA (1.26-16.67%). Similarly, for these European countries, RPE65-RP was estimated between 0.23 and 1.94%, and RPE65-IRD range was 1.2-14%. Further, in the Americas region, mutations in RPE65 were reported to cause 1-3% of RP and 0.8-3.7% of IRD cases. Lastly, the RPE65-IRD range was 4.81-8% in the Middle East region. Conclusions: There are significant variations in reporting of RPE65 proportions within

IntroductionThere is a clear need for improved care quality and quality monitoring in aged care. Aged care providers collect an abundance of data, yet rarely are these data integrated and transformed in real-time into actionable information to support evidence-based care, nor are they shared with older people and informal caregivers. This protocol describes the co-design and testing of a dashboard in residential aged care facilities (nursing or care homes) and community-based aged care settings (formal care provided at home or in the community). The dashboard will comprise integrated data to provide an ‘at-a-glance’ overview of aged care clients, indicators to identify clients at risk of fall-related hospitalisations and poor quality of life, and evidence-based decision support to minimise these risks. Longer term plans for dashboard implementation and evaluation are also outlined.MethodsThis mixed-method study will involve (1) co-designing dashboard features with aged care staff, clients, informal caregivers and general practitioners (GPs), (2) integrating aged care data silos and developing risk models, and (3) testing dashboard prototypes with users. The dashboard features will be informed by direct observations of routine work, interviews, focus groups and co-design groups with users, and a community forum. Multivariable discrete time survival models will be used to develop risk indicators, using predictors from linked historical aged care and hospital data. Dashboard prototype testing will comprise interviews, focus groups and walk-through scenarios using a think-aloud approach with staff members, clients and informal caregivers, and a GP workshop.Ethics and disseminationThis study has received ethical approval from the New South Wales (NSW) Population & Health Services Research Ethics Committee and Macquarie University’s Human Research Ethics Committee. The research findings will be presented to the aged care provider who will share results with staff members, clients, residents and informal caregivers. Findings will be disseminated as peer-reviewed journal articles, policy briefs and conference presentations.