Repeated rectal application of a hyperosmolar lubricant is associated with microbiota shifts but does not affect PrEP drug concentrations: results from a randomized trial in men who have sex with men.

INTRODUCTION: Oral pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) is highly effective in preventing HIV infection among men who have sex with men (MSM). The effects of consistent personal lubricant use in the rectum on tissue PrEP drug concentrations and the rectal microbiota are unknown. We investigated rectal PrEP drug concentrations and the microbiota in MSM before and after repeated rectal application of a hyperosmolar lubricant. METHODS: We randomized 60 HIV-negative MSM to apply 4 mL of hyperosmolar rectal lubricant daily (n = 20), take daily oral TDF/FTC (n = 19), or both (n = 21) for seven days. Blood, rectal biopsies and rectal secretions were collected via rigid sigmoidoscopy before and on day 8 after product use. Tenofovir (TFV) and FTC as well as their intracellular metabolites tenofovir-diphosphate (TFV-DP), FTC-triphosphate (FTC-TP) were measured by HPLC-mass spectrometry. Rectal mucosal microbiota was sequenced with 16S rRNA sequencing using Illumina MiSeq. RESULTS: Seven days of lubricant application was not associated with differences in PrEP drug concentrations in rectal tissue or secretions. Lubricant use was associated with a decrease in the relative abundance of the Bacteroides genus (p = 0.01) and a non-significant increase in the Prevotella genus (p = 0.09) in the rectum. PrEP drug concentrations in rectal tissue and secretions were not associated with microbiota composition or diversity either before or after lubricant use. CONCLUSIONS: Repeated rectal application of a hyperosmolar lubricant does not affect mucosal PrEP drug concentrations but is associated with changes in the rectal microbiome.

Improving care transitions from hospital to home: standardized orders for home health nursing with remote telemonitoring.

A task force at a multihospital health care system partnered with home health agencies to improve gaps during the discharge transition process. A standardized order template for home health nursing and remote telemonitoring was developed to decrease discrepancies in communication between hospital health care providers and home health nurses caring for patients with heart failure. Pilot results showed significantly improved communication with no readmissions, using the order template.

Reverse polarity pacing: the hemodynamic benefit of anodal currents at lead tips for cardiac resynchronization therapy.

BACKGROUND: Myocardial depolarization can be achieved with currents of either anodal or cathodal polarity. In contrast to conventional cathodal pacing, anodal pacing initially hyperpolarizes tissue and improves myocardial contractility in animal models. METHODS AND RESULTS: In 13 patients undergoing cardiac resynchronization therapy (CRT) device implantation, we compared the mean left ventricular outflow velocity-time integral (LV-VTI) for anodal and cathodal polarities in three different pacing configurations. Intraoperative continuous-wave Doppler measurements were taken at a fixed interrogation angle, while polarities were switched during unipolar left ventricular, unipolar biventricular, and shared-coil biventricular pacing. Comparisons used identical pacing rates, intervals, and stimulus strengths. Patients had a mean ejection fraction of 0.18 +/- 0.08 and a mean QRS duration of 140 +/- 34 ms. All capture thresholds were less than 4.5 volts at a pulse width of 0.4 ms. Data were suitable for analysis in 37 of the 39 pairs of Doppler measurements. Anodal polarity significantly increased average LV-VTI in 36 of these 37 comparisons. The mean increase in LV-VTI for each configuration with anodal versus cathodal polarity was 2.8 +/- 2.6 cm (P < 0.001). The combined mean LV-VTI for all configurations was similarly higher for anodal polarity (24.4 +/- 11.7 cm) versus cathodal polarity (21.7 +/- 10.9 cm; P < 0.001). CONCLUSION: Anodal pacing polarity significantly improves a measure of LV function compared to traditional cathodal currents. Anodal pacing, which can be achieved by a simple reversal of pacing circuit polarity, may represent an important therapeutic addition to future resynchronization devices.