Inverse Treatment Research Articles

Abstract PO1-17-05: Real-world effectiveness of palbociclib plus aromatase inhibitors (AI) in metastatic breast cancer patients with cardiovascular diseases

Abstract Background Breast cancer survivors are at risk for mortality from cardiovascular diseases (CVD). CVD and their treatments can impact breast cancer treatment selection and clinical outcomes. A cyclin dependent kinase 4/6 inhibitor (CDK4/6i) combined with endocrine therapy (ET) is more effective than ET alone for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2) metastatic breast cancer (MBC). CDK4/6i plus ET is now the standard of care in the first-line setting for HR+/HER2 MBC. However, data on the effectiveness of CDK4/6i in MBC patients with CVD are limited. We compared overall survival (OS) and real-world progression-free survival (rwPFS) of palbociclib plus AI (PAL+AI) vs AI alone in HR+/HER2 MBC patients with CVD in routine US clinical practices. Methods The Flatiron Health longitudinal database contains electronic health records from >280 cancer clinics, representing >3 million actively treated cancer patients in the US. Using the Flatiron database, we conducted a retrospective analysis of 469 patients with HR+/HER2 MBC and CVD who started PAL+AI or AI as first-line therapy between February 2015 and March 2020. CVD prior to the initiation of PAL+AI or AI were identified based on their definitions within the National Cancer Institute-Comorbidity Index (NCI-CI), including myocardial infarction, congestive heart failure, peripheral vascular diseases, and cerebrovascular diseases. Patients were assessed from start of PAL+AI or AI to September 30, 2020 (data cutoff date), death, or last visit, whichever came first. OS was defined as months from start of PAL+AI or AI to death. rwPFS was defined as months from start of PAL+AI or AI to death or disease progression, evaluated based on clinical assessment or radiographic scan/tissue biopsy. Stabilized inverse probability treatment weighting (sIPTW) as primary analysis was used to balance baseline demographics and clinical characteristics. Cox proportional-hazards models were used to estimate the relative effectiveness of PAL+AI vs AI alone. Results Of the 469 eligible patients, 160 (34.1%) were treated with PAL+AI and 309 (65.9%) were treated with AI alone. Compared with AI-alone patients, those treated with PAL+AI were younger and were more likely to have de novo MBC, ≥2 metastatic sites, and lung/liver involvement. After sIPTW, patient characteristics were generally balanced. After sIPTW, median OS (95% confidence interval [CI]) was 40.7 months (30.956.0) in PAL+AI patients and 26.5 months (23.337.3) in AI patients (hazard ratio [HR]=0.732, 95% CI=0.5370.997, p=0.0476). Median rwPFS (95% CI) was 20.0 months (11.7–27.5) in PAL+AI patients and 12.5 months (9.718.3) in AI patients (HR=0.679, 95% CI=0.5120.900, p=0.0070). Consistent results were observed with multivariate Cox proportional-hazards models as sensitivity analysis. See Table for baseline patient characteristics and outcome results. Conclusions First-line PAL in combination with AI is associated with prolonged OS and rwPFS in patients with HR+/HER2 MBC and CVD in a real-world setting compared with AI alone. Further studies with larger cohorts and comprehensive assessments of comorbidities are needed to provide additional evidence of outcomes and safety of CDK4/6i plus AI for MBC patients with various comorbid conditions in routine clinical practice. Citation Format: Adam Brufsky, Xianchen Liu, Benjamin Li, Lynn McRoy, Connie Chen, Doris Makari, Rachel Layman, Hope Rugo. Real-world effectiveness of palbociclib plus aromatase inhibitors (AI) in metastatic breast cancer patients with cardiovascular diseases [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-17-05.

Comparative Genitourinary Safety of In-class Sodium-Glucose Cotransporter-2 Inhibitors among Patients with Heart Failure with Preserved Ejection Fraction: A Cohort Study.

The American Heart Association recommended sodium-glucose cotransporter-2 inhibitors (SGLT2i) for the management of heart failure with preserved ejection fraction (HFpEF). However, little is known about their real-world in-class comparative safety in patients with HFpEF. We aimed to assess the comparative safety of SGLT2i in the risk of urinary tract infection (UTI) or genital infection separately or as a composite outcome among patients with HFpEF. This cohort study using MarketScan® Commercial and Medicare supplemental databases (2012-2020) included patients aged ≥18 years with a diagnosis of HFpEF who initiated SGLT2i therapy. Three pairwise comparison groups were established: cohort 1, dapagliflozin versus canagliflozin; cohort 2, empagliflozin versus canagliflozin; and cohort 3, dapagliflozin versus empagliflozin. After stabilized inverse probability treatment weighting, Cox proportional hazards regression was used to compare the risk of UTI or genital infection separately or as a composite outcome in each cohort. The risk of the composite outcome did not significantly differ between canagliflozin and dapagliflozin (adjusted hazard ratio [aHR] 0.64; 95% confidence interval [CI] 0.36-1.14) or between empagliflozin and canagliflozin (aHR 1.25; 95% CI 0.77-2.05). Similarly, there was no evidence of difference between dapagliflozin and empagliflozin in this risk (aHR 0.76; 95% CI 0.48-1.21). The results of analyses separately assessing UTI or genital infection were similar. There was no significant difference in the risk of UTI or genital infection among patients with HFpEF who initiated canagliflozin, dapagliflozin, or empagliflozin.

