Category: Statistics

JAMA Netw Open. 2024 Dec 2;7(12):e2451707. doi: 10.1001/jamanetworkopen.2024.51707.

ABSTRACT

IMPORTANCE: Previous research has examined outcomes among very preterm newborns by the birthing parent’s race and ethnicity, but knowledge about these trends during the COVID-19 pandemic is limited.

OBJECTIVE: To examine trends in outcomes among Black, Hispanic, and Asian preterm newborns compared with White preterm newborns.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study (2018-2022) took place at 774 neonatal intensive care units in the Vermont Oxford Network. Participants were newborns born at 22 to 29 weeks’ gestation.

EXPOSURE: Race and ethnicity.

MAIN OUTCOMES AND MEASURES: The primary outcomes were mortality and complications, including respiratory distress syndrome, necrotizing enterocolitis (NEC), early-onset sepsis, late-onset sepsis (LOS), severe intraventricular hemorrhage (sIVH), severe retinopathy of prematurity, chronic lung disease, pneumothorax, and complication-free survival.

RESULTS: Among 90 336 newborns (47 215 male [52.3%]; 43 121 female [47.7%]; mean [SD] gestational age, 26.4 [2.1] weeks), 4734 (5.2%) were born to Asian, 20 345 (22.3%) to Hispanic, 31 264 (34.3%) to non-Hispanic Black, and 33 993 (37.3%) to non-Hispanic White birthing individuals. Rates of in-hospital mortality (4831 Black newborns [15.6%]; 3009 Hispanic newborns [14.9%]; and 4886 White newborns [14.4%]), NEC (2374 Black newborns [7.8%]; 1359 Hispanic newborns [6.9%]; and 2137 White newborns [6.5%]), LOS (3846 Black newborns [13.5%]; 2258 Hispanic newborns [12.3%]; and 3575 White newborns [11.5%]), and sIVH (2919 Black newborns [10.3%]; 1673 Hispanic newborns [9.2%]; and 2800 White newborns [9.1%]) were highest among Black and lowest among White newborns. Chronic lung disease and pneumothorax rates were lowest among Black and highest among White newborns. Over the study period, mortality rate differences were slightly higher for Black than White newborns, with no differences by 2022. NEC and LOS rates were consistently higher among Black than White newborns. By 2022, Black newborns had higher rates of NEC (rate difference, 1.3 percentage points; 95% CI, 0.46-2.2 percentage points) and LOS (rate difference, 2.7 percentage points; 95% CI, 1.4-4.0 percentage points). sIVH rates were higher for Black newborns in some years, whereas severe retinopathy of prematurity rates were lower. Hispanic newborns had mortality and complication rates similar to those of White newborns. Black and Hispanic newborns had lower respiratory complication rates and higher complication-free survival than White newborns.

CONCLUSIONS AND RELEVANCE: In this cohort study, there were no differences in mortality rates between Black and White newborns, but Black newborns had higher rates of NEC and LOS. Continued quality improvement and addressing social determinants of health are critical for promoting health equity in hospital outcomes and beyond.

PMID:39699894 | DOI:10.1001/jamanetworkopen.2024.51707

JAMA Netw Open. 2024 Dec 2;7(12):e2451715. doi: 10.1001/jamanetworkopen.2024.51715.

ABSTRACT

IMPORTANCE: Prior studies have shown that the benefits, harms, and costs of colorectal cancer (CRC) screening at older ages are associated with a patient’s sex, health, and screening history. However, these studies were hypothetical exercises and not directly informed by data on CRC risk.

OBJECTIVE: To identify the optimal stopping ages for CRC screening by sex, comorbidity, and screening history from a cost-effectiveness perspective.

DESIGN, SETTING, AND PARTICIPANTS: This economic evaluation first validated the MISCAN-Colon (Microsimulation Screening Analysis-Colon) model against community-based CRC incidence and mortality rates for 2 subcohorts of the PRECISE (Optimizing Colorectal Cancer Screening Precision and Outcomes in Community-Based Populations) cohort. Subsequently, different CRC screening scenarios were simulated in older individuals. Cohorts of US adults aged 76 to 90 years varied by sex and comorbidity status (none, low, moderate, or severe). Statistical and sensitivity analyses were performed from March 2023 to May 2024.

