Drug interactions: a review of the unseen danger of experimental COVID-19 therapies.

As global health services respond to the coronavirus pandemic, many prescribers are turning to experimental drugs. This review aims to assess the risk of drug-drug interactions in the severely ill COVID-19 patient. Experimental therapies were identified by searching ClinicalTrials.

Engendering health systems in response to national rollout of dolutegravir-based regimens among women of childbearing potential: a qualitative study with stakeholders in South Africa and Uganda.

Background: In the era of rapid dolutegravir rollout, concerns about neural tube defects have complicated the health systems response among women of childbearing potential. This qualitative study, which was nested within the DolPHIN-2 clinical trial, examined the current and future health system opportunities and challenges associated with the transition to dolutegravir-based regimen as first line antiretroviral therapy among women of childbearing potential in South Africa and Uganda.

Method: Semi-structured in-depth interviews with members of antiretroviral therapy guideline development groups and affiliates were conducted.

Longitudinal Pharmacokinetic-Pharmacodynamic Biomarkers Correlate With Treatment Outcome in Drug-Sensitive Pulmonary Tuberculosis: A Population Pharmacokinetic-Pharmacodynamic Analysis.

Background: This study aims to explore relationships between baseline demographic covariates, plasma antibiotic exposure, sputum bacillary load, and clinical outcome data to help improve future tuberculosis (TB) treatment response predictions.

Methods: Data were available from a longitudinal cohort study in Malawian drug-sensitive TB patients on standard therapy, including steady-state plasma antibiotic exposure (154 patients), sputum bacillary load (102 patients), final outcome (95 patients), and clinical details. Population pharmacokinetic and pharmacokinetic-pharmacodynamic models were developed in the software package NONMEM.

Safety perspectives on presently considered drugs for the treatment of COVID-19.

Intense efforts are underway to evaluate potential therapeutic agents for the treatment of COVID-19. In order to respond quickly to the crisis, the repurposing of existing drugs is the primary pharmacological strategy. Despite the urgent clinical need for these therapies, it is imperative to consider potential safety issues.

Polypharmacy and potential drug-drug interactions for people with HIV in the UK from the Climate-HIV database.

Objectives: People with HIV (PWHIV) are likely to need therapies for comorbidities as they age. We assessed risk of drug-drug interactions (DDIs) in PWHIV.

Methods: The Climate-HIV electronic recording system was used to cross-sectionally analyse records from PWHIV aged ≥ 18 years attending four UK HIV units with a current antiretroviral (ARV) prescription in February 2018.

Prevalence of Potential Drug-Drug Interactions in Patients of the Swiss HIV Cohort Study in the Era of HIV Integrase Inhibitors.

Background: Prevalence of potential drug-drug interactions (PDDIs) between antiretroviral drugs (ARVs) and co-medications was high in 2008 in a Swiss HIV Cohort Study (SHCS) survey. We reassessed the prevalence of PDDIs in the era of human immunodeficiency virus (HIV) integrase inhibitors (INIs), characterized by more favorable interaction profiles.

Methods: The prevalence of PDDIs in treated HIV-positive individuals was assessed for the period 01-12/2018 by linkage of the Liverpool HIV drug interactions and SHCS databases.

A Base-Stabilized Silylene-Promoted C(sp)-H Borylation and H Activation.

Treatment of the amidinato amidosilylene [L{(MeSi)N}Si:] [, L = PhC(NBu)] with a slight excess of borane-tetrahydrofuran complex [BH·THF] in toluene at room temperature afforded the silylene-borane adduct [L{(MeSi)N}Si:→BH] (). A triflate substituent was introduced on the boron center by reacting with methyl triflate [MeOTf] (OTf = OSOCF) in toluene at room temperature to form [L{(MeSi)N}Si:→BHOTf] (), with the elimination of CH gas. The intramolecular C(sp)-H borylation and H elimination occurred by reacting complex with in refluxing toluene to form a C-B bond in the resulting silylene-boronium ion .

