Intervention Trial Research Articles

Developmental Outcomes of Preterm Infants Enrolled in a Randomized Clinical Trial of a Parent-Administered Sensorimotor Intervention in the NICU

Abstract Date Presented 03/22/24 This study revealed that a parent-administered sensorimotor intervention can enhance motor function in preterm infants, supporting the importance of OT’s advocacy for early parent-delivered interventions in the neonatal intensive care unit. Primary Author and Speaker: Sandra Fucile Contributing Authors: Laurie Snider, Kimberly Dow

Effect of Stroke Etiology on Endovascular Treatment for Acute Basilar-Artery Occlusion: A Post Hoc Analysis of the ATTENTION Randomized Trial.

Stroke etiology could influence the outcomes in patients with basilar-artery occlusion (BAO). This study aimed to evaluate the differences in efficacy and safety of best medical treatment (BMT) plus endovascular treatment (EVT) versus BMT alone in acute BAO across different stroke etiologies. The study was a post hoc analysis of the ATTENTION trial (Trial of Endovascular Treatment of Acute Basilar-Artery Occlusion), which was a multicenter, randomized trial at 36 centers in China from February 2021 to September 2022. Patients with acute BAO were classified into 3 groups according to stroke etiology (large-artery atherosclerosis [LAA], cardioembolism, and undetermined cause/other determined cause [UC/ODC]). The primary outcome was a favorable outcome (modified Rankin Scale score of 0-3) at 90 days. Safety outcomes included symptomatic intracranial hemorrhage and 90-day mortality. A total of 340 patients with BAO were included, 150 (44.1%) had LAA, 72 (21.2%) had cardioembolism, and 118 (34.7%) had UC/ODC. For patients treated with BMT plus EVT and BMT alone, respectively, the rate of favorable outcome at 90 days was 49.1% and 23.8% in the LAA group (odds ratio, 3.08 [95% CI, 1.38-6.89]); 52.2% and 30.8% in the cardioembolism group (odds ratio, 2.45 [95% CI, 0.89-6.77]); and 37.5% and 17.4% in the UC/ODC group (odds ratio, 2.85 [95% CI, 1.16-7.01]), with P=0.89 for the stroke etiology×treatment interaction. The rate of symptomatic intracranial hemorrhage in EVT-treated patients with LAA, cardioembolism, and UC/ODC was 8.3%, 2.2%, and 3.2%, respectively, and none of the BMT-treated patients. Lower 90-day mortality was observed in patients with EVT compared with BMT alone across 3 etiology groups. Among patients with acute BAO, EVT compared with BMT alone might be associated with favorable outcomes and lower 90-day mortality, regardless of cardioembolism, LAA, or UC/ODC etiologies. The influence of stroke etiology on the benefit of EVT should be explored by further trials. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04751708.

Transforaminal versus posterior lumbar interbody fusion for symptomatic single-level spondylolisthesis (LIFT): a multicentre controlled, patient blinded, randomised non-inferiority trial

The effectiveness of transforaminal lumbar interbody fusion (TLIF) compared to posterior lumbar interbody fusion (PLIF) in patients with single-level spondylolisthesis has not been substantiated. To address the evidence gap, a well-powered randomized controlled non-inferiority trial comparing the effectiveness of TLIF with PLIF, entitled the Lumbar Interbody Fusion Trial (LIFT), was conducted. In a multicenter randomized controlled non-inferiority trial among five Dutch hospitals, 161 patients were randomly allocated to either TLIF or PLIF (1:1), stratified according to study site. Patients and statisticians were blinded for group assignment. All patients were over 18 years old with symptomatic single-level degenerative, isthmic or iatrogenic lumbar spondylolisthesis, and eligible for lumbar interbody fusion surgery through a posterior approach. The primary outcome was change in disability measured with the Oswestry Disability Index (ODI) from preoperative to one year postoperative. The non-inferiority limit was set to 7.0 points based on the MCID of ODI. Secondary outcomes were change in quality-adjusted life years (QALY) assessed with EuroQol 5 Dimensions, 5 Levels (EQ-5D-5L) and Short Form Health Survey (SF-36), as well as back and leg pain (Numerical rating scale, NRS), anxiety and depression (Hospital Anxiety Depression Scale; HADS), perioperative blood loss, duration of surgery, duration of hospitalization, and complications. Trial registration: Netherlands Trial Registry, number 5722 (registration date March 30, 2016), Lumbar Interbody Fusion Trial (LIFT): A randomized controlled multicenter trial for surgical treatment of lumbar spondylolisthesis. Patients were included between August 2017 and November 2020. The total study population was 161 patients. Total loss-to-follow-up after one year was 16 patients. Per-protocol analysis included 66 patients in each group. In the TLIF group (mean age 61.6, 36 females), ODI improved from 46.7 to 20.7, whereas in the PLIF group (mean age 61.9, 41 females), it improved from 46.0 to 24.9. This difference (-4.9, 90% CI-12.2 to+2.4) did not reach the non-inferiority limit of 7.0 points in ODI. A significant difference in the secondary outcome measurement, QALY (SF-36), was observed in favor of TLIF (P<0.05). However, this was not clinically relevant. No difference was found for all other secondary outcome measurements; PROMs (EQ-5D, NRS leg/back, HADS), perioperative blood loss, duration of surgery, duration of hospitalization, and perioperative and postoperative complications. For patients with single-level spondylolisthesis, TLIF is non-inferior to PLIF in terms of clinical effectiveness. Disability (measured with ODI) did not differ over time between groups. No funding was received for this trial.

