Transvaginal and transabdominal cerclage procedures have become established interventions to prevent mid-trimester pregnancy loss and preterm birth. Transabdominal cerclage seems to be superior to transvaginal cerclage in women with a history of a failed transvaginal cerclage. However, with the availability of a less invasive laparoscopic procedure, there is limited evidence concerning which type of cerclage to recommend to many other risk groups. The objective of this trial is to compare laparoscopic abdominal cerclage and transvaginal cerclage in women at moderate to high risk of spontaneous preterm birth.
The trial is an open, multicentre, superiority, parallel arm randomised controlled investigator-initiated trial with an embedded internal pilot. Women in whom the clinician has clinical equipoise between laparoscopic and transvaginal cerclage are randomised to either laparoscopic abdominal or transvaginal cerclage in a ratio of 1:1. The trial extends from sites in Denmark, Finland and Norway. The primary outcome is birth
The Central Denmark Region Committee on Biomedical Research Ethics, Denmark, Helsinki University Hospital Ethics committee, Finland and the Regional Committees for Medical and Health Research Ethics, Norway approved the trial. This protocol is published prior to complete data collection and analysis. Important protocol changes will be made publicly available on ClinicalTrials.org, on the trial website and distributed electronically to all active sites. Positive, inconclusive as well as negative results from the trial will be published in peer-reviewed international scientific journals.
Little research has been done on post-COVID symptoms at 24 months postinfection and on the association these may have on health-related quality of life (HRQOL).
We assessed the prevalence and severity of post-COVID symptoms and quantified EuroQol 5 Dimension 5 Level (EQ-5D-5L), self-perceived health question (EuroQol Visual Analogue Scale (EQ-VAS)) and health utility scores (HUS) up to 24 months follow-up.
The longitudinal multiple cohort CORona Follow-Up (CORFU) study combines seven COVID-19 patient cohorts and a survey among the general public. The participants received questionnaires on several time points. Participants were stratified by: without a known SARS-CoV-2 infection (control group), proven SARS-CoV-2 infection but non-hospitalised, proven SARS-CoV-2 infection hospitalised to the ward, and proven SARS-CoV-2 infection hospitalised to the intensive care unit (ICU).
In this study, data of seven COVID-19 patient cohorts and a survey among the general public are included.
Former COVID-19 patients and controls participated in this cohort study.
Former COVID-19 patients and non-COVID-19 controls were sent questionnaires on symptoms associated with post-COVID condition. The CORFU questionnaire included 14 symptom questions on post-COVID condition using a five-level Likert-scale format. Furthermore, HRQOL was quantified using the EuroQol EQ-5D-5L questionnaire: EQ-VAS and the EQ-5D-5L utility score. The EQ-5D-5L questionnaire includes five domains that are scored on a five-point Likert scale: mobility, self-care, usual activities, pain/discomfort and anxiety/depression.
A total of 901 participants (and 434 controls) responded at 24 months follow-up. In all former COVID-19 patients, the presence of post-COVID condition at 24 months was observed in 62 (42.5%, 95% CI 34.3% to 50.9%) of the non-hospitalised patients, 333 (65.0%, 95% CI 60.7% to 69.2%) of the hospitalised ward patients and 156 (63.2%, 95% CI 56.8% to 69.2%) of the ICU patients, respectively (p
Many former COVID-19 patients experience post-COVID symptoms at 24 months follow-up, with the highest prevalence in hospitalised participants. Also, former patients reported a lower HRQOL.
