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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).

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Continence care quality from the perspective of older adults in long-term care or in receipt of home care: a scoping review

Por: Silverglow · A. · Milsom · I. · Kennedy · M. · Wijk · H. · Wagg · A.
Objectives

To assess the state of the research literature addressing what is known about the quality of continence care from the perspective of older adults in long-term care or in receipt of home care.

Design

Scoping review of the literature according to the Joanna Briggs Institute method, reported according to Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. Participant: older adults (>65 years of age), either in receipt of home health or social care services or older adult residents of long-term care (nursing homes). Concept: older adult perspectives on quality of continence care (access, care to meet needs, continuity, goals, expectations, delivery, experiences, personalised care, partnerships in care, well-being and social support). Context: older adults in long-term care or in receipt of home care.

Results

We identified 14 articles from the academic literature. Sources originated from the USA (7), Australia (4), Canada (2) and 1 from Italy. Long-term care residents were the focus of 12 of the articles. Older adults reported limited access and information regarding continence care and services and variable abilities of care staff to deliver care. Older adults wanted to be actively involved in decisions about their care, preserve their autonomy and independence and wanted care to enhance their well-being.

Conclusions

Studies examining the perspectives of older adults regarding the quality of their continence care are few. Older adults value person-centredness, expert advice regarding their condition, allowing preservation of self-determination and independence where possible. Older people value meaningful relationships with empathetic care providers. There remains a need for education of care providers in continence care and for policies and practices to support continence in a dignity-preserving framework.

Registration

Open Science Framework (https://osf.io/bprq9/).

Diet and diet-related challenges with specific focus on carbohydrates and carbohydrate counting in adults with type 1 diabetes: a cross-sectional study

Por: Sterner Isaksson · S. · Hellman · J. · Wijkman · M. · Imberg · H. · Olafsdottir · A. F. · Axelsen · M. · Lind · M.
Objectives

To explore dietary intake, diet-related challenges in glucose management and perceived needs for dietary support among Swedish adults with type 1 diabetes (T1D).

Design

Cross-sectional observational study based on an electronic survey that included the validated Meal-Q food frequency questionnaire and additional questions on dietary habits and management. Participant characteristics were retrieved from the Swedish National Diabetes Register. Descriptive and correlation analyses were conducted.

Setting

Three diabetes specialist clinics in Sweden.

Participants

375 adults with T1D.

Main outcome measures

Dietary intake and diet-related challenges in glucose management.

Results

A total of 191 persons (mean age 48 years; 48% female) consented to participate. The mean (SD) glycated haemoglobin A1c was 56 (13) mmol/mol, mean glucose 8.8 (2.2) mmol/L, time in range (TIR) 64% (18%) and BMI 27 (4.3) kg/m²; 41% used insulin pumps. Mean carbohydrate intake was 183 g/day (41% of energy, E%). Fibre intake was 23 g/day (3.1 g/MJ), and saturated fat intake was 29 g/day (15 E%), both inconsistent with dietary recommendations. About half (51%) found carbohydrate counting challenging, with 53% estimating carbohydrate intake visually and only 18% using advanced methods. Additionally, 48% reported reducing carbohydrate intake, and 61% avoided certain carbohydrate-rich foods due to glucose management difficulties. Approximately 40% of participants reported insufficient dietary guidance from their healthcare providers since diagnosis, 33% expressed interest in further dietitian support and 39% believed dietary changes could improve glucose control.

Conclusions

Participants reported lower fibre intake and higher saturated fat intake compared with dietary guidelines. Many found carbohydrate counting and carbohydrate-rich meals challenging. One-third expressed a wish for additional dietary support. These findings highlight the importance of improving access to tailored dietary counselling in routine T1D care.

Evaluation of the Implementation of Prenatal Home Visits in Youth Healthcare in the Netherlands: A Mixed Methods Study

ABSTRACT

Aim

Preventing maternal stress is important for the healthy development of a child. Prenatal home visits were introduced as an integral part of the Dutch preventive youth healthcare for this purpose. This study aims to gain insight into the current state of prenatal home visits.

Design

Mixed methods explanatory sequential design.

Methods

Two questionnaires, one for managers and one for nurses, were distributed to all 38 Dutch youth healthcare organisations. These could be filled in from 29 February to 15 April 2024. Respondents were subsequently invited to participate in an explanatory focus group on 12 June 2024, to help interpret the findings. Questionnaire data were analysed descriptively. Focus group data were analysed qualitatively using open inductive coding. Informed consent was obtained through a privacy statement included with the questionnaire.

