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Whether a conservative strategy of medical therapy alone or a strategy of medical therapy plus invasive treatment is more beneficial in older adults with non-ST-segment elevation myocardial infarction (NSTEMI) remains unclear. We conducted a prospective, multicenter, randomized trial involving patients 75 years of age or older with NSTEMI at 48 sites in the United Kingdom. The patients were assigned in a 1:1 ratio to a conservative strategy of the best available medical therapy or an invasive strategy of coronary angiography and revascularization plus the best available medical therapy. Patients who were frail or had a high burden of coexisting conditions were eligible. The primary outcome was a composite of death from cardiovascular causes (cardiovascular death) or nonfatal myocardial infarction assessed in a time-to-event analysis. A total of 1518 patients underwent randomization; 753 patients were assigned to the invasive-strategy group and 765 to the conservative-strategy group. The mean age of the patients was 82 years, 45% were women, and 32% were frail. A primary-outcome event occurred in 193 patients (25.6%) in the invasive-strategy group and 201 patients (26.3%) in the conservative-strategy group (hazard ratio, 0.94; 95% confidence interval [CI], 0.77 to 1.14; P = 0.53) over a median follow-up of 4.1 years. Cardiovascular death occurred in 15.8% of the patients in the invasive-strategy group and 14.2% of the patients in the conservative-strategy group (hazard ratio, 1.11; 95% CI, 0.86 to 1.44). Nonfatal myocardial infarction occurred in 11.7% in the invasive-strategy group and 15.0% in the conservative-strategy group (hazard ratio, 0.75; 95% CI, 0.57 to 0.99). Procedural complications occurred in less than 1% of the patients. In older adults with NSTEMI, an invasive strategy did not result in a significantly lower risk of cardiovascular death or nonfatal myocardial infarction (the composite primary outcome) than a conservative strategy over a median follow-up of 4.1 years. (Funded by the British Heart Foundation; BHF SENIOR-RITA ISRCTN Registry number, ISRCTN11343602.).

In a trial of percutaneous coronary intervention or conservative treatment in patients undergoing TAVI, PCI was associated with a lower risk of a composite of death, MI, or urgent revascularization at a median of 2 years.

It remains unclear whether urgent endoscopic retrograde cholangiopancreatography (ERCP) with biliary sphincterotomy improves the outcome of patients with gallstone pancreatitis without concomitant cholangitis. We did a randomised trial to compare urgent ERCP with sphincterotomy versus conservative treatment in patients with predicted severe acute gallstone pancreatitis. In this multicentre, parallel-group, assessor-masked, randomised controlled superiority trial, patients with predicted severe (Acute Physiology and Chronic Health Evaluation II score ≥8, Imrie score ≥3, or C-reactive protein concentration >150 mg/L) gallstone pancreatitis without cholangitis were assessed for eligibility in 26 hospitals in the Netherlands. Patients were randomly assigned (1:1) by a web-based randomisation module with randomly varying block sizes to urgent ERCP with sphincterotomy (within 24 h after hospital presentation) or conservative treatment. The primary endpoint was a composite of mortality or major complications (new-onset persistent organ failure, cholangitis, bacteraemia, pneumonia, pancreatic necrosis, or pancreatic insufficiency) within 6 months of randomisation. Analysis was by intention to treat. This trial is registered with the ISRCTN registry, ISRCTN97372133. Between Feb 28, 2013, and March 1, 2017, 232 patients were randomly assigned to urgent ERCP with sphincterotomy (n=118) or conservative treatment (n=114). One patient from each group was excluded from the final analysis because of cholangitis (urgent ERCP group) and chronic pancreatitis (conservative treatment group) at admission. The primary endpoint occurred in 45 (38%) of 117 patients in the urgent ERCP group and in 50 (44%) of 113 patients in the conservative treatment group (risk ratio [RR] 0·87, 95% CI 0·64–1·18; p=0·37). No relevant differences in the individual components of the primary endpoint were recorded between groups, apart from the occurrence of cholangitis (two [2%] of 117 in the urgent ERCP group vs 11 [10%] of 113 in the conservative treatment group; RR 0·18, 95% CI 0·04–0·78; p=0·010). Adverse events were reported in 87 (74%) of 118 patients in the urgent ERCP group versus 91 (80%) of 114 patients in the conservative treatment group. In patients with predicted severe gallstone pancreatitis but without cholangitis, urgent ERCP with sphincterotomy did not reduce the composite endpoint of major complications or mortality, compared with conservative treatment. Our findings support a conservative strategy in patients with predicted severe acute gallstone pancreatitis with an ERCP indicated only in patients with cholangitis or persistent cholestasis. The Netherlands Organization for Health Research and Development, Fonds NutsOhra, and the Dutch Patient Organization for Pancreatic Diseases.

