Category: Statistics

J Bras Nefrol. 2025 Oct-Dec;47(4):e20250028. doi: 10.1590/2175-8239-JBN-2025-0028en.

ABSTRACT

INTRODUCTION: Stress hyperglycemia in patients with sepsis has not been consistently associated with an increased risk of acute kidney injury (AKI).

OBJECTIVE: To evaluate the effect of blood glucose levels on the occurrence of AKI requiring dialysis in critically ill patients with sepsis.

METHODS: Retrospective cohort study of patients with sepsis admitted to the ICU of a private hospital between December 2017 and August 2021. Clinical, laboratory, and severity variables were collected. Mean blood glucose levels in the first week of ICU stay (primary exposure variable) were stratified into tertiles. The effect of blood glucose on the occurrence of dialysis-requiring AKI was assessed using multivariate logistic regression.

RESULTS: Of the 1,317 patients evaluated, 86.6% had clinical conditions as the underlying cause of sepsis. AKI requiring hemodialysis occurred in 12.2% of the sample. Patients with mean blood glucose levels above the third tertile (≥160 mg/dl), compared to those with mean blood glucose levels below the first two tertiles (<160 mg/dl), had a higher prevalence of diabetes (69.1% vs. 7.1%; p < 0.001). Patients with mean blood glucose levels ≥160 mg/dl had a 62% higher odds of developing AKI requiring dialysis compared to those with mean blood glucose levels < 160 mg/dl (crude OR = 1.62; 95% CI 1.16-2.26; p = 0.005). After adjustment for other variables, mean blood glucose levels ≥180 mg/dl did not increase the likelihood of AKI (OR = 1.27; 95% CI 0.76-2.12; p = 0.359).

CONCLUSION: In this patient group, sepsis and mean blood glucose levels ≥160 mg/dl were not independently associated with the occurrence of dialysis-requiring AKI.

PMID:40779693 | DOI:10.1590/2175-8239-JBN-2025-0028en

Clin Drug Investig. 2025 Aug 8. doi: 10.1007/s40261-025-01470-7. Online ahead of print.

ABSTRACT

BACKGROUND: SHR7280 is an oral small-molecule gonadotropin-releasing hormone (GnRH) antagonist that can be developed as therapeutic agent for the treatment of hormone-dependent pathologies, including prostate, breast, and ovarian cancers. SHR7280 dry suspension formulation is being developed to provide an alternative mode of administration for order patients, those using nutritional tubes, and those unable to swallow solid dosage forms.

OBJECTIVE: This study evaluated the relative bioavailability, pharmacokinetics (PK), and safety of SHR7280 dry suspension and tablets administered in a single dose in healthy Chinese volunteers.

METHODS: A randomized, open, two-preparation, two-sequence, two-cycle, double-crossover design was used in this study. The plasma drug concentration was determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The main PK parameters of the two formulations of SHR7280 were calculated by noncompartmental analysis using Phoenix WinNonlin (version 8.3.4) software. A total of 16 healthy participants were randomized to receive SHR7280 (200 mg) as tablets (n = 8) or dry suspension (n = 8) formulation.

RESULTS: The geometric least squares mean ratio (90% confidence interval [CI]) for maximum concentration of drug in blood plasma (C_max) and area under the plasma concentration-time curve from time 0 to t (AUC_0-t) and from time 0 to infinity (AUC_0-∞) between the dry suspension of SHR7280 and its tablets were calculated as follows: C_max-101.90% (90% CI 79.50-130.62), AUC_0-t-111.58% (90% CI 91.71-135.76), and AUC_0-∞-111.44% (90% CI 91.70-135.43). A total of nine (56.3%) subjects experienced treatment-emergent adverse events (TEAEs).

CONCLUSIONS: The bioavailability of SHR7280 tablets was found to be comparable to that of dry suspension. The safety profile of two formulations was favorable. No serious adverse events or adverse drug reactions were reported.

TRIAL REGISTRATION: ClinicalTrials.gov (NCT05868057; 22 May 2023).

PMID:40779283 | DOI:10.1007/s40261-025-01470-7

Obes Surg. 2025 Aug 8. doi: 10.1007/s11695-025-08155-2. Online ahead of print.

