Single-centre, double-blinded, randomised placebo-controlled trial to determine the effect of a 12-week home-based programme of footplate neuromuscular electrical stimulation on walking capacity in people with peripheral artery disease: a protocol for the Foot-PAD trial

Introduction
Patients with peripheral artery disease (PAD) can experience intermittent claudication, which limits walking capacity and the ability to undertake daily activities. While exercise therapy is an established way to improve walking capacity in people with PAD, it is not feasible in all patients. Neuromuscular electrical stimulation (NMES) provides a way to passively induce repeated muscle contractions and has been widely used as a therapy for chronic conditions that limit functional capacity. Preliminary trials in patients with PAD demonstrate that stimulation of the leg muscles using a footplate-NMES device can be performed without pain and may lead to significant gains in walking capacity. Studies, to date, have been small and have not been adequately controlled to account for any potential placebo effect. Therefore, the current trial will compare the effect of a 12-week programme of footplate-NMES with a placebo-control on walking capacity (6 min walking distance) and other secondary outcomes in patients with PAD.

Methods and analysis
The Foot-PAD trial is a double-blinded, randomised placebo-controlled trial to determine the effect of a 12-week home-based programme of footplate NMES on walking capacity in people with PAD. This is a single-centre trial with numerous recruitment locations. A total of 180 participants with stable PAD and intermittent claudication will be randomly assigned (1:1 ratio) to receive either footplate-NMES (intervention condition) or footplate-placebo (control condition) for two 30 min periods each day for 12 weeks. The footplate-NMES device will deliver stimulation sufficient to induce contraction of the leg muscles and repeated plantar and dorsiflexion at the ankles. The footplate-placebo device will deliver a momentary low-intensity transient stimulation that is insufficient to induce contraction of the leg muscles. Outcomes will be assessed at baseline (week 0), mid-intervention (week 6), postintervention (week 12) and 6 weeks after the completion of the intervention (week 18). The primary outcome is walking capacity at week 12, measured as maximum walking distance during the 6 min walk test. Secondary outcomes will include pain-free walking distance during the 6 min walk test; pain-free and maximum walking time during a graded treadmill walking test; disease-specific quality of life (Intermittent Claudication Questionnaire), self-reported walking impairment (Walking Impairment Questionnaire) and accelerometer-derived physical activity levels. Exploratory outcomes will include the Ankle-Brachial Index; leg vascular function; perception of device-use experience and symptom monitoring throughout the trial using the Claudication Symptom Instrument and a pain Visual Analogue Scale.

Ethics and dissemination
The Foot-PAD trial has received ethics approval from the Human Research Ethics Committees of Queensland Health Metro North Hospital and Health Service (78962) and the University of the Sunshine Coast (A21659). Regardless of the study outcomes, the study findings will be published in peer-reviewed scientific journals and presented at scientific meetings.

Trial registration number
ACTRN12621001383853.

Leggi
Gennaio 2025

Subnational trends and inequalities of under-immunisation and zero-dose among children aged 12-23 months in Uganda: a national population-based cross-sectional study

Objective
Despite the Global Vaccine Action Plan’s goal of at least 90% vaccine coverage for all children, Uganda has made limited progress in vaccination over the past decade. The objective of this study was to examine the subnational trends in the prevalence and inequalities in under-immunisation and zero-dose among children aged 12–23 months in Uganda.

Study design
A retrospective national cross-sectional study.

Setting
Uganda

Participants
Uganda Demographic and Health Survey secondary data of only children aged 12–23 months. The samples selected for analyses were 1507 in 2006, 1409 in 2011 and 2650 children in 2016.

Outcome measure
The primary outcomes were under-immunisation and zero-dose vaccination.
Absolute and relative inequality measures were used in the analysis.

Results
From 2006 to 2016, the under-vaccination rate decreased by 21%, but remained high at 40.8%. The zero-dose vaccination rate dropped by 82%, affecting 1.2% of children in 2016. Subnational inequalities in under-vaccination increased over time with widening gaps between regions. While inequalities across wealth quintiles, maternal education levels and places of residence narrowed, children of mothers with lower education levels continued to have the highest under-vaccination rates. The rural–urban gap for zero-dose vaccination remained unchanged, with rural children disproportionately impacted.

Conclusion
While some progress was made in reducing under-vaccination rates in Uganda within the study period, no region achieved an under-vaccination rate below 20%. This indicates significant challenges in reaching the Sustainable Development Goal target of at least 80% immunisation coverage. Targeted interventions are necessary to improve healthcare access, enhance public health communication and strengthen the health system, particularly in underserved communities and among vulnerable populations.

Leggi
Gennaio 2025

Association of iron deficiency anemia with dental caries in the permanent first molars of children aged 7-12 years in Karachi, Sindh, Pakistan: protocol for an analytical cross-sectional study

Introduction
Iron deficiency anaemia (IDA) and dental caries are prevalent diseases among Pakistani children. Limited research has been done to explore their association with permanent teeth. Given the caries susceptibility of permanent first molars and their role in the development of ideal occlusion, this study aimed to estimate caries frequency in these molars and assess its association with IDA in 7–12 year-old children.