PurposeSepsis is a common reason for intensive care unit (ICU) admission and mortality in ICU patients. Despite increasing interest in treatment strategies limiting oxygen exposure in ICU patients, no trials have compared conservative vs. usual oxygen in patients with sepsis.MethodsWe undertook a post hoc analysis of the 251 patients with sepsis enrolled in a trial that compared conservative oxygen therapy with usual oxygen therapy in 1000 mechanically ventilated ICU patients. The primary end point for the current analysis was 90-day mortality. Key secondary outcomes were cause-specific mortality, ICU and hospital length of stay, ventilator-free days, vasopressor-free days, and the proportion of patients receiving renal replacement therapy in the ICU.ResultsPatients with sepsis allocated to conservative oxygen therapy spent less time in the ICU with an SpO2 ≥ 97% (23.5 h [interquartile range (IQR) 8–70] vs. 47 h [IQR 11–93], absolute difference, 23 h; 95% CI 8–38), and more time receiving an FiO2 of 0.21 than patients allocated to usual oxygen therapy (20.5 h [IQR 1–79] vs. 0 h [IQR 0–10], absolute difference, 20 h; 95% CI 14–26). At 90-days, 47 of 130 patients (36.2%) assigned to conservative oxygen and 35 of 120 patients (29.2%) assigned to usual oxygen had died (absolute difference, 7 percentage points; 95% CI − 4.6 to 18.6% points; P = 0.24; interaction P = 0.35 for sepsis vs. non-sepsis). There were no statistically significant differences between groups for secondary outcomes but point estimates of treatment effects consistently favored usual oxygen therapy.ConclusionsPoint estimates for the treatment effect of conservative oxygen therapy on 90-day mortality raise the possibility of clinically important harm with this intervention in patients with sepsis; however, our post hoc analysis was not powered to detect the effects suggested and our data do not exclude clinically important benefit or harm from conservative oxygen therapy in this patient group.Clinical Trials RegistryICU-ROX Australian and New Zealand Clinical Trials Registry number ACTRN12615000957594.

AbstractObjectiveTo assess whether a clinically relevant difference exists in patients’ perceptions of symptoms, knee function, and ability to participate in sports over a period of two years after rupture of the anterior cruciate ligament (ACL) between two commonly used treatment regimens.DesignOpen labelled, multicentre, parallel randomised controlled trial (COMPARE).SettingSix hospitals in the Netherlands, between May 2011 and April 2016.ParticipantsPatients aged 18 to 65 with an acute rupture of the ACL, recruited from six hospitals. Patients were evaluated at three, six, nine, 12, and 24 months.Interventions85 patients were randomised to early ACL reconstruction and 82 to rehabilitation followed by optional delayed ACL reconstruction after a three month period (primary non-operative treatment).Main outcomesPatients’ perceptions of symptoms, knee function, and ability to participate in sporting activities were assessed with the International Knee Documentation Committee score (optimum score 100) at each time point over 24 months.ResultsBetween May 2011 and April 2016, 167 patients were enrolled in the study and randomised to one of two treatments (mean age 31.3; 67 (40.%) women), and 163 (98%) completed the trial. In the rehabilitation and optional delayed ACL reconstruction group, 41 (50%) patients underwent reconstruction during follow-up. After 24 months, the early ACL reconstruction group had a significantly better (P=0.026) but not clinically relevant International Knee Documentation Committee score (84.7 v 79.4 (difference between groups 5.3, 95% confidence interval 0.6 to 9.9). After three months of follow-up, the International Knee Documentation Committee score was significantly better (P=0.002) for the rehabilitation and optional delayed ACL reconstruction group (difference between groups −9.3, −14.6 to −4.0). After nine months of follow-up, the difference in the International Knee Documentation Committee score changed in favour of the early ACL reconstruction group. After 12 months, differences between the groups were smaller. In the early ACL reconstruction group, four re-ruptures and three ruptures of the contralateral ACL occurred during follow-up versus two re-ruptures and one rupture of the contralateral ACL in the rehabilitation and optional delayed ACL reconstruction group.ConclusionsIn patients with acute rupture of the ACL, those who underwent early surgical reconstruction, compared with rehabilitation followed by elective surgical reconstruction, had improved perceptions of symptoms, knee function, and ability to participate in sports at the two year follow-up. This finding was significant (P=0.026) but the clinical importance is unclear. Interpretation of the results of the study should consider that 50% of the patients randomised to the rehabilitation group did not need surgical reconstruction.Trial registrationNetherlands Trial Register NL 2618.