Development and validation of HPV-associated and HPV-independent penile squamous cell carcinoma prognostic nomogram.

The aim of this study was to introduce HPV-associated and HPV-independent histologic classifications to analyze prognostic factors and develop a prognostic nomogram for patients with penile squamous cell carcinoma (PSCC). Data of 1502 PSCC patients between 2010 and 2020 were accessed from the SEER database, and the patients were randomly divided into a training set and a validation set. Independent risk factors for PSCC patients prognosis were analyzed by using univariate and multivariate COX proportional hazards regression, and was used for the construction of the nomogram, and the predictive performance of the model was evaluated by C-index, calibration curve and ROC curve. Kaplan-Meier analysis was applied to explore the impact of HPV-related factors on patient survival, while propensity score matching (PSM) and inverse probability treatment weighting (IPTW) techniques were used to balance other confounding factors like individual clinical and pathological factors, and to evaluate the differences in overall survival (OS) and cause-specific survival (CSS) between subgroups. The results indicated that histologic type, Grade classification, T/M stage, surgical methods and chemotherapy were independent risk factors affecting OS and CSS in PSCC patients. In addition, age and marital status were significantly associated with OS, while lymph node metastasis was an independent prognostic factor for CSS, the validation results of the model showed that the nomogram had a superior predictive performance compared with the American Joint Committee on Cancer staging system. In addition, subgroup analyses prior to and after IPTW and PSM adjustments showed that HPV-associated group had better OS and CSS than HPV-independent group. Our study developed and validated a nomogram using a novel histologic classification and achieved satisfactory results, which can better help clinicians to predict the prognosis of penile squamous cell carcinoma patients.

Determining individual suitability for neoadjuvant systemic therapy in breast cancer patients through deep learning.

The survival advantage of neoadjuvant systemic therapy (NST) for breast cancer patients remains controversial, especially when considering the heterogeneous characteristics of individual patients. To discern the variability in responses to breast cancer treatment at the individual level and propose personalized treatment recommendations utilizing deep learning (DL). Six models were developed to offer individualized treatment suggestions. Outcomes for patients whose actual treatments aligned with model recommendations were compared to those whose did not. The influence of certain baseline features of patients on NST selection was visualized and quantified by multivariate logistic regression and Poisson regression analyses. Our study included 94,487 female breast cancer patients. The Balanced Individual Treatment Effect for Survival data (BITES) model outperformed other models in performance, showing a statistically significant protective effect with inverse probability treatment weighting (IPTW)-adjusted baseline features [IPTW-adjusted hazard ratio: 0.51, 95% confidence interval (CI), 0.41-0.64; IPTW-adjusted risk difference: 21.46, 95% CI 18.90-24.01; IPTW-adjusted difference in restricted mean survival time: 21.51, 95% CI 19.37-23.80]. Adherence to BITES recommendations is associated with reduced breast cancer mortality and fewer adverse effects. BITES suggests that patients with TNM stage IIB, IIIB, triple-negative subtype, a higher number of positive axillary lymph nodes, and larger tumors are most likely to benefit from NST. Our results demonstrated the potential of BITES to aid in clinical treatment decisions and offer quantitative treatment insights. In our further research, these models should be validated in clinical settings and additional patient features as well as outcome measures should be studied in depth.

