Tag: pubmed

JAMA Netw Open. 2026 Jul 1;9(7):e2621622. doi: 10.1001/jamanetworkopen.2026.21622.

ABSTRACT

IMPORTANCE: Risk and protective factors for suicide mortality in youths remain poorly synthesized, as prior reviews have focused on all ages or nonfatal outcomes.

OBJECTIVE: To systematically assess factors associated with risk of suicide mortality in youths.

DATA SOURCES: MEDLINE, PsycINFO, Embase, and CINAHL from inception to March 7, 2025.

STUDY SELECTION: Case-control and cohort studies of youths (aged ≤24 years) examining risk and/or protective factors associated with suicide mortality vs living general-population controls were included. Two independent reviewers screened 9497 records.

DATA EXTRACTION AND SYNTHESIS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, 2 reviewers independently screened reports; 1 extracted data, verified by a second. Evidence was synthesized using vote counting and random-effects meta-analysis in April 2026.

MAIN OUTCOMES AND MEASURES: The primary outcome was suicide mortality at age 24 years or younger.

RESULTS: Ninety reports from 68 studies, mostly from high-income countries, identified distinct risk and/or protective factors; 54 reports contributed to 30 meta-analyses. The factors associated with the highest odds of suicide risk included schizophrenia (odds ratio [OR], 22.23; 95% CI, 12.05-41.03; I2 = 85.4%; 7 reports), mood disorders (OR, 11.32; 95% CI, 6.11-20.97; I2 = 64.6%; 7 reports), and self-harm (OR, 14.06; 95% CI, 5.58-35.39; I2 = 90.1%; 10 reports). Clinical indicators of health care use were also associated with higher risk, including mental health services use in preceding year (OR, 7.39; 95% CI, 6.45-8.47; I2 = 0.0%; 5 reports) and psychiatric admission (OR, 31.96; 95% CI, 13.83-73.86; I2 = 94.8%; 6 reports). At the socioecological level, several indicators were associated with higher risk, including maltreatment (OR, 4.03; 95% CI, 1.41-11.50; I2 = 67.1%; 5 reports), out-of-home placement (OR, 4.47; 95% CI, 2.15-9.28; I2 = 42.1%; 5 reports), youth justice system involvement (OR, 2.70; 95% CI, 1.94-3.75; I2 = 64.2%; 7 reports), and low educational attainment (OR, 2.95; 95% CI, 1.66-5.24; I2 = 76.0%; 5 reports). In contrast, indicators of family stability were associated with lower risk, including living with both parents (OR, 0.55; 95% CI, 0.48-0.62; I2 = 12.1%; 11 reports). Heterogeneity was substantial across analyses, while Newcastle-Ottawa ratings indicated moderate-to-high study quality.

CONCLUSIONS AND RELEVANCE: In this systematic review and meta-analysis, suicide mortality in youths was associated with mental disorders, health care contact, and adversity, supporting both clinical care and population-level prevention, with future research needed in underrepresented populations.

PMID:42390862 | DOI:10.1001/jamanetworkopen.2026.21622

JAMA Netw Open. 2026 Jul 1;9(7):e2621697. doi: 10.1001/jamanetworkopen.2026.21697.

ABSTRACT

IMPORTANCE: Changes in family structure in the US may be a driving force behind the growing need for friend caregivers. Yet, this segment of caregivers is often overlooked in health care settings and related research.

OBJECTIVE: To provide national estimates of friend caregivers, compare the characteristics of care provided by friend vs family caregivers, and identify characteristics of older adults associated with receiving care from friends.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional analysis of the 2023 National Health and Aging Trends Study included data on older adults (aged ≥65 years).

EXPOSURE: Sociodemographic and health-related characteristics of care recipients.

MAIN OUTCOMES AND MEASURES: The primary outcome was having a friend who provided assistance in the past month due to health or functional limitations. Adjusted Wald tests were used for continuous variables and Rao-Scott χ2 tests for categorical variables to compare characteristics of care provided by friend versus family caregivers and of care recipients receiving friend-involved versus family-only care. Multivariable logistic regression was used to identify older adult characteristics independently associated with friend involvement in care networks.

