Early Initiation of Biologics and Disease Outcomes in Adults and Children With Inflammatory Bowel Diseases: Results From the Epidemiology Group of the Nationwide Israeli Inflammatory Bowel Disease Research Nucleus Cohort.

BACKGROUND & AIMS: In this nationwide study, we explored whether early initiation of biologics is associated with improved outcomes in children and adults with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: All patients diagnosed with CD or UC in Israel (2005-2020) were included in the Epidemiology Group of the Israeli Inflammatory Bowel Disease Research Nucleus cohort, encompassing 98% of the population. We compared disease duration at biologics initiation (ie, 0-3 months, >3-12 months, >1-2 years, and >2-3 years) using the cloning, censoring, and weighting by inverse probabilities method to emulate a target trial, adjusting for time-varying confounders and selection bias. RESULTS: Of the 34,375 included patients (of whom 5240 [15%] were children), 7452 of 19,264 (39%) with CD and 2235 of 15,111 (15%) with UC received biologics. In CD, by 10 years postdiagnosis, the probability of CD-related surgery decreased gradually but modestly with earlier initiation of biologics; a significant difference was noted between >2-3 years (31%) and 0-3 months (18%; P = .02; number needed to treat, 7.7), whereas there was no difference between the 0-3-month and >3-12-month periods. The 10-year probability of steroid dependency for the 0-3-month period (19%) differed both from the >2-3-year (31%; P < .001) and 1-2-year periods (37%; P < .001). In UC, no significant differences in colectomy or steroid dependency rates were observed between the treatment initiation periods. Similar trends were noted in the pediatric population. CONCLUSIONS: Very early initiation of biologics was not associated with some outcomes except for a modest risk reduction of surgery and steroid dependency for CD, which requires confirmation in future studies. In UC, early introduction of biologics was not associated with reduced risk of colectomy or steroid dependency.

Mapping the Ecological Terrain of Stroke Prehospital Delay: A Nationwide Registry Study.

BACKGROUND: Delays in hospital presentation limit access to acute stroke treatments. While prior research has focused on patient-level factors, broader ecological and social determinants have not been well studied. We aimed to create a geospatial map of prehospital delay and examine the role of community-level social vulnerability. METHODS: We studied patients with ischemic stroke who arrived by emergency medical services in 2015 to 2017 from the American Heart Association Get With The Guidelines-Stroke registry. The primary outcome was time to hospital arrival after stroke (in minutes), beginning at last known well in most cases. Using Geographic Information System mapping, we displayed the geography of delay. We then used Cox proportional hazard models to study the relationship between community-level factors and arrival time (adjusted hazard ratios [aHR] <1.0 indicate delay). The primary exposure was the social vulnerability index (SVI), a metric of social vulnerability for every ZIP Code Tabulation Area ranging from 0.0 to 1.0. RESULTS: Of 750 336 patients, 149 145 met inclusion criteria. The mean age was 73 years, and 51% were female. The median time to hospital arrival was 140 minutes (Q1: 60 minutes, Q3: 458 minutes). The geospatial map revealed that many zones of delay overlapped with socially vulnerable areas (https://harvard-cga.maps.arcgis.com/apps/webappviewer/index.html?id=08f6e885c71b457f83cefc71013bcaa7). Cox models (aHR, 95% CI) confirmed that higher SVI, including quartiles 3 (aHR, 0.96 [95% CI, 0.93-0.98]) and 4 (aHR, 0.93 [95% CI, 0.91-0.95]), was associated with delay. Patients from SVI quartile 4 neighborhoods arrived 15.6 minutes [15-16.2] slower than patients from SVI quartile 1. Specific SVI themes associated with delay were a community's socioeconomic status (aHR, 0.80 [95% CI, 0.74-0.85]) and housing type and transportation (aHR, 0.89 [95% CI, 0.84-0.94]). CONCLUSIONS: This map of acute stroke presentation times shows areas with a high incidence of delay. Increased social vulnerability characterizes these areas. Such places should be systematically targeted to improve population-level stroke presentation times.

A stepped wedge cluster randomized trial of graphical surveillance of kidney function data to reduce late presentation for kidney replacement therapy.

