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Study design
This study was a non-randomised controlled pilot trial conducted between September 2021 and December 2022. This study was approved by the University of Southern Queensland (USQ) Human Research Ethics Committee (ethics application number: H21REA052) and registered with Australia and New Zealand Clinical trial registry (...
PMC9944478
Participants
LUPUS, RHEUMATISM
Participants were recruited through advertisement within a tertiary hospital rheumatology department and the Lupus New South Wales (NSW) association. Following initial screening, those who met the inclusion criteria and signed consent were included in the study. Inclusion criteria were age ≥ 18 years, diagnosis of SLE ...
PMC9944478
Interventions
RPE
Participants in the exercise group underwent an 8 week, 2 days per week, 45 min, individually supervised telehealth exercise program. All sessions were conducted in real-time on Zoom (Zoom Video Communications, Inc, CA, USA) by an AEP (i.e. SF delivered one session per week, and a trained research assistant delivered o...
PMC9944478
Outcomes
Baseline and post-intervention testing were conducted by a blinded investigator (SW), also an AEP. Self-reported questionnaires were sent to the participants to complete, and exercise tests were conducted in real-time on Zoom. Data were stored electronically on a university password-secured OneDrive folder.
PMC9944478
Pain and fatigue
fatigue, pain
An 11-point scale (e.g. 0 = no pain to 10 = maximum pain) was used to measure participants’ self-reported resting pain and fatigue. Lower scores indicate less pain and fatigue (lower scores are better). This scale has been visually adapted from the 10-point Borg RPE scale, with good reliability (0.898) and correlation ...
PMC9944478
Fatigue
fatigue, Fatigue
CHRONIC ILLNESS
The Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-F) was used to measure self-reported fatigue. Functional Assessment of Chronic Illness Therapy Fatigue Scale is reliable (α > 0.95) and has been validated in SLE (ρ 0.81).
PMC9944478
Quality of life
The RAND 36-Item Health Survey (version 1.0)
PMC9944478
Lower body endurance
A 30-second sit-to-stand (30sSTS) test was used to measure lower body muscular endurance because of its reliability in telehealth (ICC 0.989),
PMC9944478
Lower body strength
STS
A five-time STS (5TSTS) was used to measure lower body muscular strength because of its reliability in telehealth (ICC 0.990),
PMC9944478
Upper body endurance
A 30-second arm curl test (30sAC) was used to measure upper body muscular endurance because of its reliability in telehealth (ICC 0.992),
PMC9944478
Aerobic capacity
The 2 minute step test (2MST) was used to measure aerobic capacity because of its reliability in telehealth (ICC 0.999),
PMC9944478
Participant feedback
stroke
STROKE
Participants who completed the exercise program provided quantitative feedback about the telehealth-supervised exercise program via a face-validated questionnaire used by Galloway and colleagues in stroke,Post-intervention interview framework.
PMC9944478
Attendance
Attendance to the exercise intervention was calculated by taking the number of attended sessions as a percentage of the total number of scheduled sessions.
PMC9944478
Statistical analysis
The sample size was calculated using SF36 fatigue/energy domain results from Tench (2003)
PMC9944478
Results
PMC9944478
Participant characteristics
chronic illness, fatigue, pain
CHRONIC ILLNESS
Fifteen adults with SLE expressed interest in the study and were all eligible (control group Demographic characteristics and baseline data for the two groups.RHR: resting heart rate; Rpain: resting pain; Rfatigue: resting fatigue; FACIT-F: functional assessment of chronic illness therapy (fatigue measurement system); 5...
