Effect of a 12-week high-intensity exercise intervention: a comparison of cardiac exercise adaptations during biological disease-modifying antirheumatic drug treatment (TNF inhibitors vs IL-6 signalling inhibitors) in patients with rheumatoid arthritis – study protocol for a randomised controlled trial

Introduction
The chronic inflammatory state in rheumatoid arthritis (RA) augments the risk of cardiovascular disease (CVD), with pro-inflammatory cytokines tumour necrosis factor (TNF) and interleukin 6 (IL-6) playing a vital role. Consequently, biological disease-modifying antirheumatic drugs (bDMARDs) may attenuate that risk. IL-6 is also a myokine, secreted from exercising skeletal muscles, where IL-6 exhibits anti-inflammatory effects that may ameliorate the risk of CVD. In healthy humans treated with IL-6 signalling inhibitors (IL-6i), exercise induced loss of visceral fat mass and cardiac adaptations were abolished. We hypothesise that IL-6 signalling inhibition will impair the cardiac and metabolic adaptions to exercise training compared with TNF inhibition in RA patients.

Methods and analysis
80 RA patients treated with IL-6i (n=40) or TNF inhibitors (n=40) are included in a 12-week randomised investigator-blinded 4×4 min high-intensity interval training (HIIT) study. Patients are stratified for medical treatment and sex and allocated 1:1 to an exercise or a no exercise control group (four groups). The supervised exercise intervention comprises 3 weekly HIIT sessions on an ergometer bicycle. The primary outcome is the change in left ventricular mass (LVM), and key secondary outcome is change in visceral fat mass. Both outcomes are measured by MRI. Primary statistical analysis will evaluate LVM at follow-up in a regression model. Intention-to-treat and per protocol analyses will be conducted. The latter necessitates a minimum attendance rate of 80%, adherence to bDMARDs treatment of ≥80% and minimum 8 min (50%) of maximal heart rate above 85% per session.

Ethics and dissemination
The study has been approved by the Capital Region Ethics Committee (H-21010559 amendments 86424, 87463 and 88044) and the Danish Medicines Agency (2021-b005287-21). The trial will follow ICH-GCP guidelines. Regardless of outcome, results will be published in relevant peer-reviewed journals.

Trial registration numbers
Eudra-CT: 2021-b005287-21 and NCT05215509.

Leggi
Maggio 2023

A predictive modelling approach to illustrate factors correlating with stunting among children aged 12-23 months: a cluster randomised pre-post study

Objective
The aim of this study was to construct a predictive model in order to develop an intervention study to reduce the prevalence of stunting among children aged 12–23 months.

Design
The study followed a cluster randomised pre-post design and measured the impacts on various indicators of livelihood, health and nutrition. The study was based on a large dataset collected from two cross-sectional studies (baseline and endline).

Setting
The study was conducted in the north-eastern region of Bangladesh under the Sylhet division, which is vulnerable to both natural disasters and poverty. The study specifically targeted children between the ages of 12 and 23 months.

Main outcome measures
Childhood stunting, defined as a length-for-age z-score

Leggi
Aprile 2023

Long-term psychosocial consequences of false-positive screening mammography: a cohort study with follow-up of 12-14 years in Denmark

Objective
To compare the long-term psychosocial consequences of mammography screening among women with breast cancer, normal results and false-positive results.

Design
A matched cohort study with follow-up of 12–14 years.

Setting
Denmark from 2004 to 2019.

Participants
1170 women who participated in the Danish mammography screening programme in 2004–2005.

Intervention
Mammography screening for women aged 50–69 years.

Outcome measures
We assessed the psychosocial consequences with the Consequences Of Screening–Breast Cancer, a condition-specific questionnaire that is psychometrically validated and encompasses 14 psychosocial dimensions.

Results
Across all 14 psychosocial outcomes, women with false-positive results averagely reported higher psychosocial consequences compared with women with normal findings. Mean differences were statistically insignificant except for the existential values scale: 0.61 (95% CI (0.15 to 1.06), p=0.009). Additionally, women with false-positive results and women diagnosed with breast cancer were affected in a dose–response manner, where women diagnosed with breast cancer were more affected than women with false-positive results.

Conclusion
Our study suggests that a false-positive mammogram is associated with increased psychosocial consequences 12–14 years after the screening. This study adds to the harms of mammography screening. The findings should be used to inform decision-making among the invited women and political and governmental decisions about mammography screening programmes.