RESULTS: This study included 451 friend and 4985 family caregivers identified by 2619 older adults with activity limitations (weighted mean [SE] age, 78.7 [0.25] years; 63.2% [95% CI, 60.5%-65.9%] female) representing 2.4 million friend caregivers and 21.4 million family caregivers providing care to approximately 12.2 million recipients. Compared with family caregivers, friend caregivers were less likely to coreside with the care recipient (3.3% [95% CI, 1.6%-6.7%] vs 46.4% [95% CI, 44.2%-48.6%]; P < .001) or serve as the sole caregiver (11.1% [95% CI, 7.7%-15.9%] vs 21.2% [95% CI, 19.4%-23.3%]; P < .001). Although they provided fewer care hours per month than family caregivers (mean [SE], 18.1 [3.8] vs 66.6 [2.7] hours; P < .001), friends were more likely to help with transportation (65.7% [95% CI, 59.8%-71.2%] vs 52.7% [95% CI, 50.6%-54.8%]; P < .001), specialize in a single domain of care (66.4% [95% CI, 60.6%-71.9%] vs 33.6% [95% CI, 31.7%-35.5%]; P < .001), and share care with others. In multivariable models, being older (odds ratio [OR], 0.97; 95% CI, 0.95-0.99; P = .002) and married (OR, 0.52; 95% CI, 0.31-0.97; P = .01) were associated with a lower likelihood of having friends involved in the care network, whereas having a college degree (OR, 1.66; 95% CI, 1.14-2.43; P = .01) and living alone (OR, 2.29; 95% CI, 1.50-3.50; P < .001) were associated with a greater likelihood of having friends involved in the care network.

CONCLUSIONS AND RELEVANCE: In this cross-sectional study of Medicare beneficiaries aged 65 years and older, friend caregivers represented a specialized segment of the unpaid caregiving workforce, particularly for older adults lacking family resources. Understanding how friends provide care can help health care professionals better recognize them as an integral part of the caregiving network.

PMID:42390861 | DOI:10.1001/jamanetworkopen.2026.21697

JAMA Netw Open. 2026 Jul 1;9(7):e2622131. doi: 10.1001/jamanetworkopen.2026.22131.

ABSTRACT

IMPORTANCE: In February 2024, the South Korean government announced plans to increase medical school enrollment by 2000 students to address physician shortages, prompting opposition from the medical community. More than 90% of trainee physicians joined a nationwide walkout that continued through August 2025, but its systemwide implications remain unclear.

OBJECTIVES: To examine the association of the trainee physicians’ walkout with mortality, health care use, and spending patterns in South Korea.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used nationwide health insurance claims data and a historical-control event-study design. Data from 200 teaching hospitals before and after the walkout in week 8 of 2024 were compared, using October 2023 to September 2024 as the exposed year and October 2022 to September 2023 as the historical control.

MAIN OUTCOMES AND MEASURES: The primary outcomes were mortality, health care use, and spending per encounter measured weekly at the hospital level. The association between the trainee physicians’ walkout and hospital-level outcomes was assessed using a group-time average treatment effect framework.

RESULTS: The analysis included 7 719 828 patients with inpatient admissions (3 520 242 [45.6%] aged ≥65 years; 3 883 073 [50.3%] female) and 41 891 392 with outpatient visits (17 552 493 [41.9%] aged ≥65 years; 21 992 981 [52.5%] female). The walkout was associated with a 0.008-percentage point increase in weekly mortality among hospital users (95% CI, 0.000 to 0.015 percentage points) and a 0.39-percentage point increase in 30-day mortality after hospitalization (95% CI, 0.24 to 0.54 percentage points), concentrated among admissions for general conditions. These associations were largest early in the walkout and attenuated over time. The walkout was associated with reductions in both inpatient and outpatient use, with a larger relative decline for inpatient care (decrease of 19.2 hospitalizations per 10 million people; 95% CI, -24.1 to -14.3 per 10 million people [-17.3%] vs decrease of 158 outpatient visits per 10 million people; 95% CI, -198 to -118 visits [-8.6%]), and with higher mean spending per hospitalization (US $301; 95% CI, $202-$399). Hospitalizations for general conditions showed the largest relative decline in service volume (-23.5%) and the greatest increase in mean spending per hospitalization (US $242; 95% CI, $108 to $375), whereas mortality, use, and spending for complex conditions remained stable. Little evidence of care shifting to nonteaching hospitals was found.