Late presentation for kidney replacement therapy (KRT) is an important cause of avoidable morbidity and mortality. Here, we evaluated the effect of a complex intervention of graphical estimated glomerular filtration rate (eGFR) surveillance across 15% of the United Kingdom population on the rate of late presentation using data routinely collected by the United Kingdom Renal Registry. A stepped wedge cluster randomized trial was established across 19 sites with eGFR graphs generated from all routine blood tests (community and hospital) across the population served by each site. Graphs were reviewed by trained laboratory or clinical staff and high-risk graphs reported to family doctors. Due to delays outside the control of clinicians and researchers few laboratories activated the intervention in their randomly assigned time period, so the trial was converted to a quasi-experimental design. We studied 6,100 kidney failure events at 20 laboratories served by 17 main kidney units. A total of 63,981 graphs were sent out. After adjustment for calendar time there was no significant reduction in the rate of presentation during the intervention period. Therefore, implementation of eGFR graph surveillance did not reduce the rate of late presentation for KRT after adjustment for secular trends. Thus, graphical surveillance is an intervention aimed at reducing late presentation, but more evidence is required before adoption of this strategy can be recommended.

The impact of time to death in donors after circulatory death on recipient outcome in simultaneous pancreas-kidney transplantation.

The time to arrest donors after circulatory death is unpredictable and can vary. This leads to variable periods of warm ischemic damage prior to pancreas transplantation. There is little evidence supporting procurement team stand-down times based on donor time to death (TTD). We examined what impact TTD had on pancreas graft outcomes following donors after circulatory death (DCD) simultaneous pancreas-kidney transplantation. Data were extracted from the UK transplant registry from 2014 to 2022. Predictors of graft loss were evaluated using a Cox proportional hazards model. Adjusted restricted cubic spline models were generated to further delineate the relationship between TTD and outcome. Three-hundred-and-seventy-five DCD simultaneous kidney-pancreas transplant recipients were included. Increasing TTD was not associated with graft survival (adjusted hazard ratio HR 0.98, 95% confidence interval 0.68-1.41, P = .901). Increasing asystolic time worsened graft survival (adjusted hazard ratio 2.51, 95% confidence interval 1.16-5.43, P = .020). Restricted cubic spline modeling revealed a nonlinear relationship between asystolic time and graft survival and no relationship between TTD and graft survival. We found no evidence that TTD impacts pancreas graft survival after DCD simultaneous pancreas-kidney transplantation; however, increasing asystolic time was a significant predictor of graft loss. Procurement teams should attempt to minimize asystolic time to optimize pancreas graft survival rather than focus on the duration of TTD.

Evaluation of a delayed liver transplantation strategy for patients with HCC receiving bridging therapy: the DELTA-HCC study.

BACKGROUND & AIMS: To maximize utility and prevent premature liver transplantation (LT), a delayed LT strategy (DS) was adopted in France in 2015 in patients listed for any single HCC treated with resection or thermal ablation during the waiting phase. The DS involves postponing LT until recurrence. The purpose of this study was to evaluate the DS to make sure that it did not hamper pre- and post-LT outcomes. METHODS: Patients listed for HCC in France between 2015 and 2018 were studied. After data extraction from the national LT database, 2,025 patients were identified and classified according to six groups: single tumor entering DS, single tumor not entering DS, multiple tumors, no curative treatment, untreatable HCC or T1 tumors. Kaplan-Meier estimates of the 18-month risk of dropout for death, too sick to be transplanted or tumor progression before LT, 5-year post-LT HCC recurrence and post-LT survival rates were compared. RESULTS: Median waiting-time in the DS group was 910 days. Pre-LT dropout probability was significantly lower in the DS group compared to other groups (13% vs. 19%, p = 0.0043) and significantly higher in the T1 group (25.4%, p = 0.05). Post-LT HCC recurrence rate in the multiple nodules group was significantly higher (19.6%, p = 0.019), while 5-year post-LT survival did not differ among groups and was 74% in the DS group (p = 0.22). CONCLUSION: The DELTA-HCC study shows that DS does not negatively impact either pre- nor post-LT patient outcomes, and has the potential to allow for redistribution of organs to patients in more urgent need of LT. It can reasonably be proposed and pursued. The unexpectedly high risk of dropout in T1 patients seems related to the MELD-based offering rules underserving this subgroup. IMPACTS AND IMPLICATIONS: To maximize utility and prevent premature liver transplantation (LT), a delayed LT strategy was adopted in France in 2015. It involves postponing LT until recurrence in patients listed for any single HCC curatively treated by surgical resection or thermal ablation. The DELTA-HCC study was conducted to evaluate this nationwide strategy. It shows in a European LT program that delayed strategy does not negatively impact pre- nor post-LT patient outcomes and is relevant to up to 20% of LT candidates; thus, it could potentially enable the redistribution of organs to patients in more urgent need of LT. Such a delayed strategy can reasonably be pursued and extended to other LT programs. Of note, an unexpectedly high risk of dropout in T1 patients, seemingly related to MELD-based offering rules which underserve these patients, calls for further scrutinization and revision of allocation rules in this subgroup.