Findings

The manager questionnaire had 17 respondents (from 17 organisations), of which 10 participated in the focus group, while the nurse questionnaire had 124 respondents (from 34 organisations), with 8 in the focus group. This study found large differences between youth healthcare organisations regarding collaboration agreements with municipalities, collaboration with referrers, the organisational process and the execution of prenatal home visits in practice. Managers and nurses encounter difficulties with assessing vulnerability in practice and how the intended target group should be reached effectively. While effective collaboration with potential referrers is believed to be essential for achieving accurate and appropriate referrals, the process was experienced as overly complex. No standardised system for documenting data from prenatal home visits was found.

Conclusion

Significant variations exist in organisation and implementation of prenatal home visits across youth healthcare organisations in the Netherlands. The unclear definition of ‘potential vulnerability’ results in an insufficiently defined target group. The lack of standardised data registration hinders the monitoring of the quality, continuity and effectiveness of these visits.

Implications

Variations in organisation and implementation of prenatal home visits may lead to unequal access to care and support for pregnant women and their unborn children across Dutch regions.The lack of a clear definition for ‘potential vulnerability’ results in challenges in identifying and reaching the intended target group, potentially excluding individuals who would benefit most from these services. The absence of a standardised system for data documentation prevents systematic monitoring and evaluation, making it difficult to assess the effectiveness of prenatal home visits and identify areas for improvement. This threatens the long-term embedding of prenatal home visits in the Netherlands. Further research should also aim to gain insight into the perspective of parents and midwives.

Reporting Method

The paper adheres to the Standards for Reporting Qualitative Research (SRQR) and the Good Reporting of a Mixed Methods Study (GRAMMS) checklists.

Patient or Public Contribution

There was no patient or public contribution to our study.

Do people prefer to take part in a clinical trial from home or come to site? A discrete choice experiment in type 2 diabetes mellitus

Por: Kopanz · J. · Lagerwaard · B. · Veldwijk · J. · Mader · J. K. · Tews · D. · van Sloten · T. T. · Grobbee · D. E. · Zuidgeest · M. G. P. · on behalf of the Trials@Home consortium
Objectives

To determine what drives participation in clinical trials with decentralised elements and to estimate trial participation probabilities for trials with different degrees of decentralisation.

Design

Patient preference study using a discrete choice experiment.

Setting

Recruitment in primary, secondary, tertiary care and other settings in the Netherlands (NL), Austria (AT) and Germany (DE).

Participants

People with type 2 diabetes mellitus (T2DM) aged ≥18 years. A total of 787 people (NL n=276, AT n=265, DE n=246) participated in the study.

Main outcome measures

Preferences for participation in clinical trials with different options for location and type of contact with the study team, activities to perform by participant, use of digital technologies by participant, number of scheduled contacts, trial duration, known safety and efficacy of the drug.

Results

How much was known about the safety and efficacy of the drug was the most important element in the decision whether to participate in a clinical trial in all countries. The trial duration, location and type of contact with the study team, and number of scheduled contacts were other important elements. Participation probabilities for hypothetical trial scenarios differed between countries, with the highest rates for a decentralised trial involving video contact (NL: 89%; AT: 99%; DE: 84%).

Conclusions

People with T2DM prefer to take part in clinical trials with decentralised approaches. Information on preferences can help trialists and protocol developers to design and plan future trials that integrate patients’ needs and thus reduce barriers to participation.

Evaluating a population-based screening programme for early detection of liver fibrosis and cirrhosis in primary care in Germany: a cost assessment study

Por: Ortner · J. · Van Ewijk · R. · Velthuis · L. · Labenz · C. · Arslanow · A. · Nguyen-Tat · M. · Wörns · M.-A. · Reichert · M. C. · Farin-Glattacker · E. · Binder · H. · Fichtner · U. A. · Graf · E. · Stelzer · D. · Galle · P. R. · Lammert · F.
Objectives

Structured Early detection of Asymptomatic Liver fibrosis and cirrhosis (SEAL) is a population-based screening programme using non-invasive tests for the early detection of liver fibrosis. This study evaluates the cost implications if the SEAL programme were to be implemented in routine care in Germany.