Relationship Between Early-Pregnancy Glycemia and Adverse Outcomes: Findings From the TOBOGM Study.

We evaluated associations between early-pregnancy oral glucose tolerance test (OGTT) glucose and complications in the Treatment of Booking Gestational Diabetes Mellitus (TOBOGM) cohort to inform prognostic OGTT thresholds. Individuals with risk factors for hyperglycemia were recruited for an international, multicenter, randomized controlled gestational diabetes mellitus (GDM) (World Health Organization 2013 criteria) treatment trial. A 2-h 75-g OGTT was performed at <20 weeks' gestation. Individuals with early treated hyperglycemia in pregnancy were excluded from the primary analysis. Early OGTT glucose concentrations were analyzed continuously and in glycemic categories (normal, low band, and high band). Overall, 3,645 individuals had an OGTT at (mean ± SD) 15.6 ± 2.5 weeks. For each 1-SD increase in fasting, 1-h, and 2-h glucose values, there were continuous positive associations with late GDM: adjusted odds ratio (aOR) 2.04 (95% CI 1.82-2.27), 3.05 (2.72-3.43), and 2.21 (1.99-2.45), respectively. There were continuous positive associations between 1-h and 2-h glucose and the perinatal composite (birth <37 + 0 weeks, birth trauma, birth weight ≥4,500 g, respiratory distress, phototherapy requirement, stillbirth/neonatal death, and shoulder dystocia), with aOR 1.15 (95% CI 1.04-1.26) and 1.14 (1.04-1.25), respectively, and with large-for-gestational-age offspring, with aOR 1.18 (1.06-1.31) and 1.26 (1.01-1.25), respectively. Significant associations were also observed between 1-h glucose and cesarean section and between fasting and 2-h glucose and neonatal hypoglycemia. In categorical analysis, only the high-band 1-h glucose (≥10.6 mmol/L [191 mg/dL]) predicted the perinatal composite. There is a continuous positive association between early-pregnancy OGTT glucose and complications. In individuals with hyperglycemia risk factors, only the high-glycemic-band 1-h glucose corresponded to increased risk of major perinatal complications.

Assessing the Effectiveness of eHealth Interventions to Manage Multiple Lifestyle Risk Behaviors Among Older Adults: Systematic Review and Meta-Analysis.

Developing adverse lifestyle behaviors increases the risk of a variety of chronic age-related diseases, including cardiovascular disease, obesity, and Alzheimer disease. There is limited evidence regarding the effectiveness of eHealth-based multiple health behavior change (MHBC) interventions to manage lifestyle risk behaviors. The purpose of this systematic evaluation was to assess the effectiveness of eHealth MHBC interventions in changing ≥2 major lifestyle risk behaviors in people aged ≥50 years. The literature search was conducted in 6 electronic databases-PubMed, Embase, Web of Science, Scopus, Cochrane Library, and SPORTDiscus-from inception to May 1, 2024. Eligible studies were randomized controlled trials of eHealth interventions targeting ≥2 of 6 behaviors of interest: alcohol use, smoking, diet, physical activity (PA), sedentary behavior, and sleep. A total of 34 articles with 35 studies were included. eHealth-based MHBC interventions significantly increased smoking cessation rates (odds ratio 2.09, 95% CI 1.62-2.70; P<.001), fruit intake (standardized mean difference [SMD] 0.18, 95% CI 0.04-0.32; P=.01), vegetable intake (SMD 0.17, 95% CI 0.05-0.28; P=.003), self-reported total PA (SMD 0.22, 95% CI 0.02-0.43; P=.03), and objectively measured moderate to vigorous PA (SMD 0.25, 95% CI 0.09-0.41; P=.002); in addition, the interventions decreased fat intake (SMD -0.23, 95% CI -0.33 to -0.13; P<.001). No effects were observed for alcohol use, sedentary behavior, or sleep. A sensitivity analysis was conducted to test the robustness of the pooled results. Moreover, the certainty of evidence was evaluated using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework. eHealth-based MHBC interventions may be a promising strategy to increase PA, improve diet, and reduce smoking among older adults. However, the effect sizes were small. Further high-quality, older adult-oriented research is needed to develop eHealth interventions that can change multiple behaviors. PROSPERO International Prospective Register of Systematic Reviews CRD42023444418; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023444418.

