IntroductionHip osteoarthritis (OA) is the leading cause for total hip arthroplasty (THA). Although, being considered as the surgery of the century up to 23% of the patients report long-term pain, ...and deficits in physical function and muscle strength may persist after THA. Progressive resistance training (PRT) appears to improve multiple outcomes moderately in patients with hip OA. Current treatment selection is based on low-level evidence as no randomised controlled trials have compared THA to non-surgical treatment. The primary aim of this trial is to investigate whether THA followed by standard care is superior to 12 weeks of supervised PRT followed by 12 weeks of optional unsupervised PRT for improving hip pain and function in patients with severe hip OA.Methods and analysisThis is a protocol for a multicentre, parallel-group, assessor-blinded, randomised controlled superiority trial conducted at four hospitals across three healthcare regions in Denmark. 120 patients aged ≥50 years with clinical and radiographic hip OA found eligible for THA by an orthopaedic surgeon will be randomised to THA followed by standard care, or 12 weeks of PRT (allocation 1:1). The primary outcome will be change in patient-reported hip pain and function, measured using the Oxford Hip Score, from baseline to 6 months after initiating the treatment. Key secondary outcomes will be change in the Hip disability and Osteoarthritis Outcome Score subscales, University of California Los Angeles Activity Score, 40 m fast-paced walk test, 30 s chair stand test and occurrence of serious adverse events. Patients declining participation in the trial will be invited into a prospective observational cohort study.Ethics and disseminationThe trial has been approved by The Regional Committees on Health Research Ethics for Southern Denmark (Project-ID: S-20180158). All results will be presented in peer-reviewed scientific journals and international conferences.Trial registration numberClinicalTrials.gov (NCT04070027).
Background Early diagnosis of cerebral palsy (CP) is important to enable intervention at a time when neuroplasticity is at its highest. Current mean age at diagnosis is 13 months in Denmark. Recent ...research has documented that an early-diagnosis set-up can lower diagnostic age in high-risk infants. The aim of the current study is to lower diagnostic age of CP regardless of neonatal risk factors. Additionally, we want to investigate if an early intervention program added to standard care is superior to standard care alone. Methods The current multicentre study CP-EDIT (Early Diagnosis and Intervention Trial) with the GO-PLAY intervention included (Goal Oriented ParentaL supported home ActivitY program), aims at testing the feasibility of an early diagnosis set-up and the GO-PLAY early intervention. CP-EDIT is a prospective cohort study, consecutively assessing approximately 500 infants at risk of CP. We will systematically collect data at inclusion (age 3-11 months) and follow a subset of participants (n = 300) with CP or at high risk of CP until the age of two years. The GO-PLAY early intervention will be tested in 80 infants with CP or high risk of CP. Focus is on eight areas related to implementation and perspectives of the families: early cerebral magnetic resonance imaging (MRI), early genetic testing, implementation of the General Movements Assessment method, analysis of the GO-PLAY early intervention, parental perspective of early intervention and early diagnosis, early prediction of CP, and comparative analysis of the Hand Assessment for Infants, Hammersmith Infant Neurological Examination, MRI, and the General Movements method. Discussion Early screening for CP is increasingly possible and an interim diagnosis of "high risk of CP" is recommended but not currently used in clinical care in Denmark. Additionally, there is a need to accelerate identification in mild or ambiguous cases to facilitate appropriate therapy early. Most studies on early diagnosis focus on identifying CP in infants below five months corrected age. Little is known about early diagnosis in the 50% of all CP cases that are discernible later in infancy. The current study aims at improving care of patients with CP even before they have an established diagnosis. Trial registration ClinicalTrials.gov ID 22013292 (reg. date 31/MAR/2023) for the CP-EDIT cohort and ID 22041835 (reg. date 31/MAR/2023) for the GO-PLAY trial. Keywords: Cerebral palsy, Early diagnosis, General movements assessment, Genomics, Hand assessment for infants, Brain imaging, Intervention
Nalmefene is a newly approved drug for alcohol use disorder, but the risk of harms has not been evaluated from empirical trial evidence.
To assess the harm of nalmefene administered to individuals ...diagnosed with substance use or impulse control disorders by performing a systematic review and meta-analysis of randomised controlled trials.
A search was performed in Cochrane Central Register of Controlled Trials (CENTRAL, 2014), MEDLINE via PubMed (1950), EMBASE via Ovid (1974), and Clinicaltrials.gov through December 2014.