ABSTRACT

BACKGROUND: Endoscopic sleeve gastroplasty (ESG) has been shown to be effective for inducing weight loss. Liraglutide, a glucagon-like peptide-1 agonist, has been successfully used for weight loss and remission of comorbidities in patients with obesity. So far, there are no clinical studies comparing short-term outcomes in patients treated with ESG or Liraglutide. The aim of the study is to assess the efficacy and safety of ESG versus Liraglutide in patients with obesity over a 12 months follow-up period.

METHODS: A prospective, randomized controlled, monocentric study was performed. A total of 43 patients with class I and II obesity were included in the study. Twenty-three patients underwent ESG, and 20 patients were treated with Liraglutide. All participants received standardized follow-up protocols with assessments by both surgeon and nutritionist in the bariatric ambulatory setting. Weight loss outcomes, including the percentage of excess weight loss (%EWL), total weight loss (%TWL), and resolution of obesity-related comorbidities were assessed at 3, 6, and 12 months post-intervention.

RESULTS: After 3 and 6 months, %EWL and %TWL were greater in the ESG group (P = 0.001). However, at 12 months, these differences were no longer statistically significant, suggesting that the ESG group was experiencing some weight regain, while the Liraglutide group had a slower but more consistent weight loss. Regarding the resolution of comorbidities, there were no statistically significant differences at 3, 6 and 12 months between the two groups. None of the patients had major complications or significant side effects.

CONCLUSIONS: Both ESG and Liraglutide guarantee weight loss and remission of comorbidities in class I and II obesity patients. However, ESG induces a more rapid weight loss in the first six months, after which two patients seem experience weight regain. Liraglutide provides a slower weight loss in terms of %EWL and %TWL but patients continue losing weight also after six months. Larger samples with a longer follow-up are needed to confirm our results.

PMID:40779281 | DOI:10.1007/s11695-025-08155-2

Obes Surg. 2025 Aug 8. doi: 10.1007/s11695-025-08144-5. Online ahead of print.

ABSTRACT

BACKGROUND: Roux-en-Y gastric bypass (RYGB) has long been established as one of the most efficient therapeutic options for patients with obesity and associated medical conditions. However, the impact of concurrent vagal transection during pouch creation on postoperative outcomes remains underreported.

METHODS: This retrospective cohort study examined patients who underwent RYGB between January 2011 and December 2023, with 1 to 5 years of follow-up. Patients were stratified into two groups: vagal sparing RYGB (VS) and non-vagal sparing RYGB (NVS). Data collected included postoperative complications, intraoperative characteristics, weight trajectories, resolution of obesity-related medical conditions, and mortality. Statistical analysis methods included paired t-tests, multivariate regression, and Cox regression models.

RESULTS: Out of 1521 patients, 374 (24.6%) underwent VS-RYGB and 1147 (75.4%) had NVS-RYGB. Patients were predominantly female (80.8%), with a mean age of 47.6 ± 12.1 years and body mass index (BMI) of 46.0 ± 7.7 kg/m². NVS had significantly longer operative times (p < 0.001) and a higher lysis of adhesions rate (p < 0.001). Marginal ulcer rate was also significantly higher in NVS compared to VS (p = 0.03). In contrast, the rate of dumping syndrome (p = 0.13) and cholelithiasis (p = 0.65) was not significantly different between groups. While overall weight outcomes were similar, VS reached maximum percentage of total weight loss (%TWL) earlier (p = 0.02). Both groups showed comparable obesity-related condition outcomes.

CONCLUSION: NVS-RYGB was associated with higher operative time. Additionally, vagal transection was significantly associated with marginal ulcer occurrence. Our findings support the potential advantage of vagal-sparing RYGB.

PMID:40779279 | DOI:10.1007/s11695-025-08144-5

JAMA Netw Open. 2025 Aug 1;8(8):e2525252. doi: 10.1001/jamanetworkopen.2025.25252.

ABSTRACT

IMPORTANCE: Clostridioides difficile is a leading cause of health care-associated infections. Understanding the association among C difficile carriage, antibiotic use, and infection hazard is essential for infection prevention.

