Holmwerner3808

OBJECTIVES To assess associations between polymorphisms within genes encoding proximal tubule transporters implicated in tenofovir renal clearance and kidney tubular dysfunction (KTD), chronic kidney disease (CKD) and individual biochemical parameters. PATIENTS AND METHODS The study included a cohort of HIV-positive Ghanaians receiving regimens containing tenofovir disoproxil fumarate (n = 66) for at least 6 months prior to study enrolment. SNPs in ABCC10, ABCC2 and ABCC4 were selected for analysis based on previous published associations. All SNPs were genotyped by real-time PCR allelic discrimination. Creatinine clearance (CLCR), serum and urine creatinine concentrations and biochemical measures of KTD were assessed. Statistical significance was determined through univariate linear or binary logistical regression (P ≤ 0.05). RESULTS None of the SNPs evaluated was associated with CKD or KTD. A trend between body weight and higher incidence of CKD (P = 0.012, OR = 0.9) was observed. ABCC10 2843T>C (rs2125739) was significantly associated with lower log10 baseline creatinine (P = 0.001, β= -0.4), higher baseline CLCR (P = 0.008, β = 65.2) and lower CLCR after 1 year (P = 0.024, β= -26.6). CONCLUSIONS This study demonstrates an association of ABCC10 rs2125739 with indicators of declining renal function and builds on current knowledge of this interaction within a Ghanaian cohort. © The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email journals.permissions@oup.com.To assess, for the first time, the extent (by hour channel) and nature (e.g. persuasive marketing techniques (PMT) and health-related claims) of unhealthy food advertisements (ads) targeted at children (3-11 years) on the six most-watched television (TV) channels in Guatemala. We recorded 864 h of video on the six most popular channels featuring children's programmes. We classified food and beverage ads as permitted or non-permitted for marketing to children, according to the 2015 World Health Organisation (WHO) nutrient profile. Furthermore, we also analysed PMT (i.e. premium offers, promotional characters, brand benefit claims) and health-related claims. Most food ads (85%) were non-permitted to be marketed to children. Non-permitted food ads were six times more likely, either on weekdays or weekends, for all programme and channel categories compared with permitted food ads. There was no difference in the frequency of non-permitted food ads between peak and non-peak hours, weekend and weekdays or children and non-children programmes. PMT and health-related claims were present in all food ads (5.3 ± 1.9 techniques/claims per ad). There is a need to regulate food ads on TV channels featuring children's programmes in Guatemala as a result of a high frequency of non-permitted food ads and extensive use of PMT together with health-related claims. © The Author(s) 2020. Published by Oxford University Press.OBJECTIVE Several studies have investigated the utility of electronic decision support alerts in diagnostic stewardship for Clostridioides difficile infection (CDI). However, it is unclear if alerts are effective in reducing inappropriate CDI testing and/or CDI rates. The aim of this systematic review was to determine if alerts related to CDI diagnostic stewardship are effective at reducing inappropriate CDI testing volume and CDI rates among hospitalized adult patients. DESIGN We searched Ovid MEDLINE and 5 other databases for original studies evaluating the association between alerts for CDI diagnosis and CDI testing volume and/or CDI rate. Two investigators independently extracted data on study characteristics, study design, alert triggers, co-interventions, and study outcomes. RESULTS Eleven studies met criteria for inclusion. Studies varied significantly in alert triggers and in study outcomes. Six of eleven studies demonstrated a statistically significant decrease in CDI testing volume, six of six studies evaluating appropriateness of CDI testing found a significant reduction in the proportion of inappropriate testing, and four of seven studies measuring CDI rate demonstrated a significant decrease in the CDI rate in the post- vs pre-intervention periods. The magnitude of the increase in appropriate CDI testing varied, with some studies reporting an increase with minimal clinical significance. CONCLUSIONS The use of electronic alerts for diagnostic stewardship for C. difficile was associated with reductions in CDI testing, the proportion of inappropriate CDI testing, and rates of CDI in most studies. However, broader concerns related to alerts remain understudied, including unintended adverse consequences and alert fatigue. © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.BACKGROUND Ryanodine receptor (RyR) dysfunction in skeletal muscle (RyR1) leads to malignant hyperthermia, and in cardiac muscle (RyR2) triggers cardiac arrhythmias. We hypothesized that RyR dysfunction in vascular smooth muscle could increase vascular resistance and hypertension, and may contribute to increased atrial fibrillation (AF) in hypertension. Thus, stabilizing RyR function with chronic dantrolene treatment may attenuate hypertension and AF inducibility in spontaneously hypertensive rats (SHR). METHODS Male SHR (16 weeks-old) were randomized into vehicle- (n=10) and dantrolene-treated (10mg/kg/d, n=10) groups for 4-weeks. Wistar Kyoto (WKY, n=11) rats served as controls. Blood pressures (BP) were monitored before and during the 4-week treatment. After 4- week treatment, direct BP, echocardiography and hemodynamics were recorded. Voruciclib mouse AF inducibility tests were performed in vivo at baseline and repeated under sympathetic stimulation (SS). RESULTS Compared with WKY, SHR had significantly higher BP throughout the experimental period. Dantrolene treatment had no effect on BP levels in SHR (final systolic BP 212±9mmHg in vehicle group versus 208±16 mmHg in dantrolene group, p>0.05). AF inducibility was very low and not significantly different between 5-month old WKY and SHR at baseline. However, under SS, AF inducibility and duration were significantly increased in SHR (20% in WKY versus 60% in SHR-vehicle, p less then 0.05). Dantrolene treatment significantly attenuated AF inducibility under SS in SHR (60% in vehicle versus 20% in dantrolene, p less then 0.05). CONCLUSIONS Stabilizing RyR with chronic dantrolene treatment does not affect hypertension development in SHR. SHR has increased vulnerability to AF induction under SS, which can be attenuated with dantrolene treatment. © American Journal of Hypertension, Ltd 2020. All rights reserved. For Permissions, please email journals.permissions@oup.com.