This study included only randomised controlled trials with placebo or active controls that administered nalmefene to adult individuals for treating impulse control and/or substance use disorders. Both published and unpublished randomised controlled trials were eligible for inclusion.
Internal validity was assessed using the Cochrane risk-of-bias tool. Published information from the trials was supplemented by contact between reviewers and industry sponsor. Data were combined using two meta-approaches in fixed effects models; Peto Odds Ratios and risk differences were reported with 95% confidence intervals (95%CIs).
Number of patients with serious adverse events, including specific psychiatric serious adverse events and withdrawals due to adverse events.
Of 20 potentially relevant studies, 15 randomised controlled trials met the inclusion criteria, and 8 of these provided data enabling the meta-analysis. Overall, serious adverse events did not occur more often in the nalmefene group than in the placebo group (Peto Odds Ratio = 0.97 95% CI 0.64-1.44; P = 0.86). Risk of psychiatric serious adverse events was slightly elevated, albeit not at a statistically significant level (Peto Odds Ratio = 1.32 95% CI 0.62, 2.83; P = 0.47). Withdrawals due to adverse events were significantly more likely to occur with nalmefene compared to placebo (Peto Odds Ratio = 3.22 95% CI 2.46-4.22; P<0.001).
The three-fold increased risk of withdrawal from treatment on nalmefene due to adverse events is a matter of safety concern. The nature of these adverse events cannot be elucidated further without access to individual patients data.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
IntroductionThe purpose of the study is to assess the effectiveness of video consultations in patients with type 1 diabetes mellitus (DM) treated with insulin pumps in the outpatient clinic.Methods ...and analysisA 52 weeks’ duration, open-label, randomised controlled trial will be conducted, enrolling 100 patients with type 1 DM currently treated with insulin pump.Patients will be recruited from the diabetes outpatient clinic at Hospital of Southern Jutland, Department of internal medicine, Sønderborg. Participants will be randomised to either video consultations (experimental intervention) or standard care (control comparator). Participants in the video consultation group will follow their standard care treatment but will have all of their scheduled and non-scheduled appointments by video consultation. The control group will follow their standard care treatment as usual, having all their appointments at the outpatient centre. Primary outcome will be change from baseline of time in range (3.9–10.0 mmol/L).Ethics and disseminationThe study has been approved by the Regional Committe on Health Research Ethics for Southern Denmark, S-20200039G Acadre 20/12922. We will present the results of the trial at international conferences as well as publish the results of the trial in (a) peer-reviewed scientific journal(s).Trial registration numberNCT04612933.
IntroductionInflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, can be challenging to diagnose, and treatment outcomes are difficult to predict. In the NORDTREAT ...cohort study, a Nordic prospective multicentre study, we aim to identify novel molecular biomarkers of diagnostic value by assessing the diagnostic test accuracy (cross-sectionally), as well as the prognostic utility when used as prognostic markers in the long-term (cohort study). In the diagnostic test accuracy study, the primary outcome is a successful diagnosis using one or more novel index tests at baseline compared with the ECCO criteria as the reference standard. The composite outcome of the prognostic utility study is ‘severe IBD’ within 52 weeks from inclusion, defined as one or more of the following three events: IBD-related surgery, IBD-related hospitalisation or IBD-related death.Methods and analysisWe aim to recruit 800 patients referred on suspicion of IBD to this longitudinal observational study, a collaboration between 11 inclusion sites in Denmark, Iceland, Norway and Sweden. Inclusion will occur from February 2022 until December 2023 with screening and baseline visits for all participants and three outcome visits at weeks 12, 26 and 52 after baseline for IBD-diagnosed patients. Biological material (blood, faeces, biopsies, urine and hair), clinical data and lifestyle information will be collected during these scheduled visits.Ethics and disseminationThis study will explore novel biomarkers to improve diagnostic accuracy and prediction of disease progression, thereby improving medical therapy and the quality of life for patients with IBD.The study is approved by the Ethics Committee (DK: S-20200051, v1.4, 16.10.2021; IS: VSNb2021070006/03.01, NO: 193064; SE: DNR 2021-05090) and the Danish Data Protecting Agency (20/54594). Results will be disseminated through peer-reviewed journals, patient associations and presentations at international conferences.Clinical trial registration number NCT05414578; Pre-results.
