Primary Trial Outcome Research Articles

Heterogeneity and Gaps in Reporting Primary Outcomes From Neonatal Trials.

Clear outcome reporting in clinical trials facilitates accurate interpretation and application of findings and improves evidence-informed decision-making. Standardized core outcomes for reporting neonatal trials have been developed, but little is known about how primary outcomes are reported in neonatal trials. Our aim was to identify strengths and weaknesses of primary outcome reporting in recent neonatal trials. Neonatal trials including ≥100 participants/arm published between 2015 and 2020 with at least 1 primary outcome from a neonatal core outcome set were eligible. Raters recruited from Cochrane Neonatal were trained to evaluate the trials' primary outcome reporting completeness using relevant items from Consolidated Standards of Reporting Trials 2010 and Consolidated Standards of Reporting Trials-Outcomes 2022 pertaining to the reporting of the definition, selection, measurement, analysis, and interpretation of primary trial outcomes. All trial reports were assessed by 3 raters. Assessments and discrepancies between raters were analyzed. Outcome-reporting evaluations were completed for 36 included neonatal trials by 39 raters. Levels of outcome reporting completeness were highly variable. All trials fully reported the primary outcome measurement domain, statistical methods used to compare treatment groups, and participant flow. Yet, only 28% of trials fully reported on minimal important difference, 24% on outcome data missingness, 66% on blinding of the outcome assessor, and 42% on handling of outcome multiplicity. Primary outcome reporting in neonatal trials often lacks key information needed for interpretability of results, knowledge synthesis, and evidence-informed decision-making in neonatology. Use of existing outcome-reporting guidelines by trialists, journals, and peer reviewers will enhance transparent reporting of neonatal trials.

Point-of-care viral load testing to manage HIV viraemia during the rollout of dolutegravir-based ART in South Africa: a randomised feasibility study (POwER).

Data is required regarding the feasibility of conducting a randomised trial of point-of-care viral load (VL) testing to guide management of HIV viraemia, and to provide estimates of effect to guide potential future trial design. Two public South African clinics during the dolutegravir-based antiretroviral therapy (ART) rollout. We randomised adults receiving first-line ART, with recent VL ≥1000 copies/mL, in a 1:1 ratio to receive point-of-care Xpert HIV-1 VL versus standard-of-care laboratory VL testing, after 12 weeks. Feasibility outcomes included proportions of eligible patients enrolled and completing follow-up, and VL process outcomes. Estimates of effect were assessed using the trial primary outcome of VL <50 copies/mL after 24 weeks. From August 2020-March 2022 we enrolled 80 eligible participants, an estimated 24% of those eligible. 47/80 (58.8%) were women, and median age was 38.5 years (IQR 33-45). 44/80 (55.0%) were receiving dolutegravir and 36/80 (465.0%) were receiving efavirenz. After 12 weeks, point-of-care participants received VL results after median 3.1 hours (IQR 2.6-3.8), versus 7 days (IQR 6-8, p<0.001) in standard-of-care. 12-week follow-up VL was ≥1000 copies/mL in 13/39 (33.3%) point-of-care participants and in 16/41 (39.0%) standard-of-care participants; 11/13 (84.6%) and 12/16 (75.0%) switched to second-line ART respectively. After 24 weeks, 76/80 (95.0%) completed follow-up. 27/39 (69.2% [95%CI 53.4-81.4]) point-of-care participants achieved VL <50 copies/ml versus 29/40 (72.5% [57.0-83.9]) standard-of-care participants. Point-of-care participants had median 3 (IQR 3-4) clinic visits versus 4 (IQR 4-5) in standard-of-care (p<0.001). It was feasible to conduct a trial of point-of-care VL testing to manage viraemia. Point-of-care VL lead to quicker results and fewer clinical visits, but estimates of 24-week VL suppression were similar between arms.