The association between albumin-corrected calcium and prognosis in patients with cardiac arrest: a retrospective study based on the MIMIC-IV database

BackgroundCardiac arrest (CA) is one of the leading causes of death globally, characterized by high incidence and mortality. It is of particular significance to determine the prognosis of patients with CA early and accurately. Therefore, we aim to investigate the correlation between albumin-corrected calcium (ACC) and the prognosis in patients diagnosed with CA.MethodsWe retrospectively collected data from medical information mart for intensive care IV database. Patients were divided into two groups (survival and non-survival groups), according to the 90-day prognosis. In the Restricted cubic spline (RCS) analysis, the cut-off values (8.86 and 10.32) were obtained to categorize patients into three groups: low ACC group (< 8.86), moderate ACC group (8.86–10.32), and high ACC group (> 10.32). The least absolute shrinkage and selection operator with a ten-fold cross-validation regression analysis was performed to identify variables linked to the mortality. The inverse probability treatment weighting (IPTW) was used to address the confounding factors, and a weighted cohort was generated. RCS, Kaplan–Meier curve, and Cox regression analyses were used to explore the relationship between ACC and the mortality. Sensitivity analysis was employed to validate the stability of the results.ResultsCut-off values for ACC of 8.86 and 10.32 were determined. RCS analyses showed that there was an overall non-linear trend relationship between ACC and the risk of 90-day and 360-day mortalities. After IPTW adjustment, compared to the moderate ACC group, the 90-day and 360-day mortalities in the high ACC group were higher (P < 0.05). The Cox analyses before and after IPTW adjustment showed that both low ACC and high ACC group were independent risk factors for 90-day and 360-day all-cause mortality in patients with CA (P < 0.05). The results obtained from sensitivity analyses indicated the stability of the findings. The Kaplan–Meier survival curves indicated that 90- and 360-day cumulative survival rates in the low ACC and high ACC groups were lower than that in the moderate ACC group (χ2 = 11.350, P = 0.003; χ2 = 14.110, P = 0.001).ConclusionBoth low ACC (< 8.86) and high ACC groups (> 10.32) were independent risk factors for 90-day and 360-day all-cause mortality in patients with CA (P < 0.05). For those CA patients with high and low ACC, it deserved the attention of clinicians.

No evidence of difference in mortality with amoxicillin versus co-amoxiclav for hospital treatment of community-acquired pneumonia

Current guidelines recommend broad-spectrum antibiotics for high-severity community-acquired pneumonia (CAP), potentially contributing to antimicrobial resistance (AMR). We aim to compare outcomes in CAP patients treated with amoxicillin (narrow-spectrum) versus co-amoxiclav (broad-spectrum), to understand if narrow-spectrum antibiotics could be used more widely. We analysed electronic health records from adults (≥16y) admitted to hospital with a primary diagnosis of pneumonia between 01-January-2016 and 30-September-2023 in Oxfordshire, United Kingdom. Patients receiving baseline ([-12h,+24h] from admission) amoxicillin or co-amoxiclav were included. The association between 30-day all-cause mortality and baseline antibiotic was examined using propensity score (PS) matching and inverse probability treatment weighting (IPTW) to address confounding by baseline characteristics and disease severity. Subgroup analyses by disease severity and sensitivity analyses with missing covariates imputed were also conducted. Among 16,072 admissions with a primary diagnosis of pneumonia, 9685 received either baseline amoxicillin or co-amoxiclav. There was no evidence of a difference in 30-day mortality between patients receiving initial co-amoxiclav vs. amoxicillin (PS matching: marginal odds ratio 0.97 [0.76-1.27], p=0.61; IPTW: 1.02 [0.78-1.33], p=0.87). Results remained similar across stratified analyses of mild, moderate, and severe pneumonia. Results were also similar with missing data imputed. There was also no evidence of an association between 30-day mortality and use of additional macrolides or additional doxycycline. There was no evidence of co-amoxiclav being advantageous over amoxicillin for treatment of CAP in 30-day mortality at a population-level, regardless of disease severity. Wider use of narrow-spectrum empirical treatment of moderate/severe CAP should be considered to curb potential for AMR.

Three-year incidence of pacemaker implantation in patients with atrial fibrillation and sinus node dysfunction receiving ablation versus antiarrhythmic drugs

BackgroundSinus node dysfunction (SND) is commonly seen in patients with atrial fibrillation (AF). The purpose of this study was to compare the incidence of pacemaker implantation among patients with SND and AF treated with catheter ablation (CA) versus anti-arrhythmic drugs (AADs).MethodsThe 2013–2022 Optum Clinformatics database, an administrative claims database for commercially insured individuals in the United States (US), was used for this study. Patients with AF and SND and a history of at least one AAD prescription were identified and classified into CA or AAD cohorts based on subsequent treatment received. Inverse probability treatment weighting was applied to balance socio-demographic and clinical characteristics between the cohorts. Weighted Cox regression modeling was used to evaluate the differential risk of incident permanent pacemaker (PPM) implantation. Sub-analyses were performed by AF type (paroxysmal versus persistent).ResultsA total of 1206 patients in the AAD cohort and 1624 patients in the CA cohort were included. Study cohorts were well-balanced post-weighting. The incidence rate of PPM implantation (per 1000 person–year) was 55.8 for the CA cohort and 117.8 for the AAD cohort. Regression analysis demonstrated that the CA cohort had 42% lower risk of incident PPM implantation than those treated with AADs (hazard ratio [HR], 0.58; 95% CI, 0.46–0.72, p < 0.001). CA-treated patients had lower risks of PPM implantation versus AAD-treated patients among those with paroxysmal AF (HR, 0.48; 95% CI, 0.34–0.69, p < 0.001) and persistent AF (HR, 0.57; 95% CI, 0.40–0.81, p = 0.002).ConclusionsPatients with AF and SND treated with CA have significantly lower risks of incident PPM implantation compared with those treated with an AAD.Graphical