The CORFU study was registered at clinicaltrials.gov (registration number NCT05240742).
by Kaylee R. Jacobs, Caleb M. Ardizzone, Arkaprabha Banerjee, Evelyn Toh, Xiaoli Zhang, David E. Nelson
Chlamydia are obligate intracellular bacterial pathogens that infect a wide range of vertebrate hosts. Despite having highly conserved genomes, closely related Chlamydia species can exhibit distinct host and tissue tropisms. The host tropisms of the human pathogen Chlamydia trachomatis and the closely related mouse pathogen Chlamydia muridarum are influenced by their ability to evade host immune responses, particularly those mediated by interferon gamma. However, there is evidence that tissue tropism is driven by additional poorly understood host and Chlamydia factors. In this study, we used a forward genetic approach to investigate the mechanisms that mediate C. muridarum tissue tropism. We conducted a tropism screen using a randomly mutagenized C. muridarum library and murine cell lines representing different tissues. We identified a mutant isolate whose growth was restricted in murine rectal and oviduct epithelial cells in an interferon gamma-independent manner. This phenotype was mapped to a missense mutation in tc0237, a gene that mediates the affinity of C. muridarum for cultured human epithelial cells. Our analysis of growth dynamics showed that the tc0237 mutant exhibits a developmental delay in rectal epithelial cells. Together, these results suggest that TC0237 plays a role in C. muridarum tissue tropism.Tuberculosis (TB) remains a significant public health challenge in many African communities, where underreporting and underdiagnosis are prevalent due to barriers in accessing care and inadequate diagnostic tools. This is particularly concerning in hard-to-reach areas with a high burden of TB/HIV co-infection, where missed or delayed diagnoses exacerbate disease transmission, increase mortality and lead to severe economic and health consequences. To address these challenges, it is crucial to evaluate innovative, cost-effective, community-based screening strategies that can improve early detection and linkage to care.
We conduct a prospective, community-based, diagnostic, pragmatic trial in communities of the Butha Buthe District in Lesotho and the Greater Edendale area of Msunduzi Municipality, KwaZulu-Natal in South Africa to compare two strategies for population-based TB screening: computer-aided detection (CAD) technology alone (CAD4TBv7 approach) versus CAD combined with point-of-care C reactive protein (CRP) testing (CAD4TBv7-CRP approach). Following a chest X-ray, CAD produces an abnormality score, which indicates the likelihood of TB. Score thresholds informing the screening logic for both approaches were determined based on the WHO’s target product profile for a TB screening test. CAD scores above a threshold prespecified for the CAD4TBv7 approach indicate confirmatory testing for TB (Xpert MTB/RIF Ultra). For the CAD4TBv7-CRP approach, a CAD score within a predefined window requires the conduct of the second screening test, CRP, while a score above the respective upper threshold is followed by Xpert MTB/RIF Ultra. A CRP result above the selected cut-off also requires a confirmatory TB test. Participants with CAD scores below the (lower) threshold and those with CRP levels below the cut-off are considered screen-negative. The trial aims to compare the yield of detected TB cases and cost-effectiveness between two screening approaches by applying a paired screen-positive design. 20 000 adult participants will be enrolled and will receive a posterior anterior digital chest X-ray which is analysed by CAD software.
The protocol was approved by National Health Research Ethics Committee in Lesotho (NH-REC, ID52-2022), the Human Sciences Research Council Research Ethics Committee (HSRC REC, REC 2/23/09/20) and the Provincial Health Research Committee of the Department of Health of KwaZulu-Natal (KZ_202209_022) in South Africa and from the Swiss Ethics Committee Northwest and Central Switzerland (EKNZ, AO_2022–00044). This manuscript is based on protocol V.4.0, 19 January 2024. Trial findings will be disseminated through peer-reviewed publications, conference presentations and through communication offices of the consortium partners and the project’s website (https://tbtriage.com/).
ClinicalTrials.gov (NCT05526885), South African National Clinical Trials Register (SANCTR; DOH-27-092022-8096).
Patients with stage III non-small cell lung cancer (NSCLC) are at high risk of developing post-treatment recurrences (50–78%) during follow-up. As more effective treatments are now available, especially for patients with oligometastatic disease, earlier detection of recurrences may prolong survival and health-related quality of life (HRQOL). With the use of 2'-deoxy-2'-[18F]fluoroglucose positron emission tomography/CT ([18F]FDG PET/CT) during follow-up, recurrences may be detected earlier. Therefore, the primary objective of this study is to compare the 3-year overall survival of patients with stage III NSCLC during follow-up surveillance with [18F]FDG PET/CT versus follow-up with conventional CT (usual care). Secondary objectives address the number, location and timing of recurrences, as well as HRQOL, cost-effectiveness and patient experiences of PET/CT scans.