The NuroSleeve, a user-centered 3D printed hybrid orthosis for individuals with upper extremity impairment

BackgroundActive upper extremity (UE) assistive devices have the potential to restore independent functional movement in individuals with UE impairment due to neuromuscular diseases or injury-induced chronic weakness. Academically fabricated UE assistive devices are not usually optimized for activities of daily living (ADLs), whereas commercially available alternatives tend to lack flexibility in control and activation methods. Both options are typically difficult to don and doff and may be uncomfortable for extensive daily use due to their lack of personalization. To overcome these limitations, we have designed, developed, and clinically evaluated the NuroSleeve, an innovative user-centered UE hybrid orthosis.MethodsThis study introduces the design, implementation, and clinical evaluation of the NuroSleeve, a user-centered hybrid device that incorporates a lightweight, easy to don and doff 3D-printed motorized UE orthosis and a functional electrical stimulation (FES) component. Our primary goals are to develop a customized hybrid device that individuals with UE neuromuscular impairment can use to perform ADLs and to evaluate the benefits of incorporating the device into occupational therapy sessions. The trial is designed as a prospective, open-label, single-cohort feasibility study of eight-week sessions combined with at-home use of the device and implements an iterative device design process where feedback from participants and therapists informs design improvement cycles.ResultsAll participants learned how to independently don, doff, and use the NuroSleeve in ADLs, both in clinical therapy and in their home environments. All participants showed improvements in their Canadian Occupational Performance Measure (COPM), which was the primary clinical trial outcome measure. Furthermore, participants and therapists provided valuable feedback to guide further development.ConclusionsOur results from non-clinical testing and clinical evaluation demonstrate that the NuroSleeve has met feasibility and safety goals and effectively improved independent voluntary function during ADLs. The study’s encouraging preliminary findings indicate that the NuroSleeve has met its technical and clinical objectives while improving upon the limitations of the existing UE orthoses owing to its personalized and flexible approach to hardware and firmware design.Trial Registration: ClinicalTrials.gov identifier: NCT04798378, https://clinicaltrials.gov/ct2/show/NCT04798378, date of registration: March 15, 2021.

Sample size estimation in clinical trials using ventilator-free days as the primary outcome: a systematic review

BackgroundVentilator-free days (VFDs) are a composite endpoint increasingly used as the primary outcome in critical care trials. However, because of the skewed distribution and competitive risk between components, sample size estimation remains challenging. This systematic review was conducted to systematically assess whether the sample size was congruent, as calculated to evaluate VFDs in trials, with VFDs’ distribution and the impact of alternative methods on sample size estimation.MethodsA systematic literature search was conducted within the PubMed and Embase databases for randomized clinical trials in adults with VFDs as the primary outcome until December 2021. We focused on peer-reviewed journals with 2021 impact factors greater than five. After reviewing definitions of VFDs, we extracted the sample size and methods used for its estimation. The data were collected by two independent investigators and recorded in a standardized, pilot-tested forms tool. Sample sizes were calculated using alternative statistical approaches, and risks of bias were assessed with the Cochrane risk-of-bias tool.ResultsOf the 26 clinical trials included, 19 (73%) raised “some concerns” when assessing risks of bias. Twenty-four (92%) trials were two-arm superiority trials, and 23 (89%) were conducted at multiple sites. Almost all the trials (96%) were unable to consider the unique distribution of VFDs and death as a competitive risk. Moreover, significant heterogeneity was found in the definitions of VFDs, especially regarding varying start time and type of respiratory support. Methods for sample size estimation were also heterogeneous, and simple models, such as the Mann–Whitney–Wilcoxon rank-sum test, were used in 14 (54%) trials. Finally, the sample sizes calculated varied by a factor of 1.6 to 17.4.ConclusionsA standardized definition and methodology for VFDs, including the use of a core outcome set, seems to be required. Indeed, this could facilitate the interpretation of findings in clinical trials, as well as their construction, especially the sample size estimation which is a trade-off between cost, ethics, and statistical power.Systematic review registration PROSPERO ID: CRD42021282304. Registered 15 December 2021 (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021282304).