Association of Medicaid Expansion with Reduction in Racial Disparities in the Timely Delivery of Upfront Surgical Care for Patients With Early-Stage Breast Cancer.

OBJECTIVE: We evaluated the association between Medicaid expansion and time to surgery among patients with early-stage breast cancer (BC). BACKGROUND: Delays in surgery are associated with adverse outcomes. It is known that underrepresented minorities are more likely to experience treatment delays. Understanding the impact of Medicaid expansion on reducing racial and ethnic disparities in health care delivery is critical. METHODS: This was a population-based study including women ages 40 to 64 with stage I-II BC who underwent upfront surgery identified in the National Cancer Database (2010-2017) residing in states that expanded Medicaid on January 1, 2014. Difference-in-difference analysis compared rates of delayed surgery (>90 d from pathological diagnosis) according to time period (preexpansion [2010-2013] and postexpansion [2014-2017]) and race/ethnicity (White vs. racial and ethnic minority), stratified by insurance type (private vs. Medicaid/uninsured). Secondary analyses included logistic and Cox proportional hazards (PH) regression. All analyses were conducted among a cohort of patients in the nonexpansion states as a falsification analysis. Finally, a triple-differences approach compared preexpansion with the postexpansion trend between expansion and nonexpansion states. RESULTS: Among Medicaid expansion states, 104,569 patients were included (50,048 preexpansion and 54,521 postexpansion). In the Medicaid/uninsured subgroup, Medicaid expansion was associated with a -1.8% point (95% CI: -3.5% to -0.1, P =0.04) reduction of racial disparity in delayed surgery. Cox regression models demonstrated similar findings (adjusted difference-in-difference hazard ratio 1.12 [95% CI: 1.05 to 1.21]). The falsification analysis showed a significant racial disparity reduction among expansion states but not among nonexpansion states, resulting in a triple-difference estimate of -2.5% points (95% CI: -4.9% to -0.1%, P =0.04) in this subgroup. CONCLUSIONS: As continued efforts are being made to increase access to health care, our study demonstrates a positive association between Medicaid expansion and a reduction in the delivery of upfront surgical care, reducing racial disparities among patients with early-stage BC.

Delays in presentation, diagnosis, and treatment in Sudanese women with breast cancer: a cross-sectional study.

BACKGROUND: The poor prognosis of breast cancer in Sudan could be due to delayed treatment and diagnosis at an advanced stage. Our study aimed to assess the extent of delays from onset of symptoms to treatment in Sudanese women with breast cancer, as well as identify factors contributing to these delays. MATERIALS AND METHODS: We conducted a multi-center cross sectional study between March and April 2023. Data were collected from the medical records and interviews with women with breast cancer in the two main oncology centers in Sudan. Linear regression was used to identify the predictors of delayed presentation. RESULTS: We interviewed 601 women with breast cancer. The majority of women (50.1%) were diagnosed at locally advanced or metastatic disease. The median interval from the onset of symptoms to receiving oncologic treatment was 221 days (IQR = 92, 496). The longest delay was the presentation delay 61 (31 244) days. The median duration for diagnosis delay and treatment delay was 21 (10.57) days and 27 (10.64) days, respectively. Predictors of early presentation included, being young (ß = -5.3; 95% CI = 0.06 to 10), married (ß = -264; 95% CI = -427 to -101), divorced (ß = -306; 95% CI = -549 to -63), or widowed (ß = -320; 95% CI = --543 to -97), urban residence (ß = -107; 95% CI = -213 to -2.3), and seeking traditional healer (ß = -204; 95% CI = -383 to -26). CONCLUSION: Most Sudanese women with breast cancer experience significant patient delays, often presenting at advanced stages. Factors like being single, older, and living in rural areas contribute to these delays. Increasing breast cancer education, improving healthcare access and addressing sociodemographic barriers can potentially expedite diagnosis and improve outcomes.

Door-to-diuretic time and mortality in patients with acute heart failure: A systematic review and meta-analysis.