In this multicentre randomised controlled clinical trial, 690 patients with stage III NSCLC (8th edition International Association for the Study of Lung Cancer (IASLC) Tumor, Nodes, Metastasis (TNM) classification) who completed curative intended treatment and started follow-up care (which may include adjuvant therapy) will be randomised 1:1 to either the intervention ([18F]FDG PET/CT) or the control group (CT). Patients will undergo follow-up scans during visits at 6, 12, 18, 24 and 36 months. Data will be collected using validated questionnaires, electronic case report forms and data extractions from the electronic health records. Additionally, blood samples will be collected, and interviews will be conducted.
The study protocol has been approved by the Medical Ethical Committee of the Radboudumc and review boards of all participating centres. Written informed consent will be obtained from all participants. Study results will be published in international peer-reviewed scientific journals and presented at relevant scientific conferences. Data will be published in a data repository or other online data archive.
To develop models to predict opportunities for improvement in trauma care and compare the performance of these models to the currently used audit filters.
Retrospective registry-based study.
Single-centre, Scandinavian level one equivalent trauma centre.
8220 adult trauma patients screened for opportunities for improvement between 2013 and 2022.
Two machine learning models (logistic regression and XGBoost) and the currently used audit filters were compared. Internal validation by an expanding window approach with annual updates was used for model evaluation. Performance measured by discrimination, calibration, sensitivity and false positive rate of opportunities for improvement prediction.
A total of 8220 patients, with a mean age of 45 years, were analysed; 69% were men with a mean injury severity score of 12. Opportunities for improvement were identified in 496 (6%) patients. Both the logistic regression and XGBoost models were well-calibrated, with intercalibration indices of 0.02 and 0.02, respectively. The models demonstrated higher areas under the receiver operating characteristic curve (AUCs) (logistic regression: 0.71; XGBoost: 0.74). The XGBoost model had a lower false positive rate at a similar sensitivity (false positive rate: 0.63). The audit filters had an AUC of 0.62 and a false positive rate of 0.67.
The logistic regression and XGBoost models outperformed audit filters in predicting opportunities for improvement among adult trauma patients and can potentially be used to improve systems for selecting patients for trauma peer review.
Our study was designed to assess whether paired normal-tumour testing increased access to targeted therapy, clinical trials and influenced cancer screening recommendations given to patients and their families.
Prospective cohort study.
Academic cancer centre in the Pacific Northwest region of the USA.
Patients newly diagnosed between 01 January 2021 and 31 December 2022 with cancers of the oesophagus, gastro-oesophageal junction and stomach (CEGEJS) were included. All other cancer diagnoses such as head and neck, duodenal and lower gastrointestinal tract cancers were excluded.
Paired germline and tumour genetic test within 90 days of new patient visit.
Number of targeted therapies received (or not) when eligible, follow-up treatment data and number of inherited predispositions to cancers identified. No secondary outcome measures.
Of 42 patients, 32 (76.2%) were eligible for at least one targeted therapy. 19 patients received immunotherapy, when 16 had a biomarker predicting immunotherapy benefit, and benefit of immunotherapy was unclear for 3. Another 11 did not have this biomarker, and 6 of them received immunotherapy. Six pathogenic variants were identified in four high-risk genes. By 01 January 2024, 18 patients (42.9%) had died of complications of cancer.
More than 75% of patients who received tumour testing were eligible for a targeted therapy regardless of their stage at diagnosis, emphasising the need to expand access to testing with staging workup to improve survival outcomes. Six families received personalised screening recommendations, thanks to this study.
Adolescents’ experiences (10–19 years-old) with tuberculosis (TB) remain poorly understood. Descriptions of adolescent TB experiences, particularly how they interact with the health system, are scarce. We aimed to understand adolescents’ experiences of TB health services in the Western Cape, South Africa. We focused on how TB services were aided or hindered through interactions with healthcare providers and health system processes.