The impact of an e-newsletter or animated video to disseminate outdoor free-play information in relation to COVID-19 guidelines in New South Wales early childhood education and care services: a randomised controlled trial

BackgroundState-based Guidelines were issued for Early Childhood Education and Care (ECEC) services (caring for children 0–6 years) recommending greater time outdoors and inclusion of indoor-outdoor programs to facilitate social distancing to reduce spread of COVID-19. The aim of this 3-arm randomised controlled trial (RCT) was to examine the impact of different dissemination strategies on increasing ECEC service intentions to adopt recommendations from the Guidelines.MethodsThis was a post-intervention only RCT. A sample of eligible ECEC services in New South Wales (n = 1026) were randomly allocated to one of three groups; (i) e-newsletter resource; (ii) animated video resource; or (iii) control (standard email). The intervention was designed to address key determinants of guideline adoption including awareness and knowledge. Following delivery of the intervention in September 2021, services were invited to participate in an online or telephone survey from October-December 2021. The primary trial outcome was the proportion of services intending to adopt the Guidelines, defined as intention to; (i) offer an indoor-outdoor program for the full day; or (ii) offer more outdoor play time. Secondary outcomes included awareness, reach, knowledge and implementation of the Guidelines. Barriers to Guideline implementation, cost of the dissemination strategies and analytic data to measure fidelity of intervention delivery were also captured.ResultsOf the 154 services that provided post-intervention data, 58 received the e-newsletter (37.7%), 50 received the animated video (32.5%), and 46 received the control (29.9%). Services who received the animated video had nearly five times the odds (OR: 4.91 [1.03, 23.34] p = 0.046) than those in the control group, to report having intentions to adopt the Guidelines. There were no statistically significant differences in awareness or knowledge of the Guidelines between either intervention or control services. Development costs were greatest for the animated video. The extent to which the dissemination strategy was viewed in full, were similar for both the e-newsletter and animated video.ConclusionThis study found potential for the inclusion of interactive strategies to disseminate policy and guideline information within the ECEC setting, in the context of the need for rapid communication. Further research should explore the added benefits of embedding such strategies within a multi-strategy intervention.Trial registrationRetrospectively registered with the Australian New Zealand Clinical Trials Registry (ANZCTR) on the 23/02/2023 (ACTRN 12,623,000,198,628).

Protocol: carrageenan for the prevention of oral HPV infection – a feasibility randomised clinical trial

IntroductionHead and neck cancers (HNCs) are a significant health burden worldwide. Oral human papillomavirus (HPV) infection is a major risk factor for HNCs. Unfortunately, currently available prophylactic vaccines have limited...

Baseline Findings of PreventE4: A Double-Blind Placebo Controlled Clinical Trial Testing High Dose DHA in APOE4 Carriers before the Onset of Dementia

IntroductionLower blood levels of the omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) are correlated with worse cognitive functions, particularly among APOE ε4 carriers. Whether DHA supplementation in APOE ε4 carriers with limited DHA consumption and dementia risk factors can delay or slow down disease progression when started before the onset of clinical dementia is not known.MethodsPreventE4 is a double-blind, single site, randomized, placebo-controlled trial in cognitively unimpaired individuals with limited omega-3 consumption and dementia risk factors (n=368). Its objectives are to determine (1) whether carrying the APOE ε4 allele is associated with lower delivery of DHA to the brain; and (2) whether high dose DHA supplementation affects brain imaging biomarkers of AD and cognitive function.Results365 cognitively unimpaired individuals between 55 and 80 (mean age 66) were randomized to 2 grams of DHA per day or identically appearing placebo for a period of 2 years. Half the participants were asked to complete lumbar punctures at baseline and 6-month visits to obtain cerebrospinal fluid (CSF). The primary trial outcome measure is the change in CSF DHA to arachidonic acid ratio after 6 months of the intervention (n=181). Secondary trial outcomes include the change in functional and structural connectivity using resting state functional MRI at 24 months (n=365). Exploratory outcomes include the change in Repeatable Battery of the Assessment of Neuropsychological Status at 24 months (n=365).ConclusionsFindings from PreventE4 will clarify the brain delivery of DHA in individuals carrying the APOE ε4 allele with implications for dementia prevention strategies. Trial was registered as NCT03613844.