Early decongestion therapy with intravenous diuretics may be associated with improved outcomes in acute heart failure (AHF), however data is conflicting. This meta-analysis sought to evaluate the impact of door-to-IV diuretic (D2D) time on mortality in patients with AHF. Pooled estimates from observational studies comprising 28,124 patients, early IV diuresis (reference time 30-105 minutes) was associated with a 23% reduction in 30-day mortality in AHF (OR 0.77; 95% CI 0.64-0.93), despite no significant in-hospital death reduction (OR 0.84; 95% CI 0.57-1.24).

Effect of patient factors, center, and era on Fontan timing: An observational study using the Pediatric Health Information Systems Database.

BACKGROUND: There are no consensus guidelines defining optimal timing for the Fontan operation, the last planned surgery in staged palliation for single-ventricle heart disease. OBJECTIVES: Identify patient-level characteristics, center-level variation, and secular trends driving Fontan timing. METHODS: A retrospective observational study of subjects who underwent Fontan from 2007 to 2021 at centers in the Pediatric Health Information Systems database was performed using linear mixed-effects modeling in which age at Fontan was regressed on patient characteristics and date of operation with center as random effect. RESULTS: We included 10,305 subjects (40.4% female, 44% non-white) at 47 centers. Median age at Fontan was 3.4 years (IQR 2.6-4.4). Hypoplastic left heart syndrome (-4.4 months, 95%CI -5.5 to -3.3) and concomitant conditions (-2.6 months, 95%CI -4.1 to -1.1) were associated with younger age at Fontan. Subjects with technology-dependence (+4.6 months, 95%CI 3.1-6.1) were older at Fontan. Black (+4.1 months, 95%CI 2.5-5.7) and Asian (+8.3 months, 95%CI 5.4-11.2) race were associated with older age at Fontan. There was significant variation in Fontan timing between centers. Center accounted for 10% of variation (ICC 0.10, 95%CI 0.07-0.14). Center surgical volume was not associated with Fontan timing (P = .21). Operation year was associated with age at Fontan, with a 3.1 month increase in age for every 5 years (+0.61 months, 95%CI 0.48-0.75). CONCLUSIONS: After adjusting for patient-level characteristics there remains significant inter-center variation in Fontan timing. Age at Fontan has increased. Future studies addressing optimal Fontan timing are warranted.

Real-World Implications of Updated Surviving Sepsis Campaign Antibiotic Timing Recommendations.

OBJECTIVE: To evaluate real-world implications of updated Surviving Sepsis Campaign (SSC) recommendations for antibiotic timing. DESIGN: Retrospective cohort study. SETTING: Twelve hospitals in the Southeastern United States between 2017 and 2021. PATIENTS: One hundred sixty-six thousand five hundred fifty-nine adult hospitalized patients treated in the emergency department for suspected serious infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We determined the number and characteristics of patients affected by updated SSC recommendations for initiation of antibiotics that incorporate a risk- and probability-stratified approach. Using an infection prediction model with a cutoff of 0.5 to classify possible vs. probable infection, we found that 30% of the suspected infection cohort would be classified as shock absent, possible infection and thus eligible for the new 3-hour antibiotic recommendation. In real-world practice, this group had a conservative time to antibiotics (median, 5.5 hr; interquartile range [IQR], 3.2-9.8 hr) and low mortality (2%). Patients categorized as shock absent, probable infection had a median time to antibiotics of 3.2 hours (IQR, 2.1-5.1 hr) and mortality of 3%. Patients categorized as shock present, the probable infection had a median time to antibiotics 2.7 hours (IQR, 1.7-4.6 hr) and mortality of 17%, and patients categorized as shock present, the possible infection had a median time to antibiotics 6.9 hours (IQR, 3.5-16.3 hr) and mortality of 12%. CONCLUSIONS: These data support recently updated SSC recommendations to align antibiotic timing targets with risk and probability stratifications. Our results provide empirical support that clinicians and hospitals should not be held to 1-hour targets for patients without shock and with only possible sepsis.

An assessment of the association between patient characteristics and timely lung cancer treatment.

