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Hoy — Marzo 4th 2026Tus fuentes RSS

Population-based study of pharmacogenetics and pharmacokinetics in Southern African patients with multidrug-resistant tuberculosis (PoPG): a protocol for the Namibian cohort

Por: Boois · L. · Ekandjo · H. · Shavuka · O. · Nepolo · E. · Ndong Sima · C. A. · Oelofse · C. · Uren · C. · Petersen · D. C. · Möller · M. · Wijk · M. · Kellermann · T. · Decloedt · E. · McIlleron · H. · Denti · P. · Claassens · M. M.
Background

Multidrug-resistant tuberculosis (MDR-TB) is an urgent public health challenge in Namibia, with profound socioeconomic consequences. The high burden of both tuberculosis and HIV complicates treatment and underscores the need for optimised drug therapies. Precision medicine, which leverages patient-specific genetic and molecular information, offers promise for improving MDR-TB outcomes. However, its effective application relies on population-specific data, particularly understanding how individuals metabolise tuberculosis drugs and how genetic diversity drives variability in treatment response. Currently, no pharmacokinetic (PK) or pharmacogenetic (PG) data on TB treatment exist for Namibian populations. This gap is particularly concerning, given the country’s genetic diversity, environmental factors and comorbidities that may uniquely influence drug metabolism. This study aims to generate PK and PG data to inform dose optimisation and support personalised treatment strategies for MDR-TB in Namibia. The findings will contribute to improved patient care and inform health system strengthening based on locally relevant evidence.

Methods

This cross-sectional study will consist of 100 Namibian participants with matched human DNA and PK data of MDR-TB cases receiving isoniazid, clofazimine, bedaquiline and the fluoroquinolones (levofloxacin or moxifloxacin). PK sampling will be divided as follows: 30 individuals will undergo intensive PK sampling, while the remaining (n=70) will undergo sparse PK sampling. DNA will be extracted at Stellenbosch University (SU), and samples will be genotyped using the H3Africa microarray. Sequences will be aligned to the human reference genome, hg38 (GRCh38p13), using the freely available Burrows-Wheeler Aligner. A subset of the samples (n=20–30) will undergo whole genome sequencing (WGS) to verify imputation results and identify novel genetic variants potentially affecting PK in this population.

Data analysis

Quality control and variant call format file generation will be performed using the Genome Analysis Toolkit best practices (V.3.5). Intensive and sparse PK data will be pooled for the development of a population PK (popPK) model using a non-linear mixed-effects modelling approach. The popPK model will characterise the relationship between TB drug dose and exposure, including quantifying covariates, including genetic variation, explaining PK variability, providing a foundation for dose optimisation and personalised treatment strategies.

Ethics and dissemination

Ethics approval was obtained from the University of Namibia Human Research Ethics Committee for Health (Ref. SOM18/2024), the Ministry of Health and Social Services (Ref. 22/4/2/3), the SU Health Research Ethics Committee (Ref. N21/11/136) and the University of Cape Town Human Research Ethics Committee (Ref. 500/2022).

Publication Dynamics Where Evidence Is Missing: Mapping Empty Reviews in Nursing

ABSTRACT

Introduction

The production of science is characterized by socio-political and technological forces that influence what knowledge is produced. In this context, empty reviews have received little attention, with debate ranging over the pros and cons of their publication. However, their dissemination may improve the ability to recognize and prioritize research gaps. The main aim of the study was to map empty reviews published in nursing science.

Materials and Methods

A scoping review in accordance with Arksey and O'Malley, Joanna Briggs Institute and Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews. The review protocol was registered in the Open Science Framework database in April 2025. Four databases and grey literature were searched; there were eligible scoping or systematic reviews defined as “empty” in the field of nursing. A modified framework of Patterns, Advances, Gaps, Evidence for practice, and Research recommendations was used to summarize the extracted data.

Results

Fifteen empty reviews were identified. In terms of Patterns, the empty reviews were mainly published in high-income countries over the last 10 years and related to clinical practise and outcomes, education and training, organizational and human resources, and approaches to maternity care, mental health, and nursing education. In general, reporting guidelines were used, while funding was not documented. In terms of Recommendations, more primary studies, the development of tools and the strategic use of empty reviews to inform the funding and research agenda were suggested.

Linking Evidence to Action

Empty reviews in nursing may indicate neglected or emerging areas that can help orient research agendas to ensure equity-oriented priorities and reduce the marginalization of under-investigated topics. Recognizing empty reviews as legitimate scholarly outputs supports transparent mapping of knowledge gaps, helping funders, institutions, and research programs direct resources to under-investigated areas. Dedicated registries that publicly report empty reviews, establish minimum reporting standards, and require explicit keywords in titles and abstracts would improve transparency and accessibility, and stimulate targeted primary research that can turn “empty” areas into active inquiry. From this perspective, empty reviews may attract research investment rather than be seen as methodological failures.

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