Cell-free DNA in plasma and ascites as a biomarker of bevacizumab response: A translational sub-study of the REZOLVE (ANZGOG-1101) clinical trial.

5561 Background: The REZOLVE clinical trial investigated the effect of administering bevacizumab via the intraperitoneal route to reduce re-accumulation of ascites in patients with ovarian cancer who were not suitable for further chemotherapy. Plasma and ascites were collected throughout for translational research. Ascites contains cell-free DNA (cfDNA), a large proportion of which is tumour derived (ctDNA). There is increasing interest in cfDNA in plasma, yet little is known of it in ascites. Objectives: To compare cfDNA in ascites and plasma in terms of total concentration, tumour proportion and endothelial-cell derived (ec-cfDNA) proportion and investigate their association with clinical outcomes (paracentesis-free interval, overall survival) and CA125 level. Methods: Longitudinal plasma and ascites samples were collected from 20/24 participants and stored at -70°C for up to 8.5 years. cfDNA was extracted from 0.3-1 mL fluid using conventional protocols. Standard and methylation-specific PCR was used to measure total cfDNA, ctDNA and ec-cfDNA. Values were correlated with time to paracentesis pre- and post-bevacizumab treatment (the primary trial outcome) as well as overall survival, using log-rank tests. Relationships with clinical CA125 levels were tested by Pearson’s correlation coefficient. Comparisons between plasma and ascites used non-parametric analyses. Results: cfDNA was detected in all samples, with higher yield in ascites (average 669 ng/mL) than plasma (average 75 ng/mL, p&lt;0.0001). ctDNA was detected in 30/32 (94%) ascites samples and 37/56 (68%) plasma samples. ctDNA was detected in plasma and/or ascites from each patient at at least 1 time point. ctDNA proportion was higher in ascites than plasma (p&lt;0.0001) and ec-cfDNA proportion was higher in plasma than ascites (p=0.002). High ctDNA (&gt;75%) in ascites at baseline was associated with significantly shorter paracentesis-free interval (median interval 47.5 versus 84 days, hazard ratio (HR) 2.21, 95% confidence interval (CI) 0.85 to 5.73, p=0.039). ctDNA presence in plasma at baseline was unfavourable for survival (median survival 56 versus 242 days, HR 3.21, 95% CI 1.15 to 9.00, p=0.008). A significant positive correlation was observed between ctDNA proportion in plasma and CA125 level measured within 7 days (p=0.0006). No difference in total cfDNA, ctDNA nor ec-cfDNA was observed between participants who were bevacizumab responders and non-responders in the trial. Conclusions: Sufficient cfDNA was obtained from plasma and ascites to perform qPCR for three biomarkers. Ascites was found to contain proportionately more ctDNA, while plasma contained more ec-cfDNA. The early evidence presented here supports the potential value of cfDNA biomarkers in plasma and ascites, however incorporation of their collection in future clinical trials will allow further investigation.

Use of a targeted, computer/web-based guided self-help psychoeducation toolkit for distressing hallucinations (MUSE) in people with an at-risk mental state for psychosis: protocol for a randomised controlled feasibility trial

IntroductionIndividuals who access at-risk mental state (ARMS) services often have unusual sensory experiences and levels of distress that lead them to seek help. The Managing Unusual Sensory Experiences (MUSE) treatment...

Cardiorenal protective effects of canagliflozin in CREDENCE according to glucose lowering

IntroductionRelationships between glycemic-lowering effects of sodium glucose co-transporter 2 inhibitors and impact on kidney and cardiovascular outcomes are uncertain.Research design and methodsWe analyzed 4395 individuals with prebaseline and postbaseline hemoglobin...

