Role of co-trimoxazole prophylaxis in reducing mortality in HIV infected adults being treated for tuberculosis: randomised clinical trial

Objective To assess the impact of prophylactic oral co-trimoxazole in reducing mortality in HIV positive Zambian adults being treated for pulmonary tuberculosis

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Impact of missing data due to selective dropouts in cohort studies and clinical trials.

BACKGROUND: Many cohort studies and clinical trials use repeated measurements of laboratory markers to track disease progression and to evaluate new therapies. A major problem in the analysis of such studies is that marker data are censored in some patients owing to withdrawal, loss to follow-up, or death. The objective of this paper is to evaluate the impact of selective dropouts attributable to death or disease progression on the estimates of marker change among different groups. METHODS: Data on CD4 cell count in human immunodeficiency virus 1-infected individuals from a clinical trial and a cohort study are used to illustrate this problem and a possible solution. Simulation studies are also presented. RESULTS: When the rate of dropout is greater in subjects whose marker status is declining rapidly, commonly used methods, like random effects models, that ignore informative dropouts lead to overoptimistic statements about the marker trends in all compared groups, because subjects with steeper marker drops tend to have shorter follow-up times and hence are weighted less in the estimation of the group rate of the average marker decline. CONCLUSIONS: The potential biases attributable to incomplete data require greater recognition in longitudinal studies. Sensitivity analyses to assess the effect of dropouts are important

Estimating glomerular filtration rate in HIV-infected adults in Africa: comparison of Cockcroft-Gault and Modification of Diet in Renal Disease formulae.

BACKGROUND: Cockcroft-Gault (CG) and Modification of Diet in Renal Disease (MDRD) formulae are recommended for glomerular filtration rate (GFR) estimation, but neither has been validated or directly compared longitudinally in HIV-infected patients or in Africa. METHODS: We investigated differences between formulae in baseline GFR, GFR changes and incidence of impaired GFR after initiation of antiretroviral therapy (ART) in 3,316 HIV-infected adults in Africa, considering sex, age, body mass index and baseline laboratory parameters as predictors. RESULTS: Participants were 65% women, median age 36.8 years, median weight 56.7 kg. Baseline GFR was lower using CG (median 89 ml/min/1.73 m2, 7.4% <60 ml/min/1.73 m2) versus MDRD (103 ml/min/1.73 m2, 3.1% <60 ml/min/1.73 m2). At 36 weeks, median CG-GFR increased (92 ml/min/1.73 m2), whereas MDRD-GFR decreased (96 ml/min/1.73 m2). Weight (explicitly a factor in CG only) concurrently increased to 62.0 kg. GFR changes from weeks 36-96 (after weight stabilization) were similar across formulae. By 96 weeks, 56 patients developed severe GFR impairment (<30 ml/min/1.73 m2) using one or both formulae (both n=45, CG n=7, MDRD n=4) compared with only 24 by serum creatinine alone. Multivariate models identified different sets of predictors for each formula. CONCLUSIONS: Although severe GFR impairments are similarly classified by different formulae, moderate impairments were more frequently identified using CG-GFR versus MDRD-GFR (with Black ethnicity correction factor 1.21), and creatinine alone had low sensitivity. Given overestimation in underweight patients and sensitivity to weight changes, this MDRD formula might not necessarily be superior for monitoring ART in African HIV-infected adults

Prevalence, incidence and predictors of severe anaemia with zidovudine-containing regimens in African adults with HIV infection within the DART trial.

OBJECTIVE: To describe the prevalence, incidence and predictors of severe anaemia in previously untreated symptomatic HIV-infected adults with CD4+ T-cells or =36, respectively. Overall, 219 (6.6%) participants developed grade 4 anaemia by week 48; women and those with lower haemoglobin, CD4+ T-cell count and BMI at baseline were at significantly higher risk (P<0.05), but not those with lower neutrophils or receiving cotrimoxazole at baseline. CONCLUSIONS: We observed a higher incidence of grade 4 anaemia than in studies from industrialized countries, which is likely to be due in part to population characteristics and in part to a higher rate of concurrent HIV-related clinical events. Clinical vigilance and haemoglobin measurements 4, 8 and 12 weeks after starting zidovudine could help to manage serious anaemia

Quality versus quantity: The complexities of quality of life determinations for neonatal nurses

© 2016, © The Author(s) 2016. Background: The ability to save the life of an extremely premature baby has increased substantially over the last decade. This survival, however, can be associated with unfavourable outcomes for both baby and family. Questions are now being asked about quality of life for survivors of extreme prematurity. Quality of life is rightly deemed to be an important consideration in high technology neonatal care; yet, it is notoriously difficult to determine or predict. How does one define and operationalise what is considered to be in the best interest of a surviving extremely premature baby, especially when the full extent of the outcomes might not be known for several years? Research question: The research investigates the caregiving dilemmas often faced by neonatal nurses when caring for extremely premature babies. This article explores the issues arising for neonatal nurses when they considered the philosophical and ethical questions about quality of life in babies ≤24 weeks gestation. Participants: Data were collected via a questionnaire to Australian neonatal nurses and semi-structured interviews with 24 neonatal nurses in New South Wales, Australia. Ethical considerations: Ethical processes and procedures have been adhered to by the researchers. Findings: A qualitative approach was used to analyse the data. The theme ‘difficult choices’ was generated which comprised three sub-themes: ‘damaged through survival’, ‘the importance of the brain’ and ‘families are important’. The results show that neonatal nurses believed that quality of life was an important consideration; yet they experienced significant inner conflict and uncertainty when asked to define or suggest specific elements of quality of life, or to suggest how it might be determined. It was even more difficult for the nurses to say when an extremely premature baby’s life possessed quality. Their previous clinical and personal experiences led the nurses to believe that the quality of the family’s life was important, and possibly more so than the quality of life of the surviving baby. This finding contrasts markedly with much of the existing literature in this field. Conclusion: Quality of life for extremely premature babies was an important consideration for neonatal nurses; however, they experienced difficulty deciding how to operationalise such considerations in their everyday clinical practice