Design

This study models cost differences with and without the SEAL screening programme. We regress costs of care on patient characteristics (age, comorbidities, sex, liver diseases, liver cancer and liver fibrosis and cirrhosis (LCI) stage) using statutory health insurance (SHI) data from routine care patients with LCI (n=4177). Based on these results, we predict per-patient costs for the patients newly diagnosed with LCI by SEAL (n=45). Costs with and without screening are estimated using patient age and LCI stage distributions from either SEAL or routine care.

Setting

SEAL was conducted in two German states. Initial screening was performed by patients’ primary care physicians.

Participants

Individuals insured by SHI without a prior diagnosis of LCI, eligible for Check-up 35, a general health check-up programme primarily targeting adults aged 35 and older, conducted by primary care physicians.

Interventions

Screening via aspartate aminotransferase to platelet ratio index in primary care, for further evaluation serological diagnostics and ultrasound examinations in secondary care and specific assessment for definite diagnosis including transient elastography and liver biopsy for selected cases in tertiary care.

Primary and secondary outcome measures

Primary outcome measures: expected 5-year cost changes for SEAL patients diagnosed with fibrosis or cirrhosis compared to costs without a screening programme. Secondary outcome measures: case mix of leading chronic liver disease and LCI stages among patients diagnosed with advanced fibrosis or cirrhosis in SEAL versus routine care without screening.

Results

Screening leads to fewer decompensated cases at initial diagnosis (4.6% in SEAL vs 22.8% in routine care) and thus savings in the costs of care within the first years of diagnosis: total expected costs per case were 2175 lower (bias-corrected bootstrap CIs (BCI): 527 to 3734), and LCI-associated costs were reduced by 1218 (BCI: 296 to 2164). Comparing the savings to the additional costs of diagnosis (range: 1575–1726 per detected LCI case) reveals that average changes in costs with screening range from moderate savings to moderate extra costs.

Conclusions

SEAL liver screening identifies patients in less advanced stages of LCI. If only costs were considered that are directly attributable to LCI, savings within 5 years are unlikely to fully outweigh the costs of screening. However, since this approach might miss additional LCI-related costs, SEAL appears to be cost-neutral compared with routine care when considering total healthcare costs.

Registration number

The SEAL registration number is DRKS00013460. This study relates to its results.

Effect of medical-grade honey (L-Mesitran) for cervical intraepithelial neoplasia II: protocol for a multicentre cohort pilot study (HONEY FOR CIN II study)

Por: Prop · J. · De Vos van Steenwijk · P. · Lardenoije · C. M. J. G. · Cremers · N. A. J. · Morre · S. A. · Mongula · J.
Introduction

High-grade squamous intraepithelial lesions are caused by persistent high-risk human papillomavirus (hr-HPV) infections and are subdivided into cervical intraepithelial neoplasia (CIN) lesions: CIN II (moderate) and CIN III (severe). Current treatment options for CIN II include large loop excision of the transformation zone, imiquimod and expectant management. Each treatment option has its drawbacks, and therefore, a non-invasive treatment is desirable. Preliminary evidence shows that medical-grade honey (MGH) has antiviral activity and might be able to modulate the vaginal microbiome, reduce local inflammation or directly influence the intralesional immune response within cervical tissues. Therefore, this study aims to investigate the possible effect of MGH on hr-HPV clearance and to investigate the possible underlying mechanisms contributing to the regression of CIN II lesions.

Methods and analysis

This study is performed in the Zuyderland Medical Centre and Maastricht University Medical Centre+. A total of 60 eligible women with newly histologically confirmed CIN II will receive MGH (L-Mesitran Soft) for intravaginal use for 6 months. The primary objective is to investigate the effect of MGH on the hr-HPV clearance after 6 months. Secondary aims are the effect of MGH on the regression of CIN II lesions, clearance of hr-HPV at 12 and 24 months and the role of the vaginal microbiome, local immune system and intravaginal inflammatory status in response to MGH. Moreover, data on quality of life, side effects and compliance will be collected.

Ethics and dissemination

Ethical approval from the Medical Ethics Review Committee of the Zuyderland Medical Centre Heerlen has been obtained (NL86044.096.24 on 24 April 2024). The results will be presented to researchers and healthcare professionals through conferences, meetings and publications in international journals.

Trial registration number

NCT06219018.

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