School-based interventions targeting substance use among young people in low-and-middle-income countries: A scoping review.

Globally, harmful substance use is among the leading causes of premature deaths in the general population, and most of these behaviours are initiated during pre-adolescence to young adulthood. Preventing the onset or reducing the prevalence of substance use among young people is thus a global health priority. Diverse school-based interventions have been implemented in low-and-middle-income countries (LMICs); however, evidence regarding their theoretical underpinnings and core components is lacking. The aim of this scoping review was to identify the underlying (social/behavioural) theories, models or frameworks (TMF) and core (practical) components of school-based interventions in LMICs aimed at preventing the onset or reducing the prevalence of substance use among young people. Using the Joanna Briggs Institute (JBI) guidance for conducting scoping reviews, we searched scientific literature databases for articles published from 1995 to 2022. A further search was conducted using the reference lists of included articles. We selected randomized and non-randomized trials of school-based interventions in LMICs that aimed at preventing the onset or reducing the prevalence of substance use among young people. We used Covidence software to screen titles and abstracts, as well as full texts. We then extracted the data and analysed it using a descriptive content analysis approach. Two reviewers conducted the screening, extraction and data analysis and discussed discrepancies, and clarified doubts and uncertainties through consultation with the other team members. A total of 58 articles were included in the review. Most articles (63.8%) used either a single or combination of two or more TMFs to inform their interventions. The most widely used TMF was social learning theory followed by theory of planned behaviour. We identified six core components of substance use prevention interventions: education, school environment, school policy, parental involvement, peer engagement and counselling. This scoping review outlines the core components of school-based substance use prevention interventions used in low-and-middle-income countries and the common theories, models or frameworks that underpin the design of those interventions.

The relationship between trust in federal oversight of vaccine safety and willingness to participate in COVID-19 clinical trials: a repeated measures study of Philadelphia residents (September 2021 – March 2023)

BackgroundThe Coronavirus Disease 2019 (COVID-19) pandemic precipitated an urgent need for clinical trials to discover safe and efficacious treatments. We examined how COVID-19 experiences, clinical trial awareness, and trust in the vaccine safety process were associated with willingness to participate in COVID-19 clinical trials. The objective was to investigate the relationship between trust in federal oversight of vaccine safety and willingness to participate in clinical trials for COVID-19 treatment across four distinct time points over an 18-month period during the COVID-19 pandemic.MethodsWe used four waves of data collected from September 2021 to March 2023 among 582 Philadelphia residents (with a missing data rate of 0.9%). Generalized estimating equations estimated the association between willingness to participate in COVID-19 clinical trials and participants’ trust in the federal government’s oversight of COVID-19 vaccine safety, COVID-19-related variables (COVID-19 related health challenges, history of COVID-19 infection), awareness of clinical trials and how to enroll in them, and sociodemographic characteristics (age, race/ethnicity, sexual orientation, gender, parental status, education, and insurance).ResultsOn average, willingness to participate in a COVID-19 clinical trial was positively associated with greater trust in the federal government’s oversight of vaccine safety [β = 0.34, 95% confidence interval (CI): 0.15–0.53], having COVID-19 (β = 0.40, 95% CI: 0.08–0.73), awareness of clinical trials (β = 0.38, 95% CI: 0.04–0.73), and knowledge of how to enroll (β = 0.83, 95% CI: 0.44–1.23). Among sociodemographic characteristics, race/ethnicity (p = 0.001) and gender (p = 0.018) were identified as predictors for COVID-19 trial willingness.ConclusionWillingness to participate in clinical trials may be bolstered by strengthening the public’s trust in the federal government’s role within vaccine safety oversight, increasing the perceived relevance of clinical trials to individuals’ health and well-being, and offering tailored information to educate diverse communities about ongoing trials and how to enroll in them.