EXPOSURES: CRC screening histories including fecal immunochemical test (FIT) or colonoscopy, such as a negative colonoscopy result from 10, 15, 20, 25, or 30 years before the index age; 1 to 5 negative FIT results within 5 years of the index age, with different patterns of recency; or a combination of negative colonoscopy and negative FIT results.

MAIN OUTCOMES AND MEASURES: The main outcomes included estimated lifetime clinical outcomes, incremental costs, and quality-adjusted life-years gained (QALYG) associated with 1 additional FIT or colonoscopy. Optimal stopping age for screening, defined as the oldest age for which the incremental cost-effectiveness ratio was still below the willingness-to-pay threshold of $100 000 per QALYG, was evaluated.

RESULTS: The first of the 2 PRECISE subcohorts used in validating the simulation model included 25 974 adults (15 060 females [58.0%]; 54.7% aged 76 to 80 years) with a negative colonoscopy result 10 years before the index date. The second subcohort consisted of 118 269 adults (67 058 females [56.7%]; 90.5% aged 76 to 80 years) with a negative FIT result 1 year before the index date. Older age, male sex, higher comorbidity levels, and recent CRC screenings were associated with reduced incremental benefit and cost-effectiveness of additional screening. For the reference cohort of 76-year-old females without comorbidities and a negative colonoscopy result 10 years before the index age, 1 additional colonoscopy cost $38 226 per QALYG. For cohorts with otherwise equivalent characteristics, associated costs increased to $1 689 945 per QALYG for females at age 90 years without comorbidities and a negative colonoscopy results 10 years before the index age, $51 604 per QALYG for males at age 76 years without comorbidities and a negative colonoscopy result 10 years before the index age, and $108 480 per QALYG for females at age 76 years with severe comorbidities and a negative colonoscopy result 10 years before the index age and decreased to $16 870 per QALYG for females without comorbidities and a negative colonoscopy result 30 years before the index age. The optimal stopping ages across different cohorts ranged from younger than 76 to 86 years for colonoscopy and younger than 76 to 88 years for FIT.

CONCLUSIONS AND RELEVANCE: In this economic evaluation, age, sex, screening history, comorbidity, and future screening modality were associated with the clinical outcomes, cost-effectiveness, and optimal stopping age for CRC screening. These results can inform guideline development and patient-directed informed decision-making.

PMID:39699893 | DOI:10.1001/jamanetworkopen.2024.51715

JAMA Netw Open. 2024 Dec 2;7(12):e2451799. doi: 10.1001/jamanetworkopen.2024.51799.

ABSTRACT

IMPORTANCE: Physical activity, as a modifiable factor, emerges as a primary intervention strategy for the prevention and management of gestational diabetes (GD). Among women with GD, the association of physical activity during pregnancy with preterm birth remains unclear.

OBJECTIVE: To examine the association of accelerometer-derived physical activity metrics and patterns with preterm birth among women with GD.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study recruited pregnant women with GD in Hangzhou, China, from August 2019 to August 2023 as part of the Westlake Precision Birth Cohort study. Statistical analysis was performed between August and November 2023.

EXPOSURES: Wearable accelerometer-derived physical activity metrics and patterns. Measurements of physical activity via wearable accelerometer were performed at a median (IQR) of 25.4 (24.6-26.6) weeks’ gestation.

MAIN OUTCOMES AND MEASURES: Preterm birth was determined through the examination of delivery records. Incident preterm birth was defined as the delivery of infants before completing 37 weeks of gestation.

RESULTS: Among the 1427 women meeting the inclusion criteria, the mean (SD) age was 31.3 (3.8) years, and there were 80 cases of preterm birth. An increase in moderate-to-vigorous intensity physical activity (MVPA) and the fraction of physical activity energy expenditure derived from MVPA exhibited an inverse association with preterm birth, with an odds ratio per 30 minutes of 0.64 (95% CI, 0.42-0.98) and an odds ratio per SD of 0.69 (95% CI, 0.55-0.88). In the dose-response analysis, there was a progressive decrease in the odds of preterm birth with increasing duration of MVPA per day, reaching a plateau at approximately 74 minutes per day. Furthermore, the findings indicated that active MVPA (MVPA ≥30 minutes per day), whether it was concentrated into a few days or followed a more regular pattern, had similar beneficial association with preterm birth.

CONCLUSIONS AND RELEVANCE: In this prospective cohort study, MVPA during pregnancy exhibited an inverse association with preterm birth among women with GD. Concentrated physical activity was associated with similar benefits in reducing preterm birth risk as regular physical activity.

