Point-of-Care Ultrasound for Tuberculosis Management in Sub-Saharan Africa-A Balanced SWOT Analysis.

Point-of-care ultrasound (POCUS) is an increasingly accessible skill, allowing for the decentralization of its use to non-specialist healthcare workers to guide routine clinical decision making. The advent of ultrasound-on-a-chip has transformed the technology into a portable mobile health device. Due to its high sensitivity to detect small consolidations, pleural effusions and sub pleural nodules, POCUS has recently been proposed as a sputum-free likely triage tool for tuberculosis (TB). To make an objective assessment of the potential and limitations of POCUS in routine TB management, we present a Strengths, Weaknesses, Opportunities & Threats (SWOT) analysis based on a review of the relevant literature and focusing on Sub-Saharan Africa (SSA). We idenitified numerous strengths and opportunities of POCUS for TB management e.g.; accessible, affordable, easy to use & maintain, expedited diagnosis, extra-pulmonary TB detection, safer pleural/pericardial puncture, use in children/pregnant women/PLHIV, targeted screening of TB contacts, monitoring TB sequelae, and creating AI decision support. Weaknesses and external threats such as operator dependency, lack of visualization of central lung pathology, poor specificity, lack of impact assessments and data from Sub-Saharan Africa must be taken into consideration to ensure that the potential of the technology can be fully realized in research as in practice

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Factors Influencing the Implementation of Antimicrobial Stewardship in Primary Care: A Narrative Review.

Antimicrobial resistance (AMR) is directly driven by inappropriate use of antibiotics. Although the majority of antibiotics (an estimated 80%) are consumed in primary care settings, antimicrobial stewardship (AMS) activities in primary care remain underdeveloped and factors influencing their implementation are poorly understood. This can result in promising stewardship activities having little-to-no real-world impact. With this narrative review, we aim to identify and summarize peer-reviewed literature reporting on (1) the nature and impact of AMS interventions in primary care and (2) the individual and contextual factors influencing their implementation. Reported activities included AMS at different contextual levels (individual, collective and policy). AMS activities being often combined, it is difficult to evaluate them as stand-alone interventions. While some important individual and contextual factors were reported (difficulty to reach physicians leading to a low uptake of interventions, tight workflow of physicians requiring implementation of flexible and brief interventions and AMS as a unique opportunity to strengthen physician-patients relationship), this review identified a paucity of information in the literature about the factors that support or hinder implementation of AMS in primary care settings. In conclusion, identifying multilevel barriers and facilitators for AMS uptake is an essential step to explore before implementing primary care AMS interventions

A battery of tandem mass spectrometry assays with stable isotope-dilution for the quantification of 15 anti-tuberculosis drugs and two metabolites in patients with susceptible-, multidrug-resistant- and extensively drug-resistant tuberculosis.

Anti-tuberculosis (antiTB) drugs are characterized by an important inter-interindividual pharmacokinetic variability poorly predictable from individual patients' characteristics. Therapeutic drug monitoring (TDM) may therefore be beneficial for patients with Mycobacterium tuberculosis infection, especially for the management of multidrug/extensively drug resistant- (MDR/XDR)-TB. Our objective was to develop robust HPLC-MS/MS methods for plasma quantification of 15 antiTB drugs and 2 metabolites, namely rifampicin, isoniazid plus N-acetyl-isoniazid, pyrazinamide, ethambutol (the conventional quadritherapy for susceptible TB) as well as combination of agents against MDR/XDR-TB: bedaquiline, clofazimine, delamanid and its metabolite M1, levofloxacin, linezolid, moxifloxacin, pretomanid, rifabutin, rifapentine, sutezolid, and cycloserine. Plasma protein precipitation was used for all analytes except cycloserine, which was analyzed separately after derivatization with benzoyl chloride. AntiTB quadritherapy drugs (Pool1) were separated by Hydrophilic Interaction Liquid Chromatography (column Xbridge BEH Amide, 2.1 × 150 mm, 2.5 μm, Waters®) while MDR/XDR-TB agents (Pool 2) and cycloserine (as benzoyl derivative) were analyzed by reverse phase chromatography on a column XSelect HSS T3, 2.1 × 75 mm, 3.5 µm (Waters®). All runs last <7 min. Quantification was performed by selected reaction monitoring electrospray tandem mass spectrometry, using stable isotopically labelled internal standards. The method covers the clinically relevant plasma levels and was extensively validated based on FDA recommendations, with intra- and inter-assay precision (CV) < 15% over the validated ranges. Application of the method is illustrated by examples of TDM for two patients treated for drug-susceptible- and MDR-TB. Such convenient extraction methods and the use of stable isotope-labelled drugs as internal standards provide an accurate and precise quantification of plasma concentrations of all major clinically-used antiTB drugs regimens and is optimally suited for clinically efficient TDM against tuberculosis