Leggi
Aprile 2023

C reactive protein-guided prescription of antibiotics for children under 12 years with respiratory symptoms in Kyrgyzstan: protocol for a randomised controlled clinical trial with 14 days follow-up

Introduction
While lower respiratory tract infections are the main cause of death for children under 5 globally, only a small proportion of children with respiratory tract infections need antibiotics. Overuse of antibiotics globally is leading to increasing rates of antibiotic resistance. In Kyrgyzstan, healthcare workers regularly prescribe antibiotics when clinical uncertainty is present to err on the side of caution. Targeting antibiotic use with biomarkers of inflammation such as C reactive protein (CRP) testing at the point-of-care test (POCT) has been shown to reduce antibiotic use in general, but only few studies have been done in children and no studies exist from Central Asia. This study aims to assess whether the use of a CRP POCT can safely decrease prescription of antibiotics for children with acute respiratory symptoms in primary level healthcare centres in Kyrgyzstan.

Methods and analysis
Multicentre, open-label, individually randomised, controlled clinical trial with 14 days follow-up (follow-up by phone on days 3, 7 and 14) in rural lowland Chui and highland Naryn regions of Kyrgyzstan. The population are children aged 6 months to 12 years attending the primary level healthcare centres during normal business hours with acute respiratory symptoms. CRP POCT equipment will be supplied to healthcare centres, along with a short training session in CRP use, including the interpretation of results to support the clinical evaluation of the child with acute respiratory infection. The primary outcomes are the proportion of patients prescribed an antibiotic within 14 days of index consultation (superiority analysis) and days to recovery (non-inferiority analysis). Secondary outcomes are antibiotics prescribed at index consultation, reconsultations, hospital admission and vital status within 14 days. Analysis of the first primary outcome, antibiotic use, will be intention to treat using a logistic regression model. Analysis of the second primary outcome, days to recovery, will be per protocol using a linear regression model and a non-inferiority margin of 1 day.

Ethics and dissemination
The study was approved on 18 June 2021 by the Ethics Committee (ref: no. 1) of the National Centre of Maternity and Childhood Care, Bishkek, Kyrgyzstan. The results of the study regardless of the conclusion will be presented at international conferences and published in peer-reviewed scientific medical journals along with policy briefs and technical reports.

Trial registration number
NCT05195866.

Leggi
Aprile 2023

IMPROVEMENT IN BOWEL URGENCY IS ASSOCIATED WITH STOOL FREQUENCY AND RECTAL BLEEDING REMISSION AT 12 AND 52 WEEKS IN PATIENTS WITH MODERATELY-TO-SEVERELY ACTIVE ULCERATIVE COLITIS

Mirikizumab, an anti-IL23p19 antibody, has demonstrated safety and efficacy versus placebo across clinical remission, symptomatic remission, and endoscopic and histologic endpoints in patients with moderately-to-severely active ulcerative colitis (UC) in a Phase 3, double-blind, 12-week induction study (LUCENT-1/NCT03518086) and 40-week maintenance study (LUCENT-2/NCT03524092). Here, we examine the relationship between bowel urgency (BU) clinically meaningful improvement (CMI) and BU remission with rectal bleeding (RB) remission and stool frequency (SF) remission (Table 1 for definitions).

Leggi
Marzo 2023

Course of fear of falling after hip fracture: findings from a 12-month inception cohort

Objectives
To examine the course of fear of falling (FoF) up to 1 year after hip fracture, including the effect of prefracture FoF on the course.

Design
Observational cohort study with assessment of FoF at 6, 12 and 52 weeks after hip fracture.

Setting
Haaglanden Medical Centre, the Netherlands.

Participants
444 community-dwelling adults aged 70 years and older, admitted to hospital with a hip fracture.

Main outcome measure
Short Falls Efficacy Scale International (FES-I), with a cut-off score ≥11 to define elevated FoF levels.

Results
Six weeks after hip fracture the study population-based mean FES-I was located around the cut-off value of 11, and levels decreased only marginally over time. One year after fracture almost one-third of the population had FoF (FES-I ≥11). Although the group with prefracture FoF (42.6%) had slightly elevated FES-I levels during the entire follow-up, the effect was not statistically significant. Patients with persistent FoF at 6 and 12 weeks after fracture (26.8%) had the highest FES-I levels, with a mean well above the cut-off value during the entire follow-up. For the majority of patients in this group, FoF is still present 1 year after fracture (84.9%).