Clinical trials of new therapies for mucopolysaccharidoses

Background: Mucopolysaccharidoses (MPS) are a group of rare genetic diseases with a metabolic background. Currently, there are no effective methods of treating MPS, and new ways of treating patients are constantly being sought.Aim of the study: The purpose of this article is to review the available literature on clinical trials of new treatments for mucopolysaccharidoses.Material and methods: The review of research literature published between 1999 and 2023 was conducted, with a specific focus on the last ten years. The literature for this article was selected from publications available online in databases such as Google Scholar or PubMed. Research was based on keywords like: mucopolysaccharidoses, clinical trials, gene therapy, MPS. Results: A total of 104 publications were considered in the study, including 95 scientific articles and 9 clinical trial reports (consisting of 1 FDA approval). Out of those 104 articles, 82 discussed potential future therapies for patients with MPS. Among them, as many as 51 focused on gene therapy.Conclusions: The only currently approved treatments for mucopolysaccharidoses are enzyme replacement therapy and hematopoietic stem cell transplantation, which are not suitable for all types of MPS and have their limitations. In addition, there is no single therapy for all types of MPS, as they are the result of mutations in different genes and result from the deficiency of different enzymes. Numerous preclinical and clinical studies are being conducted on therapies for mucopolysaccharidoses. These include therapies that allow manipulation of cellular pathways, substrate reduction, or gene therapy, which is the most promising form of treatment. Some of the studies have successfully passed the first and second research phases.

How do care-related beliefs contribute to depression and anxiety in family caregivers of people with dementia? Testing a cognitive vulnerability-stress model.

Care-related beliefs are considered risk factors for decreased mental health in family caregivers of people with dementia. However, their exact role in the caregiver stress process remains unclear. Hence, we tested a cognitive vulnerability-stress model of depression and anxiety in family caregivers of people with dementia. A cross-sectional study was conducted using baseline data from a caregiver intervention trial (N = 322). Within Bayesian moderated mediation analysis, we examined mediation of effects of objective demands (severity of dementia, challenging behavior, caregiving intensity, caregiving duration) on depression and anxiety via subjective caregiver burden and moderation by care-related beliefs in four domains (dysfunctional caregiving standards, dysfunctional attitudes towards dementia, functional self-care-related beliefs, functional acceptance-related beliefs). The relation between objective demands and subjective burden was amplified by dysfunctional caregiving standards and dysfunctional attitudes towards dementia and mitigated by functional self-care-related beliefs. Further, functional acceptance-related beliefs attenuated the effect of subjective caregiver burden on depression. The study provides preliminary evidence for a cognitive vulnerability-stress model of depression and anxiety in family caregivers of people with dementia. The results indicate that the four-domain model of care-related beliefs is a valuable framework for future research and may serve as a heuristic model for cognitive-behavioral therapy in this population.

Progression of Gestational Subclinical Hypothyroidism and Hypothyroxinemia to Overt Hypothyroidism After Pregnancy: Pooled Analysis of Data from Two Randomized Controlled Trials.

