Pleural Tuberculosis in Patients with Early HIV Infection Is Associated with Increased TNF-Alpha Expression and Necrosis in Granulomas

Although granulomas may be an essential host response against persistent antigens, they are also associated with immunopathology. We investigated whether HIV co-infection affects histopathological appearance and cytokine profiles of pleural granulomas in patients with active pleural tuberculosis (TB). Granulomas were investigated in pleural biopsies from HIV positive and negative TB pleuritis patients. Granulomas were characterised as necrotic or non-necrotic, graded histologically and investigated for the mRNA expression of IL-12, IFN-γ, TNF-α and IL-4 by in situ hybridisation. In all TB patients a mixed Th1/Th2 profile was noted. Necrotic granulomas were more evident in HIV positive patients with a clear association between TNF-α and necrosis. This study demonstrates immune dysregulation which may include TNF-α-mediated immunopathology at the site of disease in HIV infected pleural TB patients

Less Bone Loss With Maraviroc- Versus Tenofovir-Containing Antiretroviral Therapy in the AIDS Clinical Trials Group A5303 Study

Background. There is a need to prevent or minimize bone loss associated with antiretroviral treatment (ART) initiation. We compared maraviroc (MVC)- to tenofovir disoproxil fumarate (TDF)–containing ART

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

A study of the educational outcomes of the teacher-in-industry program

Due to the character of the original source materials and the nature of batch digitization, quality control issues may be present in this document. Please report any quality issues you encounter to [email protected], referencing the URI of the item.Includes bibliographical references.Not availabl

Lay health workers in primary and community health care.

BACKGROUND: Lay health workers (LHWs) are widely used to provide care for a broad range of health issues. However, little is known about the effectiveness of LHW interventions. OBJECTIVES: To assess the effects of LHW interventions in primary and community health care on health care behaviours, patients' health and wellbeing, and patients' satisfaction with care. SEARCH STRATEGY: We searched the Cochrane Effective Practice and Organisation of Care and Consumers and Communication specialised registers (to August 2001); the Cochrane Central Register of Controlled Trials (to August 2001); MEDLINE (1966- August 2001); EMBASE (1966-August 2001); Science Citations (to August 2001); CINAHL (1966-June 2001); Healthstar (1975-2000); AMED (1966-August 2001); the Leeds Health Education Effectiveness Database and the reference lists of articles. SELECTION CRITERIA: Randomised controlled trials of any intervention delivered by LHWs (paid or voluntary) in primary or community health care and intended to promote health, manage illness or provide support to patients. A 'lay health worker' was defined as any health worker carrying out functions related to health care delivery; trained in some way in the context of the intervention; and having no formal professional or paraprofessional certificated or degreed tertiary education. There were no restrictions on the types of consumers. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data onto a standard form and assessed study quality. Studies that compared broadly similar types of interventions were grouped together. Where feasible, the results of included studies were combined and an estimate of effect obtained. MAIN RESULTS: Forty three studies met the inclusion criteria, involving more than 210,110 consumers. These showed considerable diversity in the targeted health issue and the aims, content and outcomes of interventions. Most were conducted in high income countries (n=35), but nearly half of these focused on low income and minority populations (n=15). Study diversity limited meta-analysis to outcomes for five subgroups (n=15 studies) (LHW interventions to promote the uptake of breast cancer screening, immunisation and breastfeeding promotion [before two weeks and between two weeks and six months post partum] and to improve diagnosis and treatment for selected infectious diseases). Promising benefits in comparison with usual care were shown for LHW interventions to promote immunisation uptake in children and adults (RR=1.30 [95% CI 1.14, 1.48] p=0.0001) and LHW interventions to improve outcomes for selected infectious diseases (RR=0.74 [95% CI 0.58, 0.93) p=0.01). LHWs also appear promising for breastfeeding promotion. They appear to have a small effect in promoting breast cancer screening uptake when compared with usual care. For the remaining subgroups (n=29 studies), the outcomes were too diverse to allow statistical pooling. We can therefore draw no general conclusions on the effectiveness of these subgroups of interventions. AUTHORS' CONCLUSIONS: LHWs show promising benefits in promoting immunisation uptake and improving outcomes for acute respiratory infections and malaria, when compared to usual care. For other health issues, evidence is insufficient to justify recommendations for policy and practice. There is also insufficient evidence to assess which LHW training or intervention strategies are likely to be most effective. Further research is needed in these areas

Predominance of interleukin-22 over interleukin-17 at the site of disease in human tuberculosis

The inflammatory response to Mycobacterium tuberculosis (M.tb) at the site of disease is Th1 driven. Whether the Th17 cytokines, IL-17 and IL-22, contribute to this response in humans is unknown. We hypothesized that IL-17 and IL-22 contribute to the inflammatory response in pleural and pericardial disease sites of human tuberculosis (TB)