PURPOSE: Prior data have demonstrated relationships between patient characteristics, the use of surgery to treat lung cancer, and the timeliness of treatment. Our study examines whether these relationships were observable in 2019 in patients with Medicare Advantage health plans being treated for lung cancer. METHODS: Claims data pertaining to patients with Medicare Advantage health plans who had received radiation therapy (RT) or surgery to treat lung cancer within 90 days of diagnostic imaging were extracted. Other databases were used to determine patients' demographics, comorbidities, the urbanicity of their ZIP code, the median income of their ZIP code, and whether their treatment was ordered by a physician at a hospital. Multivariable logistic and Cox Proportional Hazards models were used to assess the association between patient characteristics, receipt of surgery, and time to non-systemic treatment (surgery or RT), respectively. RESULTS: A total of 2,682 patients were included in the analysis. In an adjusted analysis, patients were significantly less likely to receive surgery if their first ordering physician was based in a hospital, if they were older, if they had a history of congestive heart failure (CHF), if they had a history of chronic obstructive pulmonary disease, or if they had stage III lung cancer. Likewise, having stage III cancer was associated with significantly shorter time to treatment. CONCLUSIONS: Within a Medicare Advantage population, patient demographics were found to be significantly associated with the decision to pursue surgery, but factors other than stage were not significantly associated with time to non-systemic treatment.

Minorities Face Delays to Pancreatic Cancer Treatment Regardless of Diagnosis Setting.

INTRODUCTION: Our analysis was designed to characterize the demographics and disparities between the diagnosis of pancreas cancer during emergency presentation (EP) and the outpatient setting (OP) and to see the impact of our institutions pancreatic multidisciplinary clinic (PMDC) on these disparities. METHODS: Institutional review board-approved retrospective review of our institutional cancer registry and PMDC databases identified patients diagnosed/treated for pancreatic ductal adenocarcinoma between 2014 and 2022. Chi-square tests were used for categorical variables, and one-way ANOVA with a Bonferroni correction was used for continuous variables. Statistical significance was set at p < 0.05. RESULTS: A total of 286 patients met inclusion criteria. Eighty-nine patients (31.1%) were underrepresented minorities (URM). Fifty-seven (64.0%) URMs presented during an EP versus 100 (50.8%) non-URMs (p = 0.037). Forty-one (46.1%) URMs were reviewed at PMDC versus 71 (36.0%) non-URMs (p = 0.10). No differences in clinical and pathologic stage between the cohorts (p = 0.28) were present. URMs took 22 days longer on average to receive treatment (66.5 days vs. 44.8 days, p = 0.003) in the EP cohort and 18 days longer in OP cohort (58.0 days vs. 40.5 days, p < 0.001) compared with non-URMs. Pancreatic Multidisciplinary Clinic enrollment in EP cohort eliminated the difference in time to treatment between cohorts (48.3 days vs. 37.0 days; p = 0.151). RESULTS: Underrepresented minorities were more likely to be diagnosed via EP and showed delayed times to treatment compared with non-URM counterparts. Our PMDC alleviated some of these observed disparities. Future studies are required to elucidate the specific factors that resulted in these findings and to identify solutions.

The Association Between Oncology Outreach and Timely Treatment for Rural Patients with Breast Cancer: A Claims-Based Approach.

BACKGROUND: Oncology outreach is a common strategy for increasing rural access to cancer care, where traveling oncologists commute across healthcare settings to extend specialized care. Examining the extent to which physician outreach is associated with timely treatment for rural patients is critical for informing outreach strategies. METHODS: We identified a 100% fee-for-service sample of incident breast cancer patients from 2015 to 2020 Medicare claims and apportioned them into surgery and adjuvant therapy cohorts based on treatment history. We defined an outreach visit as the provision of care by a traveling oncologist at a clinic outside of their primary hospital service area. We used hierarchical logistic regression to examine the associations between patient receipt of preoperative care at an outreach visit (preoperative outreach) and > 60-day surgical delay, and patient receipt of postoperative care at an outreach visit (postoperative outreach) and > 60-day adjuvant delay. RESULTS: We identified 30,337 rural-residing patients who received breast cancer surgery, of whom 4071 (13.4%) experienced surgical delay. Among surgical patients, 14,501 received adjuvant therapy, of whom 2943 (20.3%) experienced adjuvant delay. In adjusted analysis, we found that patient receipt of preoperative outreach was associated with reduced odds of surgical delay (odds ratio [OR] 0.75, 95% confidence interval [CI] 0.61-0.91); however, we found no association between patient receipt of postoperative outreach and adjuvant delay (OR 1.04, 95% CI 0.85-1.25). CONCLUSIONS: Our findings indicate that preoperative outreach is protective against surgical delay. The traveling oncologists who enable such outreach may play an integral role in catalyzing the coordination and timeliness of patient-centered care.

Immigration Status and Breast Cancer Surgery Quality of Care Metrics: A Population-Level Analysis.