OBJECTIVE: To evaluate the hazard of C difficile infection (CDI) among asymptomatic carriers vs noncarriers of C difficile and whether it is associated with antibiotic exposure.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study conducted between June 18, 2017, and June 21, 2023, analyzed hospitalizations from Sheba Medical Center in Ramat Gan, Israel, which routinely screens for C difficile in high-risk patients admitted to internal medicine. Adult patients (aged >18 years) without active CDI at admission were included.

EXPOSURE: Antibiotic exposure during hospitalization, including specific classes.

MAIN OUTCOMES AND MEASURES: The primary outcome was the development of CDI, as confirmed by laboratory testing for C difficile. Antibiotic exposure was assessed as a time-varying variable.

RESULTS: The study included 33 756 hospitalizations among 23 001 patients (median [IQR] age, 78 [68-87] years; 52.8% men). C difficile infection occurred in 67 of 1624 hospitalizations (4.1%) with positive screening results and in 47 of 32 132 hospitalizations (0.1%) with negative screening results. A positive C difficile screening result at admission was associated with a high hazard of infection (hazard ratio [HR], 27.5; 95% CI, 18.7-40.3). Antibiotic exposure was associated with an increased hazard for CDI (HR, 1.98; 95% CI, 1.24-3.16). Piperacillin and tazobactam showed the most pronounced hazard for CDI (HR, 2.18; 95% CI, 1.41-3.36). Among asymptomatic carriers, antibiotic exposure was not significantly associated with a further increase in CDI hazard (HR, 1.07; 95% CI, 0.73-1.58).

CONCLUSIONS AND RELEVANCE: In this cohort study, carriers of C difficile had a substantially higher baseline hazard for hospital-onset CDI. Antibiotic exposure was associated with an increased hazard among noncarriers but was not significantly associated with additional hazard among carriers. These findings suggest that while antibiotic stewardship may reduce CDI risk in noncarriers, additional strategies may be needed for carriers given their elevated baseline risk.

PMID:40779269 | DOI:10.1001/jamanetworkopen.2025.25252

JAMA Netw Open. 2025 Aug 1;8(8):e2525809. doi: 10.1001/jamanetworkopen.2025.25809.

ABSTRACT

IMPORTANCE: Suicide is a leading cause of death in the US. Suicide-specific cognitive behavior therapy (CBT) is effective for reducing suicide attempts but is difficult to implement.

OBJECTIVE: To evaluate the efficacy of a smartphone-based digital therapeutic intervention designed to deliver suicide-focused CBT in reducing suicidal behavior among patients hospitalized for a suicide attempt or suicidal ideation.

DESIGN, SETTING, AND PARTICIPANTS: This multisite, double-blind, randomized clinical trial was conducted in 6 psychiatric inpatient units across the US. Adult patients admitted with elevated suicide risk from April 2022 to April 2024 were included. Participants completed a baseline assessment and were randomly assigned to either the digital therapeutic group or control application group. The trial was stopped early by the Data Management Safety Board because it surpassed the prespecified futility boundary for the primary end point. Statistical analysis followed the intention-to-treat principle.

INTERVENTIONS: The digital therapeutic intervention includes 12 sessions of smartphone-based educational modules (lasting 10-15 minutes each) drawn from CBT for suicide prevention. The active control is a 12-session smartphone-based application that delivers safety planning and psychoeducation about suicide. For both interventions, the first session was completed prior to hospital discharge and the remaining self-paced sessions could be completed after discharge. All participants also received treatment as usual, which included suicide risk assessment, supportive listening, crisis resources, clinician assessment, safety planning, and referral to outpatient treatment.

MAIN OUTCOMES AND MEASURES: The primary end point was time (days) to first actual suicide attempt during follow-up. The secondary end points were change in suicidal ideation from baseline to week 24 (quantified as a change in the Scale for Suicide Ideation total score) and clinician-rated clinical improvement at week 24. The nonprespecified sensitivity analysis end point for suicide attempts was the rate of suicide attempts (actual, aborted, and interrupted). Prespecified subgroup analyses were also conducted to examine treatment effects among patients with vs without prior suicide attempts.

