JAMA Network Open最新文献

Importance: Eligibility criteria for randomized clinical trials (RCTs) are designed to select clinically relevant patient populations. However, not all eligibility criteria are strongly justified, potentially excluding marginalized groups, and limiting the generalizability of trial findings.

Objective: To summarize and evaluate the justification of exclusion criteria in published RCTs in critical care medicine.

Evidence review: A systematic sampling review of parallel-group RCTs published in the top 5 general internal medicine journals by impact factor (The Lancet, New England Journal of Medicine, Journal of the American Medical Association, British Medical Journal, and Annals of Internal Medicine) between January 1, 2018, and February 23, 2023, was conducted. RCTs enrolling adults in intensive care units (ICUs) and RCTs enrolling critically ill patients who required life-sustaining interventions typically initiated in the ICU were included. All study exclusion criteria were categorized as either poorly justified, potentially justified, or strongly justified, adapting previously established criteria, independently and in duplicate.

Findings: In total, 225 studies were identified, 75 of which were included. The median (IQR) number of exclusion criteria per trial was 19 (14-24), with 1455 total exclusion criteria. Common exclusion criteria were related to the risk of adverse reaction to interventions (302 criteria [20.8%]), followed by inability to obtain consent (120 criteria [8.2%]), and treatment limitation decisions (97 criteria [6.7%]). Most exclusion criteria were either strongly justified (1080 criteria [74.2%]) or potentially justified (297 criteria [20.4%]), whereas 5.4% (78 criteria) were poorly justified. Of the 78 poorly justified exclusion criteria, the most common were pregnancy (19 criteria [24.4%]), communication barriers (11 criteria [14.1%]), lactation (10 criteria [12.8%]), and lack of health insurance (10 criteria [12.8%]). Overall, 45 of 75 studies (60.0%) had at least 1 poorly justified exclusion criteria.

Conclusions and relevance: Most exclusion criteria in critical care medicine RCTs were strongly justifiable. Across poorly justified criteria, the most common exclusions were pregnant or lactating persons, those with communication barriers, and individuals without health insurance. This highlights the need to carefully consider exclusion criteria when designing trials to minimize the inappropriate exclusion of participants and enhance generalizability.

Importance: Nelonemdaz selectively antagonizes the 2B subunit of the N-methyl-d-aspartate glutamate receptor and scavenges free radical species.

Objective: To evaluate whether nelonemdaz enhances the clinical outcomes of patients with acute ischemic stroke undergoing emergent reperfusion therapy.

Design, setting, and participants: This multicenter double-blind placebo-controlled randomized phase 3 trial (December 25, 2021, to June 30, 2023, in South Korea) recruited patients with acute ischemic stroke who met the following criteria: National Institutes of Health Stroke Scale score greater than or equal to 8, Alberta Stroke Program Early Computed Tomography score greater than or equal to 4, and endovascular thrombectomy within 12 hours after stroke onset.

Intervention: Patients were assigned in a 1:1 ratio to receive intravenous infusions of nelonemdaz twice a day for 5 days or a matching placebo.

Main outcomes and measures: The primary end point was a favorable shift in the modified Rankin scale (mRS) 12 weeks after stroke onset. The secondary end points included various composites of the mRS at 5 and 12 weeks, symptomatic intracranial hemorrhage, and infarct volume. Both intention-to-treat and per-protocol analyses were conducted.

Results: A total of 496 patients were enrolled across 24 Korean stroke centers, of whom 39 dropped out (254 men [55.6%]; mean [SD] age, 72.9 [12.1] years). Baseline characteristics of study participants did not significantly differ. For the primary end point, the distribution of the mRS scores at 12 weeks did not significantly differ between the nelonemdaz and placebo groups (common odds ratio, 0.95; 95% CI, 0.69-1.31). For the secondary end points, a median of mRS at 5 weeks (3 vs 3) and mRS 0 at 12 weeks (18.1% vs 18.2%) did not differ substantially between groups. The occurrence of symptomatic intracranial hemorrhage (2.7% vs 0.9%) and infarct volume within 24 hours of the last trial drug infusion (42 vs 38 mL) did not differ significantly between groups. No serious adverse events were reported regarding the trial drug and placebo.