CONCLUSIONS AND RELEVANCE: In this retrospective cohort study of teaching hospitals in South Korea, the trainee physicians’ walkout was associated with small, short-term increases in mortality, reductions in hospital use, and higher spending per encounter, concentrated among admissions for general conditions. Outcomes for complex conditions were largely unchanged, suggesting that teaching hospitals prioritized high-acuity care. Rapid hospital and governmental responses may have helped limit harm and support resource allocation.

PMID:42390860 | DOI:10.1001/jamanetworkopen.2026.22131

JAMA Netw Open. 2026 Jul 1;9(7):e2622603. doi: 10.1001/jamanetworkopen.2026.22603.

ABSTRACT

IMPORTANCE: Meningioma is a known adverse reaction of high-dose progestogens, but evidence regarding the risk associated with progestogens used as contraception is limited.

OBJECTIVE: To examine whether different progestogens used as hormonal contraception are associated with increased risk of meningiomas.

DESIGN, SETTING, AND PARTICIPANTS: This nested case-control study conducted over a 25-year study period from January 1, 2000, to December 31, 2024, is a Danish nationwide population-based register study, which included 3 million females aged 15 to 59 years with residence in Denmark. Meningioma cases were dentified, and for each case, 10 controls were matched on age, birthplace, and marital status and randomly selected from the cohort if considered eligible on the day of the case’s meningioma diagnosis. Data were analyzed from July 10, 2025, to May 12, 2026.

EXPOSURE: Use of progestogens was identified in the registers by date of dispensing or procedural records and grouped by route of administration and active substance. Exposure time was determined by redeemed daily doses or product duration. If a female switched to a different product or became pregnant, her exposure time was changed to the new exposure. The females included were allocated to their most recent use, defined as the exposure closest to the matching date.

MAIN OUTCOMES AND MEASURES: The main outcome was incident meningioma and was identified in the Danish National Cancer Register using validated International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnoses and International Classification of Diseases for Oncology, Third Edition codes.

RESULTS: A total of 1473 cases and 14 717 controls with a median age of 48 years (IQR, 42-53 years) were included in the nested cohort. For combined oral contraceptives, the estimated odds ratios (ORs) for the association between use of progestogens and meningioma were 1.61 (95% CI, 1.00-2.59) with cyproterone, 1.66 (95% CI, 1.31-2.10) with desogestrel, 1.58 (95% CI, 1.05-2.37) with drospirenone, 1.44 (95% CI, 1.17-1.77) with gestodene, 1.40 (95% CI, 1.12-1.76) with levonorgestrel, 1.38 (95% CI, 0.77-2.47) with norethisterone, and 1.04 (95% CI, 0.70-1.54) with norgestimate. For oral progestogen-only contraceptives, the ORs were 1.73 (95% CI, 1.17-2.56) with desogestrel and 0.95 (95% CI, 0.57-1.57) with norethisterone. For injectable medroxyprogesterone, the OR was 4.55 (95% CI, 2.19-9.45). For intrauterine devices (IUDs) with high-dose levonorgestrel, the OR was 1.58 (95% CI, 1.28-1.94), and for IUDs with low-dose levonorgestrel, the OR was 1.14 (95% CI, 0.59-2.22). Exposure within the past year was associated with the highest risk.

CONCLUSIONS AND RELEVANCE: In this case-control study conducted using data from the entire Danish population, recent use of the contraceptive progestogens cyproterone, desogestrel, drospirenone, gestodene, levonorgestrel, injectable medroxyprogesterone, and high-dose IUD was associated with increased risk of meningioma. These findings are considered relevant information for the treated women and the prescribing physicians.