RESULTS: A total of 339 participants (mean [SD] age, 27.9 [10.7] years; 224 females [66.1%]) were included. Follow-up data were available from 266 participants (78.5%). Time to first actual suicide attempt, the primary end point, was not significantly different across treatment groups (log-rank χ21 = 3.6; P = .06). Among the 170 participants with prior suicide attempts, nonprespecified sensitivity analyses indicated that the adjusted rate of follow-up suicide attempts was 58.3% lower in the digital therapeutic group than the control application group (0.70 vs 1.68 attempts per person-year; rate ratio [RR], 0.42 [95% CI, 0.18-0.95]; P = .04), and the odds of clinical improvement were higher in the digital therapeutic group than the control application group (97.9% vs 87.5%; odds ratio, 7.59; 95% CI, 1.14-153.62; P = .04). Trajectories of suicidal ideation significantly differed between the digital therapeutic and control application groups (F3,206 = 2.9, P = .04), with decreased suicidal ideation through week 24 in the digital therapeutic group, but in the control application group, suicidal ideation decreased through week 12 and then increased at week 24. Nonprespecified dose-response analyses indicated the suicide attempt rate among patients with a prior suicide attempt decreased by 14.0% for every digital therapeutic module completed (adjusted RR, 0.86; 95% CI, 0.76-0.98; P = .02).

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, the digital therapeutic intervention did not change the time to first actual suicide attempt but helped to sustain reductions in suicidal ideation among inpatients with elevated suicide risk. However, among patients with prior suicide attempts, the digital therapeutic intervention helped reduce recurrent suicide attempts and increased the percentage of inpatients with clinician-rated clinical improvement.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05144685.

PMID:40779267 | DOI:10.1001/jamanetworkopen.2025.25809

JAMA Netw Open. 2025 Aug 1;8(8):e2526013. doi: 10.1001/jamanetworkopen.2025.26013.

ABSTRACT

IMPORTANCE: Semaglutide, a glucagon-like peptide-1 receptor agonist, has demonstrated substantial weight reduction and cardiovascular benefits in clinical trials. However, its association with clinical outcomes and health care expenditures remains underexplored.

OBJECTIVE: To evaluate changes in cardiovascular risk factors and health care expenditures among patients prescribed semaglutide across multicenter cohorts.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included 23 522 adults (≥18 years) who received an initial semaglutide prescription between January 1, 2018, and January 1, 2025, at Sentara Healthcare and between January 1, 2018, and May 1, 2025, at Yale New Haven Health System.

EXPOSURE: The first prescription of semaglutide identified at the ingredient level, stratified by type 2 diabetes status.

MAIN OUTCOMES AND MEASURES: Primary outcomes included changes in weight (% baseline), blood pressure (BP), total cholesterol, and hemoglobin A1c. Secondary outcomes assessed health care expenditures using Medicare-based cost estimates. A staggered difference-in-differences design compared outcomes of patients after the first semaglutide prescription with those of patients who had not yet received their prescription during the same period.

RESULTS: The study cohort included 23 522 patients (mean [SD] age at initiation of semaglutide, 56.2 [12.9] years; 66.7% female; 68.6% with diabetes). In the overall cohort, initiation of semaglutide was significantly associated with a -3.8% (95% CI, -3.9% to -3.7%) reduction in weight at 13 to 24 months, with a -5.1% (95% CI, -5.5% to -4.7%) reduction in weight among patients without diabetes. Significant reductions in diastolic BP (-1.5 mm Hg; 95% CI, -1.7 to -1.4 mm Hg), systolic BP (-1.1 mm Hg; 95% CI, -1.4 to -0.8 mm Hg), and total cholesterol (-12.8 mg/dL; 95% CI, -14.3 to -11.4 mg/dL) were also observed. Hemoglobin A1c reductions were greater among patients with diabetes (-0.3%; 95% CI, -0.3% to -0.2%) compared with patients without diabetes (-0.1%; 95% CI, -0.2% to -0.01%). Imputed health care expenditures, excluding the cost of semaglutide, increased by $80 per month (95% CI, $68-$92 per month) during the 13- to 24-month period, which was associated with inpatient stays shifting to more expensive circulatory and metabolic diagnoses.

