Tag: pubmed

JAMA Surg. 2024 Nov 27. doi: 10.1001/jamasurg.2024.5227. Online ahead of print.

ABSTRACT

IMPORTANCE: Evidence suggests that prophylactic abdominal drainage after gastrectomy for cancer may reduce postoperative morbidity and hospital stay but this evidence comes from small studies with a high risk of bias. Further research is needed to determine whether drains safely meet their primary purpose of identifying and managing postoperative intraperitoneal collections without the need for reoperation or additional percutaneous drainage.

OBJECTIVE: To determine whether avoiding routine abdominal drainage increased postoperative invasive procedures.

DESIGN, SETTING, AND PARTICIPANTS: The Abdominal Drain in Gastrectomy (ADIGE) Trial was a multicenter prospective randomized noninferiority trial. Enrollment spanned from December 2019 to January 2023. Follow-up evaluations were completed at 30 and 90 days. Eleven centers within the Italian Research Group for Gastric Cancer, encompassing both academic medical centers and community hospitals, were included. Patients with gastric cancer undergoing subtotal or total gastrectomy with curative intent were eligible, excluding those younger than 18 years, with serious comorbidities, or undergoing procedure types outside the scope of the study. Of 803 patients assessed for eligibility, 404 were randomized and 390 were included in final analyses.

INTERVENTIONS: Patients were randomized 1:1 into prophylactic drain or no drain arms.

MAIN OUTCOMES AND MEASURES: The primary end point was a modified intention-to-treat (mITT) analysis measuring reoperation or percutaneous drainage within 30 postoperative days. The null hypothesis was rejected when the 90% CI upper limit of the proportion difference did not exceed 3.56%. The calculated sample size to achieve 80% power with a 10% dropout rate was 404 patients (202 in each group). Surgeons and patients were blinded until gastrointestinal reconstruction.

RESULTS: Of the 404 patients randomized 226 (57.8%) were male; the median (IQR) age was 71 (62-78) years. Intraoperative identification of nonresectable disease occurred in 14 patients, leading to their exclusion from the study, leaving 390 patients. In the mITT analysis, 15 patients (7.7%) in the drain group needed reoperation or percutaneous drainage by postoperative day 30 vs 29 (15%) in the no drain group, favoring the drain group (difference, 7.2%; 90% CI, 2.1-12.4; P = .02). Of note, the difference in the primary composite end point was entirely due to a similar difference in reoperation (5.1% in the drain group vs 12.4% in the no drain group; P = .01). Drain-related complications occurred in 4 patients.

CONCLUSIONS AND RELEVANCE: The findings of this study indicate that refraining from prophylactic drain use after gastrectomy heightened the risk of postoperative invasive procedures, discouraging its avoidance. Future studies identifying high-risk groups could optimize prophylactic drainage decisions.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04227951.

PMID:39602143 | DOI:10.1001/jamasurg.2024.5227

JAMA Dermatol. 2024 Nov 27. doi: 10.1001/jamadermatol.2024.4796. Online ahead of print.

ABSTRACT

IMPORTANCE: Prurigo nodularis (PN) is a chronic and debilitating skin condition, characterized by intense itch with multiple nodular lesions. Nemolizumab demonstrated significant improvements in itch and skin nodules in adults with moderate to severe PN in a previous 16-week phase 3 study (OLYMPIA 2).

OBJECTIVE: To assess the efficacy and occurrence of adverse events in adults with moderate to severe PN treated with nemolizumab vs those receiving placebo.

DESIGN, SETTING, AND PARTICIPANTS: OLYMPIA 1 was a multicenter, placebo-controlled, phase 3 randomized clinical trial, conducted from August 2020 to March 2023 at 77 centers across 10 countries in adults with moderate to severe PN (at least 20 nodules and an Investigator’s Global Assessment [IGA] score ≥3) and Peak Pruritus Numerical Rating Scale (PP-NRS) score of at least 7.0; consisted of screening (up to 4 weeks), 24-week treatment, and 8-week follow-up periods.