Methods and analysis
This analytical cross-sectional study will include 141 children aged 7–12 years visiting physicians in the paediatric OPD of Dr. Ruth K.M. Pfau, Civil Hospital Karachi. Using consecutive sampling, children who met initial screening criteria were further evaluated to determine eligibility for the study. Data collection will involve physical examinations (including weight and height), oral examinations (including the relevant oral hygiene and caries assessments) and laboratory examinations (including the prescribed tests). In addition, questions will be asked about sociodemographic characteristics, history of IDA, oral hygiene habits, smokeless tobacco use and the frequency of cariogenic dietary consumption. Exposure variable will include the presence of IDA, assessed using complete blood count, C-reactive protein and ferritin tests and treated as a dichotomous variable. Outcome variable will include dental caries in at least one permanent first molar, assessed using the Decayed, Missing, and Filled Teeth index and also treated as a dichotomous variable. Analysis will include Poisson regression with robust variance, reporting prevalence ratios with 95% CIs for the association of IDA and dental caries in the permanent first molars. Frequency of children with carious permanent first molars with 95% CIs will also be reported.

Ethics and dissemination
This research has been approved by ethical review committee of Aga Khan University (Reference number: 2024-9692-30593) and the institutional review board of Dow University of Health Sciences (IRB Reference: IRB-3556/DUHS/Approval/2024/196) before participant recruitment. Results will be disseminated through seminars and peer-reviewed publications.

Leggi
Gennaio 2025

Early prediction of long COVID-19 syndrome persistence at 12 months after hospitalisation: a prospective observational study from Ukraine

Objective
To identify the early predictors of a self-reported persistence of long COVID syndrome (LCS) at 12 months after hospitalisation and to propose the prognostic model of its development.

Design
A combined cross-sectional and prospective observational study.

Setting
A tertiary care hospital.

Participants
221 patients hospitalised for COVID-19 who have undergone comprehensive clinical, sonographic and survey-based evaluation predischarge and at 1 month with subsequent 12-month follow-up. The final cohort included 166 patients who had completed the final visit at 12 months.

Main outcome measure
A self-reported persistence of LCS at 12 months after discharge.

Results
Self-reported LCS was detected in 76% of participants at 3 months and in 43% at 12 months after discharge. Patients who reported incomplete recovery at 1 year were characterised by a higher burden of comorbidities (Charlson index of 0.69±0.96 vs 0.31±0.51, p=0.001) and residual pulmonary consolidations (1.56±1.78 vs 0.98±1.56, p=0.034), worse blood pressure (BP) control (systolic BP of 138.1±16.2 vs 132.2±15.8 mm Hg, p=0.041), renal (estimated glomerular filtration rate of 59.5±14.7 vs 69.8±20.7 mL/min/1.73 m2, p=0.007) and endothelial function (flow-mediated dilation of the brachial artery of 10.4±5.4 vs 12.4±5.6%, p=0.048), higher in-hospital levels of liver enzymes (alanine aminotransferase (ALT) of 76.3±60.8 vs 46.3±25.3 IU/L, p=0.002) and erythrocyte sedimentation rate (ESR) (34.3±12.1 vs 28.3±12.6 mm/h, p=0.008), slightly higher indices of ventricular longitudinal function (left ventricular (LV) global longitudinal strain (GLS) of 18.0±2.4 vs 17.0±2.3%, p=0011) and higher levels of Hospital Anxiety and Depression Scale anxiety (7.3±4.2 vs 5.6±3.8, p=0.011) and depression scores (6.4±3.9 vs 4.9±4.3, p=0.022) and EFTER-COVID study physical symptoms score (12.3±3.8 vs 9.2±4.2, p

Leggi
Gennaio 2025

Serial Paediatrics Omics Tracking in Myalgic Encephalomyelitis (SPOT-ME): protocol paper for a multidisciplinary, observational study of clinical and biological markers of paediatric myalgic encephalomyelitis/chronic fatigue syndrome in Australian adolescents aged 12-19 years

Introduction
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling condition that can affect adolescents during a vulnerable period of development. The underlying biological mechanisms for ME/CFS remain unclear and have rarely been investigated in the adolescent population, despite this period representing an age peak in the overall incidence. The primary objective of this is to provide a foundational set of biological data on adolescent ME/CFS patients. Data generated will be compared with controls and over several time points within each patient to potentially develop a biomarker signature of the disease, identify subsets or clusters of patients, and to unveil the pathomechanisms of the disease.

Methods and analysis
This protocol paper outlines a comprehensive, multilevel, longitudinal, observational study in paediatric ME/CFS. ME/CFS patients aged 12–19 years and controls will donate biosamples of urine, blood, and peripheral blood mononuclear cells for an in-depth omics profiling analysis (whole-genome sequencing, metabolomics and quantitative proteomics) while being assessed by gold-standard clinical and neuropsychological measures. ME/CFS patients will then be provided with a take-home kit that enables them to collect urine and blood microsamples during an average day and during days when they are experiencing postexertional malaise. The longitudinal repeated-measures study design is optimal for studying heterogeneous chronic diseases like ME/CFS as it can detect subtle changes, control for individual differences, enhance precision and boost statistical power. The outcomes of this research have the potential to identify biomarker signatures, aid in understanding the underlying mechanisms, and ultimately, improve the lives of children with ME/CFS.

Ethics and dissemination
This project was approved by the Royal Children’s Hospital’s Human Research Ethics Committee (HREC 74175). Findings from this study will be disseminated through peer-reviewed journal publications and presentations at relevant conferences. All participants will be provided with a summary of the study’s findings once the project is completed.

Leggi
Dicembre 2024