CONCLUSIONS AND RELEVANCE: In this cohort study of adults prescribed semaglutide, initiation was associated with reductions in weight and cardiovascular risk factors but increases in health care expenditures, excluding semaglutide costs. These findings suggest potential clinical benefits in routine practice, while highlighting the need to evaluate the long-term impact of semaglutide on economic outcomes.

PMID:40779264 | DOI:10.1001/jamanetworkopen.2025.26013

JAMA Netw Open. 2025 Aug 1;8(8):e2526912. doi: 10.1001/jamanetworkopen.2025.26912.

ABSTRACT

IMPORTANCE: Rural patients face unique barriers in obtaining high-quality cancer care. Research is lacking in determining whether these disparities translate to negative clinical outcomes.

OBJECTIVE: To determine if there are differences in the rate of biochemical recurrence in prostate cancer between rural and urban men.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used patient data that was abstracted from the North Carolina Prostate Cancer Comparative Effectiveness and Survivorship Study, a population-based cohort that prospectively followed patients with newly diagnosed prostate cancer from the Rapid Case Ascertainment system of the North Carolina Central Cancer Registry from January 1, 2011, to June 30, 2013. Patients were identified who had received either surgery or radiation within 1 year of diagnosis. Data were analyzed from January 2011 to December 2022.

EXPOSURE: Patients were categorized as rural or urban using the Rural-Urban Continuum Code.

MAIN OUTCOME AND MEASURES: Recurrence was determined by prostate-specific antigen testing. Demographic differences between rural and urban patients were assessed using 2-sample independent t test and χ2 test. Prostate cancer recurrence was analyzed using Cox proportional hazard models.

RESULTS: A total of 778 patients were included with a median (IQR) follow-up of 4.6 (2.0 to 6.9) years and a mean (SD) age of 63 (7.4) years. Additionally, 213 were Black men (27.4%), 565 were White men (72.6%), 350 were Medicare insured (45.1%), 324 had an income ranging from $40 000 to $90 000 (43.1%), 370 were a National Comprehensive Cancer Network (NCCN) intermediate risk group (47.6%), 449 were treated with radical prostatectomy (57.7%), and 690 were in good to excellent health (88.7%) with 191 living in a rural setting (24.6%). On univariable analysis, rural residence (hazard ratio [HR], 2.19 [95% CI, 1.38 to 3.46]; P < .001), NCCN risk group (HR, 4.13 [95% CI, 2.25 to 7.57]; P < .001), and having had fewer than 12 biopsies (HR, 1.70 [95% CI, 1.08 to 2.67]; P = .02) were significantly associated with biochemical recurrence. On multivariable analysis adjusted for location of residence, marital status, overall health, number of cores biopsied, NCCN risk group, and treatment type, rural residence was significantly associated with recurrence (HR, 1.74 [95% CI, 1.07 to 2.82]; P = .03), while radiation therapy was inversely associated with recurrence (HR, 0.51 [95% CI, 0.31 to 0.85]; P = .01).

CONCLUSIONS AND RELEVANCE: In this cohort study of patients with newly diagnosed prostate cancer, rural patients with prostate cancer had higher rates of biochemical recurrence. The etiology of this disparity is unclear but is likely multifactorial. Factors that may play a role include socioeconomic status, delay and disruptions in care, and access to multidisciplinary cancer care.

PMID:40779263 | DOI:10.1001/jamanetworkopen.2025.26912

JAMA Health Forum. 2025 Aug 1;6(8):e252284. doi: 10.1001/jamahealthforum.2025.2284.

ABSTRACT

IMPORTANCE: Patient cost sharing liability has risen in recent years, increasing the costs associated with care for patient households and imposing collections challenges for hospitals and clinicians.

OBJECTIVE: To measure patient repayment of cost sharing over recent years, and how that varies across patient, hospital, and service characteristics.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study of billing and payment data from a revenue cycle management company examined patient accounts at 217 US hospitals from 2018 to 2024. Participants included 24.5 million and 6.2 million patient episodes of care with positive patient out-of-pocket liability for individuals with private insurance and Medicare Advantage, respectively.