PMID:42390859 | DOI:10.1001/jamanetworkopen.2026.22603

JAMA Otolaryngol Head Neck Surg. 2026 Jul 2. doi: 10.1001/jamaoto.2026.1749. Online ahead of print.

ABSTRACT

IMPORTANCE: Squamous cell carcinomas of the oral cavity (OCSCC), oropharynx (OPSCC), hypopharynx (HPSCC), and larynx (LSCC) are the most common forms of head and neck cancer globally. Epidemiological studies have identified variations in blood trace metal concentrations as potential risk factors for the development of these cancers, but these studies are susceptible to multiple biases.

OBJECTIVE: To determine if variations in genetically predicted blood manganese are associated with risk of OCSCC, OPSCC, HPSCC, and LSCC.

DESIGN, SETTING, AND PARTICIPANTS: This population-based 2-sample cis-mendelian randomization study used a genetic instrument for blood manganese derived from a meta-analysis of 3 individual-level genome-wide association study datasets of 6564 Scandinavian participants. Genetic associations for the development of the specified cancers were obtained from a nonoverlapping, multi-ancestral meta-analysis that combined individual-level genome-wide association study datasets comprising 38 857 healthy controls, 5596 case patients with OCSCC, 2212 case patients with human papillomavirus (HPV)-positive OPSCC, 1473 case patients with HPV-negative OPSCC, 898 case patients with HPSCC, and 4409 case patients with LSCC.

EXPOSURES: Increases in genetically predicted whole blood manganese concentration proxied by a genetic instrument including 2 cis-variants (single-nucleotide variants) selected due to their known functions in regulating manganese metabolism.

MAIN OUTCOMES AND MEASURES: The primary outcomes were the risk of OCSCC, OPSCC (HPV positive and HPV negative), HPSCC, and LSCC, evaluated by estimating the odds ratio (OR) and 95% CI of each outcome per 1-SD increase in whole blood manganese concentration after rank-based inverse normalization transformation.

RESULTS: Genetically predicted higher blood manganese was found to have a statistically significant association with increased risk of OCSCC (OR, 1.25; 95% CI, 1.10-1.43; P < .001) and HPV-positive OPSCC (OR, 1.23; 95% CI, 1.04-1.45; P = .02). Associations between blood manganese and HPV-negative OPSCC (OR, 1.20; 95% CI, 0.95-1.50; P = .13), HPSCC (OR, 1.25; 95% CI, 0.75-2.07; P = .39), and LSCC (OR, 1.10; 95% CI, 0.92-1.32; P = .28) were directionally concordant but not statistically significant.

CONCLUSIONS AND RELEVANCE: This cis-mendelian randomization study demonstrates statistically significant associations between higher blood manganese concentrations and risk of OCSCC and HPV-positive OPSCC. Further work should aim to establish the pathophysiological mechanisms underlying this association to inform potential public health strategies for the prevention of these cancers.

PMID:42390852 | DOI:10.1001/jamaoto.2026.1749

JAMA Oncol. 2026 Jul 2. doi: 10.1001/jamaoncol.2026.2157. Online ahead of print.

ABSTRACT

IMPORTANCE: Hepatocellular carcinoma (HCC) surveillance in patients with cirrhosis remains suboptimal, with inadequate early-stage detection. α-Fetoprotein (AFP) demonstrates insufficient sensitivity. Circulating methylated septin 9 (SEPT9) has shown diagnostic promise.

OBJECTIVE: To determine whether methylated SEPT9 improves detection of HCC when combined with AFP in patients with cirrhosis undergoing surveillance.

DESIGN, SETTING, AND PARTICIPANTS: In this prospective, cross-sectional, diagnostic accuracy study, patients with cirrhosis undergoing routine HCC surveillance with ultrasonography and AFP were enrolled at 2 French academic centers from February 2018 through October 2024. HCC was diagnosed per international guidelines with centralized radiologic review, blinded to methylated SEPT9 results. Data were analyzed from October 2025 to January 2026.