INTERVENTIONS: Patients were randomized (2:1) to nemolizumab monotherapy, 30 mg or 60 mg (depending on baseline weight of less than 90 kg vs 90 kg or greater, respectively), or matching placebo administered every 4 weeks for 24 weeks.

MAIN OUTCOMES AND MEASURES: The primary end points were the proportion of patients with itch response (≥4-point improvement from baseline in weekly average PP-NRS) and IGA success (score of 0/1 [clear/almost clear] and 2-grade or more improvement from baseline) at week 16.

RESULTS: Of 286 patients (mean [SD] age, 57.5 [13.0] years; mean [SD] body weight, 85.0 [20.7] kg; 166 [58.0%] female), 190 were randomized to receive nemolizumab, and 96 were randomized to placebo. A significantly greater proportion of patients assigned to nemolizumab vs placebo achieved itch response (111/190 [58.4%] vs 16/96 [16.7%]; Δ, 40.1% [95% CI, 29.4%-50.8%]; P < .001) and IGA success (50/190 [26.3%] vs 7/96 [7.3%]; Δ, 14.6% [95% CI, 6.7%-22.6%]; P = .003) at week 16. At week 24, the proportion of patients with itch response was 58.3% vs 20.4% (Δ, 38.7% [95% CI, 27.5%-49.9%]) in the ad hoc analysis, and IGA success was 58/190 (30.5%) vs 9/96 (9.4%) (Δ, 19.2% [95% CI, 10.3%-28.1%]) in the nemolizumab-treated vs placebo group. During the treatment period, 134 patients (71.7%) receiving nemolizumab vs 62 patients (65.3%) receiving placebo had at least 1 adverse event; most events were of mild to moderate severity.

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, nemolizumab monotherapy led to clinically meaningful and statistically significant improvements in core signs and symptoms of PN.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04501666.

PMID:39602139 | DOI:10.1001/jamadermatol.2024.4796

Plant J. 2024 Nov 27. doi: 10.1111/tpj.17164. Online ahead of print.

ABSTRACT

Cannabis sativa L., known for its medicinal and psychoactive properties, has recently experienced rapid market expansion but remains understudied in terms of its fundamental biology due to historical prohibitions. This pioneering study implements GS and ML to optimize cannabinoid profiles in cannabis breeding. We analyzed a representative population of drug-type cannabis accessions, quantifying major cannabinoids and utilizing high-density genotyping with 250K SNPs for GS. Our evaluations of various models-including ML algorithms, statistical methods, and Bayesian approaches-highlighted Random Forest’s superior predictive accuracy for single and multi-trait genomic predictions, particularly for THC, CBD, and their precursors. Multi-trait analyses elucidated complex genetic interdependencies and identified key loci crucial to cannabinoid biosynthesis. These results demonstrate the efficacy of integrating GS and ML in developing cannabis varieties with tailored cannabinoid profiles.

PMID:39602132 | DOI:10.1111/tpj.17164

JAMA Dermatol. 2024 Nov 27. doi: 10.1001/jamadermatol.2024.4832. Online ahead of print.

NO ABSTRACT

PMID:39602129 | DOI:10.1001/jamadermatol.2024.4832

JAMA Netw Open. 2024 Nov 4;7(11):e2446684. doi: 10.1001/jamanetworkopen.2024.46684.

ABSTRACT

IMPORTANCE: Heart failure (HF) hospitalization is a common end point in HF trials; however, how HF hospitalization is associated with all-cause hospitalization in terms of proportionality, correlation of treatment effects, and concomitant reporting has not been studied.

OBJECTIVE: To determine the ratio of HF to all-cause hospitalizations, whether reported treatment effects on HF hospitalization are associated with treatment effects on all-cause hospitalization, and how often all-cause hospitalization is reported alongside HF hospitalization.

DATA SOURCES: PubMed was searched from inception to September 2, 2024, for randomized clinical trials (RCTs) of HF treatments using MeSH (medical subject heading) terms and keywords associated with heart failure, ventricular failure, ventricular dysfunction, and cardiac failure, as well as the names of specific journals.

STUDY SELECTION: RCTs of HF treatments and reporting on HF hospitalization published in 1 of 3 leading medical journals (New England Journal of Medicine, The Lancet, or JAMA).