MAIN OUTCOMES AND MEASURES: Percentage of owed patient cost sharing actually paid among patients with private insurance and Medicare Advantage measured over time, for inpatient and outpatient care and by bill size.

RESULTS: Across the full sample of 217 US hospitals (30.7 million patient episodes), mean (SD) patient liability per person, including those with no liability, was higher for individuals with private insurance ($375.41 [$51.55]) than those with Medicare Advantage ($172.50 [$14.84]). Consistent with high-deductible plan design with annual resetting, mean patient liability was higher for visits in January than December, particularly among the privately insured (eg, mean [SD] patient liability for visits among the privately insured in January: $479.44 [$29.21] vs December: $321.63 [$14.29]). Prior to the COVID-19 pandemic (January 2018-February 2020), mean repayment rates were 53.9% and 54.0% for patients with private or Medicare Advantage insurance, respectively, and repayment rates declined in more recent years. Across the entire sample, patients with private or Medicare Advantage insurance paid either 0% or 100% of their owed cost sharing in 92.2% and 94.1% of cases, respectively. Repayment rates varied by bill size with lower repayment rates on the largest bills and the smallest bills, and higher repayment rates on midsized bills.

CONCLUSIONS AND RELEVANCE: This cross-sectional study found that patient cost sharing repayments were incomplete and have fallen in more recent years, which result in both medical debts for patients and collections shortfalls for hospitals and clinicians. These findings suggest that changes to insurance plan design or the treatment of medical debt are among several factors that may contribute to observed results; if declines in cost sharing repayment continue, hospitals and clinicians may increasingly seek payment of cost sharing ahead of service, when allowable.

PMID:40779258 | DOI:10.1001/jamahealthforum.2025.2284

JAMA Health Forum. 2025 Aug 1;6(8):e252329. doi: 10.1001/jamahealthforum.2025.2329.

ABSTRACT

IMPORTANCE: Achieving equitable access to medicines requires understanding of how pharmaceutical use and spending vary by race and ethnicity across the US.

OBJECTIVE: To quantify variation in prescription drug utilization and spending per capita and per prevalent case by race, ethnicity, health condition, payer, and US state.

DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, the US Disease Expenditure project was extended to incorporate disaggregation by race and ethnicity for state-level retail prescription drug utilization and spending-in addition to 143 health conditions, 38 age and sex groups, and 4 payers (Medicare, Medicaid, private insurance, and out of pocket)-across the 2019 population in all 50 states and Washington, DC. Data were analyzed from October 2023 to April 2025.

EXPOSURE: Four mutually exclusive racial and ethnic groups (Asian or Pacific Islander, Black, Hispanic, and White).

MAIN OUTCOME AND MEASURES: Outcomes include prescriptions dispensed and spending for retail pharmaceuticals. Estimates were standardized by population size, population age, and-where data permitted-by disease burden (52 conditions). Das Gupta decomposition was used to estimate the relative contribution of 3 factors (disease prevalence, prescriptions per prevalent case, and spending per prescription) on observed disparities in age-standardized per capita pharmaceutical spending.

RESULTS: In 2019, age-standardized pharmaceutical utilization and spending per person with a given disease was substantially lower than the all-population mean for Black populations, close to the mean for Hispanic populations, and often higher than the mean for Asian or Pacific Islander and White populations. These trends-particularly those for the Black population-were generally consistent across 52 health conditions but varied widely across payers and US states. The decomposition analysis for these 52 conditions showed that differences in per capita pharmaceutical spending across race and ethnicity groups were primarily explained by disease prevalence for Black populations (associated with increased per capita spending) and by utilization rates per prevalent case for Hispanic populations (also associated with increased spending). In contrast, differences in drug price or product type (spending per prescription) contributed less to observed spending disparities.

CONCLUSIONS AND RELEVANCE: In this cross-sectional study, racial and ethnic disparities in medication use persisted, most notably the underutilization of medicines relative to disease burden among Black populations. These patterns varied by state, highlighting the need for local- and condition-specific approaches to advancing pharmacoequity in the US.

PMID:40779257 | DOI:10.1001/jamahealthforum.2025.2329