Category: Statistics

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

Insights Imaging. 2024 Dec 19;15(1):302. doi: 10.1186/s13244-024-01852-z.

ABSTRACT

BACKGROUND: To investigate the efficacy of three-compartment restriction spectrum imaging (RSI), diffusion kurtosis imaging (DKI), and diffusion-weighted imaging (DWI) in the assessment of lymph node metastases (LNM) in rectal cancer.

METHODS: A total of 77 patients with rectal cancer who underwent pelvic MRI were enrolled. RSI-derived parameters (f₁, f₂, and f₃), DKI-derived parameters (D_app and K_app), and the DWI-derived parameter (ADC) were calculated and compared using a Mann-Whitney U test or independent samples t-test. Logistic regression (LR) analysis was used to identify independent predictors of LNM status. Area under the receiver operating characteristic curve (AUC) and Delong analysis were performed to assess the diagnostic performance of each parameter.

RESULTS: The LNM-positive group exhibited significantly higher f₁ and K_app levels and significantly lower f₃, D_app, and ADC levels compared to the LNM-negative group (p < 0.05). There was no difference in f₂ levels between the two groups (p = 0.783). LR analysis showed that D_app and K_app were independent predictors of a positive LNM status. AUC and Delong analysis showed that DKI (D_app + K_app) exhibited significantly higher diagnostic efficacy (AUC = 0.908; sensitivity = 87.10%; specificity = 86.96%) than RSI (f₁ + f₃) and DWI (ADC), with AUCs were 0.842 and 0.771 (Z = 2.113, 3.453; p = 0.035, < 0.001, respectively). The AUC performance between RSI and DWI was also statistically significant (Z = 1.972, p = 0.049).

CONCLUSION: The RSI model is superior to conventional DWI but inferior to DKI in differentiation between LNM-positive and LNM-negative rectal cancers. Further study is needed before it could serve as a promising biomarker for guiding effective treatment strategies.

CRITICAL RELEVANCE STATEMENT: The three-compartment restriction spectrum imaging was able to differentiate between LNM-positive and LNM-negative rectal cancers with high accuracy, which has the potential to serve as a promising biomarker that could guide treatment strategies.

KEY POINTS: Three-compartment restriction spectrum imaging could differentiate lymph node metastases in rectal cancer. Diffusion kurtosis imaging and diffusion-weighted were associated with lymph node metastases in rectal cancer. The combination of different parameters has the potential to serve as a promising biomarker.

PMID:39699826 | DOI:10.1186/s13244-024-01852-z

J Robot Surg. 2024 Dec 19;19(1):30. doi: 10.1007/s11701-024-02193-1.

ABSTRACT

Robotic distal gastrectomy (RDG) has been increasingly used for the treatment of gastric cancer, however, its comparative safety and efficacy against the laparoscopic approach (LDG), remains unclear, especially when accounting the reconstruction method as a confounder. This systematic review and meta-analysis aims to evaluate the short-term outcomes of RDG vs LDG In patIents with gastric cancer, undergoing Billroth I and II reconstruction. A systematic review was conducted in accordance with PRISMA guidelines. We searched Pubmed, Scopus and the Cochrane Library, up to October 22nd, 2024. The primary outcomes analyzed were the blood loss, operative duration, and the number of harvested lymph nodes and the secondary outcomes included overall complications, time to oral intake, duration of hospitalization and time to first flatus. Random-effects models were used to calculate weighted mean differences (WMD) and Odds ratios (OR) with 95% confidence intervals (CI), and heterogeneity was assessed using the I² statistic. P values were also calculated. Sensitivity analysis was performed for outcomes with moderate to high heterogeneity. Five studies were included, involving 811 patients (RDG: n = 289, LDG: n = 522). RDG was associated with a significantly longer operative duration compared to LDG (WMD = 34.14 min, 95%CI 10.92 to 57.35, P = 0.004, I² = 91%). RDG patients initiated oral intake earlier (WMD = -0.20 days, 95%CI -0.39 to -0.01, P = 0.03, I² = 45%). RDG resulted in shorter hospital stays (WMD = -1.48 days, 95%CI -2.91 to -0.04, P = 0.04, I² = 86%). RDG patients had a faster return to bowel function (time to first flatus) (WMD = -0.33 days, 95%CI -0.50 to -0.15, P = 0.00003, I² = 57%). No statistically significant differences were observed regarding blood loss between RDG and LDG (WMD = -3.88 mL, 95%CI -21.63 to 13.87, P = 0.67, I² = 78%). There was no statistically significant difference in complication rates (OR = 0.61, 95%CI 0.36 to 1.03, P = 0.06, I² = 0%). No significant differences were observed regarding the number of lymph nodes harvested (WMD = -0.49, 95%CI -3.02 to 2.04, P = 0.70, I² = 24%). Sensitivity analysis confirmed the robustness of the findings of operative duration and time to first flatus. RDG with BI/ BII requires longer operative duration, but it associated with faster recovery compared to LDG. No differences were observed between RDG and LDG with regards to overall complications, number of harvested lymph nodes and blood loss, showing that RDG is as safe and oncological equivalent to LDG. Future studies particularly, multi-center randomized clinical trials, should have a longer follow up period and examine the type of reconstruction separately. PROSPERO registration: CRD42024605895.

PMID:39699804 | DOI:10.1007/s11701-024-02193-1