INTRODUCTION: As immigrant women face challenges accessing health care, we hypothesized that immigration status would be associated with fewer women with breast cancer receiving surgery for curable disease, fewer undergoing breast conserving surgery (BCS), and longer wait time to surgery. METHODS: A population-level retrospective cohort study, including women aged 18-70 years with Stage I-III breast cancer diagnosed between 2010 and 2016 in Ontario was conducted. Multivariable analysis was performed to assess odds of undergoing surgery, receiving BCS and wait time to surgery. RESULTS: A total of 31,755 patients were included [26,253 (82.7%) Canadian-born and 5502 (17.3%) immigrant women]. Immigrant women were younger (mean age 51.6 vs. 56.1 years) and less often presented with Stage I/II disease (87.4% vs. 89.8%) (both p < .001). On multivariable analysis, there was no difference between immigrant women and Canadian-born women in odds of undergoing surgery [Stage I OR 0.93 (95% CI 0.79-1.11), Stage II 1.04 (0.89-1.22), Stage III 1.22 (0.94-1.57)], receiving BCS [Stage I 0.93 (0.82-1.05), Stage II 0.96 (0.86-1.07), Stage III 1.00 (0.83-1.22)], or wait time [Stage I 0.45 (-0.61-1.50), Stage II 0.33 (-0.86-1.52), Stage III 3.03 (-0.05-6.12)]. In exploratory analysis, new immigrants did not have surgery more than established immigrants (12.9% vs. 10.1%), and refugee women had longer wait time compared with economic-class immigrants (39.5 vs. 35.3 days). CONCLUSIONS: We observed differences in measures of socioeconomic disadvantage and disease characteristics between immigrant and Canadian-born women with breast cancer. Upon adjusting for these factors, no differences emerged in rate of surgery, rate of BCS, and time to surgery. The lack of disparity suggests barriers to accessing basic components of breast cancer care may be mitigated by the universal healthcare system in Canada.

Variation in Time-to-Gender-Affirming Hormone Therapy in US Active Duty Service Members.

BACKGROUND: Beginning in July 2016, transgender service members in the US military were allowed to receive gender-affirming medical care, if so desired. OBJECTIVE: This study aimed to evaluate variation in time-to-hormone therapy initiation in active duty Service members after the receipt of a diagnosis indicative of gender dysphoria in the Military Health System. RESEARCH DESIGN: This retrospective cohort study included data from those enrolled in TRICARE Prime between July 2016 and December 2021 and extracted from the Military Health System Data Repository. PARTICIPANTS: A population-based sample of US Service members who had an encounter with a relevant International Classification of Diseases 9/10 diagnosis code. MEASURES: Time-to-gender-affirming hormone initiation after diagnosis receipt. RESULTS: A total of 2439 Service members were included (M age 24 y; 62% white, 16% Black; 12% Latine; 65% Junior Enlisted; 37% Army, 29% Navy, 25% Air Force, 7% Marine Corps; 46% first recorded administrative assigned gender marker female). Overall, 41% and 52% initiated gender-affirming hormone therapy within 1 and 3 years of diagnosis, respectively. In the generalized additive model, time-to-gender-affirming hormone initiation was longer for Service members with a first administrative assigned gender marker of male relative to female ( P <0.001), and Asian and Pacific Islander ( P =0.02) and Black ( P =0.047) relative to white Service members. In time-varying interactions, junior enlisted members had longer time-to-initiation, relative to senior enlisted members and junior officers, until about 2-years postinitial diagnosis. CONCLUSION: The significant variation and documented inequities indicate that institutional data-driven policy modifications are needed to ensure timely access for those desiring care.

Delays in the diagnosis and surgical treatment of drug-resistant epilepsy: A cohort study.