Pulmonary diseases are significant contributors to morbidity and mortality in patients with rheumatoid arthritis (RA). RA-associated interstitial lung disease (RA-ILD) may be prevalent in up to 30% ...and clinically evident in 10% of patients with RA. Feasible methods to detect concomitant ILD in RA are warranted. Our objective is to determine the diagnostic accuracy of thoracic ultrasound (TUS) for ILD in patients with RA with respiratory symptoms, by using chest high-resolution CT (HRCT) as the reference standard. Further, we aim to evaluate the diagnostic accuracy for the promising blood biomarkers surfactant protein-D and microfibrillar-associated protein 4 in the detection of ILD in this group of patients.
By use of a standardised 14 zone protocol patients suspected of having RA-ILD will undergo TUS as index test performed by a junior resident in rheumatology (BKS), who is certified by the European Respiratory Society in performing TUS assessments. Participants form a consecutive series of up to 80 individuals in total. The anonymised TUS images will be stored and scored by the junior resident as well as two senior rheumatologists, who have received training in TUS, and a TUS-experienced pulmonologist. HRCT will be used as the gold standard for ILD diagnosis (reference standard). The two basic measures for quantifying the diagnostic test accuracy of the TUS test are the sensitivity and specificity in comparison to the HRCT.
Data will be collected and stored in the Research Electronic Data Capture database. The study is approved by the Committees on Health Research Ethics and the Danish Data Protection Agency. The project is registered at clinicaltrials.gov (NCT05396469, pre-results) and data will be published in peer-reviewed journals.
Abstract
The Assessment of SpondyloArthritis international Society (ASAS) has defined core sets for (i) symptom-modifying anti-rheumatic drugs (SM-ARD), (ii) clinical record keeping, and (iii) ...disease-controlling anti-rheumatic therapy (DC-ART). These include the following domains for all three core sets: “physical function,” “pain,” “spinal mobility,” “spinal stiffness,” and “patient’s global assessment” (PGA). The core set for clinical record keeping further includes the domains “peripheral joints/entheses” and “acute phase reactants,” and the core set for DC-ART further includes the domains “fatigue” and “spine radiographs/hip radiographs.” The Outcome Measures in Rheumatology (OMERACT) endorsed the core sets in 1998.
Using empirical evidence from axSpA trials, we investigated the efficacy (i.e., net benefit) according to the ASAS/OMERACT core outcome set for axSpA across all interventions tested in trials included in subsequent Cochrane reviews. For all continuous scales, we combined data using the standardized mean difference (SMD) to meta-analyze outcomes involving the same domains. Also, through meta-regression analysis, we examined the effect of the separate SMD measures (independent variables) on the primary endpoint (log
OR
, dependent variable) across all trials.
Based on 11 eligible Cochrane reviews, from these, 85 articles were screened; we included 43 trials with 63 randomized comparisons. Mean (SD) number of ASAS/OMERACT core outcome domains measured for SM-ARD/physical therapy trials was 4.2 (1.7). Six trials assessed all proposed domains. Mean (SD) for number of core outcome domains for DC-ART trials was 5.8 (1.7). No trials assessed all nine domains. Eight trials (16%) were judged to have inadequate (i.e., high risk of) selective outcome reporting bias. The most responsible core domains for achieving success in meeting the primary objective per trial were pain, OR (95% CI) 5.19 (2.28, 11.77), and PGA, OR (95% CI) 1.87 (1.14, 3.07). In conclusion, selective outcome reporting (and “missing data”) should be reduced by encouraging the use of the endorsed ASAS/OMERACT outcome domains in clinical trials. Overall outcome reporting was good for SM-ARD/physical therapy trials and poor for DC-ART trials. Our findings suggest that both PGA and pain provide a valuable holistic construct for the assessment of improvement beyond more objective measures of spinal inflammation.
Exercise reduces the amount of visceral adipose tissue (VAT) and the risk of cardiometabolic diseases. The underlying mechanisms responsible for these exercise-induced adaptations are unclear, but ...they may involve lipolytic actions of interleukin-6 (IL-6). Contracting skeletal muscles secrete IL-6, leading to increased circulating IL-6 levels in response to exercise. The aim of this study is to investigate whether IL-6 is involved in mediating the effects of exercise on visceral and epicardial adipose tissue volume and glycaemic control.