Effect of resistance training on HbA1c and other cardiovascular risk factors in patients with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Obesity, hypertension, hyperlipidemia, and other cardiovascular risk factors are commonly clustered in patients with diabetes type II (T2DM). As a result, patients with T2DM are at increased cardiovascular (CV) risk. Exercise therapy is recommended in the prevention and management of patients with T2DM. In the last decade, dynamic resistance training has attracted more interest as an exercise therapy in the management of patients with diabetes. Though, the primary outcome in these intervention trials has mostly been glycated hemoglobin (HbA1c). Given the high prevalence of other CV risk factors in patients with T2DM, knowledge on the impact of dynamic resistance training on the overall CV risk profile of these patients is important. Purpose To perform a systematic review with meta-analysis to investigate the effects of resistance training on HbA1c and other traditional cardiovascular risk factors in patients with T2DM. Methods and analyses A systematic search was conducted in the electronic databases MEDLINE, Embase, SPORTdiscus and PEDro from the earliest date available until the first of September 2021 to identify peer reviewed randomized controlled trials investigating the effect of resistance training on HbA1C in adults with T2DM. Primary outcome was HbA1C. Secondary outcomes included traditional CV risk factors (i.e. blood pressure, blood lipids, body composition) and physical fitness (muscle strength, exercise capacity). Effect sizes were calculated using random effect models. Data are reported as weighted mean and 95% confidence limits. Results Fourteen trials could be included in the meta-analysis. Resistance training was found to significantly reduce HbA1c [-0.35 % (95% CL -0.61 to -0.11)], systolic blood pressure [-4.6 mmHg (95%CL -8.7 to -0.39)], diastolic blood pressure -2.25 (95%CL -4.45 to -0.048)) and body fat (-0 0.038). Muscle strength was significantly improved in the three studies reporting this outcome. Other cardiovascular risk factors including fasting plasma glucose, high-density-lipoprotein, low-density-lipoprotein, triglycerides and peak oxygen uptake capacity (VO2 peak) remained unchanged after resistance training in patients with T2DM. Conclusion The available data suggests that resistance training can exert favorable effects on HbA1C but also on blood pressure, body composition and muscle strength of patients with type 2 diabetes. Further research is needed to determine the impact of different resistance training characteristics such as volume, frequency and type of training on the overall CV risk profile of patients with type 2 diabetes.

Impact of surrogate outcomes in randomized controlled trials for shoulder rotator cuff tears.

Surrogate outcomes are clinical endpoints that are used as substitutes for direct measures of how a patient feels, functions, or survives. The present study aims to analyze the impact of surrogate outcomes on the results of randomized controlled trials on shoulder rotator cuff tears disorders. Randomized controlled trials (RCTs) related to rotator cuff tear conditions published up until 2021 were retrieved from the PubMed and ACCESSSS databases. The primary outcome of the article was considered a surrogate outcome when the authors used radiological, physiologic, or functional variables. The result of the article was considered positive when results supported the intervention based on the trial's primary outcome. We recorded the sample size, the mean follow-up, and the type of funding. Statistical significance was set at p < 0.05. A total of 112 papers were included in the analysis. The mean sample size was 87.6 patients; mean follow-up period was 25.97months. Thirty-six out of 112 RCTs used a surrogate outcome as a primary endpoint. More than half of papers using surrogate outcomes reported a positive finding (20 out of 36), while 10 out of 71 RCTs using patient-centered outcomes favored the intervention (14.08%, p < 0.001) [RR = 3.94 (95% CI 2.07-7.51)]. The mean sample size was smaller in trials using surrogate endpoints (75.11 vs 92.35 patients, respectively, p = 0.049), while the follow-up was shorter (14.12m vs. 31.9m, p < 0.001). Approximately 25% of the papers that reported surrogate endpoints (22.58%) were industry-funded projects. The substitution of surrogate endpoints for patient-important outcomes in shoulder rotator cuff trials quadruplicates the chances of obtaining a favorable result that favors the analyzed intervention.

Robustness of Randomized Control Trials Supporting Current Neurosurgery Guidelines.