OBJECTIVE: Delay in referral for epilepsy surgery of patients with drug-resistant epilepsy (DRE) is associated with decreased quality of life, worse surgical outcomes, and increased risk of sudden unexplained death in epilepsy (SUDEP). Understanding the potential causes of delays in referral and treatment is crucial for optimizing the referral and treatment process. We evaluated the treatment intervals, demographics, and clinical characteristics of patients referred for surgical evaluation at our level 4 epilepsy center in the U.S. Intermountain West. METHODS: We retrospectively reviewed the records of patients who underwent surgery for DRE between 2012 and 2022. Data collected included patient demographics, DRE diagnosis date, clinical characteristics, insurance status, distance from epilepsy center, date of surgical evaluation, surgical procedure, and intervals between different stages of evaluation. RESULTS: Within our cohort of 185 patients with epilepsy (99 female, 53.5%), the mean ± standard deviation (SD) age at surgery was 38.4 ± 11.9 years. In this cohort, 95.7% of patients had received definitive epilepsy surgery (most frequently neuromodulation procedures) and 4.3% had participated in phase 2 intracranial monitoring but had not yet received definitive surgery. The median (1st-3rd quartile) intervals observed were 10.1 (3.8-21.5) years from epilepsy diagnosis to DRE diagnosis, 16.7 (6.5-28.4) years from epilepsy diagnosis to surgery, and 1.4 (0.6-4.0) years from DRE diagnosis to surgery. We observed significantly shorter median times from epilepsy diagnosis to DRE diagnosis (p < .01) and epilepsy diagnosis to surgery (p < .05) in patients who traveled further for treatment. Patients with public health insurance had a significantly longer time from DRE diagnosis to surgery (p < .001). SIGNIFICANCE: Both shorter distance traveled to our epilepsy center and public health insurance were predictive of delays in diagnosis and treatment intervals. Timely referral of patients with DRE to specialized epilepsy centers for surgery evaluation is crucial, and identifying key factors that may delay referral is paramount to optimizing surgical outcomes.

Has time to chemotherapy from primary debulking surgery in advanced ovarian cancer an impact on survival? - A population-based nationwide SweGCG study.

OBJECTIVE: The aim of the study was to investigate if time to start chemotherapy (TTC) after primary debulking surgery (PDS) impacted relative survival (RS) in advanced epithelial ovarian/fallopian tube/primary peritoneal cancer (EOC). METHODS: Nationwide population-based study of women with EOC FIGO stages IIIC-IV, registered 2008-2018 in the Swedish Quality Register for Gynecologic Cancer, treated with PDS and chemotherapy. TTC was categorized into; ≤21 days, 22-28 days, 29-35 days, 36-42 days and > 42 days. Relative survival (RS) was estimated using the Pohar-Perme estimate of net survival. Multivariable analyses of excess mortality rate ratios (EMRRs) were estimated by Poisson regression models. RESULTS: In total, 1694 women were included. The median age was 65.0 years. Older age and no residual disease were more common in TTC >42 days than 0-21 days. The RS at 5-years was 37.9% and did not differ between TTC groups. In the R0 (no residual disease) cohort (n = 806), 2-year RS was higher in TTC ≤21 days (91.6%) and 22-28 days (91.4%) than TTC >42 days (79.1%). TTC >42 days (EMRR 2.33, p = 0.026), FIGO stage IV (EMRR 1.83, p = 0.007) and non-serous histology (EMRR 4.20, p < 0.001) were associated with 2-year worse excess mortality compared to TTC 0-21 days, in the R0 cohort. TTC was associated with 2-year survival in the R0 cohort in FIGO stage IV but not in stage IIIC. TTC was not associated with RS in patients with residual disease. CONCLUSIONS: For the entire cohort, stage IV, non-serous morphology and residual disease, but not TTC, influenced 5-year relative survival. However, longer TTC was associated with a poorer 2-year survival for those without residual disease after PDS.

The impact of cancer patient pathway on timing of radiotherapy and survival: a cohort study in glioblastoma patients.

PURPOSE: Glioblastoma (GBM) is an aggressive brain tumor in which primary therapy is standardized and consists of surgery, radiotherapy (RT), and chemotherapy. However, the optimal time from surgery to start of RT is unknown. A high-grade glioma cancer patient pathway (CPP) was implemented in Norway in 2015 to avoid non-medical delays and regional disparity, and to optimize information flow to patients. This study investigated how CPP affected time to RT after surgery and overall survival. METHODS: This study included consecutive GBM patients diagnosed in South-Eastern Norway Regional Health Authority from 2006 to 2019 and treated with RT. The pre CPP implementation group constituted patients diagnosed 2006-2014, and the post CPP implementation group constituted patients diagnosed 2016-2019. We evaluated timing of RT and survival in relation to CPP implementation. RESULTS: A total of 1212 patients with GBM were included. CPP implementation was associated with significantly better outcomes (p < 0.001). Median overall survival was 12.9 months. The odds of receiving RT within four weeks after surgery were significantly higher post CPP implementation (p < 0.001). We found no difference in survival dependent on timing of RT below 4, 4-6 or more than 6 weeks (p = 0.349). Prognostic factors for better outcomes in adjusted analyses were female sex (p = 0.005), younger age (p < 0.001), solitary tumors (p = 0.008), gross total resection (p < 0.001), and higher RT dose (p < 0.001). CONCLUSION: CPP implementation significantly reduced time to start of postoperative RT. Survival was significantly longer in the period after the CPP implementation, however, timing of postoperative RT relative to time of surgery did not impact survival.