PMID:39699891 | DOI:10.1001/jamanetworkopen.2024.51799

Transl Vis Sci Technol. 2024 Dec 2;13(12):33. doi: 10.1167/tvst.13.12.33.

ABSTRACT

PURPOSE: Mutations affecting the CRB1 gene can result in a range of retinal phenotypes, including early onset severe retinal dystrophy/Leber congenital amaurosis (EOSRD/LCA), retinitis pigmentosa, cone-rod dystrophy (CORD), and macular dystrophy (MD). As research into treatment strategies advances towards clinical translation, there is a need to establish reliable outcome metrics. This study explores the contrast sensitivity function (CSF) across different spatial frequencies in individuals with CRB1-retinopathies using the child-friendly PopCSF test, an iPad-based “gamified” assessment.

METHODS: Prospective cross-sectional study of 20 patients with molecularly confirmed biallelic CRB1 pathogenic variants from Moorfields Eye Hospital, London, UK, was conducted. Best-corrected visual acuity (BCVA), contrast sensitivity using the Pelli-Robson chart, and the PopCSF test were performed.

RESULTS: Of the 20 CRB1 patients, seven had EOSRD/LCA, three had CORD, and 10 had MD. There was no statistically significant difference between the mean BCVA between phenotypes (P = 0.066). However, a significant difference was found between groups in the mean letter log contrast sensitivity (logCS) and area under the contrast sensitivity function (AUCSF) with P = 0.047 and P < 0.001, respectively. A moderate positive correlation was observed between Pelli-Robson and PopCSF (r = 0.53, P = 0.020). The CRB1 cohort had significantly lower CSF at both low and high spatial frequencies compared to controls. Among the CRB1 phenotypes, patients with EOSRD/LCA, exhibited the lowest CSF.

CONCLUSIONS: This study is the first to examine CSF across spatial frequencies in patients with CRB1-retinopathies using the novel PopCSF test.

TRANSLATIONAL RELEVANCE: The CSF holds promise as a potential functional vision trial endpoint.

PMID:39699888 | DOI:10.1167/tvst.13.12.33

Clin Exp Rheumatol. 2024 Dec;42(12):2420-2426. doi: 10.55563/clinexprheumatol/ku7y1q. Epub 2024 Dec 19.

ABSTRACT

OBJECTIVES: In primary Sjögren’s disease (pSjD), in addition to glandular inflammation and atrophy, functional secretion impairment may contribute to dryness. Altered protein distribution and antibodies against aquaporin-5 (anti-AQP5) and poly-U-binding factor 60kDa protein (anti-PUF60) have been reported in pSjD and may be specifically implicated in the glandular secretive processes. This study aimed to assess the occurrence of serum anti-AQP5 and anti-PUF60 antibodies and their correlations with clinical and laboratory features of pSjD.

METHODS: Blood samples from pSjD patients and healthy donors (HD) were collected, and anti-AQP5 and anti-PUF60 antibodies were detected using an enzyme-linked immunosorbent assay. Differences between groups were evaluated using appropriate statistical tests, and odds ratios (OR) of high disease activity were assessed by multivariate stepwise backward multiple regression and adjusted for clinical covariates.

RESULTS: Serum samples from 36 pSjD patients and 8 HD were analysed, and anti-AQP5 and anti-PUF60 antibody levels were not significantly different between groups. However, pSjD patients with high disease activity (n. 10) had significantly higher levels of anti-AQP5 antibodies compared to those with low-moderate disease activity (p<0.001). At logistic regression analysis, variables associated with high disease activity were anti-AQP5 (OR 128.9, 95% CI 2.7-615), C-reactive protein (OR 12.9, 95% CI 1.2-137.2), and C4 <10 mg/dl (OR 60, 95% CI 1.1-318.9).

CONCLUSIONS: Our pilot study confirms that anti-AQP5 antibodies may discriminate pSjD patients with high disease activity. These findings offer valuable clinical implications for managing pSjD patients, potentially identifying patients at high risk of glandular deterioration.

PMID:39699867 | DOI:10.55563/clinexprheumatol/ku7y1q

Oncology (Williston Park). 2024 Dec 3;38(12):462-468. doi: 10.46883/2024.25921032.