Treatment guidelines in neurosurgery are often based on evidence obtained from randomized controlled trials (RCTs). To evaluate the robustness of RCTs supporting current central nervous tumor and cerebrovascular disease guidelines by calculating their fragility index (FI)-the minimum number of patients needed to switch from an event to nonevent outcome to change significant trial primary outcome. We analyzed RCTs referenced in the Congress of Neurological Surgeons and American Association of Neurological Surgeons guidelines on central nervous tumor and cerebrovascular disease management. Trial characteristics, finding of a statistically significant difference in the primary endpoint favoring the experimental intervention, the FI, and FI minus number lost to follow-up were assessed. Of 312 RCTs identified, 158 (50.6%) were published from 2000 to 2010 and 106 (34%) after 2010. Sixty-three trials (19.2%) were categorized as surgical trials, and the rest studied medical treatment (82.0%) or percutaneous intervention (8.33%). The trials had a median power of 80.0% (IQR 80.0-90.0). Of these, 120 trials were eligible for FI calculation. The median FI was 7.0 (IQR 2.0-16.25). Forty-four (36.6%) trials had FI ≤ 3 indicating very low robustness. After adjusting for covariates, recently published trials and trials studying percutaneous interventions were associated with significantly higher FI compared with older trials and trials comparing surgical approaches, respectively. Trials limited to single centers were associated with significantly lower FI. Trials supporting current guidelines on neuro-oncological and neurovascular surgical interventions have low robustness. While the robustness of trials has improved over time, future guidelines must take into consideration this metric in their recommendations.

Exercise-Induced Left Atrial Hypertension in Heart Failure With Preserved Ejection Fraction

BackgroundMany patients with heart failure and preserved ejection fraction have no overt volume overload and normal resting left atrial (LA) pressure. ObjectivesThis study sought to characterize patients with normal resting LA pressure (pulmonary capillary wedge pressure [PCWP] <15 mm Hg) but exercise-induced left atrial hypertension (EILAH). MethodsThe REDUCE LAP-HF II (A Study to Evaluate the Corvia Medical, Inc. IASD System II to Reduce Elevated Left Atrial Pressure in Patients With Heart Failure) trial randomized 626 patients with ejection fraction ≥40% and exercise PCWP ≥25 mm Hg to atrial shunt or sham procedure. The primary trial outcome, a hierarchical composite of death, heart failure hospitalization, intensification of diuretics, and change in health status was compared between patients with EILAH and those with heart failure and resting left atrial hypertension (RELAH). ResultsPatients with EILAH (29%) had similar symptom severity, but lower natriuretic peptide levels, higher 6-minute walk distance, less atrial fibrillation, lower left ventricular mass, smaller LA volumes, lower E/e′, and better LA strain. PCWP was lower at rest, but had a larger increase with exercise in EILAH. Neither group as a whole had a significant effect from shunt therapy vs sham. Patients with EILAH were more likely to have characteristics associated with atrial shunt responsiveness (peak exercise pulmonary vascular resistance <1.74 WU) and no pacemaker (63% vs 46%; P < 0.001). The win ratio for the primary outcome was 1.56 (P = 0.08) in patients with EILAH and 1.51 (P = 0.04) in those with RELAH when responder characteristics were present. ConclusionsPatients with EILAH had similar symptom severity but less advanced myocardial and pulmonary vascular disease. This important subgroup may be difficult to diagnose without invasive exercise hemodynamics, but it has characteristics associated with favorable response to atrial shunt therapy. (A Study to Evaluate the Corvia Medical, Inc. IASD System II to Reduce Elevated Left Atrial Pressure in Patients With Heart Failure [REDUCE LAP-HF TRIAL II]; NCT03088033)

The effect of dichotomization of skewed adjustment covariates in the analysis of clinical trials

