OBJECTIVE: The value of upfront primary tumor resection (PTR) for asymptomatic unresectable metastatic colorectal cancer (mCRC) patients remains contentious. This meta-analysis aimed to assess the prognostic significance of upfront PTR for asymptomatic unresectable mCRC.
METHODS: A systematic literature search was performed on June 21st, 2024. To minimize the bias and ensure robust evidence, only randomized controlled trials (RCTs) and case-matched studies (CMS) that compared PTR followed by chemotherapy to chemotherapy alone were included. The primary outcome was overall survival (OS), while cancer-specific survival (CSS) served as the secondary outcome.
RESULTS: Eight studies (three RCTs and five CMS) involving 1221 patients were included. Compared to chemotherapy alone, upfront PTR followed by chemotherapy did not improve OS (hazard ratios [HR] 0.91, 95% confidence interval [CI] 0.79-1.04, P = 0.17), but was associated with slightly better CSS (HR 0.59, 95% CI 0.40-0.88, P = 0.009).
CONCLUSIONS: The current limited evidence indicates that upfront PTR does not improve OS but may enhance CSS in asymptomatic unresectable mCRC patients. Ongoing trials are expected to provide more reliable evidence on this issue.

暂无摘要。

BACKGROUND: Obstructive sleep apnoea (OSA) is a common, but underdiagnosed, sleep disorder. If untreated, it leads to poor health outcomes, including Alzheimer\'s disease, cancer, cardiovascular disease and all-cause mortality. Our aim is to determine the feasibility and cost-effectiveness of moving the testing for OSA into general practice and how general practitioner (GP)-based screening affects overall detection rates.
METHODS: Randomised controlled trial of case finding of OSA in general practice using a novel Medicines and Healthcare products Regulatory Agency-registered device (AcuPebble SA100) compared with usual care with internal feasibility phase. A diverse sample of general practices (approximately 40) from across the West Midlands Clinical Research Network will identify participants from their records. Eligible participants will be aged 50-70 years with body mass index >30 kg/m2 and diabetes (type 1 or 2) and/or hypertension (office blood pressure >145/90 mm Hg or on treatment). They will exclude individuals with known OSA or chronic obstructive pulmonary disease, or those they deem unable to take part. After eligibility screening, consent and baseline assessment, participants will be randomised to either the intervention or control group. Participants in the intervention arm will receive by post the AcuPebble sleep test kit. Those in the control arm will continue with usual care. Follow-up questionnaires will be completed at 6 months. The study is powered (90%) to detect a 5% difference and will require 606 patients in each arm (713 will be recruited to each arm to allow for attrition). Due to the nature of the intervention, participants and GPs will not be blinded to the allocation.
RESULTS: Primary: Detection rate of moderate-to-severe OSA in the intervention group versus control group. Secondary: Time to diagnosis and time to treatment for intervention versus control group for mild, moderate and severe OSA; cost-effectiveness analysis comparing the different testing pathways.
BACKGROUND: The trial started on 1 November 2022. Ethical approval was granted from the South Central Oxford A Research Ethics Committee on 9 June 2023 (23/SC/0188) (protocol amendment version 1.3; update with amendment and approval to renumber to V2.0 on 29 August 2023). Patient recruitment began on 7 January 2024; initial planned end date will be on 31 April 2025.Results will be uploaded to the ISRCTN register within 12 months of the end of the trial date, presented at conferences, submitted to peer-reviewed journals and distributed via our patient and public involvement networks.The University of Warwick will act as the trial sponsor. The trial will be conducted in accordance with the Sponsor and Primary Care Clinical Trials Unit standard operating procedures.
BACKGROUND: ISRCTN 16982033.