AGILE-ACCORD: A Randomized, Multicentre, Seamless, Adaptive Phase I/II Platform Study to Determine the Optimal Dose, Safety and Efficacy of Multiple Candidate Agents for the Treatment of COVID-19: A structured summary of a study protocol for a randomised platform trial.

Objectives: Phase I - To determine the optimal dose of each candidate (or combination of candidates) entered into the platform. Phase II - To determine the efficacy and safety of each candidate entered into the platform, compared to the current Standard of Care (SoC), and recommend whether it should be evaluated further in a later phase II & III platforms.

Trial Design: AGILE-ACCORD is a Bayesian multicentre, multi-arm, multi-dose, multi-stage open-label, adaptive, seamless phase I/II randomised platform trial to determine the optimal dose, activity and safety of multiple candidate agents for the treatment of COVID-19.

Potentially inappropriate medications in older adults living with HIV.

Objectives: We assessed the prevalence of potentially inappropriate medication (PIM) among older (≥ 65 years) people living with HIV (O-PLWH) in the region of Madrid.

Methods: We analysed the dispensation registry of community and hospital pharmacies from the Madrid Regional Health Service (SERMAS) for the period between 1 January and 30 June 2017, looking specifically at PIMs according to the 2019 Beers criteria. Co-medications were classified according to the Anatomical Therapeutic Chemical (ATC) classification system.

Dose prediction for repurposing nitazoxanide in SARS-CoV-2 treatment or chemoprophylaxis.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been declared a global pandemic by the World Health Organisation and urgent treatment and prevention strategies are needed. Many clinical trials have been initiated with existing medications, but assessments of the expected plasma and lung exposures at the selected doses have not featured in the prioritisation process. Although no antiviral data is currently available for the major phenolic circulating metabolite of nitazoxanide (known as tizoxanide), the parent ester drug has been shown to exhibit activity against SARS-CoV-2.

Prioritization of Anti-SARS-Cov-2 Drug Repurposing Opportunities Based on Plasma and Target Site Concentrations Derived from their Established Human Pharmacokinetics.

There is a rapidly expanding literature on the in vitro antiviral activity of drugs that may be repurposed for therapy or chemoprophylaxis against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). However, this has not been accompanied by a comprehensive evaluation of the target plasma and lung concentrations of these drugs following approved dosing in humans. Accordingly, concentration 90% (EC ) values recalculated from in vitro anti-SARS-CoV-2 activity data was expressed as a ratio to the achievable maximum plasma concentration (C ) at an approved dose in humans (C /EC ratio).

Biomarkers for Temporomandibular Disorders: Current Status and Future Directions.

Numerous studies have been conducted in the previous years with an objective to determine the ideal biomarker or set of biomarkers in temporomandibular disorders (TMDs). It was recorded that tumour necrosis factor (TNF), interleukin 8 (IL-8), IL-6, and IL-1 were the most common biomarkers of TMDs. As of recently, although the research on TMDs biomarkers still aims to find more diagnostic agents, no recent study employs the biomarker as a targeting point of pharmacotherapy to suppress the inflammatory responses.

Associations Between Social Capital and Depressive Symptoms Among College Students in 12 Countries: Results of a Cross-National Study.

Introduction: A mental health crisis has hit university campuses across the world. This study sought to determine the prevalence and social determinants of depressive symptoms among university students in twelve countries. Particular focus was placed on the association between social capital and depressive symptoms.

Dolutegravir versus efavirenz in women starting HIV therapy in late pregnancy (DolPHIN-2): an open-label, randomised controlled trial.

Background: Late initiation of HIV antiretroviral therapy (ART) in pregnancy is associated with not achieving viral suppression before giving birth and increased mother-to-child transmission of HIV. We aimed to investigate virological suppression before giving birth with dolutegravir compared with efavirenz, when initiated during the third trimester.

Methods: In this randomised, open-label trial, DolPHIN-2, we recruited pregnant women in South Africa and Uganda aged at least 18 years, with untreated but confirmed HIV infection and an estimated gestation of at least 28 weeks, initiating ART in third trimester.

Association between insight and internalized stigma and other clinical factors among patients with depression: A cross-sectional study.