DATA EXTRACTION AND SYNTHESIS: The PRISMA guidelines were followed. Data extraction was performed by 2 reviewers, and disagreements were resolved by consensus. Trial baseline characteristics and outcome data on HF and all-cause hospitalizations were extracted. The ratio of HF to all-cause hospitalizations was calculated. The association of HF hospitalization effects with all-cause hospitalization effects was evaluated using hierarchical bayesian models with weak priors. The posterior distribution was used to calculate the HF hospitalization treatment effects that would need to be observed before a high probability (97.5%) of a reduction in all-cause hospitalization could be achieved. The proportion of trials reporting all-cause hospitalization was calculated.

MAIN OUTCOMES AND MEASURES: HF and all-cause hospitalizations.

RESULTS: Of 113 trials enrolling 261 068 patients (median proportion of female participants, 25.4% [IQR, 21.3%-34.2%]; median age, 66.2 [IQR, 62.8-70.0] years), 60 (53.1%) reported on all-cause hospitalization. The weighted median ratio of HF to all-cause hospitalizations was 45.9% (IQR, 30.7%-51.7%). This ratio was higher in trials with greater proportions of New York Heart Association class III or IV HF, with lower left ventricular ejection fractions, investigating nonpharmaceutical interventions, and that restricted recruitment to patients with HF and reduced ejection fraction. Reported effects on HF and all-cause hospitalizations were well-correlated (R2 = 90.1%; 95% credible interval, 62.3%-99.8%). In a large trial, the intervention would have to decrease the odds of HF hospitalization by 16% to ensure any reduction, 36% to ensure a 10% reduction, and 56% to ensure a 20% reduction in the odds of all-cause hospitalization with 97.5% probability.

CONCLUSIONS AND RELEVANCE: In this meta-analysis of HF trials, all-cause hospitalization was underreported despite a large burden of non-HF hospitalizations. Large reductions in HF hospitalization must be observed before clinically relevant reductions in all-cause hospitalization can be inferred.

PMID:39602122 | DOI:10.1001/jamanetworkopen.2024.46684

JAMA Netw Open. 2024 Nov 4;7(11):e2447102. doi: 10.1001/jamanetworkopen.2024.47102.

ABSTRACT

IMPORTANCE: Individuals with type 2 diabetes (T2D) have high rates of mortality following myocardial infarction (MI). Hospitalization is an opportunity to initiate or continue evidence-based treatment to reduce risk in individuals with T2D and acute coronary syndrome (ACS).

OBJECTIVE: To determine patterns of evidence-based medication use during the period of transition from admission to discharge after hospitalization for MI or coronary revascularization among individuals with T2D and ACS.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used data from the Centers for Medicare & Medicaid Services (CMS) for January 1, 2018, to June 30, 2020. Medicare beneficiaries older than 18 years with T2D with a qualifying hospitalization were included. Individuals were followed before admission (90 days prior), at discharge (≤90 days), and after discharge (91-180 days after) from a hospitalization for MI or coronary revascularization. Data analysis was performed in June 2023.

EXPOSURES: Demographic data (race, sex, rural vs urban location of care, and comorbidities) were abstracted from CMS data using Master Beneficiary and Summary Files and International Statistical Classification of Diseases, Tenth Revision codes.

MAIN OUTCOME AND MEASURES: Medicare Part D prescription fill records were examined for the following agents: (1) angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), or angiotensin receptor-neprilysin inhibitors (ARNIs); (2) β-blockers; (3) platelet adenosine diphosphate receptor inhibitors (P2Y12Is); (4) statins or proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9Is); and (5) glucagon-like peptide 1 receptor agonists (GLP-1RAs) or sodium glucose cotransporter 2 inhibitors (SGLT2Is). Logistic regression analysis was used to examine the association between covariates and lack of prescription fills in the postdischarge period.