PMC9944478
Quantitative results
PMC9944478
Fatigue (FACIT-F)
There was no statistically significant difference between the exercise and control group (
PMC9944478
Lower body strength (5TSTS)
There was no statistically significant difference between the exercise and control group for lower body strength (
PMC9944478
Lower body endurance (30sSTS)
There was no statistically significant difference between the exercise and control group for lower body endurance (
PMC9944478
Upper body endurance (30sAC)
There was no statistically significant difference between the exercise and control group for upper body endurance (
PMC9944478
Aerobic capacity (2MST)
There was no statistically significant difference between the exercise and control group for aerobic capacity (
PMC9944478
Participant feedback
Participants either strongly agreed or agreed that Zoom was easy to learn and use after the first few sessions. Participants strongly disagreed that they needed someone at home to help them use the system, strongly agreed they were able to use the system by themselves, and rated the audio and video quality as acceptabl...
PMC9944478
Attendance
UTI
Attendance to the exercise program was high (110/112, 98%), with two sessions missed: one due to general malaise, and the other due to a suspected UTI.
PMC9944478
Qualitative results
PMC9944478
Discussion
stroke, fatigue
STROKE, DISEASE, RECRUITMENT
Our main qualitative and quantitative findings suggest that an individually telehealth-supervised exercise program was suitable to and well-accepted by adults with SLE. However, due to a limited number of participants and the possibility that they were more likely to be motivated to exercise and/or have more stable dis...
PMC9944478
ORCID iD
Stephanie Frade
PMC9944478
References
PMC9944478
Objectives
rheumatoid arthritis, RA-ILD
RHEUMATOID ARTHRITIS, INTERSTITIAL LUNG DISEASE, PULMONARY FIBROSIS
Some patients with rheumatoid arthritis develop interstitial lung disease (RA-ILD) that develops into progressive pulmonary fibrosis. We assessed the efficacy and safety of nintedanib versus placebo in patients with progressive RA-ILD in the INBUILD trial.
PMC10412475
Methods
reticular abnormality, fibrosing ILD, pulmonary fibrosis
PULMONARY FIBROSIS, TRACTION BRONCHIECTASIS
The INBUILD trial enrolled patients with fibrosing ILD (reticular abnormality with traction bronchiectasis, with or without honeycombing) on high-resolution computed tomography of >10% extent. Patients had shown progression of pulmonary fibrosis within the prior 24 months, despite management in clinical practice. Subje...
PMC10412475
Results
In the subgroup of 89 patients with RA-ILD, the rate of decline in FVC over 52 weeks was −82.6 mL/year in the nintedanib group versus −199.3 mL/year in the placebo group (difference 116.7 mL/year [95% CI 7.4, 226.1]; nominal
PMC10412475
Supplementary Information
The online version contains supplementary material available at 10.1007/s10067-023-06623-7.
PMC10412475
Keywords
PMC10412475
Introduction
rheumatoid arthritis, RA, ILD
RHEUMATOID ARTHRITIS, INTERSTITIAL LUNG DISEASE
Interstitial lung disease (ILD) may occur as a manifestation of rheumatoid arthritis (RA) [Disease-modifying anti-rheumatic drugs (DMARDs) and glucocorticoids are the standard of care for RA [
PMC10412475
Methods
PMC10412475
Trial design
USUAL INTERSTITIAL PNEUMONIA
The INBUILD trial (NCT02999178) was a randomised, double-blind, placebo-controlled trial conducted in 15 countries [Patients were randomised to receive nintedanib 150 mg twice daily (bid) or placebo, stratified by fibrotic pattern on HRCT (usual interstitial pneumonia [UIP]-like fibrotic pattern or other fibrotic patte...
PMC10412475
Outcomes
We assessed the rate of decline in FVC (mL/year) over 52 weeks in all patients with RA-ILD, in subgroups of patients with RA-ILD based on high sensitivity C-reactive protein (hs-CRP) at baseline (<1 vs ≥1 mg/L; <3 vs ≥3 mg/L) and in patients with RA-ILD taking DMARDs and/or glucocorticoids at baseline. DMARDs were iden...
PMC10412475
Analyses
REGRESSION
Analyses were based on data from patients who received ≥1 dose of trial drug. The rate of decline in FVC (mL/year) over 52 weeks was analysed in patients with RA-ILD using a random coefficient regression model (with random slopes and intercepts) including baseline FVC (mL), HRCT pattern (UIP-like fibrotic pattern or ot...