Background: To examine the incidence of overt hypothyroidism 1 and 5 years after pregnancies where screening before 21 weeks identified subclinical hypothyroidism (SH) or hypothyroxinemia (HT). Methods: Secondary analysis of two multicenter treatment trials for either SH or HT diagnosed between 8 and 20 weeks gestation. Current analyses focus only on individuals randomized to the placebo groups in the two parallel studies. SH was diagnosed with thyrotropin (TSH) ≥4.0 mU/L and normal free T4 (fT4) (0.86-1.9 ng/dL). HT was diagnosed with normal TSH (0.08-3.99 mU/L) but fT4 <0.86 ng/dL. Serum from initial testing was stored for later thyroid peroxidase (TPO) antibody assay; results were not returned for clinical management. At 1 and 5 years after delivery, participants were asked whether they had either been diagnosed with or were being treated for a thyroid condition. Maternal serum was collected at these visits and thyroid function measured. Subsequent overt hypothyroidism was defined as TSH ≥4.0 mU/L with fT4 <0.86 ng/dL. Results: Data for 1- and 5-year follow-up were available in 307 of the 338 participants with SH and 229 of the 261 with HT. Subsequent hypothyroidism was more common both at year 1 (13.4% vs. 3.1%, p < 0.001) and year 5 (15.6% vs. 2.6%, p < 0.001) for participants with SH compared with those with HT. This progression was more common in individuals with TSH values >10 mIU/mL. Baseline TPO level >50 IU/mL in participants with SH was associated with higher rates of hypothyroidism at year 1 (26.7% vs. 6.5%, odds ratio [OR] = 5.3 [confidence interval (CI) 2.6-10.7]) and year 5 (30.5% vs. 7.5%, OR = 5.4 [CI: 2.8-10.6]) compared with those with TPO levels ≤50 IU/mL. For participants with HT, no differences in overt hypothyroidism were seen at 1 year related to baseline TPO level >50 IU/mL (1/10 (10%) vs. 6/218 (2.8%), OR = 3.9 [CI: 0.43-36.1]), but more participants with TPO levels >50 IU/mL developed hypothyroidism by year 5 (2/10 (20%) vs. 4/218 (1.8%), OR = 13.4 [CI: 2.1-84.1]). Conclusion: SH is associated with higher rates of overt hypothyroidism or thyroid replacement therapy within 5 years of delivery than is HT when these conditions are diagnosed in the first half of pregnancy.

Methodology of clinical trials on sodium-glucose cotransporter 2 inhibitors registered on ClinicalTrials.gov: a cross-sectional study

Background/ObjectiveThe research on sodium-glucose cotransporter 2 (SGLT2) inhibitors has been increasing rapidly in the last decade, as well as indications for their use. This study aimed to analyze the methodological characteristics of clinical trials on SGLT2 inhibitors registered on ClinicalTrials.gov.DesignWe conducted a cross-sectional study of trials on SGLT2 inhibitors registered on ClinicalTrials.gov up to November 11, 2022. We included clinical trials that tested SGLT2 inhibitors for any clinical condition, as a single or combined SGLT2 therapy, compared to any other medication or placebo and mapped their characteristics.ResultsWe identified 1102 eligible trials on 14 different SGLT2 inhibitors. The first trial registration was in 2005. There were 993 (90%) interventional and 109 (10%) observational trials. Most trials were in Phase 1 (29%), Phase 3 (23%), or Phase 4 (24%). Interventional trials were mostly randomized (85%); almost half of them did not use masking (44%). Trials on empagliflozin, dapagliflozin, and canagliflozin accounted for 75% of all trials. More than 60% of trials included patients with diabetes mellitus, 13% included only healthy subjects, and 12% included patients with heart diseases. Overall, these trials included more than 9.5 million participants (~ 312,000 of which in interventional studies). Almost 65% of all clinical trials were industry-funded. Most trials were completed (60%) and 35% of those reported results. For trials that are obligated to report results by the Food and Drugs Administration (FDA), 88% of them did so. Trials fully or partially funded by industry more frequently published results compared to non-industry funded trials (46.1% vs. 11.2%; p < 0.001).ConclusionsThe number of registered trials on SGLT2 inhibitors is increasing progressively along with expanding indications for its use, shifting from diabetes mellitus to cardiovascular and renal diseases. Public reporting of trial results improved with time but remains suboptimal.

Accelerating evidence synthesis for safety assessment through ClinicalTrials.gov platform: a feasibility study

BackgroundStandard systematic review can be labor-intensive and time-consuming meaning that it can be difficult to provide timely evidence when there is an urgent public health emergency such as a pandemic. The ClinicalTrials.gov provides a promising way to accelerate evidence production.MethodsWe conducted a search on PubMed to gather systematic reviews containing a minimum of 5 studies focused on safety aspects derived from randomized controlled trials (RCTs) of pharmacological interventions, aiming to establish a real-world dataset. The registration information of each trial from eligible reviews was further collected and verified. The meta-analytic data were then re-analyzed by using 1) the full meta-analytic data with all trials and 2) emulated rapid data with trials that had been registered and posted results on ClinicalTrials.gov, under the same synthesis methods. The effect estimates of the full meta-analysis and rapid meta-analysis were then compared.ResultsThe real-world dataset comprises 558 meta-analyses. Among them, 56 (10.0%) meta-analyses included RCTs that were not registered in ClinicalTrials.gov. For the remaining 502 meta-analyses, the median percentage of RCTs registered within each meta-analysis is 70.1% (interquartile range: 33.3% to 88.9%). Under a 20% bias threshold, rapid meta-analyses conducted through ClinicalTrials.gov achieved accurate point estimates ranging from 77.4% (using the MH model) to 83.1% (using the GLMM model); 91.0% to 95.3% of these analyses accurately predicted the direction of effects.ConclusionsUtilizing the ClinicalTrials.gov platform for safety assessment with a minimum of 5 RCTs holds significant potential for accelerating evidence synthesis to support urgent decision-making.