Spatiotemporal Distribution, Time to Treatment Outcome Clustering and Determinants of Esophageal Cancer in Ethiopia, a Scoping Study.

INTRODUCTION: Esophageal cancer was the eighth and sixth leading cause of morbidity of all cancers in the world, and the 15th and 12th in Ethiopia, respectively. There is a lack of comprehensive data regarding Ethiopia's esophageal cancer hotspot, treatment outcome clustering, and other factors. OBJECTIVE: This scoping review was designed to understand the extent and type of existing evidence regarding spatiotemporal distribution, time to treatment outcome clustering, and determinants of esophageal cancer in Ethiopia up to March 28, 2023. METHODS: Three-step search strategies were employed for the scoping review from March 15 to 28, 2023. Targeted databases included PubMed/Medline, PubMed Central (PMC), Google Scholar, Hinari, and Cochrane for published studies and different websites for unpublished studies for evidence synthesis. Data were extracted using the Joanna Briggs Institute (JBI) manual format. RESULTS: Our final analysis comprised 17 (16 quantitative and 1 qualitative) studies. Three studies attempted to depict the country's temporal distribution, whereas 12 studies showed the spatial distribution of esophageal cancer by proportion. The regional state of Oromia recorded a high percentage of cases. Numerous risk factors linked to the tumor have been identified in 8 investigations. Similarly, 5 studies went into detail regarding the likelihood of survival and the factors that contribute to malignancy, while 2 studies covered the results of disease-related treatments. CONCLUSIONS: The substantial body of data that underpins this finding supports the fact that esophageal cancer has several risk factors and that its prevalence varies greatly across the country and among regions. Surgery, radiotherapy, or chemotherapy helped the patient live longer. However, no research has investigated which treatment is best for boosting patient survival and survival clustering. Therefore, research with robust models for regional distribution, clustering of time to treatment outcomes, and drivers of esophageal cancer will be needed.

The review was based on 17 studies searched from five electronic databases, and six additional sources. Esophageal cancer incidence varies across the nation (from region to region). The median survival time of esophageal cancer cases were four months, and six months. No study investigated the better treatment that improved the survival of patients with esophageal cancer. A contradicting report were found about the link b/n khat chewing and esophageal cancer. The temporal distribution of the tumor was controversial.

Service delivery in acute ischemic stroke patients: Does sex matter?

BACKGROUND AND PURPOSE: Women with acute ischemic stroke (AIS) are older and have greater preexisting handicap than men. Given that these factors do not fully explain their poorer long-term outcomes, we sought to investigate potential sex differences in the delivery of acute stroke care in a large cohort of consecutive AIS patients. METHODS: We analyzed all patients from ASTRAL (Acute Stroke Registry and Analysis of Lausanne) from March 2003 to December 2019. Multivariable analyses were performed on acute time metrics, revascularization therapies, ancillary examinations for stroke workup, subacute symptomatic carotid artery revascularization, frequency of change in goals of care (palliative care), and length of hospital stay. RESULTS: Of the 5347 analyzed patients, 45% were biologically female and the median age was 74.6 years. After multiple adjustments, female sex was significantly associated with higher onset-to-door (adjusted hazard ratio [aHR] = 1.09, 95% confidence interval [CI] = 1.04-1.14) and door-to-endovascular-puncture intervals (aHR = 1.15, 95% CI = 1.05-1.25). Women underwent numerically fewer diagnostic examinations (adjusted odds ratio [aOR] = 0.94, 95% CI = 0.85-1.04) and fewer subacute carotid revascularizations (aOR = 0.69, 95% CI = 0.33-1.18), and had longer hospital stays (aHR = 1.03, 95% CI = 0.99-1.07), but these differences were not statistically significant. We found no differences in the rates of acute revascularization treatments, or in the frequency of change of goals of treatments. CONCLUSIONS: This retrospective analysis of a large, consecutive AIS cohort suggests that female sex is associated with unfavorable pre- and in-hospital time metrics, such as a longer onset-to-door and door-to-endovascular-puncture intervals. Such indicators of less effective stroke care delivery may contribute to the poorer long-term functional outcomes in female patients and require further attention.