PMC10412475
Results
PMC10412475
Patients
RA, RA-ILD
Of 663 patients in the INBUILD trial, 89 (13.4%) had RA-ILD. The RA diagnosis was confirmed by a rheumatologist in 83 of the 84 patients for whom these data were available. The baseline characteristics of the patients with RA-ILD have been described [
PMC10412475
Exposure to medications
Median exposure to trial drug over the whole trial was 17.4 months in both groups. Based on medications taken at baseline, during treatment with trial drug, or following discontinuation of trial drug, the immunomodulatory therapies that were restricted at baseline were taken by higher proportions of patients in the pla...
PMC10412475
Acute exacerbations, hospitalisations, progression of ILD, and death
EVENT
Time to event endpoints over the whole trial are shown in Table
PMC10412475
Safety and tolerability
diarrhoea
ADVERSE EVENTS, ADVERSE EVENT, ADVERSE EVENT
The most common adverse event reported in these patients with RA-ILD was diarrhoea, which was reported in 61.9% of patients in the nintedanib group and 27.7% of patients in the placebo group (Table Adverse events in patients with RA-ILD in the INBUILD trialBased on adverse events reported between first trial drug intak...
PMC10412475
Discussion
fibrosing RA-ILD, RA, IPF, inflammation
ADVERSE EVENTS, DISEASE PROGRESSION, ADVERSE EVENT, INFLAMMATION
These data from the INBUILD trial show that nintedanib reduced the rate of decline in FVC over 52 weeks in patients with progressive fibrosing RA-ILD by 59% compared with placebo, similar to the relative treatment effect observed in the overall trial population [Decline in FVC in patients with ILDs is reflective of dis...
PMC10412475
Conclusions
fibrosing RA-ILD
ADVERSE EVENTS
In the INBUILD trial, nintedanib slowed the rate of decline in FVC in patients with progressive fibrosing RA-ILD, with adverse events that were largely manageable. The efficacy and safety of nintedanib in these patients were consistent with the overall trial population.
PMC10412475
Acknowledgements
We thank the patients who participated in the INBUILD trial.
PMC10412475
Author contribution
HM, LM, and MK contributed to the study conception and design. MK contributed to data collection. HM conducted the data analysis. All authors were involved in interpretation of the data and the writing and critical review of the manuscript. All authors and read and approved the final manuscript.
PMC10412475
Funding
The INBUILD trial was supported by Boehringer Ingelheim International GmbH (BI). The authors did not receive payment for development of this manuscript. Writing assistance was provided by Elizabeth Ng and Wendy Morris of FleishmanHillard, London, UK, which was contracted and funded by BI.
PMC10412475
Data availability
To ensure independent interpretation of clinical study results and enable authors to fulfill their role and obligations under the ICMJE criteria, Boehringer Ingelheim grants all external authors access to relevant clinical study data. In adherence with the Boehringer Ingelheim Policy on Transparency and Publication of ...
PMC10412475
Compliance with ethical standards
PMC10412475
Ethics approval
The INBUILD trial was conducted in accordance with the protocol, the principles of the Declaration of Helsinki, and the Harmonised Tripartite Guideline for Good Clinical Practice from the International Conference on Harmonisation and was approved by local authorities.
PMC10412475
Consent to participate
Written informed consent was obtained from all patients before study entry.
PMC10412475
Consent for publication
All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.
PMC10412475
Competing Interests
Arthritis, Musculoskeletal
ARTHRITIS, SKIN DISEASES
Eric L Matteson reports royalties from UpToDate; consulting fees from Alvotech and Boehringer Ingelheim (BI); fees for speaking from BI and Practice Point Communications; has participated on Data Safety Monitoring Boards or Advisory Boards for Horizon Therapeutics and the National Institutes of Health (NIH)/National In...