Baseline imbalance in covariates associated with the primary outcome in clinical trials leads to bias in the reporting of results. Standard practice is to mitigate that bias by stratifying by those covariates in the randomization. Additionally, for continuously valued outcome variables, precision of estimates can be (and should be) improved by controlling for those covariates in analysis. Continuously valued covariates are commonly thresholded for the purpose of performing stratified randomization, with participants being allocated to arms such that balance between arms is achieved within each stratum. Often the thresholding consists of a simple dichotomization. For simplicity, it is also common practice to dichotomize the covariate when controlling for it at the analysis stage. This latter dichotomization is unnecessary, and has been shown in the literature to result in a loss of precision when compared with controlling for the covariate in its raw, continuous form. Analytic approaches to quantifying the magnitude of the loss of precision are generally confined to the most convenient case of a normally distributed covariate. This work generalises earlier findings, examining the effect on treatment effect estimation of dichotomizing skew-normal covariates, which are characteristic of a far wider range of real-world scenarios than their normal equivalents.

A protocol for a cluster randomized trial of care delivery models to improve the quality of smoking cessation and shared decision making for lung cancer screening

BackgroundPatients eligible for lung cancer screening (LCS) are those at high risk of lung cancer due to their smoking histories and age. While screening for LCS is effective in lowering lung cancer mortality, primary care providers are challenged to meet beneficiary eligibility for LCS from the Centers for Medicare & Medicaid Services, including a patient counseling and shared decision-making (SDM) visit with the use of patient decision aid(s) prior to screening. MethodsWe will use an effectiveness-implementation type I hybrid design to: 1) identify effective, scalable smoking cessation counseling and SDM interventions that are consistent with recommendations, can be delivered on the same platform, and are implemented in real-world clinical settings; 2) examine barriers and facilitators of implementing the two approaches to delivering smoking cessation and SDM for LCS; and 3) determine the economic implications of implementation by assessing the healthcare resources required to increase smoking cessation for the two approaches by delivering smoking cessation within the context of LCS. Providers from different healthcare organizations will be randomized to usual care (providers delivering smoking cessation and SDM on site) vs. centralized care (smoking cessation and SDM delivered remotely by trained counselors). The primary trial outcomes will include smoking abstinence at 12-weeks and knowledge about LCS measured at 1-week after baseline. ConclusionThis study will provide important new evidence about the effectiveness and feasibility of a novel care delivery model for addressing the leading cause of lung cancer deaths and supporting high-quality decisions about LCS. ClinicalTrials.gov protocol registrationNCT04200534 Trial registrationClinicalTrials.govNCT04200534

Pulmonary important outcomes after extremely preterm birth: Parental perspectives.

To describe pulmonary important outcomes (PIO) reported by parents of children born extremely preterm. Over 1-year, all parents of children aged 18 months-7-years born <29 weeks' GA were asked regarding their perspectives. The proportion of parents who described PIO and the themes they invoked were examined. Results were analysed using mixed methods. Among parental responses (n= 285, 98% participation rate), 44% spoke about PIO, invoking 24 themes pertaining to NICU hospitalisation and/or long-term respiratory health. Some themes had an impact primarily on the child (e.g. exercise limitation), while the majority had an impact on the whole family (e.g. hospital readmissions). None mentioned oxygen at 36 weeks nor bronchopulmonary dysplasia (BPD). The proportion of responses invoking PIO were statistically similar between parents of children with and without BPD, born before or after 25 weeks or with birthweight < or ≥750 g. PIO were more likely to be mentioned in males and among those readmitted for respiratory problems. Parents describe many PIO, most related to the functional impact of lung disease on their child (and family), rather than the diagnosis of BPD itself. Most of these PIO are not primary outcomes in large neonatal trials nor collected in neonatal databases.