EXPOSURES: Plasma methylated SEPT9 was analyzed from 3 independent plasma aliquots and classified by number of positive replicates (single-positive, double-positive, or triple-positive). Serum AFP was evaluated at a threshold of 20 ng/mL. Biomarkers were evaluated individually and in combination using disjunction logic (tier 1; maximizing sensitivity) or conjunction logic (tier 2; maximizing specificity).

MAIN OUTCOMES AND MEASURES: The primary outcome was the presence of HCC at enrollment. The primary end point was comparison of the area under the receiver operating characteristic curve (AUROC) between methylated SEPT9 and AFP. Secondary end points included diagnostic performance stratified by Barcelona Clinic Liver Cancer (BCLC) stage.

RESULTS: Among 574 participants, 414 (72.1%) were male, and the median (IQR) age was 63 (57-70) years. A total of 118 had HCC, including 51 (43.2%) with BCLC stage 0-A. Methylated SEPT9 outperformed AFP (AUROC: 0.79 [95% CI, 0.74-0.84] vs 0.71 [95% CI, 0.66-0.76], respectively; P = .002; posterior probability of superiority >99.8%). Tier 1a (at least single-positive methylated SEPT9 or AFP >20 ng/mL) achieved 87.8% (95% CI, 81.6-93.5) sensitivity and a negative likelihood ratio of 0.2 (95% CI, 0.1-0.3). Among 64 HCC cases missed by AFP, tier 1a recovered 50 (78%). For BCLC 0-A disease, tier 1a sensitivity was 74.5% (95% CI, 62.2-86.5) vs 23.5% (95% CI, 12.5-35.8) for AFP, 3.2-fold increase. Tier 2 (triple-positive methylated SEPT9 and AFP >20 ng/mL) achieved 99.6% (95% CI, 98.9-100) specificity, a positive likelihood ratio of 76.0 (95% CI, 26.9-181.0), and a diagnostic odds ratio of 112.1 (95% CI, 37.8-294.7).

CONCLUSIONS AND RELEVANCE: In this diagnostic study, combining methylated SEPT9 with AFP substantially improved HCC detection in patients with cirrhosis, particularly for early-stage disease amenable to curative treatment. Prospective studies are needed to determine whether improved detection translates into survival benefit.

PMID:42390849 | DOI:10.1001/jamaoncol.2026.2157

Ther Innov Regul Sci. 2026 Jul 2. doi: 10.1007/s43441-026-01007-w. Online ahead of print.

ABSTRACT

QTLs aim to ensure that the impact of risks on critical quality aspects of the trial remains within an acceptable range. Action limits can serve as an effective mechanism for the early detection of potential risks, emphasizing the importance of continuous, real-time data monitoring throughout the course of a clinical trial. A breach of an action limit constitutes an early warning of a potential negative impact on trial quality, which could subsequently affect statistical analyses. This paper presents practical examples to elucidate common characteristics of QTL parameters, thresholds, and their associated action limits.

PMID:42390815 | DOI:10.1007/s43441-026-01007-w

Cancer Causes Control. 2026 Jul 2;37(7):119. doi: 10.1007/s10552-026-02204-6.

ABSTRACT

PURPOSE: Mailed stool-based fecal immunochemical testing (FIT) can improve colorectal cancer (CRC) screening rates. We aim to determine whether enhancing communications with evidence-based behavioral economics principles in mailed FIT kits further improves screening rates.

METHODS: This study focused predominantly on Medicare patients at average-risk for colon cancer who were not up-to-date on CRC screening. Patients were randomly assigned to one of two interventions: original communication (a series of standard communications, including a pre-mailing letter, FIT kit and letter, and reminders via text or robo-call); or enhanced communication (the same sequence, but incorporating behavioral economics principles to encourage FIT completion). We compared the rate of FIT tests completed at 90 days and factors associated with completion.

RESULTS: 4,070 patients were included. Within 90 days, 27% of all patients successfully completed the FIT test: 28.1% of patients receiving the enhanced communication had FIT test completed compared to 25.5% of patients receiving the original communication. The adjusted risk difference for obtaining patients’ FIT tests within 90 days was 2.2% (95% CI = -0.4%, 4.9%) for the enhanced communication outreach compared to the original communication (p = 0.094). Younger participants and patients experiencing greater area-level deprivation were less likely to complete the screening.