PMC10412475
References
PMC10412475
Background
OSA, preeclampsia
HIGH-RISK PREGNANCY, OBSTRUCTIVE SLEEP APNEA, PREECLAMPSIA
Obstructive sleep apnea (OSA) during pregnancy is a risk factor for preeclampsia possibly through a link to placental physiology. This study evaluates the efficacy of continuous positive airway pressure (CPAP) on the modulation of blood pressure and the reduction in preeclampsia in women with high-risk pregnancy and OS...
PMC10294320
Methods
obesity, gestational diabetes, OSA, respiratory disturbance, preeclampsia, diabetes
OBESITY, GESTATIONAL DIABETES, HYPERTENSION, PREECLAMPSIA, DIABETES
A multicenter open-label, randomized controlled trial comparing CPAP treatment versus usual antenatal care was conducted in three academic hospitals in Bangkok, Thailand. Participants included singleton pregnant women aged older than 18 years with any high-risk condition (i.e., chronic hypertension, obesity, history of...
PMC10294320
Results
Of 340 participants, 96.5% were recruited during the first trimester. Thirty participants were later excluded leaving 153 and 157 participants in the CPAP and usual-care groups for the modified-intention-to-treat analysis. CPAP adherence rate was 32.7% with average use of 2.5 h/night. Overall, CPAP treatment significan...
PMC10294320
Supplementary Information
The online version contains supplementary material available at 10.1186/s12931-023-02445-y.
PMC10294320
Keywords
PMC10294320
Background
oxygen desaturation, OSA, Preeclampsia, arousals, reduction of blood pressure
COLLAPSE, PREECLAMPSIA, ENDOTHELIAL DYSFUNCTION
Preeclampsia is a leading cause of maternal and fetal morbidity and mortality [OSA is characterized by repetitive upper airway collapse during sleep leading to apneas/hypopneas, causing oxygen desaturation, arousals, sympathetic activation, and endothelial dysfunction [Although, continuous positive airway pressure (CPA...
PMC10294320
Methods
PMC10294320
Study design and oversight
We conducted a multicenter, open-label, parallel-group RCT at three academic hospitals in Bangkok, Thailand. Methodologic details of the design and analysis plan have been registered via ClinicalTrial.gov (NCT03356106) and are provided in the full protocol in the supplement (the Additional file
PMC10294320
Patients and procedures
obesity, hypopneas, chronic infection, cardiac or kidney disease, oxygen desaturation, OSA, hypertension, preeclampsia
OBESITY, CHRONIC INFECTION, THYROID DISEASE, HIV INFECTION, TUBERCULOSIS, NEUROMUSCULAR DISEASE, GESTATIONAL HYPERTENSION, SLEEP; APNEA, HYPERTENSION, PREECLAMPSIA
Pregnant women attending antenatal care at all collaborating hospitals were recruited for OSA screening if they met all of the following inclusion criteria: (1) singleton high-risk pregnant woman aged > 18 years without significant medical conditions (separate from those used as inclusion criteria), including immunocom...
PMC10294320
Randomization and interventions
Randomization was stratified by trimesters with varying block sizes of 4–8. After each participant agreed to participate and signed informed consent, clinical data were entered into a centralized computer system for automatic randomization sequence generation and subsequent immediate allocation. Participants receiving ...
PMC10294320
Study measurements
HYPERTENSION IN PREGNANCY, SECONDARY, PREGNANCY COMPLICATIONS
Data were collected during GA 18–20, 24–28, 32–34 weeks during regular scheduled antenatal care and delivery using case record forms that captured demographic data, sleep questionnaires, primary and secondary endpoints, and CPAP adherence. BP measurements by sphygmomanometer were obtained twice on both arms in resting-...
PMC10294320
Study endpoints
GDM
HYPERTENSIVE DISORDER, GESTATIONAL HYPERTENSION, GDM, PREECLAMPSIA
The primary outcomes were systolic (SBP) and diastolic BP (DBP) measured during the scheduled antenatal care visit (between 10 am–12 pm) during each specific gestational time-point. For participants randomized during the 2nd-trimester, only outcome data after randomization was included for analyses. Secondary outcomes ...