In a single-center, randomized trial involving 128 patients with sciatica lasting 4 to 12 months and lumbar disk herniation, diskectomy was superior to conservative care in reducing leg-pain intensity at 6 months after enrollment. Among the patients assigned to conservative care, 34% crossed over to undergo surgery.

AbstractObjectiveTo determine whether an injection of platelet rich plasma improves outcomes after acute Achilles tendon rupture.DesignRandomised, placebo controlled, two arm, parallel group, participant and assessor masked, superiority trial.SettingSecondary care trauma units across 19 hospitals in the United Kingdom’s health service.ParticipantsRecruitment commenced in July 2015 and follow-up was completed in March 2018. 230 adults aged 18 years and over were included, with acute Achilles tendon rupture presenting within 12 days of injury and managed with non-surgical treatment. Exclusions were injury at the insertion or musculotendinous junction, major leg injury or deformity, diabetes mellitus, platelet or haematological disorder, systemic corticosteroids, anticoagulation treatment, and other contraindicating conditions.InterventionsParticipants were randomised 1:1 to platelet rich plasma (n=114) or placebo (dry needle; n=116) injection. All participants received standard rehabilitation care (ankle immobilisation followed by physiotherapy).Main outcomes and measuresPrimary outcome was muscle tendon function at 24 weeks, measured objectively with the limb symmetry index (injured/uninjured×100) in maximal work done during the heel rise endurance test (an instrumented measure of repeated single leg heel rises until fatigue). Secondary outcomes included patient reported function (Achilles tendon rupture score), quality of life (short form 12 version 2®), pain (visual analogue scale), goal attainment (patient specific functional scale), and adverse events. A central laboratory analysed the quality and content of platelet rich plasma. Analyses were by modified intention to treat.ResultsParticipants were 46 years old on average, and 57 (25%) of 230 were female. At 24 weeks, 202 (88%) participants completed the heel rise endurance test and 216 (94%) the patient reported outcomes. The platelet rich plasma was of good quality, with expected growth factor content. No difference was detected in muscle tendon function between participants receiving platelet rich plasma injections and those receiving placebo injections (limb symmetry index, mean 34.7% (standard deviation 17.7%) v 38.5% (22.8%); adjusted mean difference −3.9% (95% confidence interval −10.5% to 2.7%)) or in any secondary outcomes or adverse event rates. Complier average causal effect analyses gave similar findings.ConclusionsThere is no evidence to indicate that injections of platelet rich plasma can improve objective muscle tendon function, patient reported function, or quality of life after acute Achilles tendon rupture compared with placebo, or that they offer any patient benefit.Trial registrationISRCTN54992179.

Objective To study whether stopping elastic compression stockings (ECS) after 12 months is non-inferior to continuing them for 24 months after proximal deep venous thrombosis.Design Multicentre single blind non-inferiority randomised controlled trial.Setting Outpatient clinics in eight teaching hospitals in the Netherlands, including one university medical centre.Participants Patients compliant with compression therapy for 12 months after symptomatic, ultrasound proven proximal deep venous thrombosis of the leg.Interventions Continuation or cessation of ECS 12 months after deep venous thrombosis.Main outcome measures The primary outcome was the incidence of post-thrombotic syndrome 24 months after diagnosis of deep venous thrombosis, as assessed by the standardised Villalta scale in an intention to treat analysis. The predefined non-inferiority margin was 10%. The main secondary outcome was quality of life (VEINES-QOL/Sym).Results 518 patients compliant with ECS and free of post-thrombotic syndrome were randomised one year after diagnosis of deep venous thrombosis to stop or continue ECS therapy for another year. In the stop-ECS group, 51 of 256 patients developed post-thrombotic syndrome, with an incidence of 19.9% (95% confidence interval 16% to 24%). In the continue-ECS group, 34 of 262 patients developed post-thrombotic syndrome (incidence 13.0%, 9.9% to 17%), of whom 85% used ECS six or seven days a week during the study period, for an absolute difference of 6.9% (95% confidence interval upper limit 12.3%). Because the upper limit of the 95% confidence interval exceeds the predefined margin of 10%, non-inferiority was not reached. The number needed to treat to prevent one case of post-thrombotic syndrome by continuing ECS was 14 (95% confidence interval lower limit 8). Quality of life did not differ between the two groups.Conclusion Stopping ECS after one year in compliant patients with proximal deep venous thrombosis seemed not to be non-inferior to continuing ECS therapy for two years in this non-inferiority trial.Trial registration Netherlands Trial Register NTR1442.