RESULTS: A total of 188 651 eligible Medicare beneficiaries with T2D and hospitalization for MI or coronary revascularization were identified. Their median age was 73.0 (IQR, 67.0-79.0) years, and more than half (111 982 [59.4%]) were men; 18 383 (9.7%) were Black and 153 461 (81.3%) were White. Not filling a cardiovascular medication after hospitalization was associated with not filling that medication at the time of discharge (adjusted risk ratio, 0.27 [95% CI, 0.27-0.28] for ACEIs, ARBs, or ARNIs; 0.24 [0.24-0.25] for β-blockers; 0.20 [0.19-0.20] for P2Y12Is; 0.31 [0.31-0.32] for statins or PCSK9Is; and 0.27 [0.26-0.28] for SGLT2Is or GLP-1RAs).

CONCLUSIONS AND RELEVANCE: In this cohort study of Medicare beneficiaries with T2D, longer-term medication use following hospitalization for MI was associated with medication use at the time of discharge. These findings highlight the critical importance of this period to optimize preventive care for these high-risk individuals. Further implementation science research is needed to develop strategies to improve use of these evidence-based medications.

PMID:39602121 | DOI:10.1001/jamanetworkopen.2024.47102

JAMA Netw Open. 2024 Nov 4;7(11):e2447530. doi: 10.1001/jamanetworkopen.2024.47530.

ABSTRACT

IMPORTANCE: There is a need for biomarkers that predict late recurrence risk and extended endocrine therapy (EET) benefit among patients with early-stage breast cancer (EBC). MammaPrint, a 70-gene expression risk-of-recurrence assay, has been found to project significant EET benefit in patients with assay-classified low-risk tumors.

OBJECTIVE: To determine the test’s utility in identifying which patients with EBC in the IDEAL (Investigation on the Duration of Extended Adjuvant Letrozole) trial could benefit from 5-year vs 2.5-year letrozole treatment.

DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis of the IDEAL randomized clinical trial evaluated postmenopausal women with hormone receptor-positive EBC who were assigned to either 2.5 or 5 years of EET, with 10 years of follow-up after randomization. A 70-gene assay was used to classify tumors as high, low, or ultralow risk. Adverse event (AE) frequency and treatment compliance were evaluated. Statistical analyses were performed from April 2022 to September 2024.

INTERVENTIONS: After 5 years of endocrine therapy, patients were randomized to 2.5 or 5 years of EET with letrozole.

MAIN OUTCOMES AND MEASURES: Primary end point was distant recurrence (DR). Cox proportional hazard regression models and likelihood ratios tested the interaction between treatment and gene expression assay.

RESULTS: Among 515 women included (mean [SD] age at randomization, 59.9 [9.5] years), 265 were in the 2.5-year treatment arm and 250 in the 5-year treatment arm. Of these patients, 223 (43.3%) patients with 70-gene assay-classified low-risk tumors had a significant absolute benefit of 10.1% for DR (hazard ratio, 0.32; 95% CI, 0.12-0.87; P = .03). Treatment interaction was not significant for DR. Of patients with either 70-gene assay-classified high-risk tumors (259 [50.3%]) or ultralow risk tumors (33 [6.4%]), 5 years vs 2.5 years of EET was not associated with improved benefit for DR. As expected, rates of AEs and treatment discontinuation were comparable among the different 70-gene assay risk groups in each treatment arm.

CONCLUSIONS AND RELEVANCE: This secondary analysis of the IDEAL trial found that the 70-gene assay identified patients with low-risk tumors who could benefit from 5-year vs 2.5-year EET. These findings suggest that this gene expression assay could go beyond guiding neoadjuvant and adjuvant chemotherapy decisions to informing the optimal duration of adjuvant endocrine therapy.

TRIAL REGISTRATION: EU Clinical Trials Register Eudra CT: 2006-003958-16.

PMID:39602119 | DOI:10.1001/jamanetworkopen.2024.47530

JAMA Netw Open. 2024 Nov 4;7(11):e2447649. doi: 10.1001/jamanetworkopen.2024.47649.

ABSTRACT

IMPORTANCE: Cancer and its care impose significant time commitments on patients and care partners. The oncology community has only recently conceptualized these commitments and the associated burden as the “time toxicity” of cancer care. As the concept gains traction, there is a critical need to fundamentally understand the perspectives of multiple stakeholders on the time burdens of cancer care.