Teen TB, an observational study in Cape Town, enrolled 50 newly diagnosed adolescents with multidrug-resistant and drug-susceptible TB. A subset of 20 was selected for serial qualitative data collection, with 19 completing all tasks between December 2020 and September 2021. 52 interviews were conducted and thematically analysed using a case descriptive process for experiences across the TB care cascade.
Adolescents criticised the difficulties and delays they encountered in obtaining an accurate TB diagnosis. Initial misdiagnoses and delayed TB diagnoses were reported, despite seeking help from multiple healthcare providers at different facilities. Adolescents questioned whether the financial, social and emotional costs of TB care outweighed the costs of delaying treatment initiation and adherence. Adolescents reported that the treatment regimen, adherence support processes and interactions with the health system posed significant challenges to maintaining adherence. Encouragingly, however, most adolescents reported being well treated and cared for by health workers.
Our study shows that adolescents experience challenges throughout their TB treatment journeys. More adolescent-focused research is needed to tailor treatment and healthcare processes to their needs.
The ‘Developing and evaluating an adapted behavioural activation intervention for depression and diabetes in South Asia (DiaDeM)’ trial investigates a psychological intervention, behavioural activation (BA), on people with both diabetes and depression in Bangladesh and Pakistan. This study aimed to aid the intervention and trial design.
This was a modelling study using microsimulation to assess the intervention’s cost-effectiveness. Diabetes was modelled using the UK Prospective Diabetes Study model based on Pakistani patients and depression was modelled using Patient Health Questionnaire-9 (PHQ-9) trajectories allowing for multiple depressive episodes. It was assumed that diabetes-related adverse events increased depression recurrence, while depression impacted haemoglobin A1c, increasing diabetes-related events. The model estimated (1) maximum cost of BA which would be cost-effective (headroom analysis) to inform intervention design, and (2) value of reducing uncertainty around different measures (value of information analysis) to prioritise data collection in the DiaDeM study.
Analysis was conducted from a Pakistani healthcare perspective over a lifetime with costs and outcomes discounted at 3%.
BA plus usual care was compared against usual care. BA involved six sessions by a trained (non-mental health) facilitator. The usual care comparator was the prevailing mix of pharmacological and non-pharmacological treatments used in Pakistan.
The primary outcome was disability-adjusted life-years (DALYs). Secondary outcomes included life years, healthcare costs and the rate of depression and diabetes-related events.
Over their lifetime, individuals receiving BA plus usual care avoid 3.2 (95% credible interval: 2.7 to 3.8) years of mild depression and experience fewer diabetes-related events. BA plus usual care resulted in an additional 0.27 (0.03 to 0.52) life years, 0.98 (0.45 to 1.86) DALYs averted and had incremental healthcare costs of –US$97 (–US$517 to US$142), excluding BA costs. The maximum cost per BA course at which was cost-effective is US$83 (US$9 to US$214). Value of information analysis found the most important measures to include in the trial are the impact of depression on diabetes and PHQ-9 over time.
This is the first model to jointly model depression and diabetes for South Asia and uses novel methods to reflect the diseases and inform intervention and trial design. This evidence has helped to inform the design of the DiaDeM intervention and the trial to evaluate it.
DiaDeM trial: ISRCTN40885204, DOI: ; pre-results, DOI:
Caregivers of patients undergoing haematopoietic stem cell transplantation (HSCT) experience tremendous psychological distress before, during and after HSCT. However, few interventions are tailored to the protracted needs of these caregivers while considering scalability and accessibility. We previously developed an evidence-based intervention for caregivers of patients undergoing HSCT that improved quality of life (QOL), caregiving burden and mood. We have since adapted this clinician-delivered intervention into a self-administered, digital health application (BMT-CARE app) and are currently evaluating the effect of this intervention on QOL in caregivers of patients receiving HSCT.