Post‑COVID‑19 Syndrome in Outpatients: a Cohort Study.

After mild COVID-19, some outpatients experience persistent symptoms. However, data are scarce and prospective studies are urgently needed. To characterize the post-COVID-19 syndrome after mild COVID-19 and identify predictors. Outpatients with symptoms suggestive of COVID-19 with (1) PCR-confirmed COVID-19 (COVID-positive) or (2) SARS-CoV-2 negative PCR (COVID-negative). Monocentric cohort study with prospective phone interview between more than 3 months to 10 months after initial visit to the emergency department and outpatient clinics. Data of the initial visits were extracted from the electronic medical file. Predefined persistent symptoms were assessed through a structured phone interview. Associations between long-term symptoms and PCR results, as well as predictors of persistent symptoms among COVID-positive, were evaluated by multivariate logistic regression adjusted for age, gender, smoking, comorbidities, and timing of the survey. The study population consisted of 418 COVID-positive and 89 COVID-negative patients, mostly young adults (median age of 41 versus 36 years in COVID-positive and COVID-negative, respectively; p = 0.020) and healthcare workers (67% versus 82%; p = 0.006). Median time between the initial visit and the phone survey was 150 days in COVID-positive and 242 days in COVID-negative patients. Persistent symptoms were reported by 223 (53%) COVID-positive and 33 (37%) COVID-negative patients (p = 0.006) and proportions were stable among the periods of the phone interviews. Overall, 21% COVID-positive and 15% COVID-negative patients (p = 0.182) attended care for this purpose. Four surveyed symptoms were independently associated with COVID-19: fatigue (adjusted odds ratio 2.14, 95% CI 1.04-4.41), smell/taste disorder (26.5, 3.46-202), dyspnea (2.81, 1.10-7.16), and memory impairment (5.71, 1.53-21.3). Among COVID-positive, female gender (1.67, 1.09-2.56) and overweight/obesity (1.67, 1.10-2.56) were predictors of persistent symptoms. More than half of COVID-positive outpatients report persistent symptoms up to 10 months after a mild disease. Only 4 of 14 symptoms were associated with COVID-19 status. The symptoms and predictors of the post-COVID-19 syndrome need further characterization as this condition places a significant burden on society

Point-of-Care Ultrasound for Tuberculosis Management in Sub-Saharan Africa-A Balanced SWOT Analysis.

Point-of-care ultrasound (POCUS) is an increasingly accessible skill, allowing for the decentralization of its use to non-specialist healthcare workers to guide routine clinical decision making. The advent of ultrasound-on-a-chip has transformed the technology into a portable mobile health device. Due to its high sensitivity to detect small consolidations, pleural effusions and sub pleural nodules, POCUS has recently been proposed as a sputum-free likely triage tool for tuberculosis (TB). To make an objective assessment of the potential and limitations of POCUS in routine TB management, we present a Strengths, Weaknesses, Opportunities & Threats (SWOT) analysis based on a review of the relevant literature and focusing on Sub-Saharan Africa (SSA). We idenitified numerous strengths and opportunities of POCUS for TB management e.g.; accessible, affordable, easy to use & maintain, expedited diagnosis, extra-pulmonary TB detection, safer pleural/pericardial puncture, use in children/pregnant women/PLHIV, targeted screening of TB contacts, monitoring TB sequelae, and creating AI decision support. Weaknesses and external threats such as operator dependency, lack of visualization of central lung pathology, poor specificity, lack of impact assessments and data from Sub-Saharan Africa must be taken into consideration to ensure that the potential of the technology can be fully realized in research as in practice

Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3–7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease