OBJECTIVE: This retrospective real-world study compared overall survival (OS) between patients with BRCA wild-type (BRCAwt) recurrent epithelial ovarian cancer (OC) who received niraparib second-line maintenance (2LM) versus active surveillance (AS) using target trial emulation, cloning, inverse probability of censoring weighting (IPCW) methodology to minimize immortal time bias.
METHODS: Eligible patients from a United States-based, deidentified, electronic health record-derived database were diagnosed with epithelial OC (January 1, 2011-May 31, 2021), were BRCAwt, and completed second-line (2L) therapy (January 1, 2017-March 2, 2022). Patient data were cloned at index (2L last treatment date), assigned to niraparib 2LM and AS cohorts, and censored when treatment deviated from clone assignment. Follow-up was measured from index to earliest of study end (May 31, 2022), last activity, or death. Median OS (mOS) and hazard ratios were estimated from stabilized IPCW Kaplan-Meier curves and Cox regression models.
RESULTS: Overall, 199 patients received niraparib 2LM, and 707 had their care managed with AS. Key characteristics were balanced across cohorts after cloning and stabilized IPCW. Median follow-up was 15.6- and 9.3-months pre-cloning. IPCW mOS was 24.1 months (95% CI: 20.9-29.5) and 18.4 months (95% CI: 15.1-22.8) in niraparib 2LM and AS cohorts, respectively (hazard ratio, 0.77; 95% CI: 0.66-0.89).
CONCLUSIONS: This real-world study provides supportive evidence of an OS benefit for patients with BRCAwt recurrent OC who received 2LM niraparib monotherapy compared with those whose care was managed with AS. The analytic strategies implemented were useful in minimizing immortal time bias and measured confounding.

OBJECTIVE: We investigated whether a 52-gene signature was associated with transplant-free survival and other clinically meaningful outcomes in patients with idiopathic pulmonary fibrosis (IPF) in the IPF-PRO Registry, which enrolled patients who were and were not taking antifibrotic therapy.
METHODS: The 52-gene risk signature was implemented to classify patients as being at \"high risk\" or \"low risk\" of disease progression and mortality. Transplant-free survival and other outcomes were compared between patients with a low-risk versus high-risk signature.
RESULTS: The 52-gene signature classified 159 patients as at low risk and 86 as at high risk; in these groups, respectively, 56.6% and 51.2% used antifibrotic therapy at enrollment. Among those taking antifibrotic therapy, patients with a low-risk versus high-risk signature were at decreased risk of death, a composite of lung transplant or death, and a composite of decline in DLco % predicted > 15%, lung transplant, or death. Similar results were observed in the overall cohort.
CONCLUSIONS: These data suggest that the 52-gene signature can be used in patients with IPF treated with antifibrotic therapy to distinguish patients at higher risk of disease progression and mortality.

OBJECTIVE: To establish trust in real-world evidence (RWE) derived from CareLink Personal (CP), Medtronic\'s data management system for MiniMed system users, we show that this database and its analyses strictly adhere to the principles of RWE.
METHODS: The methodology is applicable to all MiniMed iterations. We described every step from raw data to predefined outcomes. In addition, we showed CP\'s fitness-for-research by the below metrics (using last year\'s MiniMed 780G system data as a case study): representative population, relevant endpoints, appropriate granularity, high data completeness, high data representativity and consistency in results.
RESULTS: The process from raw data to outcomes has been validated, and metrics/logics adhere to established definitions. Over 95% of users have a CP account; with 96% providing consent, this allows the use of >91% of the census population. There is no rationale for an over-representation of a specific phenotype among users not included. CP includes >50 endpoints, including \'International Consensus on Time in Range\' based metrics. Data are recorded at 5-min intervals (maximum 288 per day), and on average there were 263 data points per person per day. Ninety-nine per cent of uploads were automated. For the last year, only 1 in 6 users had a data gap >1 day, and 1 in 50 had a gap >1 week. The time in range from in-silico studies was similar to that of real-world studies from different geographies and with ever growing populations.
CONCLUSIONS: RWE from CP adheres to the principles of RWE and can serve as robust evidence on the performance and safety of MiniMed systems.

UNASSIGNED: In resource-constrained countries, inadequate access to healthcare and prognostic tools can be the Achilles\' heel in effectively managing chronic kidney disease (CKD). There is a significant similarity in the pathogenesis of CKD and liver fibrosis. The role of liver fibrosis (LF) scores in predicting short-term clinical outcomes in hospitalized patients with CKD is unknown. Our study aimed at calculating LF scores and studying the association of liver fibrosis with short-term mortality and morbidity in CKD patients.
UNASSIGNED: Patients aged above 15 years diagnosed with CKD as per the KDIGO criteria were enrolled. LF scores, namely, NFS, GPRI, and FIB-4 scores were calculated. Patients were followed up for a period of 28 days for good and poor composite outcomes, namely, the requirement of hemodialysis, non-invasive ventilation, prolonged hospital stay, and neurological and cardiovascular outcomes including death.
UNASSIGNED: Among 163 patients, 70.5% were below 60 years of age, 82.2% were male and 35% were diabetic. At 28-day follow up, 52.1% had poor composite outcome. The AUROC for GPRI and FIB-4 in predicting poor outcomes was 0.783 (95% CI: 0.71-0.855) (p < 0.001) and 0.62 (95% CI: 0.534-0.706) (p = 0.008), respectively. The AUROC for GPRI and NFS in predicting all-cause mortality was 0.735 (95% CI: 0.627-0.843) (p = 0.001) and 0.876 (95% CI, 0.8-0.952) (p < 0.001), respectively.
UNASSIGNED: We found a positive association between LF scores and CKD outcomes in hospitalized patients. The LF scores significantly predicted poor outcomes in patients with CKD. Among the scores, GPRI was found to be a stronger predictor in predicting outcomes in both diabetic and non-diabetic patients with CKD. A high GPRI score was also associated with poor outcomes and increased mortality in both diabetics and non-diabetics.

BACKGROUND: Risk scores facilitate the assessment of mortality risk in patients with community-acquired pneumonia (CAP). Despite their utilities, there is a scarcity of evidence comparing the various RS simultaneously. This study aims to evaluate and compare multiple risk scores reported in the literature for predicting 30-day mortality in adult patients with CAP.
METHODS: A retrospective cohort study on patients diagnosed with CAP was conducted across two hospitals in Colombia. The areas under receiver operating characteristic curves (ROC-curves) were calculated for the outcome of survival or death at 30 days using the scores obtained for each of the analyzed questionnaires.
RESULTS: A total of 7454 potentially eligible patients were included, with 4350 in the final analysis, of whom 15.2% (662/4350) died within 30 days. The average age was 65.4 years (SD: 21.31), and 59.5% (2563/4350) were male. Chronic kidney disease was 3.7% (9.2% vs. 5.5%; p < 0.001) (OR: 1.85) higher in subjects who died compared to those who survived. Among the patients who died, 33.2% (220/662) presented septic shock compared to 7.3% (271/3688) of the patients who survived (p < 0.001). The best performances at 30 days were shown by the following scores: PSI, SMART-COP and CURB 65 scores with the areas under ROC-curves of 0.83 (95% CI: 0.8-0.85), 0.75 (95% CI: 0.66-0.83), and 0.73 (95% CI: 0.71-0.76), respectively. The RS with the lowest performance was SIRS with the area under ROC-curve of 0.53 (95% CI: 0.51-0.56).
CONCLUSIONS: The PSI, SMART-COP and CURB 65, demonstrated the best diagnostic performances for predicting 30-day mortality in patients diagnosed with CAP. The burden of comorbidities and complications associated with CAP was higher in patients who died.

BACKGROUND: The COVID-19 pandemic prompted various containment strategies, such as work-from-home policies and reduced social contact, which significantly altered people\'s sleep routines. While previous studies have highlighted the negative impacts of these restrictions on sleep, they often lack a comprehensive perspective that considers other factors, such as seasonal variations and physical activity (PA), which can also influence sleep.
OBJECTIVE: This study aims to longitudinally examine the detailed changes in sleep patterns among working adults during the COVID-19 pandemic using a combination of repeated questionnaires and high-resolution passive measurements from wearable sensors. We investigate the association between sleep and 5 sets of variables: (1) demographics; (2) sleep-related habits; (3) PA behaviors; and external factors, including (4) pandemic-specific constraints and (5) seasonal variations during the study period.
METHODS: We recruited working adults in Finland for a 1-year study (June 2021-June 2022) conducted during the late stage of the COVID-19 pandemic. We collected multisensor data from fitness trackers worn by participants, as well as work and sleep-related measures through monthly questionnaires. Additionally, we used the Stringency Index for Finland at various points in time to estimate the degree of pandemic-related lockdown restrictions during the study period. We applied linear mixed models to examine changes in sleep patterns during this late stage of the pandemic and their association with the 5 sets of variables.
RESULTS: The sleep patterns of 27,350 nights from 112 working adults were analyzed. Stricter pandemic measures were associated with an increase in total sleep time (TST) (β=.003, 95% CI 0.001-0.005; P<.001) and a delay in midsleep (MS) (β=.02, 95% CI 0.02-0.03; P<.001). Individuals who tend to snooze exhibited greater variability in both TST (β=.15, 95% CI 0.05-0.27; P=.006) and MS (β=.17, 95% CI 0.03-0.31; P=.01). Occupational differences in sleep pattern were observed, with service staff experiencing longer TST (β=.37, 95% CI 0.14-0.61; P=.004) and lower variability in TST (β=-.15, 95% CI -0.27 to -0.05; P<.001). Engaging in PA later in the day was associated with longer TST (β=.03, 95% CI 0.02-0.04; P<.001) and less variability in TST (β=-.01, 95% CI -0.02 to 0.00; P=.02). Higher intradaily variability in rest activity rhythm was associated with shorter TST (β=-.26, 95% CI -0.29 to -0.23; P<.001), earlier MS (β=-.29, 95% CI -0.33 to -0.26; P<.001), and reduced variability in TST (β=-.16, 95% CI -0.23 to -0.09; P<.001).
CONCLUSIONS: Our study provided a comprehensive view of the factors affecting sleep patterns during the late stage of the pandemic. As we navigate the future of work after the pandemic, understanding how work arrangements, lifestyle choices, and sleep quality interact will be crucial for optimizing well-being and performance in the workforce.

BACKGROUND: Research is needed to understand and address barriers to risk management for women at high (≥20% lifetime) risk for breast cancer, but recruiting this population for research studies is challenging.
OBJECTIVE: This paper compares a variety of recruitment strategies used for a cross-sectional, observational study of high-risk women.
METHODS: Eligible participants were assigned female at birth, aged 25-85 years, English-speaking, living in the United States, and at high risk for breast cancer as defined by the American College of Radiology. Individuals were excluded if they had a personal history of breast cancer, prior bilateral mastectomy, medical contraindications for magnetic resonance imaging, or were not up-to-date on screening mammography per American College of Radiology guidelines. Participants were recruited from August 2020 to January 2021 using the following mechanisms: targeted Facebook advertisements, Twitter posts, ResearchMatch (a web-based research recruitment database), community partner promotions, paper flyers, and community outreach events. Interested individuals were directed to a secure website with eligibility screening questions. Participants self-reported method of recruitment during the eligibility screening. For each recruitment strategy, we calculated the rate of eligible respondents and completed surveys, costs per eligible participant, and participant demographics.
RESULTS: We received 1566 unique responses to the eligibility screener. Participants most often reported recruitment via Facebook advertisements (724/1566, 46%) and ResearchMatch (646/1566, 41%). Community partner promotions resulted in the highest proportion of eligible respondents (24/46, 52%), while ResearchMatch had the lowest proportion of eligible respondents (73/646, 11%). Word of mouth was the most cost-effective recruitment strategy (US $4.66 per completed survey response) and paper flyers were the least cost-effective (US $1448.13 per completed survey response). The demographic characteristics of eligible respondents varied by recruitment strategy: Twitter posts and community outreach events resulted in the highest proportion of Hispanic or Latina women (1/4, 25% and 2/6, 33%, respectively), and community partner promotions resulted in the highest proportion of non-Hispanic Black women (4/24, 17%).
CONCLUSIONS: Although recruitment strategies varied in their yield of study participants, results overall support the feasibility of identifying and recruiting women at high risk for breast cancer outside of clinical settings. Researchers must balance the associated costs and participant yield of various recruitment strategies in planning future studies focused on high-risk women.