Seventy-five physically inactive males and females aged > 18 years with a waist-to-height ratio > 0.5 and/or waist circumference ≥ 88 cm (females) or ≥ 102 cm (males) are being recruited to participate in a 12-week intervention study. Participants are randomly allocated to one of five groups (1:1:1:1:1). Two groups consist of supervised endurance exercise training combined with the IL-6 blocker tocilizumab (ET) or saline used as placebo (EP), two groups consist of no exercise combined with tocilizumab (NT) or placebo (NP), and one group consists of resistance exercise and placebo (RP). Although the study is an exploratory trial, the primary outcome is change in VAT volume from before to after intervention, with secondary outcomes being changes in (1) epicardial adipose tissue, (2) pericardial adipose tissue and (3) gastric emptying. Depots of adipose tissue are quantitated by magnetic resonance imaging Gastric emptying and glucose metabolism are assessed using mixed-meal tolerance tests.
Understanding the role of IL-6 in mediating the effects of exercise on visceral and epicardial adipose tissue and glycaemic control may lead to novel therapeutic approaches in the prevention of cardiometabolic diseases.
ClinicalTrials.gov, NCT02901496 . Registered on 1 August 2016 and posted retrospectively on 15 September 2016.
ObjectiveAntiphospholipid syndrome (APS) is a systemic autoimmune disorder characterised by venous thrombosis (VT) or arterial thrombosis (AT) and/or pregnancy morbidity and the presence of ...antiphospholipid antibodies. Direct oral anticoagulants (DOACs) hold several advantages to vitamin K antagonists (VKAs) for prevention of thrombosis and we wish to evaluate DOACs compared with VKAs in secondary prevention of thromboembolic events in patients with APS.MethodsWe conducted searches of the published literature using relevant data sources (MEDLINE, Embase and Cochrane CENTRAL), and of trial registers for unpublished data and ongoing trials. We included randomised trials examining individuals >18 years with APS classified according to the criteria valid when the trial was carried out. Randomised controlled trials had to examine any DOAC agent compared with any comparable drug. We tabulated all occurrences of events from all eligible randomised trials. Due to few events, ORs and 95% CIs were calculated using the Peto method.Results5 randomised trials comprising 624 patients met the predefined eligibility criteria. The primary outcome measure was new thrombotic events, a composite endpoint of any VT or AT, during the VKA-controlled phase of treatment. According to the I2 inconsistency index, there was evidence of statistical heterogeneity across the studies (I2=60%). Across trials, 29 and 10 thrombotic events were observed in 305 and 319 patients with APS treated with DOAC and VKA, respectively, corresponding to a combined Peto OR of 3.01 (95% CI 1.56 to 5.78, p=0.001). There was a significantly increased risk of AT while treated with DOACs compared with VKA (OR 5.5 (2.5, 12.1) p<0.0001), but no difference in the risk of VT (p=0.87). We found no significant difference in risk of bleeding.ConclusionsDOACs were associated with a significant increase in the risk of a new thrombotic event, especially AT, favouring standard prophylaxis with warfarin.PROSPERO registration numberCRD42019126720.
The treatments for trochanteric fractures try to regain early mobility and limit morbidity and risk of reoperations. The most currently used dynamic hip screw (DHS) and the proximal femoral nail ...(PFN) are both with pros and cons. We aimed to assess the comparative effectiveness of these interventions for trochanteric fractures by evaluating the surgical performance and postoperative outcomes.
PubMed, Web of Science and Cochrane Central Register were searched for RCTs comparing DHS and PFN for trochanteric fractures. All selected studies and the risk of bias were assessed. Clinical data including operative time, intraoperative blood loss, intraoperative fluoroscopy time, successful closed reduction and complications like nonunion, implant failure and reoperation were recorded. Random-effects models were used in Review Manager software, and GRADE was applied for the interpretation of the evidence.
From 286 identified trials, twelve RCTs including 1889 patients were eligible for inclusion; six RCTs directly comparing DHS with PFN, while other six compared DHS with proximal femoral nail antirotation (PFNA). Compared to DHS, PFN had shorter operative time and led to less intraoperative blood loss. However, DHS need less intraoperative fluoroscopy time than PFN. No difference was seen for the achievement of closed reduction. For risk of postoperative complications, no difference was seen between PFN and DHS for non-union, risk of implant failure and revision surgery.
PFN(A) resulted in a shorter operative time and less intraoperative blood loss compared to DHS. However, no difference was seen for postoperative complications. Trial registration PROSPERO: CRD42021239974.
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