PMC10294320
Statistical analysis
OSA
Sample size was calculated based on a 1:1 ratio of CPAP- and usual-care groups, assuming the BP lowering-effect of CPAP in the general population with OSA was 2.5 mmHg (from meta-analysis data) [Data were described using mean and SD or median and interquartile range (IQR) as appropriate for continuous variables, and pe...
PMC10294320
Results
PMC10294320
Adherence to intervention
Overall, the intervention group had mean average-CPAP use of 2.5 (SD 2.5) and median of 1.7 (IQR 0.2, 4.5) hours/night; only 50 (32.7%) participants were adherent to treatment (defined as average-CPAP use ≥ 4 h/night). The minimum, maximum, and 90th percentile pressures of auto-CPAP were 4.9 (1.3), 8.2 (1.8), and 6.3 (...
PMC10294320
Post-hoc analyses
PMC10294320
Subgroup analysis for mild OSA/upper airway resistance syndrome (UARS) and OSA
OSA [
Although all participants had RDI ≥ 5 events/hour, those with AHI < 5 were classified as mild OSA/UARS and those with AHI ≥ 5 events/hour were classified as OSA [
PMC10294320
Subgroup analysis excluding participants randomized during 2nd trimester
OSA
HYPERTENSIVE DISORDER
Analyses excluding participants with new-onset OSA randomized during the 2nd-trimester also demonstrated significant results for CPAP treatment on reductions of BP and incidence of hypertensive disorders in pregnancy (Additional file
PMC10294320
Discussion
hypoxia, apnea/hypopnea, heterogeneous disorder, OSA, mild/moderate OSA, preeclampsia
PREECLAMPSIA, HIGH-RISK PREGNANCIES, HYPOXIA, PREECLAMPSIA, HYPERTENSIVE DISORDER, HIGH-RISK PREGNANCY
We conducted an RCT of high-risk pregnant women with mild/moderate OSA (RDI IQR 5–29.8 and AHI IQR 4–13) to assess the efficacy of CPAP in reducing BP and gestational hypertensive disorders. Our findings indicate that CPAP significantly reduced BP, with larger effects on DBP and MAP than SBP. Results were robust for al...
PMC10294320
Acknowledgements
Nongluck
We would like to express our deepest gratitude towards Professor Christian Guilleminault for the initiatives of the project. We thank Associate Professor Naiphinich Kotchabahakdi for the advice on the grant; the research assistant team including Poompoung Chirakool, Punnee Phongchiewboon, Wimolwan Suksaran, Yaovarit Le...
PMC10294320
Author contributions
WS, JP, Werapath
VT initiated the study, led the work on the study design and had the responsibility for running the study, collecting the data, and was involved in analyzing and interpreting the data. VT also drafted and edited the manuscript. AI is the manuscript’s guarantor. AI was involved in the study conceptualization, initiation...
PMC10294320
Funding
This work received main funding from The National Research Council of Thailand and supplementary funding from The Development Potentials of Thai People Project, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
PMC10294320
Availability of data and materials
Available from the corresponding author on reasonable request.
PMC10294320
Declarations
PMC10294320
Ethics approval and consent to participate
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committees and with the 1964 Helsinki declaration and its later amendments (subjects read and signed a dedicated consent form). Ethics committee approval numbers of the Institutio...
PMC10294320
Consent for publication
Not applicable.
PMC10294320
Competing interests
The authors declare no competing interests.
PMC10294320
References
PMC10294320
Abstract
Preliminary results of this study were presented to the 14th Virtual Congress of the European-African Hepato-Pancreato-Biliary Association, September 2021.
PMC10077024
Background
postoperative pancreatic fistula
The potential of haemostatic patches to reduce the rate of postoperative pancreatic fistula remains unclear. The aim of this trial was to evaluate the impact of a polyethylene glycol-coated haemostatic patch on the incidence of clinically relevant postoperative pancreatic fistula after pancreatoduodenectomy.