CONCLUSION: The FIT test screening rate in the enhanced communication group was not statistically different from the original communication group. Using evidence-based behavioral economics principles in mailed FIT communications did not markedly improve the rate of CRC screening, but mailed FIT remains a key, cost-effective tool for reaching unscreened individuals.

PMID:42390812 | DOI:10.1007/s10552-026-02204-6

Surg Endosc. 2026 Jul 2. doi: 10.1007/s00464-026-13049-0. Online ahead of print.

ABSTRACT

BACKGROUND: To evaluate the comparative effectiveness of extended totally extraperitoneal plasty Rives-Stoppa retromuscular repair (eTEP-RS) and open Rives-Stoppa retromuscular repair (Open-RS) in patients undergoing ventral hernia repair.

METHODS: Clinical data from 850 patients were collected in a prospectively maintained database and retrospectively evaluated. 153 patients undergoing eTEP-RS were compared to 154 selected patients undergoing Open-RS (from the period prior to implementation of eTEP-RS at our university medical center). Short-term perioperative outcomes as well as long-term recurrence rate and quality of life by Carolina Comfort Scale (QoL) were evaluated. Results are shown as median (interquartile range).

RESULTS: Our learning curve phase (first 60 eTEP-RS cases) was compared to eTEP-RS from the steady-state phase (cases 61-153). Significant differences with regard to operation time and perioperative complications were observed indicating a relevant learning curve in the procedure. The eTEP-RS cases from the steady-state cohort were compared to the Open-RS cases. After propensity score matching, 83 eTEP-RS cases were compared to 83 Open-RS cases. While operation time was longer (Open-RS: 135 min (95-161); eTEP-RS: 160 min (126-192); i = 0.004), length of stay was shorter in the eTEP-RS cohort (Open-RS: 7 days (6-9); eTEP-RS: 4 days (3-5); p < 0.001) and postoperative pain was lower on postoperative days 2 and 3. Perioperative complications, hernia recurrence rates, and long-term QoL were not different between the two cohorts.

CONCLUSION: eTEP Rives-Stoppa repair offered superior short-term outcomes compared to open Rives-Stoppa repair in suitable patients with medium-sized ventral hernia and selected patients with large ventral hernia. Given the short follow-up period, no statistically significant differences could be observed regarding the long-term outcomes recurrence rate and QoL. Future long-term multicenter studies are necessary to evaluate long-term efficacy.

PMID:42390803 | DOI:10.1007/s00464-026-13049-0

Updates Surg. 2026 Jul 2. doi: 10.1007/s13304-026-02754-z. Online ahead of print.

ABSTRACT

We aimed to determine the effectiveness of the newly developed CANP score in determining prognosis by comparing it with the HALP score and the Modified HALP score in patients with complicated and uncomplicated acute appendicitis. After getting ethical approval and using the hospital data network, we retrospectively analyzed the demographic data, laboratory parameters, and pathology results of 80 female and 100 male patients aged from 15 to 95 years, who underwent surgery for acute appendicitis in the last two years. They were divided into patients with complicated and uncomplicated acute appendicitis. The HALP, Modified HALP, and CANP scores were compared by using statistical methods. According to the area under the ROC curve (AUC), the highest accuracy was found in the CANP score with an AUC of 0.980 (CI: 0.963-0.997), the sensitivity of 85.3%, and specificity of 97.3%. The AUC for M-HALP score was low as 0.322 (CI: 0.211-0.434), showing limited diagnostic value with a sensitivity of 26.5% and specificity of 58.9%. The AUC for the HALP score was the lowest, at 0.244 (CI: 0.161-0.328), with a sensitivity of 29.4% and specificity of 32.2%. Statistical significance was reported as p < 0.001. We showed that the CANP score, with a significantly higher AUC value and along with a higher sensitivity and specificity when compared to the HALP and M-HALP scores, was the most powerful discriminative parameter for predicting the complicated acute appendicitis, so it can be used as a more reliable scoring system in infectious diseases.

PMID:42390782 | DOI:10.1007/s13304-026-02754-z