Barriers to Uptake of Long-Acting Antiretroviral Products for Treatment and Prevention of Human Immunodeficiency Virus (HIV) in High-Income Countries.

Long-acting injectable antiretroviral therapy (LAI-ART) for the treatment and prevention of human immunodeficiency virus (HIV) holds great potential to shift treatment paradigms by offering an alternative to daily oral medication. However, significant challenges at the drug, patient, and system levels risk impeding the uptake and implementation of LAI-ART. This review aims to describe the known and anticipated barriers to uptake of LAI-ART in high-income countries, as well as the ongoing research addressing some of these barriers to improve the delivery and uptake of LAI-ART products.

Posttraumatic Stress among Pediatric Critical Care Physicians in the United States in Association with Coronavirus Disease 2019 Patient Care Experiences.

Posttraumatic stress among pediatric critical care physicians in the United States in association with coronavirus disease 2019 patient care experiences. Our objective was to assess the prevalence of posttraumatic stress (PTS) and its association with COVID-19 patient care experiences among pediatric critical care physicians. Our study was a cross-sectional study of pediatric critical care physicians in the United States. We measured PTS which included posttraumatic stress disorder (PTSD) and subthreshold posttraumatic stress disorder (SubPTSD) using validated PTSD Checklist- 5 survey tool. Association of PTS with COVID-19 patient care experiences was analyzed using regression analysis. Prevalence of PTS was noted in 120 among 294 pediatric critical care physicians (41%; 95% CI, 35-47%). The predominant symptoms were that of hyperarousal and feelings of negative cognition and mood. Among our physicians with PTS, 19% had PTSD and 81% had SubPTSD. Demographic and practice characteristics were not significant for increased PTS on regression analysis. Posttraumatic stress was significantly associated with physicians testing positive or taking time off for COVID-19 illness, self-isolation, fear of infecting their loved ones, families scared of being infected, feeling helpless, patients expressing fears of dying, having pre-existing depression, anxiety, or insomnia, working beyond comfort level of training and having thoughts of quitting (p < 0.05). Thoughts of quitting was associated with the highest significant increase in PTS scores (coefficient:11.643; 95% CI:8.551,14.735; P < 0.01) followed by feeling of helplessness (coefficient:11.055; 95% CI: 8.484,13.624; P < 0.01) and need for additional medications for depression, anxiety and insomnia (coefficient: 10.980; 95% CI: 4.970, 16.990; P < 0.01). Posttraumatic stress is high in pediatric critical care physicians and is associated with various COVID-19 patient care experiences. Thoughts of quitting was associated with highest increase in posttraumatic stress score which could have major implications for the workforce in the future. Subthreshold posttraumatic stress disorder should be recognized, and mental health issues of pediatric critical care physicians addressed.

Polymicrobial bacteraemia with Clostridioides difficile and Pseudomonas aeruginosa in an elderly man following antibiotic use.

Clostridioides difficile is a micro-organism well known to cause pseudomembranous colitis with rare extraintestinal manifestations. We present the case of an elderly male with multiple comorbidities who presented with acute onset of fever/chills and hypotension, found to have polymicrobial bacteraemia with C. difficile and Pseudomonas aeruginosa He was treated with piperacillin/tazobactam for P. aeruginosa bacteraemia, oral vancomycin for C. difficile colitis and intravenous, followed by oral metronidazole for C. difficile bacteraemia. Pseudomonas cleared after 1 day, and Clostridioides cleared after 4 days. Following an initial septic presentation, he responded appropriately to antimicrobial therapy and did well in follow-up.

Relevance of the OCT1 transporter to the antineoplastic effect of biguanides.

Epidemiologic and laboratory data suggesting that metformin has antineoplastic activity have led to ongoing clinical trials. However, pharmacokinetic issues that may influence metformin activity have not been studied in detail. The organic cation transporter 1 (OCT1) is known to play an important role in cellular uptake of metformin in the liver. We show that siRNA knockdown of OCT1 reduced sensitivity of epithelial ovarian cancer cells to metformin, but interestingly not to another biguanide, phenformin, with respect to both activation of AMP kinase and inhibition of proliferation. We observed that there is heterogeneity between primary human tumors with respect to OCT1 expression. These results suggest that there may be settings where drug uptake limits direct action of metformin on neoplastic cells, raising the possibility that metformin may not be the optimal biguanide for clinical investigation.

Relapsed Babesia microti Infection Following Allogeneic Hematopoietic Cell Transplantation in a Patient With B-cell Acute Lymphoblastic Leukemia: Case Report and Review of the Literature.

A patient with relapsed/refractory B-cell acute lymphoblastic leukemia developed babesiosis before allogeneic hematopoietic cell transplantation while on atovaquone for Pneumocystis jirovecii pneumonia prophylaxis. Despite receiving a prolonged course of atovaquone and azithromycin until whole-blood Babesia microti DNA was no longer detected by polymerase chain reaction, her post-transplant course was complicated by relapsed babesiosis. We investigate the potential host and parasite characteristics causing relapsing/persistent infection.