PMC10077024
Methods
postoperative pancreatic fistula
SECONDARY, COMPLICATION
In this randomized, single-centre, clinical trial, patients undergoing pancreatoduodenectomy were randomized 1 : 1 to receive pancreatojejunostomy reinforced with two polyethylene glycol-coated haemostatic patches (patch group) or without any reinforcement (control group). The primary outcome was clinically relevant po...
PMC10077024
Results
postoperative pancreatic fistula
MAY
From 15 May 2018 to 22 June 2020, 72 patients were randomized, and 64 were included in the analyses (31 in the patch group and 33 in the control group). The risk of clinically relevant postoperative pancreatic fistula was reduced by 90 per cent (OR 0.10, 95 per cent c.i. 0.01 to 0.89,
PMC10077024
Conclusions
postoperative pancreatic fistula
A polyethylene glycol-coated haemostatic patch reduced the incidence of clinically relevant postoperative pancreatic fistula after pancreatoduodenectomy.
PMC10077024
Registration number
fistula, postoperative pancreatic fistula
NCT03419676 (Hemopatch™ significantly reduced the incidence of clinically relevant postoperative pancreatic fistula in patients who underwent a pancreatoduodenectomy. The effectiveness of the patch was related to the fistula risk score.
PMC10077024
Introduction
Postoperative pancreatic fistula, PD, POPF
PATHOLOGY, SEQUELAE
Postoperative pancreatic fistula (POPF) is a common condition with incidences ranging from 13 to 41 per cent, and remains the most important and challenging determinant of postoperative morbidity and mortality after pancreatoduodenectomy (PD)Identifying patients at risk of having POPF, as well as predicting its develop...
PMC10077024
Methods
PMC10077024
Study design
This study was conducted in accordance with the Declaration of Helsinki (as revised in 2013), performed according to CONSORT guidelines
PMC10077024
Participants
PD
TUMOURS, DISEASES, CHRONIC PANCREATITIS, ACUTE NECROTIZING PANCREATITIS
This study assessed for eligibility consecutive patients selected for undergoing PD with benign or malignant periampullary tumours or benign diseases (that is chronic pancreatitis) with a pancreatojejunostomy (PJ) reconstruction, male and female patients, between 18 and 80 years of age, with an ASA Physical Status Clas...
PMC10077024
Surgical procedure
PD, pancreatic head and uncinate process
A standard open PD, using a reconstruction in two loops and a PJ, was performed by three surgeons with more than 10 years of experience in pancreatic surgery. Operative technique, patch placement, and drainage were standardized between the three surgeons. PD was performed without pylorus preservation. The pancreatic he...
PMC10077024
Intraoperative and postoperative management
According to the Enhanced Recovery After Surgery guideline recommendations for PD
PMC10077024
Intervention
bleeding
BLEEDING
In the patch group, two PEG-coated, collagen-based, haemostatic patches (Hemopatch™ Sealing Hemostat, Baxter Aktiengesellschaft, Vienna, Austria) with a size of 9 × 4.5 cm per patch were used in each patient. The objective was to place one patch underside and another one anterior, once the anastomosis was completed, ac...
PMC10077024
Use of drains and postoperative pancreatic fistula assessment
In both groups, a silastic Penrose
PMC10077024
Outcome measures
The primary outcome was the incidence rate of CR-POPF within 90 days defined according to the ISGPS criteria
PMC10077024
Sample size
PD
An observational study was carried out for patients undergoing PD in our institution and indicated a baseline 31 per cent CR-POPF rate. According to power calculations, 62 patients (31 per group) were required to show a decrease in CR-POPF rate from 31 to 5 per cent with 80 per cent power and two-tailed 5 per cent sign...
PMC10077024
Randomization
PD
BLIND
Patients were randomized on a 1 : 1 basis during surgery by the minimization method (preferred treatment probability 0.9), after resection but before anastomosis, to either PEG-coated patch application (patch group) or no patch (control group). Randomization was done by blocks of 10 patients, using a secure, internet-b...
PMC10077024