Longitudinal Importance of the Soluble Receptor for Advanced Glycation End-Products in Non-intubated Hospitalized Patients with COVID-19 Pneumonia.

The soluble receptor for advanced glycation end-products (sRAGE) is a marker of alveolar type I cell injury associated with outcomes COVID-19 pneumonia. How plasma sRAGE changes over time and whether it remains associated with long-term clinical outcomes beyond a single measurement in COVID-19 has not been well-studied. We studied two cohorts in randomized clinical trials of monoclonal antibody treatment for COVID-19 (bamlanivimab and tixagevimab/cilgavimab). We first studied the association between baseline plasma sRAGE and 90-day clinical outcomes, which had been previously demonstrated in the bamlanivimab cohort, among hospitalized patients with COVID-19 supported with high flow nasal oxygen (HFNO) or non-invasive ventilation (NIV) in the tixagevimab/cilgavimab study. Next, we investigated the relationship between day 3 sRAGE and 90-day outcomes and how plasma sRAGE changes over the first 3 days of hospitalization in both clinical trial cohorts. We found that plasma sRAGE in the highest quartile in the HFNO/NIV participants in the tixagevimab/cilgavimab trial was associated with a significantly lower rate of 90-day sustained recovery (recovery rate ratio 0.31, 95% CI 0.14-0.71, p=0.005) and with a significantly higher rate of 90-day mortality (HR 2.49, 95% CI 1.15-5.43, p = 0.021) compared with the lower three quartiles. Day 3 plasma sRAGE in both clinical trial cohorts remained associated with 90-day clinical outcomes. The trajectory of sRAGE was not influenced by treatment assignment. Our results indicate that plasma sRAGE is a valuable prognostic marker in COVID-19 up to three days after initial hospital presentation.

Current status and perspectives of clinical trials for tumor-infiltrating lymphocyte therapy.

Immunotherapies, mainly immune checkpoint inhibitors (ICIs), have revolutionized cancer treatment strategies over the past decade, but their limitations have limited clinical applications. Tumor-infiltrating lymphocyte (TIL) therapy is a type of adoptive cell therapy (ACT), which collects infiltrating lymphocytes at the tumor site and expands them in vitro to obtain TIL final products cloned by various T-cell receptors, subsequently reinfused TIL into the patient, which is effective for the treatment of solid tumors. The approval of Lifileucel for commercialization marks the success of TIL therapy. This review summarizes the current status of clinical trials of TIL treatment. In addition, it is suggested that the current research trend of TIL should focus on improving the survival time of TIL in vivo, reducing drug toxicity, and searching for prognostic markers. Finally, it is expected that TIL therapy can be applied to a more wide range of clinical treatments.

Gastric cancer prevention by community eradication of Helicobacter pylori: a cluster-randomized controlled trial.

Gastric cancer is a leading cause of cancer-related deaths in China. Affecting more than 40% of the world's population, Helicobacter pylori is a major risk factor for gastric cancer. While previous clinical trials indicated that eradication of H. pylori could reduce gastric cancer risk, this remains to be shown using a population-based approach. We conducted a community-based, cluster-randomized, controlled, superiority intervention trial in Linqu County, China, with individuals who tested positive for H. pylori using a 13C-urea breath test randomly assigned to receiving either (1) a 10-day, quadruple anti-H. pylori treatment (comprising 20 mg of omeprazole, 750 mg of tetracycline, 400 mg of metronidazole and 300 mg of bismuth citrate) or (2) symptom alleviation treatment with a single daily dosage of omeprazole and bismuth citrate. H. pylori-negative individuals did not receive any treatment. We examined the incidence of gastric cancer as the primary outcome. A total of 180,284 eligible participants from 980 villages were enrolled over 11.8 years of follow-up, and a total of 1,035 cases of incident gastric cancer were documented. Individuals receiving anti-H. pylori therapy showed a modest reduction in gastric cancer incidence in intention-to-treat analyses (hazard ratio 0.86, 95% confidence interval 0.74-0.99), with a stronger effect observed for those having successful H. pylori eradication (hazard ratio 0.81, 95% confidence interval 0.69-0.96) than for those who failed treatment. Moderate adverse effects were reported in 1,345 participants during the 10-day treatment. We observed no severe intolerable adverse events during either treatment or follow-up. The findings suggest the potential for H. pylori mass screening and eradication as a public health policy for gastric cancer prevention. Chinese Clinical Trial Registry identifier: ChiCTR-TRC-10000979 .