BACKGROUND: Pakistan has significantly strengthened its capacity for active case finding (ACF) for tuberculosis (TB) that is being implemented at scale in the country. However, yields of ACF have been lower than expected, raising concerns on its effectiveness in the programmatic setting. Distribution of TB in communities is likely to be spatially heterogeneous and targeting of ACF in areas with higher TB prevalence may help improve yields. The primary aim of SPOT-TB is to investigate whether a policy change to use a geographically targeted approach towards ACF supported by an artificial intelligence (AI) software, MATCH-AI, can improve yields in Pakistan.
METHODS: SPOT-TB will use a pragmatic, stepped wedge cluster randomised design. A total of 30 mobile X-ray units and their field teams will be randomised to receive the intervention. Site selection for ACF in the intervention areas will be guided primarily through the use of MATCH-AI software that models subdistrict TB prevalence and identifies potential disease hotspots. Control areas will use existing approaches towards site selection that are based on staff knowledge, experience and analysis of historical data. The primary outcome measure is the difference in bacteriologically confirmed incident TB detected in the intervention relative to control areas. All remaining ACF-related procedures and algorithms will remain unaffected by this trial.
BACKGROUND: Ethical approval has been obtained from the Health Services Academy, Islamabad, Pakistan (7-82/IERC-HSA/2022-52) and from the Common Management Unit for TB, HIV and Malaria, Ministry of Health Services, Regulation and Coordination, Islamabad, Pakistan (26-IRB-CMU-2023). Findings from this study will be disseminated through publications in peer-reviewed journals and stakeholder meetings in Pakistan with the implementing partners and public-sector officials. Findings will also be presented at local and international medical and public health conferences.
BACKGROUND: NCT06017843.

暂无摘要。

Despite progress in reducing the infant mortality in India, the neonatal mortality decline has been slower, necessitating concerted efforts to achieve Sustainable Development Goal-3. A promising strategy aiming to prevent neonatal sepsis in high-risk, vulnerable, low birth weight neonates through an innovative intervention includes probiotic supplementation. This article communicates the decision by the ProSPoNS trial investigators to establish a Central Endpoint Adjudication Committee (CEAC) as an addendum to the protocol published in Trials in 2021 for the purpose of clarifying the primary outcome. In the published protocol, the study hypothesis and primary objective are based on \"sepsis,\" the primary outcome has been specified as sepsis/PSBI, whereas the sample size estimation was performed based on the \"physician diagnosed sepsis.\" To align all the three above, the investigators meeting, held on 17th-18th August 2023, at MGIMS Sevagram, Wardha, deliberated and unanimously agreed that \"physician diagnosed sepsis\" is the primary study outcome which includes sepsis/PSBI. The CEAC, chaired by an external subject expert and members including trial statistician, a microbiologist, and all site principal investigators will employ four criteria to determine \"physician diagnosed sepsis\": (1) blood culture status, (2) sepsis screen status, (3) PSBI/non-PSBI signs and symptoms, and (4) the clinical course for each sickness event. Importantly, this clarification maintains consistency with the approved study protocol (Protocol No. 5/7/915/2012 version 3.1 dated 14 Feb 2020), emphasizing the commitment to methodological transparency and adherence to predefined standards. The decision to utilize the guidance of a CEAC is recommended as the gold standard in multicentric complex clinical trials to achieve consistency and accuracy in assessment of outcomes.Trial registrationClinical Trial Registry of India (CTRI) CTRI/2019/05/019197. Registered on 16 May 2019.

A systematic review (SR) of published efficacy studies in visceral leishmaniasis (VL) was undertaken to describe methodological aspects of design, conduct, analysis, and reporting. Studies published during 2000-2021 and indexed in the Infectious Diseases Data Observatory VL library of clinical studies were eligible for inclusion (N = 89 studies). Of the 89 studies, 40 (44.9%) were randomized, 33 (37.1%) were single-armed, 14 (15.7%) were nonrandomized multiarmed studies, and randomization status was unclear in two (2.2%). After initial screening, disease confirmation was done by microscopy in 26 (29.2%) and by a combination of serology and microscopy in 63 (70.8%). Post-treatment follow-up duration was <6 months in three (3.3%) studies, 6 months in 75 (84.3%), and >6 months in 11 (12.4%) studies. Confirmation of relapse was solely based on clinical suspicion in four (4.5%) studies, parasitological demonstration in 64 (71.9%), using molecular/serological/parasitological method in 6 (6.7%), and there was no information in 15 (16.9%). Of the 40 randomized studies, sample size calculation was reported in only 22 (55.0%) studies. This review highlights substantial variations in definitions adopted for disease diagnosis and therapeutic outcomes suggesting a need for a harmonized trials protocol.