UNASSIGNED: In this study, we aimed to evaluate and compare the effects of intravitreal aflibercept (IVA) and intravitreal faricimab (IVF) injections on the blood flow of retinal vessels in the peripapillary region and optic nerve head (ONH) in eyes with diabetic macular edema (DME) using laser speckle flowgraphy (LSFG).
UNASSIGNED: This study included 20 eyes of 18 patients treated with IVA and 15 eyes of 11 patients treated with IVF for DME. The mean blur rate (MBR) of the ONH and retinal artery and vein of the peripapillary region were measured using LSFG at baseline and 1 month after injection. Central retinal thickness (CRT) and best-corrected visual acuity (BCVA) were measured for all patients.
UNASSIGNED: CRT decreased significantly in both IVA-treated (p = 0.0003) and IVF-treated groups (p = 0.0004). Some of the MBR-related parameters of the ONH, such as MBR of all areas (MA), MBR of vascular areas (MV), and MBR of tissue areas (MT), decreased significantly 1 month after IVA and IVF compared to baseline values (MA of IVA, p < 0.0001; MT of IVA, p = 0.0220; MA of IVF, p = 0.0002; MT of IVF, p = 0.0461). MBR of the retinal artery (MBR-A) and vein (MBR-V) also decreased significantly 1 month after IVA and IVF compared with baseline values (MBR-A of IVA, p = 0.0002; MBR-V of IVA, p = 0.0010; MBR-A of IVF, p = 0.0368). No significant difference in ocular perfusion was observed between the IVA-treated and IVF-treated groups.
UNASSIGNED: Intravitreal injection led to a reduction in ocular blood flow in both retinal peripapillary vessels and the ONH in both IVA-treated and IVF-treated groups. No significant difference was observed in MBR reduction between the IVA-treated and IVF-treated groups. Our findings warrant further long-term investigations to reveal differences between aflibercept and faricimab.

OBJECTIVE: To investigate the utilization and costs of non-insulin glucose-lowering drugs (GLDs) in Australia from 2013 to 2023.
METHODS: We conducted a retrospective analysis of the Australian Pharmaceutical Benefits Scheme (PBS) administrative dataset of 118 727 494 GLD prescriptions. The main outcome measures were the annual number of GLD prescriptions dispensed, accounting for type 2 diabetes mellitus (T2DM) prevalence and healthcare system costs, adjusted for inflation.
RESULTS: Utilization of GLDs doubled from 6.4 million prescriptions in 2013 to 15.6 million in 2023. The average annual percent increase in utilization was 8.1%, compared to the average annual increase in prevalence of T2DM of 1.8%. The biggest change was in sodium-glucose cotransporter-2 (SGLT2) inhibitors, for which there was an average annual increase in utilization of 59.4% (95% confidence interval [CI] 51.7%, 68.2%; p < 0.05) from 2014 (first full year of PBS listing), followed by glucagon-like peptide-1 receptor agonists (GLP-1RAs), which showed an increase of 31.4% (95% CI 28.5%, 33.8%; p < 0.05) annually (2013 to 2023). Dipeptidyl peptidase-4 inhibitor utilization tripled, with an average annual increase of 10.9% (95% CI 8.1%, 13.8%; p < 0.05), but this plateaued from 2020. Metformin utilization increased by 4.7% (95% CI 2.0%, 6.9%; p < 0.05) annually. In contrast, sulphonylurea, glitazone and acarbose utilization declined. Total GLD costs increased threefold over the same period. Despite only accounting for 11.7% of utilization, GLP-1RAs contributed to 35% of the costs.
CONCLUSIONS: Utilization of GLDs doubled, and associated costs tripled over the past 11 years, with no sign of either utilization or costs plateauing, predominantly due to increased GLP-1RA and SGLT2 inhibitor prescribing.

OBJECTIVE: Heterotopic ossification (HO) can occur after hemiarthroplasty (HA) for femoral neck fractures (FNF). This study aimed to investigate the frequency and factors contributing to the development of HO after HA.
METHODS: The study included data from 92 of 183 patients (26 male and 66 female) who sustained FNF and underwent HA between April 2019 and January 2022. HO was identified on postoperative radiographic images. Patient background, operative duration, blood loss, and presence of free bone fragments immediately after surgery were compared between the HO and non-HO groups. Statistical analyses included the independent-sample t-test for continuous variables and the chi-squared test for categorical variables. A multivariate logistic regression analysis was performed using HO as an objective variable.
RESULTS: HO occurred in 50 of the 92 (54%) patients. There were no statistically significant differences in patient backgrounds. Univariate analysis revealed significantly longer mean operative duration and greater blood loss in the HO group. Free bone fragments in the immediate postoperative period were observed in 29 of 50 (58%) patients in the HO group and in 3 of 42 (7.1%) patients in the non-HO group, a statistically significant difference. Logistic regression analysis revealed that the presence of free bone fragments was an independent explanatory factor for HO development.
CONCLUSIONS: The presence of free bone fragments immediately after surgery may be significantly associated with the development of HO. Therefore, it is necessary to sufficiently remove such fragments during surgery because they may trigger HO.