Conclusions
In this study population, representing patients in relative good health condition that are able to attend the outpatient follow-up at 6 and 12 weeks, FoF as defined by an FES-I score ≥11 was common within the first year after hip fracture. Patients with persistent FoF at 12 weeks have the highest FES-I levels in the first year after fracture, and for most of these patients the FoF remains. For timely identification of patients who may benefit from intervention, we recommend structural assessment of FoF in the first 12 weeks after fracture.

Leggi
Marzo 2023

Determinants of childhood vaccination among children aged 12-23 months in Ethiopia: a community-based cross-sectional study

Objective
Childhood vaccination is a cost-effective, essential service to reach a larger population globally. Due to unclear reasons, new emergence and resurgence of vaccine-preventable diseases increase. Thus, the aim of this study is to identify prevalence and determinants of childhood vaccination in Ethiopia.

Design
Community-based cross-sectional study.

Setting
We used data from 2019 Ethiopia Mini Demographic and Health Survey. The survey included all the nine regional states and two city administrations of Ethiopia.

Participants
A weighted sample of 1008 children 12–23 months of age was included in the analysis.

Main outcome measures
A multilevel proportional odds model was fitted to identify determinants of childhood vaccination status. In the final model, variables with a p value of less than 5% and an adjusted OR (AOR) with a 95% CI were reported.

Result
The full childhood vaccination coverage of Ethiopia was 39.09% (95% CI: 36.06%–42.28%). Mothers who attended primary (AOR=2.16; 95% CI: 1.43–3.26), secondary (AOR=2.02; 95% CI: 1.07–3.79) and higher education (AOR=2.67; 95% CI: 1.25–5.71); being in union (AOR=2.21; 95% CI: 1.06–4.58); kept vaccination cards (AOR=26.18; 95% CI: 15.75–43.53); children receiving vitamin A1 (AOR=4.14; 95% CI: 2.9–5.9); living in Afar (AOR=0.14; 95% CI: 0.04–0.45), Somali (AOR=0.19; 95% CI: 0.06–0.60), Gambela (AOR=0.22; 95% CI: 0.06–0.77), Harari (AOR=0.14; 95% CI: 0.04–0.52) and Dire Dawa (AOR=0.23; 95% CI: 0.06–0.79) regions; and rural residents (AOR=0.53; 95% CI: 0.30–0.93) were factors significantly associated with childhood vaccination.

Conclusion
The full childhood vaccination coverage in Ethiopia was low and remained unchanged since 2016. The study identified that both the individual-level and community-level factors affected the vaccination status. Accordingly, public health interventions targeted to these identified factors can increase childhood full vaccination status.

Leggi
Marzo 2023

Comparison Of 3-6 Month Versus 12 Month Dual Antiplatelet Therapy After Coronary Intervention Using the Contemporary Drug-eluting Stents With Ultrathin Struts: The HOST-IDEA Randomized Clinical Trial

Circulation, Ahead of Print. Background:Limited data are available on short-term dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) using third-generation drug-eluting stents (DES) with ultrathin struts and advanced polymer technology. We investigated whether 3-6 month DAPT was non-inferior to 12 month one after implantation of DES with ultrathin struts and advanced polymer technology.Methods:We performed an open-label, randomized trial at 37 centers in South Korea. We enrolled patients undergoing PCI using the Orsiro biodegradable-polymer sirolimus-eluting stents (SES) or the Coroflex ISAR polymer-free SES. Patients with ST-segment elevation myocardial infarction were excluded. Patients were randomized to receive either 3-6 month or 12 month DAPT after PCI. The choice of antiplatelet medications was at the physician’s discretion. The primary outcome was a net adverse clinical event (NACE), a composite of cardiac death, target vessel myocardial infarction (TVMI), clinically driven target lesion revascularization (CD-TLR), stent thrombosis, or major bleeding, defined as Bleeding Academic Research Consortium type 3 or 5 at 12 months. The major secondary outcomes were target lesion failure (TLF), a composite of cardiac death, TVMI, CD-TLR, and major bleeding.Results:A total of 2,013 patients (mean age 65.7±10.5, 1,487 male [73.9%], 1,110 [55.1%] presented with acute coronary syndrome) were randomized to 3-6 month DAPT (n=1,002) or 12 month DAPT (n=1,011). The primary outcome occurred in 37 (3.7%) patients in the 3-6 month DAPT group and 41 (4.1%) in the 12 month DAPT group. The non-inferiority of the 3-6 month DAPT group to the 12 month DAPT group was met (absolute risk difference, -0.4% [1-sided 95% confidence interval (CI), -∞% to 1.1%; P

Leggi
Marzo 2023