ABSTRACT

INTRODUCTION: There are limited data available regarding patient outcomes in those who would have been ineligible to receive therapy based on the original clinical trial eligibility criteria. We decided to conduct a retrospective study to evaluate outcomes based on clinical trial eligibility in patients with metastatic non-small cell lung cancer (NSCLC).

METHODS: A retrospective chart review of all patients with metastatic NSCLC who received first-line systemic therapy at a single academic institution was performed. Each patient’s chart was reviewed to determine if they would have qualified for the phase 3 clinical trial that led to the approval of the specific treatment regimen which they received. Data were analyzed to determine if there was a difference in survival time between those who would have been eligible compared with those who were ineligible for the clinical trial of the treatment regimen administered.

RESULTS: There were 170 patients with a diagnosis of metastatic NSCLC who received first-line systemic therapy. Of these, 109 received combined chemotherapy, 25 received immunotherapy, and 36 received targeted therapy. There is a statistically significant difference in the restricted mean survival time between the eligible and ineligible groups in those who received combined chemotherapy (19.9 months vs 13.2 months; P = .03), but not in either the immunotherapy group (22.4 months vs 12.9 months; P = .06) or the targeted therapy group (57.7 months vs 39.0 months; P = .14).

CONCLUSION: These data support less restrictive clinical trial eligibility criteria for those with metastatic NSCLC. This is especially true regarding both targeted therapy and immunotherapy treatment regimens.

PMID:39699855 | DOI:10.46883/2024.25921032

Int J Clin Pharm. 2024 Dec 19. doi: 10.1007/s11096-024-01847-2. Online ahead of print.

ABSTRACT

BACKGROUND: The application of digital technologies has shown benefits in enhancing pharmacovigilance activities but consumers views on the use of these tools for this purpose are not well described.

AIM: To explore consumers’ views on using digital tools to report adverse drug reactions (ADRs) and identify key features that consumers want in digital tools for ADR reporting.

METHOD: An online survey was conducted among adults who had taken medicine in the previous six-months in Australia. The development of questions was guided by the Combined Technology Acceptance Model and Theory of Planned Behaviour (C-TAM-TPB) framework. Responses to closed-ended questions were analysed using descriptive statistics and chi-square/Fisher’s exact test, while free-text responses were analysed using qualitative content analysis.

RESULTS: A total of 494 responses were included in the analysis. Eighty-seven percent of respondents preferred using digital tools for reporting ADRs. Consumers indicated a free-text space for describing ADRs (90%) as important or very important features of digital tools for ADR reporting, followed by acknowledgement of their report submission (87%) and receiving summary of previously reported ADRs (87%). Women (p < 0.001), advanced smartphone users (p < 0.001), and previous digital healthcare tool users (p = 0.017) showed higher intention to use digital tools. Consumers emphasized the importance of ease-of-use, accessibility, receiving medicine safety information, feedback, and advice for reporting ADRs via digital tools.

CONCLUSION: Consumers prefer using digital tools for reporting ADRs and place high value on features such as a free-text space for describing ADRs, acknowledgement of report submissions, and access to summaries of previously submitted reports.

PMID:39699849 | DOI:10.1007/s11096-024-01847-2

Diabetes Ther. 2024 Dec 19. doi: 10.1007/s13300-024-01679-3. Online ahead of print.

ABSTRACT

INTRODUCTION: ONWARDS 5 evaluated the effectiveness and safety of insulin icodec (icodec) titrated with a dosing guide app (icodec with app) versus once-daily insulin analogs in insulin-naive adults with type 2 diabetes. The insulin glargine U300 (glargine U300) stratum was too small to enable a robust post hoc efficacy comparison. Augmentation methodology was applied to increase the glargine U300 group size using real-world data (RWD), to facilitate efficacy comparisons of icodec with app versus glargine U300, and to demonstrate the potential of the augmentation methodology to strengthen underpowered treatment comparisons (AUGMENT study).

METHODS: ONWARDS 5 data were augmented with RWD collected from the US Ambulatory Electronic Medical Records database. Randomized and augmented comparisons (propensity-score-matched) between icodec with app and glargine U300 were weighted to provide a fully augmented estimate of the primary outcome (change in glycated hemoglobin [HbA_1c] after 52 weeks). Data were adjusted for trial effects. Sensitivity analyses were conducted.