The study design is a non-blinded randomised controlled trial of a digital health intervention for caregivers of patients undergoing HSCT at the Massachusetts General Hospital Cancer Center. We are enrolling and randomising 125 caregivers to receive the BMT-CARE app or usual care in a 1:1 assignment, stratifying by transplant type (autologous vs allogeneic). Caregivers assigned to the BMT-CARE app complete five self-guided modules designed to improve coping and stress management prior to and up to 60 days post-HSCT. The modules include interactive, gamified features and video vignettes to optimise engagement. Participants complete questionnaires at baseline and days 10, 60 and 100 post-HSCT. The primary outcome is comparison of QOL at day 60 post-HSCT. Secondary outcomes include caregiver burden, anxiety and depression symptoms, as well as post-traumatic stress symptoms. We are also exploring the usability of the BMT-CARE app to inform refinements prior to future testing.
The study is funded by the Leukemia and Lymphoma Society and approved by the Dana-Farber/Harvard Cancer Center Institutional Review Board (Protocol #22–634 v.1.5). The results of this study will be reported in accordance with the Consolidated Standards of Reporting Trials statement for non-pharmacological trials. Results will be disseminated at scientific meetings and in peer-reviewed journals.
NCT05709912; Pre-results.
by Jonathan Gwasupika, Davidson H. Hamer, Victor Daka, Ephraim Chikwanda, David Mwakazanga, Ruth L. Mfune, Choolwe Jacobs
BackgroundChildren with human immunodeficiency virus (HIV) infection are disproportionately susceptible to bacterial infections. There are a wide range of antibacterial agents available to manage HIV positive children with bacterial infections. However, administration of antibiotics in most children is empirical which could lead to antimicrobial resistance.
ObjectivesThis study aimed to determine commonly prescribed antibiotics and associated symptoms in children at Arthur Davison children’s hospital antiretroviral therapy clinic in Ndola, Zambia.
MethodsThis was a cross-sectional study that analysed the antibiotic prescribing patterns from routinely collected secondary data at Arthur Davison children’s hospital. Children diagnosed with HIV before the age of 5, actively attending antiretroviral therapy clinic identified by SmartCare software and who had taken antiretroviral therapy for at least 6 months were eligible. Data were collected from files of children who met the eligibility criteria. STATA software version 16 SE (STATA Corp., College Station, Texas, USA) was used for analysis. A p-value less than 0.05 was considered statistically significant at a confidence interval of 95%.
ResultsFrom a total of 132 children included in the study, 37.9% presented with symptoms with the most common symptoms being cough (70.0%) and diarrhoea (30.0%). A larger proportion of children (62.1%) were on arbacavir/lamivudine/dolutogravr combination of antiretroviral therapy while 8.2% were on the tenoforvir alafenamide/lamivudine/dolutobravir regimen. Children who were on abacavir/lamivudine/dolutegravir regimen presented with more symptoms (48.8%) compared to those on tenofovir alafenamide/lamivudine/dolutegravir (21.0%) and tenofovir disoproxil fumarate/lamivudine/dolutegravir (18.2%) (p = 0.006). Approximately 60.0% of children presenting with symptoms were prescribed antibiotics. Co-trimoxazole was the most commonly (38.0%) prescribed, while erythromycin (2.0%) and Cephalexin (2.0%) were the least.
ConclusionsRespiratory and gastrointestinal symptoms were the most common presentations suggestive of a suspected infection requiring antibiotic prescription in HIV-positive children on ART. Despite co-trimoxazole being the prophylactic drug among HIV-positive children, it was the most common antibiotic among children presenting with symptoms suggestive of an infection. This calls for the prudent use of co-trimoxazole to avoid its resistance.