Definitions, rates and associated mortality of ICU-acquired pneumonia: A multicenter cohort study

IntroductionWe aimed to analyze intensive care unit (ICU)-acquired pneumonia according to 7 definitions, estimating associated hospital mortality. MethodsThis cohort study was nested within an international randomized trial, evaluating the effect of probiotics on ICU-acquired pneumonia in 2650 mechanically ventilated adults. Each clinically suspected pneumonia was adjudicated by two physicians blinded to allocation and center. The primary outcome was ventilator-associated pneumonia (VAP) informed by ventilation for ≥2 days, new, progressive or persistent infiltrate plus 2 of: temperature > 38 °C or < 36 °C; leukopenia (<3 × 10(Fernando et al., 20206)/L) or leukocytosis (>10 × 10(Fernando et al., 20206)/L); and purulent sputum. We also used 6 other definitions estimating the risk of hospital mortality. ResultsThe frequency of ICU-acquired pneumonia varied by definition: the trial primary outcome VAP (21.6%), Clinical Pulmonary Infection Score (CPIS) (24.9%), American College Chest Physicians (ACCP) (25.0%), International Sepsis Forum (ISF) (24.4%), Reducing Oxidative Stress Study (REDOXS) (17.6%), Centers for Disease Control (CDC) (7.8%), and invasively microbiologically confirmed (1.9%). The trial primary outcome VAP (HR 1.31 [1.08, 1.60]), ISF (HR 1.32 [1.09,1.60]), CPIS (HR 1.30 [1.08,1.58]) and ACCP definitions (HR 1.22 [1.00,1.47]) were associated with hospital mortality. ConclusionsRates of ICU-acquired pneumonia vary by definition and are associated with differential increased risk of death.

Effectiveness and cost-effectiveness of a digital health intervention to support patients with colorectal cancer prepare for and recover from surgery: study protocol of the RecoverEsupport randomised controlled trial

IntroductionSurgery is the most common treatment for colorectal cancer (CRC) and can cause relative long average length of stay (LOS) and high risks of unplanned readmissions and complications. Enhanced Recovery...

Project T-SHARP: study protocol for a multi-site randomized controlled trial of tele-harm reduction for people with HIV who inject drugs

BackgroundThe resurgence of HIV outbreaks and rising prevalence among people who inject drugs (PWID) remain exigent obstacles to Ending the HIV Epidemic in the USA. Adapting a low threshold, comprehensive treatment model for PWID with HIV can leverage syringe services programs (SSPs) to increase availability and accessibility of antiretrovirals (ART), medications for opioid use disorder (MOUD), and hepatitis C cure. We developed Tele-Harm Reduction, a telehealth-enhanced, harm reduction intervention delivered within an SSP venue.MethodsThe T-SHARP trial is an open-label, multi-site, randomized controlled superiority trial with two parallel treatment arms. Participants (n=240) recruited from SSPs in Miami, Ft. Lauderdale, and Tampa, Florida, who are PWID with uncontrolled HIV (i.e., HIV RNA>200) will be randomized to Tele-Harm Reduction or off-site linkage to HIV care. The primary objective is to compare the efficacy of Tele-Harm Reduction for initiation of ART at SSPs vs. off-site linkage to an HIV clinic with respect to viral suppression across follow-up (suppression at 3, 6, and 12 months post randomization). Participants with HIV RNA<200 copies/ml will be considered virally suppressed. The primary trial outcome is time-averaged HIV viral suppression (HIV RNA <200 copies/ml) over 3-, 6-, and 12-month follow-up. Secondary outcomes include initiation of MOUD measured by urine drug screen and HCV cure, defined as achieving 12-week sustained virologic response (negative HCV RNA at 12 weeks post treatment completion). A cost-effectiveness analysis will be performed.DiscussionThe T-SHARP Trial will be the first to our knowledge to test the efficacy of an innovative telehealth intervention with PWID with uncontrolled HIV delivered via an SSP to support HIV viral suppression. Tele-Harm Reduction is further facilitated by a peer to support adherence and bridge the digital divide. This innovative, flipped healthcare model sets aside the traditional healthcare system, reduces multi-level barriers to care, and meets PWID where they are. The T-SHARP trial is a pragmatic clinical trial that seeks to transform the way that PWID access HIV care and improve HIV clinical outcomes.Trial registrationClinicalTrials.gov NCT05208697. Trial registry name: Tele-Harm Reduction. Registration date: January 26, 2022.