Transient receptor potential canonical type 6 (TRPC6) is a nonselective receptor-operated cation channel that regulates reactive fibrosis and growth signaling. Increased TRPC6 activity from enhanced gene expression or gain-of-function mutations contribute to cardiac and/or renal disease. Despite evidence supporting a pathophysiological role, no orally bioavailable selective TRPC6 inhibitor has yet been developed and tested in vivo in disease models. Here, we report an orally bioavailable TRPC6 antagonist (BI 749327; IC 50 13 nM against mouse TRPC6, t 1/2 8.5-13.5 hours) with 85-and 42-fold selectivity over the most closely related channels, TRPC3 and TRPC7. TRPC6 calcium conductance results in the stimulation of nuclear factor of activated T cells (NFAT) that triggers pathological cardiac and renal fibrosis and disease. BI 749327 suppresses NFAT activation in HEK293T cells expressing wild-type or gain-of-function TRPC6 mutants (P112Q, M132T, R175Q, R895C, and R895L) and blocks associated signaling and expression of prohypertrophic genes in isolated myocytes. In vivo, BI 749327 (30 mg/kg/day, yielding unbound trough plasma concentration ∼180 nM) improves left heart function, reduces volume/mass ratio, and blunts expression of profibrotic genes and interstitial fibrosis in mice subjected to sustained pressure overload. Additionally, BI 749327 dose dependently reduces renal fibrosis and associated gene expression in mice with unilateral ureteral obstruction. These results provide in vivo evidence of therapeutic efficacy for a selective pharmacological TRPC6 inhibitor with oral bioavailability and suitable pharmacokinetics to ameliorate cardiac and renal stress-induced disease with fibrosis. TRPC6 | ion channels | calcium | nuclear factor of activated T cells | fibrosis

Intracameral cefuroxime and moxifloxacin reduced endophthalmitis rates compared with controls with minimal or no toxicity events at standard doses. Additionally, intracameral antibiotics alone may be as effective as intracameral plus topical antibiotics.

BackgroundAs the role of the physician assistant/associate grows globally, one question is: what is the level of patient satisfaction with PAs? Driven by legislative enactments to improve access to care, the PA has emerged as a ready and able medical professional to address workforce shortages. The aim of this study was to review the literature on patient satisfaction of PAs.ObjectivesThe basis for this review was to clarify working definitions, synthesize the evidence, and establish conceptual boundaries around the topic of patient satisfaction with PAs. The intent was to identify gaps in the literature and offer suggested undertakings for more clarification on the subject.MethodsA scoping review was undertaken. Literature from 1968 to 2019 was searched and filtered for eligibility. Those that met criteria were categorized by date, method, geography, themes, and design.ResultsIn total, there were 987 papers or reports that were identified through bibliography database searching. Additional articles found through snowball methodology-reviewing references (n = 11). Only English language articles emerged for analysis. From this effort, 25 articles surfaced from the filtering process for final inclusion. Most (72%) of the articles came from the United States of America, three from the United Kingdom, and one each from Ireland, the Netherlands, and New Zealand. Most articles were descriptive in nature. Some variations in methods emerged.ConclusionPAs are operational in 15 nations; their acceptance appears successful and satisfaction with their care largely indistinguishable from physicians. Findings from this analysis highlight one theory that when patient’s needs are met, satisfaction is high regardless of the medical provider. Areas for further research are identified.

Objectives Patient-generated health data (PGHD) are clinically relevant data captured by patients outside of the traditional care setting. Clinical use of PGHD has emerged as an essential issue. This study explored the evidence to determine the extent of and describe the characteristics of PGHD integration into electronic health records (EHRs). Methods In August 2019, we conducted a systematic scoping review. We included studies with complete, partial, or in-progress PGHD and EHR integration within a clinical setting. The retrieved articles were screened for eligibility by 2 researchers, and data from eligible articles were abstracted, coded, and analyzed. Results A total of 19 studies met inclusion criteria after screening 9463 abstracts. Most of the study designs were pilots and all were published between 2013 and 2019. Types of PGHD were biometric and patient activity (57.9%), questionnaires and surveys (36.8%), and health history (5.3%). Diabetes was the most common patient condition (42.1%) for PGHD collection. Active integration (57.9%) was slightly more common than passive integration (31.6%). We categorized emergent themes into the 3 steps of PGHD flow. Themes emerged concerning resource requirements, data delivery to the EHR, and preferences for review. Discussion PGHD integration into EHRs appears to be at an early stage. PGHD have the potential to close health care gaps and support personalized medicine. Efforts are needed to understand how to optimize PGHD integration into EHRs considering resources, standards for EHR delivery, and clinical workflows.

Background: It remains unclear whether volar locked plating (VLP) yields a better functional outcome than closed reduction and casting (CRC) for elderly patients with an acute, displaced distal radial fracture. Our purpose was to conduct a systematic review and meta-analysis of randomized controlled trials comparing outcomes of VLP and CRC for elderly patients (age, ≥60 years). Methods: Multiple databases, including MEDLINE, were searched for randomized controlled trials evaluating outcomes following distal radial fracture treatment. Raw data were obtained for studies that included patients of all ages, and the elderly subgroup was included for analysis. The primary outcome was the Disabilities of the Arm, Shoulder and Hand (DASH) score at ≥1 year of follow-up. Secondary outcomes included the 3-month DASH score, range of motion, final radiographic alignment, and complications. Effect sizes for the comparison of each outcome between groups were pooled across studies using random-effects models with the inverse variance weighting method. Changes in DASH score were compared with a minimal clinically important difference (MCID) estimate of 10 to assess clinical relevance. Results: Of 2,152 screened articles, 6 were included. Demographics were similar for the 274 VLP and 287 CRC patients. DASH scores were significantly better following VLP than CRC at the time of final follow-up (12 to 24 months postoperatively; score difference, −5.9; 95% confidence interval [CI], −8.7 to −3.1) and at 3 months (−8.9; 95% CI, −13.0 to −4.8). VLP yielded significantly better palmar tilt, radial inclination, and supination, with no differences in ulnar variance, flexion-extension, pronation, or total complication rates. Conclusions: Functional outcome was significantly better following VLP than CRC 3 months into the treatment of acute, displaced distal radial fractures in an elderly population and up to 2 years after injury. However, the observed differences in the final DASH score did not exceed published estimates of the MCID, suggesting that clinical outcomes are similar for both treatment options. Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.