OBJECTIVES: To explore time-consuming aspects of cancer care that were perceived as burdensome, identify the individuals most affected by time burdens of cancer care, and evaluate the consequences of these time burdens.

DESIGN, SETTING, AND PARTICIPANTS: Participants in this qualitative analysis were recruited from a National Cancer Institute-designated cancer center in Minnesota, where semistructured qualitative interviews were conducted from February 1 to October 31, 2023. Purposive and criterion sampling methods were used to recruit patients (adults with advanced stage gastrointestinal cancer receiving systemic cancer-directed treatment), care partners (patient-identified informal [unpaid] partners), and clinicians (physicians, physician assistants, nurse practitioners, nurses, social workers, and schedulers). Data were analyzed from February 2023 to February 2024.

MAIN OUTCOMES AND MEASURES: Thematic analysis was conducted with a hybrid (inductive and deductive methods) approach. Themes, subthemes, and illustrative quotations are presented.

RESULTS: Interviews included 47 participants (16 patients [8 aged ≤60 years; 12 women (75.0%)], 15 care partners [12 aged ≤60 years; 9 women (60.0%)], and 16 clinicians [11 women (68.7%)]). A total of 31 subthemes were identified that were grouped into 5 themes. Theme 1 captured time burdens due to health care outside the home (eg, travel, parking, and waiting time), while theme 2 identified the often invisible tasks performed at home (eg, handling insurance and medical bills, receiving formal home-based care). Theme 3 explored how care partners are affected alongside patients (eg, burdens extending to the wider network of family, friends, and community) and theme 4 represented the consequences of time burdens (eg, demoralization, seemingly short visits turned into all-day affairs). Finally, theme 5 referenced positive time spent in clinical interactions and hope for change (eg, patients value meaningful care, the “time toxicity” label is a spark for change).

CONCLUSIONS AND RELEVANCE: This qualitative analysis identifies key sources and effects of time toxicity, as well as the populations affected. The results of this study will guide the oncology community to map, measure, and address future time burdens.

PMID:39602118 | DOI:10.1001/jamanetworkopen.2024.47649

JAMA Netw Open. 2024 Nov 4;7(11):e2448003. doi: 10.1001/jamanetworkopen.2024.48003.

ABSTRACT

IMPORTANCE: Seasonal influenza is associated with substantial disease burden. The relationship between census tract-based social vulnerability and clinical outcomes among patients with influenza remains unknown.

OBJECTIVE: To characterize associations between social vulnerability and outcomes among patients hospitalized with influenza and to evaluate seasonal influenza vaccine and influenza antiviral utilization patterns across levels of social vulnerability.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective repeated cross-sectional study was conducted among adults with laboratory-confirmed influenza-associated hospitalizations from the 2014 to 2015 through the 2018 to 2019 influenza seasons. Data were from a population-based surveillance network of counties within 13 states. Data analysis was conducted in December 2023.

EXPOSURE: Census tract-based social vulnerability.

MAIN OUTCOMES AND MEASURES: Associations between census tract-based social vulnerability and influenza outcomes (intensive care unit admission, invasive mechanical ventilation and/or extracorporeal membrane oxygenation support, and 30-day mortality) were estimated using modified Poisson regression as adjusted prevalence ratios. Seasonal influenza vaccine and influenza antiviral utilization were also characterized across levels of social vulnerability.

RESULTS: Among 57 964 sampled cases, the median (IQR) age was 71 (58-82) years; 55.5% (95% CI, 51.5%-56.0%) were female; 5.2% (5.0%-5.4%) were Asian or Pacific Islander, 18.3% (95% CI, 18.0%-18.6%) were Black or African American, and 64.6% (95% CI, 64.2%-65.0%) were White; and 6.6% (95% CI, 6.4%-68%) were Hispanic or Latino and 74.7% (95% CI, 74.3%-75.0%) were non-Hispanic or Latino. High social vulnerability was associated with higher prevalence of invasive mechanical ventilation and/or extracorporeal membrane oxygenation support (931 of 13 563 unweighted cases; adjusted prevalence ratio [aPR], 1.25 [95% CI, 1.13-1.39]), primarily due to socioeconomic status (790 of 11 255; aPR, 1.31 [95% CI, 1.17-1.47]) and household composition and disability (773 of 11 256; aPR, 1.20 [95% CI, 1.09-1.32]). Vaccination status, presence of underlying medical conditions, and respiratory symptoms partially mediated all significant associations. As social vulnerability increased, the proportion of patients receiving seasonal influenza vaccination declined (-19.4% relative change across quartiles; P < .001) as did the proportion vaccinated by October 31 (-6.8%; P < .001). No differences based on social vulnerability were found in in-hospital antiviral receipt, but early in-hospital antiviral initiation (-1.0%; P = .01) and prehospital antiviral receipt (-17.3%; P < .001) declined as social vulnerability increased.