RESULTS: The nonaugmented randomized estimated treatment difference (ETD; 95% CI) between icodec with app and glargine U300 (trial stratum) for change in HbA_1c was – 0.21 (- 0.70 to 0.28) percentage points. After adjusting for trial effects, the overall fully augmented ETD (95% CI) was – 0.33 (- 0.68 to 0.01) percentage points numerically in favor of icodec with app, although not statistically significant. Sensitivity analyses supported the findings.

CONCLUSIONS: Using augmented data, the precision of the change in HbA_1c estimate was increased compared with the trial stratum analysis alone. These findings help to validate the principle of utilizing augmentation to strengthen trial outcomes.

TRIAL REGISTRATION NUMBER: The ONWARDS 5 trial is registered with ClinicalTrials.gov (NCT04760626).

PMID:39699848 | DOI:10.1007/s13300-024-01679-3

Infection. 2024 Dec 19. doi: 10.1007/s15010-024-02453-0. Online ahead of print.

ABSTRACT

PURPOSE: Bloodstream infections caused by Pseudomonas aeruginosa (PABSI) in hematological patients are associated with high morbidity and mortality. We investigated the epidemiology, risk factors, and outcomes of PABSI at our center.

METHODS: All adult hematological patients with PABSI between January 2013 and July 2023 were included. Demographic and clinical characteristics, antimicrobial susceptibilities, antibiotic therapy, fluoroquinolone-prophylaxis, source of infection, and 30-day outcome were recorded. Descriptive statistics, tests for difference, and logistic regression models were performed.

RESULTS: Fifty patients with PABSI were identified with a median age of 58.5 years (range 24-78). 37 patients (74%) had severe neutropenia, 20 (40%) received allogeneic HSCT, and 29 (58%) had acute leukemia. A total of 34 (68%) had received timely appropriate anti-pseudomonal antibiotic therapy. The most common presumed cause of PABSI was mucositis (n = 16, 32%), followed by pneumonia (8, 16%) and skin and soft tissue infections (n = 6, 12%). Empirical combination therapy was used in 16 (32%) patients, while targeted combination therapies were used in 27 (54%) patients. P. aeruginosa detection led to treatment change in 31 (62%) cases. The overall 30-day survival rate was 78% (n = 39). Carbapenem-resistance occurred in 34% (n = 17), and multidrug-resistance (MDR) in 20% (n = 10). Prior antibiotic exposure was associated with resistance. Appropriate antibiotic therapy was associated with survival, whereas antibiotic resistance and organ infection were associated with a fatal outcome.

CONCLUSION: Prior antibiotic exposure in hematological patients is associated with resistance in PABSI, which is a major risk factor for a fatal outcome. Antibiotic stewardship efforts should be intensified and fluoroquinolone prophylaxis needs to be reconsidered.

PMID:39699836 | DOI:10.1007/s15010-024-02453-0

Cardiovasc Interv Ther. 2024 Dec 19. doi: 10.1007/s12928-024-01073-7. Online ahead of print.

ABSTRACT

Patients undergoing percutaneous coronary intervention (PCI) may experience bleeding events. Bleeding risk is increased in patients with comorbid peripheral arterial disease (PADs). To evaluate whether PCI patients with PADs have worse outcome after bleeding, we assessed pooled patient-level data of 5,989 randomized all-comer trial participants and identified those who had a bleeding (BIO-RESORT:NCT01674803, BIONYX:NCT02508714). Major adverse cardiac events (MACE) and mortality were assessed from bleeding until 3 years after PCI. Of all 313 PCI patients with bleeding events, patients with PADs (n = 34, 10.9%) were older and had more complex lesions than those without PADs (n = 279, 89.1%). In patients with PADs, bleeding occurred more often during the first year after PCI (79.4% vs. 57.3%, p = 0.013). The proportion of major bleeding, and the severity and location of bleeding were similar between both groups. Multivariate analysis found no statistically significant between-group difference in MACE (43.1% vs. 34.7%, p = 0.53; adj.HR:0.86, 95%CI 0.45-1.63, p = 0.64) and mortality (33.5% vs. 22.3%, p = 0.12; adj.HR:1.45, 95%CI 0.73-2.91, p = 0.29). Bleeding occurred significantly more often during the first year after PCI in all-comer patients with concomitant PADs than in those without PADs, while we observed no significant between-group difference in bleeding severity and location, and the risk of adverse events after bleeding.

PMID:39699832 | DOI:10.1007/s12928-024-01073-7