BACKGROUND: Hematopoietic cell transplantation (HCT) is a highly invasive and life-threatening treatment for hematological neoplasms and some types of cancer that can challenge the patient\'s meaning structures. Restoring meaning (i.e., building more flexible and significant explanations of the disease and treatment burden) can be aided by strengthening psychological flexibility by means of an Acceptance and Commitment Therapy (ACT) intervention. Thus, this trial aims to examine the effect of the ACT intervention on the meaning-making process and the underlying mechanisms of change in patients following HCT compared to a minimally enhanced usual care (mEUC) control group. The trial will be enhanced with a single-case experimental design (SCED), where ACT interventions will be compared between individuals with various pre-intervention intervals.
METHODS: In total, 192 patients who qualify for the first autologous or allogeneic HCT will be recruited for a two-armed parallel randomized controlled trial comparing an online self-help 14-day ACT training to education sessions (recommendations following HCT). In both conditions, participants will receive once a day a short survey and intervention proposal (about 5-10 min a day) in the outpatient period. Double-blinded assessment will be conducted at baseline, during the intervention, immediately, 1 month, and 3 months after the intervention. In addition, 6-9 participants will be invited to SCED and randomly assigned to pre-intervention measurement length (1-3 weeks) before completing ACT intervention, followed by 7-day observations at the 2nd and 3rd post-intervention measure. The primary outcome is meaning-related distress. Secondary outcomes include psychological flexibility, meaning-making coping, meanings made, and well-being as well as global and situational meaning.
CONCLUSIONS: This trial represents the first study that integrates the ACT and meaning-making frameworks to reduce meaning-related distress, stimulate the meaning-making process, and enhance the well-being of HCT recipients. Testing of an intervention to address existential concerns unique to patients undergoing HCT will be reinforced by a statistically rigorous idiographic approach to see what works for whom and when. Since access to interventions in the HCT population is limited, the web-based ACT self-help program could potentially fill this gap.
BACKGROUND: ClinicalTrials.gov ID: NCT06266182. Registered on February 20, 2024.

BACKGROUND: Emulation of the \"target trial\" (TT), a hypothetical pragmatic randomized controlled trial (RCT), using observational data can be used to mitigate issues commonly encountered in comparative effectiveness research (CER) when randomized trials are not logistically, ethically, or financially feasible. However, cardiovascular (CV) health research has been slow to adopt TT emulation. Here, we demonstrate the design and analysis of a TT emulation using electronic health records to study the comparative effectiveness of the addition of a disease-modifying anti-rheumatic drug (DMARD) to a regimen of methotrexate on CV events among rheumatoid arthritis (RA) patients.
METHODS: We used data from an electronic medical records-based cohort of RA patients from Northwestern Medicine to emulate the TT. Follow-up began 3 months after initial prescription of MTX (2000-2020) and included all available follow-up through June 30, 2020. Weighted pooled logistic regression was used to estimate differences in CVD risk and survival. Cloning was used to handle immortal time bias and weights to improve baseline and time-varying covariate imbalance.
RESULTS: We identified 659 eligible people with RA with average follow-up of 46 months and 31 MACE events. The month 24 adjusted risk difference for MACE comparing initiation vs non-initiation of a DMARD was -1.47% (95% confidence interval [CI]: -4.74, 1.95%), and the marginal hazard ratio (HR) was 0.72 (95% CI: 0.71, 1.23). In analyses subject to immortal time bias, the HR was 0.62 (95% CI: 0.29-1.44).
CONCLUSIONS: In this sample, we did not observe evidence of differences in risk of MACE, a finding that is compatible with previously published meta-analyses of RCTs. Thoughtful application of the TT framework provides opportunities to conduct CER in observational data. Benchmarking results of observational analyses to previously published RCTs can lend credibility to interpretation.

BACKGROUND: Causal graphs are an important tool for covariate selection but there is limited applied research on how best to create them. Here, we used data from the Coronary Drug Project trial to assess a range of approaches to directed acyclic graph (DAG) creation. We focused on the effect of adherence on mortality in the placebo arm, since the true causal effect is believed with a high degree of certainty.
METHODS: We created DAGs for the effect of placebo adherence on mortality using different approaches for identifying variables and links to include or exclude. For each DAG, we identified minimal adjustment sets of covariates for estimating our causal effect of interest and applied these to analyses of the Coronary Drug Project data.
RESULTS: When we used only baseline covariate values to estimate the cumulative effect of placebo adherence on mortality, all adjustment sets performed similarly. The specific choice of covariates had minimal effect on these (biased) point estimates, but including nonconfounding prognostic factors resulted in smaller variance estimates. When we additionally adjusted for time-varying covariates of adherence using inverse probability weighting, covariates identified from the DAG created by focusing on prognostic factors performed best.
CONCLUSIONS: Theoretical advice on covariate selection suggests that including prognostic factors that are not exposure predictors can reduce variance without increasing bias. In contrast, for exposure predictors that are not prognostic factors, inclusion may result in less bias control. Our results empirically confirm this advice. We recommend that hand-creating DAGs begin with the identification of all potential outcome prognostic factors.