CONCLUSIONS AND RELEVANCE: In this cross-sectional study, social vulnerability was associated with a modestly increased prevalence of invasive mechanical ventilation and/or extracorporeal membrane oxygenation support among patients hospitalized with influenza. Contributing factors may have included worsened baseline respiratory health and reduced receipt of influenza prevention and prehospital or early in-hospital treatment interventions among persons residing in low socioeconomic areas.

PMID:39602116 | DOI:10.1001/jamanetworkopen.2024.48003

JAMA Netw Open. 2024 Nov 4;7(11):e2448010. doi: 10.1001/jamanetworkopen.2024.48010.

ABSTRACT

IMPORTANCE: Patients with a non-English language preference served within English-dominant health care settings are at increased risk of adverse events that may be associated with communication barriers and inequitable access to care.

OBJECTIVE: To investigate the association of non-English language preference with surgical wait time and postoperative outcomes in older patients undergoing hip fracture repair.

DESIGN, SETTING, AND PARTICIPANTS: This population-based, retrospective cohort study was conducted using linked databases to measure surgical wait time and postoperative outcomes among older adults (aged ≥66 years) in Ontario, Canada, who underwent hip fracture surgery between January 1, 2017, and December 31, 2022. Propensity-based overlap weighting accounting for baseline patient characteristics was used to compare primary and secondary outcomes.

EXPOSURE: Non-English language preference.

MAIN OUTCOMES AND MEASURES: The primary outcome was surgical delay beyond 24 hours. Secondary outcomes included time to surgery, surgical delay beyond 48 hours, postoperative medical complications, length of stay, discharge destination, 30-day mortality, and 30-day hospital readmission.

RESULTS: Among 35 238 patients who underwent hip fracture surgery, 28 815 individuals (81.8%) were English speakers (mean [SD] age, 84.4 [8.0] years; 19 965 female [69.3%]) and 6423 individuals (18.2%) were non-English speakers (mean [SD] age, 85.5 [7.0] years; 4556 female [70.9%]). The median (IQR) wait time for surgery was similar for English (24 [16-41] hours) and non-English (25 [16-42] hours) speakers. There was no significant difference in surgical delay beyond 24 hours between English-speaking and non-English-speaking patients (3321 patients [51.7%] vs 14 499 patients [50.3%]; adjusted relative risk [aRR], 1.00; 95% CI, 0.98-1.03). Compared with English speakers, patients with a non-English language preference had increased risk of delirium (4207 patients [14.6%] vs 1209 patients [18.8%]; aRR, 1.10; 95% CI, 1.03-1.17), myocardial infarction (150 patients [0.5%] vs 43 patients [0.7%]; aRR, 1.52; 95% CI, 1.04-2.22), longer length of stay (median [IQR], 10 [6-17] vs 11 [7-20] days; aRR per 1-day increase, 1.11; 95% CI, 1.06-1.15), and more frequent discharge to a nursing home (1814 of 26 673 patients surviving to discharge [6.8%] vs 413 of 5903 patients surviving to discharge [7.0%]; aRR, 1.13; 95% CI, 1.01-1.27).

CONCLUSIONS AND RELEVANCE: In this study of older adults with hip fracture, non-English language preference was associated with increased risk of delirium, myocardial infarction, longer length of stay, and discharge to a nursing home. These findings suggest inequities in hip fracture care for patients with a non-English language preference.

PMID:39602115 | DOI:10.1001/jamanetworkopen.2024.48010