by Oliver L. Jacobs, Katerina Andrinopoulos, Jennifer K. E. Steeves, Alan Kingstone
The classic Vandenberg and Kuse Mental Rotations Test (MRT) shows a male advantage for visuospatial rotation. However, MRTs that have been adapted for use with real or physical objects have found that sex differences are reduced or abolished. Previous work has also suggested that virtual 3D objects will eliminate sex differences, although this has not been demonstrated in a purely visuospatial paradigm without motor input. In the present study we sought to examine potential sex differences in mental rotation using a fully-immersive 3D VR adaptation of the original MRT that is purely visuospatial in nature. With unlimited time 23 females and 23 males completed a VR MRT designed to approximate the original Vandenberg and Kuse stimuli. Despite the immersive VR experience and lack of time pressure, we found a large male performance advantage in response accuracy, exceeding what has typically been reported for 2D MRTs. No sex differences were observed in response time. Thus, a male advantage in pure mental rotation for 2D stimuli can extend to 3D objects in VR, even when there are no time constraints.The World Health Organization defines quality of care as providing effective, evidence-based care, and avoiding harm. Low-value care provides little or no benefit to the patient, causes harm, and wastes limited resources. In 2017, shortly after the start of the International Choosing Wisely campaign, the first Dutch nursing “Do-not-do” list was published and has become a widely used practical tool for nurses working in daily practice. However, over the last years new guidelines are published. Therefore, an update of the list is necessary with an addition of high-value care recommendations as alternative care practices for low-value care.
In this study, a combination of designs was used. First, we searched Dutch clinical practice guidelines for low-value or high-value care recommendations. All nursing care recommendations were assessed and specified to several healthcare sectors, including hospital care, district care, nursing home care, disability care, and mental health care. Second, a prioritization among nurses regarding low-value care recommendations was done by a cross-sectional survey for each healthcare sector.
In total, 66 low-value care recommendations were found, for example, “avoid unnecessary layers under the patient at risk of pressure ulcers” and “never flush the bladder to prevent urinary tract infection.” Furthermore, 414 high-value care recommendations were selected, such as “use the Barthel Index to assess and to evaluate the degree of ADL independence” and “application of cold therapy may be considered for oncological patients with pain.” In total, 539 nurses from all healthcare sectors prioritized the low-value care recommendations, resulting in a top five low-value care practices per healthcare sector. The top five low-value care recommendations differed per healthcare sector, although “do not use physical restraints in case of a delirium” was prioritized by four out of five sectors.
Assessing low-value and high-value care recommendations for nurses will help and inspire nurses to deliver fundamental care for their patients. These initiatives regarding low-value and high-value care are essential to generate a culture of continuous quality improvement based on evidence. This is also essential to meeting the current challenges of the healthcare delivery system.
This paper provides an update of low-value care recommendations for nurses based on Dutch guidelines from 2017 to 2023, specified to five healthcare sectors, including hospital care, district care, nursing home care, disability care and mental health care, with an accompanying prioritization of these low-value care recommendations to facilitate de-implementation. This paper provides a first overview of high-value care recommendations to reflect on and create alternative care practices for low-value care. The recommendations regarding low-value and high-value care are essential to generate a culture of continuous improvement of appropriateness based on evidence, finally leading to better quality of care and improving patient outcomes.
To compare contextual factors influencing discharge practices in three intensive care units (ICUs).
A prospective observational study.
Data were collected using a discharge process report form (DPRF) between May and September 2023. Descriptive statistics were performed to analyse demographic and clinical data. One-way analysis of variance (ANOVA) was used to test the time interval differences among the three sites.
Overall, 69 patients' discharge processes were observed. Among them, 41 (59%) experienced discharge delay, and 1 in 5 patients experienced after-hours discharge. There were statistically significant differences in mean hours in various time intervals during the discharge processes among the three sites. Patients in Hospital C waited the longest time (mean = 31.9 h) for the ward bed to be ready after the bed was requested and for being eventually discharged after ICU nurses to get them ready for discharge (mean = 26.7 h) compared to Hospital A and Hospital B.
We found that discharge delay and after-hours discharge were common and there were significant differences in mean hours of various time intervals during the discharge processes occurred among the three sites. The influence of contextual factors in different hospitals/ICU needs to be considered to improve the ICU discharge process.
Researchers and clinicians should consider targeted context-specific interventions and strategies to optimise patient discharge process from ICUs.
The study findings will inform the development of tailored interventions to reduce the discharge delay and after-hours discharge and, in turn, improve the quality and safety of patient care and health service efficiency.
The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines.
Patients' discharge processes were observed, and consumer representatives were involved in the study design.