Conclusions and relevance: In this randomized clinical trial, nelonemdaz did not meet the primary efficacy end point compared with placebo.

Trial registration: ClinicalTrials.gov Identifier: NCT05041010.

Importance: Cervical cancer screening is a crucial public health intervention, but screening disparities exist for women with physical disabilities (WWPD).

Objective: To explore the experiences of WWPD with both traditional speculum examination-based screening and at-home self-sampling for cervical cancer screening.

Design, setting, and participants: This qualitative study enrolled 56 WWPD to test self-sampling kits, provide feedback via a survey, and participate in a qualitative interview. An interprofessional team conducted semistructured interviews with 16 key informants and 40 pilot participants for 56 WWPD from November 1, 2021, through April 30, 2023. All completed a self-administered quantitative survey. Key informants' experiences with 4 self-sampling devices helped determine which 2 self-sampling kits would be offered to participants in a pilot study.

Main outcomes and measures: A coding scheme was developed to represent inductive codes generated through preliminary coding and deductive codes representing domains from the Theoretical Domains Framework. This coding scheme was used to conduct a 2-pass thematic analysis.

Results: Of the 56 WWPD (mean [SD] age, 45.4 [9.1] years) who participated in the study, 28 (50.0%) were up to date with cervical cancer screening. Participants described accessibility barriers and clinician ableism that made speculum-based in-office examinations difficult, leading some participants to delay or avoid screening. In contrast, participants described self-screening as more comfortable and convenient, regardless of whether they prefer future speculum-based screening. Their responses also allowed for the exploration of how screening preferences may impact future screening behavior.

Conclusions and relevance: Interviews with WWPD suggested that access to self-sampling screening options would be more comfortable for cervical cancer screening participation. Understanding participants' experiences with self-sampling devices generates insights into improving screening experiences for WWPD.

Importance: Transportation insecurity and lack of social support are 2 understudied social determinants of health that contribute to excess morbidity, mortality, and acute health care utilization. However, whether and how these social determinants of health are associated with cancer screening has not been determined and has implications for preventive care.

Objective: To determine whether transportation insecurity or social support are associated with screening adherence for colorectal, breast, and cervical cancer.

Design, setting, and participants: This cohort study used data from the publicly available 2018 in-person National Health Interview Survey (NHIS) comprising a noninstitutionalized, civilian adult population of the United States. Participants included adults eligible for colorectal, breast, or cervical cancer screening who participated in the in-depth NHIS interview (1 selected per household). Data were acquired in December 2023 and analyzed through July 31, 2024.

Exposures: Transportation insecurity, represented dichotomously as adults who reported that they have or have not delayed medical care in the past year due to transportation difficulties, and neighborhood social support, represented as factor scores derived from 4 Likert-type questions.

Main outcomes and measures: The primary outcome was adherence to the US Preventive Services Task Force screening recommendations in place during 2018 for colorectal, breast, and cervical cancer.

Results: In 2018, of 25 417 NHIS respondents (55% female), 660 (3%) reported delaying medical care because they did not have transportation. In fully adjusted models, transportation insecurity was associated with adherence to breast cancer screening (odds ratio [OR], 0.59 [95% CI, 0.40-0.86]) but not to colorectal (OR, 0.87 [95% CI, 0.65-1.15]) or cervical (OR, 0.73 [95% CI, 0.46-1.13) cancer screening. Social support was associated with colorectal (OR, 1.12 [95% CI, 1.06-1.17]) and breast (OR, 1.13 [95% CI, 1.05-1.22]) cancer screening but not with cervical cancer screening (OR, 1.01 [95% CI, 0.93-1.10]). There were no significant interactions between transportation insecurity and social support for any cancer screening.

Conclusions and relevance: The presence of transportation insecurity was associated with a 41% reduction in the odds of breast cancer screening. Clinicians should consider screening for transportation needs at the time of mammography referral, as patients may be eligible for programs that can assist with medical transportation needs.