Designing a single-arm phase 2 clinical trial of mitapivat for adult patients with erythrocyte membranopathies (SATISFY): a framework for interventional trials in rare anaemias – pilot study protocol

IntroductionMembranopathies encompass haemolytic disorders arising from genetic variants in erythrocyte membrane proteins, including hereditary spherocytosis and stomatocytosis. Congenital dyserythropoietic anaemia type II (CDA II) is associated with the SEC23B gene...

The Legacy Effect of Intensive versus Standard Blood Pressure Control on the Incidence of Dialysis or Kidney Transplantation.

The Systolic Blood Pressure Intervention Trial (SPRINT) showed that intensive lowering of systolic blood pressure (BP) increased the risk of incident chronic kidney disease and episodes of acute kidney injury. Whether intensive treatment changes the risk of kidney failure is unknown. The goal of this study was to estimate the legacy effect of intensive versus standard systolic BP lowering on the longer-term incidence of kidney failure. Secondary analysis of a randomized, open-label clinical trial with observational follow-up. Between 2010 and 2013, patients 50 years and older with hypertension and higher cardiovascular risk excluding those with diabetes mellitus, history of stroke, proteinuria >1g / day or polycystic kidney disease were recruited from 102 clinic sites in the United States and Puerto Rico. Participants were randomized to a systolic BP goal of <120 mm Hg (intensive treatment) or <140 mm Hg (standard treatment group). We linked participants with the US Renal Data System to ascertain kidney failure (initiation of dialysis therapy or transplantation) and the US National Death Index to ascertain all-cause mortality through 2020. Based on analysis of 9279 (99.1%) of 9361 randomized participants, 101 cases of kidney failure occurred over a median follow-up of 8.6 years (interquartile range 8.0 to 9.1 years), with the majority occurring in 74 (73.3%) participants with an eGFR<45 ml/min/1.73 m2 at baseline. Intensive treatment did not significantly increase the risk of kidney failure either overall (cause-specific Hazard Ratio (HR) = 1.20, 95% CI: 0.81 - 1.78) or in the subgroup of participants with baseline eGFR<45 ml/min/1.73 m2 (HR = 1.43, 95% CI: 0.89 - 2.30). Overall, and in patients with eGFR <45 ml/min/1.73 m2, there were higher rates of dialysis or transplantation among SPRINT participants randomized to intensive treatment, but the modest differences observed were not statistically significant.

Effect of oxygen supplementation on cognitive performance among HEMS providers after acute exposure to altitude: the HEMS II randomized clinical trial