Background: Insight influences treatment adherence among patients with depression. These patients also experience considerable social and self-stigma. The relationship between insight and internalized stigma has been extensively studied among patients with schizophrenia but not patients with depression.

Examining the Criterion Validity and Diagnostic Specificity of Self-Report Measures of Narcissism and Mania.

We examined the validity of self-report measures of narcissism and mania by relating them to interview-based ratings of psychopathology. Narcissism scales were taken from the Narcissistic Personality Inventory (NPI), the Personality Diagnostic Questionnaire-4+, and the Short Dark Triad. Mania measures included the Altman Self-Rated Mania Scale (ASRM) and scales taken from the Hypomanic Personality Scale (HPS) and Expanded Version of the Inventory of Depression and Anxiety Symptoms.

Rapid diffusion-weighted MRI for the investigation of recurrent temporal bone cholesteatoma.

Background: Suspected cholesteatoma recurrence is commonly investigated with magnetic resonance imaging (MRI) of the temporal bone. Non-echo planar diffusion-weighted imaging (non-EP DWI) has become the sequence of choice.

Purpose: To assess the agreement between an MRI protocol incorporating both non-EP DWI and contrast-enhanced sequences, and a shortened protocol without contrast-enhanced sequences in the assessment of suspected cholesteatoma recurrence.

A Pilot Study of Racial and Ethnic Differences in Mental Health Outcomes During the First 6 Weeks of Trauma-Focused Treatment.

The objective of this research was to investigate the relationship between race/ethnicity, intervention type, and mental health outcomes at 6 weeks into treatment in a low-income, diverse community-based sample of adults seeking treatment for traumatic stress. Adult patients (N = 163) received either prolonged exposure (PE) or present centered therapy (PCT). Results suggest significant within group differences with moderate to large effect sizes after six sessions of PE or PCT by race/ethnicity.

Familial dysalbuminaemic hyperthyroxinaemia interferes with current free thyroid hormone immunoassay methods.

Objective: Familial dysalbuminaemic hyperthyroxinaemia (FDH), most commonly due to an Arginine to Histidine mutation at residue 218 (R218H) in the albumin gene, causes artefactual elevation of free thyroid hormones in euthyroid individuals. We have evaluated the susceptibility of most current free thyroid hormone immunoassay methods used in the United Kingdom, Europe and Far East to interference by R218H FDH.

Methods: Different, one- and two-step immunoassay methods were tested, measuring free T4 (FT4) and free T3 (FT3) in 37 individuals with genetically proven R218H FDH.

Use of Ocular Point-of-Care Ultrasound in a Difficult Pediatric Examination: A Case Report of an Emergency Department Diagnosis of Retinoblastoma.

Background: Eye examination in distressed young children can be challenging in a busy emergency department. A full, detailed evaluation is, however, often needed in ocular emergencies.

Case Report: A 2-year-old boy presented to our pediatric emergency department with refusal to open his left eye for 1 day.

Genital secretion HIV RNA shedding in HIV-positive patients on ritonavir-boosted protease inhibitor monotherapy or standard combination ART: a cross-sectional sub-study from the PIVOT Trial.

Background: Protease inhibitors (PI) have relatively low penetration into the genital tract, raising concerns about the potential for genital HIV RNA shedding in patients taking PI-based regimens, particularly PI monotherapy (PI-mono).

Methods: We measured HIV RNA and PI drug concentrations in samples of semen, cervico-vaginal and rectal mucosa secretions, and plasma in patients after 48-96 weeks on PI-mono or standard triple therapy.

Results: A total of 85 participants were recruited.

The neurologic phenotype of South African patients with HIV-associated neurocognitive impairment.

Background: The neurologic manifestations of HIV include a spectrum of HIV-associated neurocognitive disorders, as well as a cluster of neurologic symptoms and signs. The neurologic manifestations have been modified but not eradicated by antiretroviral therapy (ART). We describe the neurologic phenotype in South African patients with predominant HIV-1 subtype C infection on ART and its association with neurocognitive impairment and efavirenz and 8-hydroxy-efavirenz concentrations.