Bacterial microbiome and host inflammatory gene expression in foreskin tissue.

The penile epithelial microbiome remains underexplored. We sequenced human RNA and a segment of the bacterial 16S rRNA gene from the foreskin tissue of 144 adolescents from South Africa and Uganda collected during penile circumcision after receipt of 1-2 doses of placebo, emtricitabine + tenofovir disoproxil fumarate, or emtricitabine + tenofovir alafenamide to investigate the microbiome of foreskin tissue and its potential changes with antiretroviral use. We identified a large number of anaerobic species, including Corynebacterium acnes, which was detected more frequently in participants from South Africa than Uganda. Bacterial populations did not differ by treatment received, and no differentially abundant taxa were identified between placebo versus active drug recipients. The relative abundance of specific bacterial taxa was negatively correlated with expression of genes downstream of the innate immune response to bacteria and regulation of inflammation. Our results show no difference in the tissue microbiome of the foreskin with short-course antiretroviral use but that bacterial taxa were largely inversely correlated with inflammatory gene expression, consistent with commensal colonization.

SMA-TB: study protocol for the phase 2b randomized double-blind, placebo-controlled trial to estimate the potential efficacy and safety of two repurposed drugs, acetylsalicylic acid and ibuprofen, for use as adjunct therapy added to, and compared with, the standard WHO recommended TB regimen.

BACKGROUND: The duration and regimen of tuberculosis (TB) treatment is currently based predominantly on whether the M. tuberculosis (Mtb) strain is drug-sensitive (DS) or multidrug-resistant (MDR) with doses adjusted by patients' weight only. The systematic stratification of patients for personalized treatment does not exist for TB. As each TB case is different, individualized treatment regimens should be applied to obtain better outcomes. In this scenario, novel therapeutic approaches are urgently needed to (1) improve outcomes and (2) shorten treatment duration, and host-directed therapies (HDT) might be the best solution. Within HDT, repurposed drugs represent a shortcut in drug development and can be implemented at the short term. As hyperinflammation is associated with worse outcomes, HDT with an anti-inflammatory effect might improve outcomes by reducing tissue damage and thus the risk of permanent sequelae. METHODS: SMA-TB is a multicentre randomized, phase IIB, placebo-controlled, three-arm, double-blinded clinical trial (CT) that has been designed in the context of the EC-funded SMA-TB Project ( www.smatb.eu ) in which we propose to use 2 common non-steroidal anti-inflammatory drugs (NSAID), acetylsalicylic acid (ASA) and ibuprofen (Ibu), as an HDT for use as adjunct therapy added to, and compared with, the standard of care (SoC) World Health Organization (WHO)-recommended TB regimen in TB patients. A total of 354 South African and Georgian adults diagnosed with confirmed pulmonary TB will be randomized into SoC TB treatment + placebo, SoC + acetylsalicylic acid or SoC + ibuprofen. DISCUSSION: SMA-TB will provide proof of concept of the HDT as a co-adjuvant treatment and identify the suitability of the intervention for different population groups (different epidemiological settings and drug susceptibility) in the reduction of tissue damage and risk of bad outcomes for TB patients. This regimen potentially will be more effective and targeted: organ saving, reducing tissue damage and thereby decreasing the length of treatment and sequelae, increasing cure rates and pathogen clearance and decreasing transmission rates. It will result in better clinical practice, care management and increased well-being of TB patients. TRIAL REGISTRATION: Clinicaltrials.gov NCT04575519. Registered on October 5, 2020.

A Consensus Statement for the Management and Rehabilitation of Communication and Swallowing Function in the ICU: A Global Response to COVID-19.

OBJECTIVE: To identify core practices for workforce management of communication and swallowing functions in coronavirus disease 2019 (COVID-19) positive patients within the intensive care unit (ICU). DESIGN: A modified Delphi methodology was used, with 3 electronic voting rounds. AGREE II and an adapted COVID-19 survey framework from physiotherapy were used to develop survey statements. Sixty-six statements pertaining to workforce planning and management of communication and swallowing function in the ICU were included. SETTING: Electronic modified Delphi process. PARTICIPANTS: Speech-language pathologists (SLPs) (N=35) from 6 continents representing 12 countries. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The main outcome was consensus agreement, defined a priori as ≥70% of participants with a mean Likert score ≥7.0 (11-point scale: 0=strongly disagree, 10=strongly agree). Prioritization rank order of statements in a fourth round was also conducted. RESULTS: SLPs with a median of 15 years of ICU experience, working primarily in clinical (54%), academic (29%), or managerial positions (17%), completed all voting rounds. After the third round, 64 statements (97%) met criteria. Rank ordering identified issues of high importance. CONCLUSIONS: A set of global consensus statements to facilitate planning and delivery of rehabilitative care for patients admitted to the ICU during the COVID-19 pandemic were agreed by an international expert SLP group. Statements focused on considerations for workforce preparation, resourcing and training, and the management of communication and swallowing functions. These statements support and provide direction for all members of the rehabilitation team to use for patients admitted to the ICU during a global pandemic.