Odontoid fractures of the second cervical vertebra commonly affect elderly patients due to osteoporosis and low-energy trauma. Treatment is controversial, with prolonged cervical collar immobilization risking non-union and complications, and surgical C1-C2 stabilization involving higher upfront surgical risks. High-level evidence from randomized controlled trials to guide optimal treatment decisions is lacking. The SCORE study aims to determine whether surgical stabilization is non-inferior to conservative collar management in maintaining functional independence for elderly patients with unstable odontoid fractures. SCORE is a multicenter, parallel-group, randomized controlled non-inferiority trial enrolling 322 patients aged ≥70 years with acute (≤2 weeks) unstable odontoid Type II, III, or atypical fractures. Participants will be randomized 1:1, stratified by center, to receive surgical stabilization via posterior C1-C2 fixation or conservative management with a rigid cervical collar. The primary outcome measure is the change in Barthel Index (BI) from baseline to 12 weeks. Secondary outcomes include quality of life (EQ-5D), neck pain (Visual Analog Scale, VAS), neck disability (Neck Disability Index, NDI), radiographic fusion, treatment compliance, cross-over rates to surgery, and incidence of adverse and serious adverse events up to 6 months. Follow-ups will take place at 12 weeks and 6 months post-injury, with an additional visit at approximately 2 weeks post-surgery for surgical patients. Analysis will use mixed models for repeated measures, targeting 90% power to detect non-inferiority within a 5-point margin on the BI (one-sided α = 0.025), accounting for 15% attrition. This trial addresses a critical evidence gap by directly comparing surgical and conservative treatments, aiming to guide clinical decision-making and improve functional outcomes and quality of life in elderly patients. ClinicalTrials.gov, ID: NCT06961578.

To explore secondary outcomes at endpoint comparing treatments with adequate self-mediated physical activity combined with either night-time brace (NB), scoliosis-specific exercise (SSE), or adequate self-mediated physical activity alone (PA) in Adolescent Idiopathic Scoliosis (AIS). A longitudinal, prospective, multicenter RCT was conducted including 135 girls/boys, Cobb angle 25-40°, 9-17 years, and ≥1-year remaining growth were randomly allocated into NB, SSE, or PA group. Endpoint was curve progression of ≤6° (success) at skeletal maturity or >6° (failure). Outcomes included angle of trunk rotation (ATR), major curve Cobb angle, Spinal Appearance Questionnaire (pSAQ), Scoliosis Research Society-22r (SRS-22r), EQ-5Dimensions Youth 3Levels (EQ-5D-Y-3L), and EQ-Visual-Analogue-Scale (EQ-VAS), adherence to treatment and International Physical Activity Questionnaire (IPAQ-SF). At endpoint, 122 patients were analyzed per protocol, mean age 12.7 (±1.4) years, and mean Cobb angle 31° (±4.3). A significant difference in change for ATR favored NB group compared to SSE group -2.0º (95% CI -3.7 to -0.3). EQ-5D-Y-3L dimensions showed a significant difference in change with decrease in mobility (p=0.031), and usual activities (p=0.003) for SSE compared to NB and PA groups. Treatment adherence was adequate but slightly better in NB and PA groups compared to SSE on self-report (p=0.012), and health care provider (HCP) report was better in PA compared to SSE group (p=0.013). Higher motivation and capability explained 53% of the variability and gave better odds for higher adherence (OR = 11.12, 95% CI = 1.5 to 34.4; OR = 7.23, 95% CI = 2.9 to 43.3), respectively. Night-time brace, scoliosis-specific exercise or physical activity interventions for adolescents with idiopathic scoliosis showed small differences between groups in trunk rotation, spinal deformity and appearance, health-related quality of life, and treatment adherence but not likely reaching clinical relevance.