ImportanceEmergency medical services (EMS) providers transiently ascend to high altitude for primary missions and secondary transports in mountainous areas in helicopters that are unpressurised and do not have facilities for oxygen supplementation. The decrease in cerebral oxygen saturation can lead to impairment in attention and reaction time as well as in quality of care during acute exposure to altitude.ObjectiveThe primary aim of the current study was to investigate the effect of oxygen supplementation on cognitive performance in Helicopter EMS (HEMS) providers during acute exposure to altitude.Design, setting, and participantsThis interventional, randomized, controlled, double-blind, cross-over clinical trial was conducted in October 2021. Each trial used a simulated altitude scenario equivalent to 4000 m, in which volunteers were exposed to hypobaric hypoxia with a constant rate of ascent of 4 m/s in an environmental chamber under controlled, replicable, and safe conditions. Trials could be voluntarily terminated at any time. Inclusion criteria were being members of emergency medical services and search and rescue services with an age between 18 and 60 years and an American Society of Anesthesiologists physical status class I.ExposuresEach participant conducted 2 trials, one in which they were exposed to altitude with oxygen supplementation (intervention trial) and the other in which they were exposed to altitude with ambient air supplementation (control trial).Main outcomes and measuresMeasurements included peripheral oxygen saturation (SpO2), cerebral oxygenation (ScO2), breathing and heart rates, Psychomotor Vigilance Test (PVT), Digit-Symbol Substitution Test (DSST), n-Back test (2-BACK), the Grooved Pegboard test, and questionnaires on subjective performance, stress, workload, and positive and negative affect. Paired t-tests were used to compare conditions (intervention vs. control). Data were further analyzed using generalized estimating equations (GEE).ResultsA total of 36 volunteers (30 men; mean [SD] age, 36 [9] years; mean [SD] education, 17 [4] years) were exposed to the intervention and control trials. The intervention trials, compared with the control trials, had higher values of SpO2 (mean [SD], 97.9 [1.6] % vs. 86 [2.3] %, t-test, p = 0.004) and ScO2 (mean [SD], 69.9 [5.8] % vs. 62.1 [5.2] %, paired t-test, p = 0.004). The intervention trials compared with the control trials had a shorter reaction time (RT) on the PVT after 5 min (mean [SD], 277.8 [16.7] ms vs. 282.5 [15.3] ms, paired t-test, p = 0.006) and after 30 min (mean [SD], 276.9 [17.7] ms vs. 280.7 [15.0] ms, paired t-test, p = 0.054) at altitude. While controlling for other variables, there was a RT increase of 0.37 ms for each % of SpO2 decrease. The intervention trials showed significantly higher values for DSST number of correct responses (with a difference of mean [SD], 1.2 [3.2], paired t-test, p = 0.035). Variables in the intervention trials were otherwise similar to those in the control trials for DSST number of incorrect responses, 2-BACK, and the Grooved Pegboard test.Conclusions and relevanceThis randomized clinical trial found that oxygen supplementation improves cognitive performance among HEMS providers during acute exposure to 4000 m altitude. The use of oxygen supplementation may allow to maintain attention and timely reaction in HEMS providers. The impact of repeated altitude ascents on the same day, sleep-deprivation, and additional stressors should be investigated.Trial registration NCT05073406, ClinicalTrials.gov trial registration.

Differential attrition and engagement in randomized controlled trials of occupational mental health interventions in person and online: A systematic review and meta-analysis.

This study systematically reviewed and meta-analyzed the differential attrition and utilization of occupational mental health interventions, specifically examining delivery methods (internet-based versus in-person). The research, with papers spanning 2010-2024, involved filtering criteria and comprehensive searches across PubMed, Scopus, and Web of Science Core (PROSPERO registration n. CRD42022322394). Of 28 683 titles, 84 records were included in the systematic review, with 75 in meta-analyses. Risk of bias was assessed through the revised Cochrane risk of bias tool for randomized control trials and funnel plots. Differential attrition across studies was meta-analysed through a random-effects model with limited maximum-likelihood estimation for the degree of heterogeneity. Findings reveal higher mean differential attrition in the intervention group, indicating a potential challenge in maintaining participant engagement. The attrition rates were not significantly influenced by the mode of intervention delivery (internet versus in-person). Compensation for participation and year of publication could potentially influence differential attrition from baseline to follow-up measurements. These results suggest a need for cautious consideration of attrition in occupational mental health intervention study designs and emphasize the importance of adapting statistical analyses to mitigate potential bias arising from differential attrition.

A randomized trial of behavioral interventions yielding sustained reductions in distracted driving

Distracted driving is responsible for nearly 1 million crashes each year in the United States alone, and a major source of driver distraction is handheld phone use. We conducted a randomized, controlled trial to compare the effectiveness of interventions designed to create sustained reductions in handheld use while driving (NCT04587609). Participants were 1,653 consenting Progressive® Snapshot® usage-based auto insurance customers ages 18 to 77 who averaged at least 2 min/h of handheld use while driving in the month prior to study invitation. They were randomly assigned to one of five arms for a 10-wk intervention period. Arm 1 (control) got education about the risks of handheld phone use, as did the other arms. Arm 2 got a free phone mount to facilitate hands-free use. Arm 3 got the mount plus a commitment exercise and tips for hands-free use. Arm 4 got the mount, commitment, and tips plus weekly goal gamification and social competition. Arm 5 was the same as Arm 4, plus offered behaviorally designed financial incentives. Postintervention, participants were monitored until the end of their insurance rating period, 25 to 65 d more. Outcome differences were measured using fractional logistic regression. Arm 4 participants, who received gamification and competition, reduced their handheld use by 20.5% relative to control (P < 0.001); Arm 5 participants, who additionally received financial incentives, reduced their use by 27.6% (P < 0.001). Both groups sustained these reductions through the end of their insurance rating period.