Risk of major adverse cardiovascular events in rural vs urban settings among patients with erectile dysfunction: a propensity-weighted retrospective cohort study of 430 621 men.

The relationship between erectile dysfunction (ED) and cardiovascular (CV) events has been postulated, with ED being characterized as a potential harbinger of CV disease. Location of residence is another important consideration, as the impact of rural residence has been associated with worse health outcomes. To investigate whether men from rural settings with ED are associated with a higher risk of major adverse CV events (MACEs). A propensity-weighted retrospective cohort study was conducted with provincial health administrative databases. ED was defined as having at least 2 ED prescriptions filled within 1 year. MACE was defined as the first hospitalization for an episode of acute myocardial infarction, heart failure, or stroke that resulted in a hospital visit >24hours. We classified study groups into ED urban, ED rural, no ED urban, and no ED rural. A multiple logistic regression model was used to determine the propensity score. Stabilized inverse propensity treatment weighting was then applied to the propensity score. A Cox proportional hazard model was used to examine our primary outcome of time to a MACE. The median time to a MACE was 2731, 2635, 2441, and 2508days for ED urban (n = 32 341), ED rural (n = 18 025), no ED rural (n = 146 358), and no ED urban (n = 233 897), respectively. The cohort with ED had a higher proportion of a MACE at 8.94% (n = 4503), as opposed to 4.58% (n = 17 416) for the group without ED. As compared with no ED urban, no ED rural was associated with higher risks of a MACE in stabilized time-varying comodels based on inverse probability treatment weighting (hazard ratio, 1.06-1.08). ED rural was associated with significantly higher risks of a MACE vs no ED rural, with the strength of the effect estimates increasing over time (hazard ratio, 1.10-1.74). Findings highlight the need for physicians treating patients with ED to address CV risk factors for primary and secondary prevention of CV diseases. This is the most extensive retrospective study demonstrating that ED is an independent risk factor for MACE. Due to limitations in data, we were unable to assess certain comorbidities, including obesity and smoking. Our study confirms that ED is an independent risk factor for MACE. Rural men had a higher risk of MACE, with an even higher risk among those who reside rurally and are diagnosed with ED.

Comparative Effectiveness of Natalizumab, Fingolimod, and Injectable Therapies in Pediatric-Onset Multiple Sclerosis: A Registry-Based Study.

Patients with pediatric-onset multiple sclerosis (POMS) typically experience higher levels of inflammation with more frequent relapses, and though patients with POMS usually recover from relapses better than adults, patients with POMS reach irreversible disability at a younger age than adult-onset patients. There have been few randomized, placebo-controlled clinical trials of multiple sclerosis (MS) disease-modifying therapies (DMTs) in patients with POMS, and most available data are based on observational studies of off-label use of DMTs approved for adults. We assessed the effectiveness of natalizumab compared with fingolimod using injectable platform therapies as a reference in pediatric patients in the global MSBase registry. This retrospective study included patients with POMS who initiated treatment with an injectable DMT, natalizumab, or fingolimod between January 1, 2006, and May 3, 2021. Patients were matched using inverse probability treatment weighting. The primary outcome was time to first relapse from index therapy initiation. Secondary study outcomes included annualized relapse rate; proportions of relapse-free patients at 1, 2, and 5 years; time to treatment discontinuation; and times to 24-week confirmed disability worsening and confirmed disability improvement. A total of 1,218 patients with POMS were included in this analysis. Patients treated with fingolimod had a significantly lower risk of relapse than patients treated with injectable DMTs (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.29-0.83; p = 0.008). After adjustment for prior DMT experience in the unmatched sample, patients treated with natalizumab had a significantly lower risk of relapse than patients treated either with injectable DMTs (HR, 0.15; 95% CI 0.07-0.31; p < 0.001) or fingolimod (HR, 0.37; 95% CI 0.14-1.00; p = 0.049). The adjusted secondary study outcomes were generally consistent with the primary outcome or with previous observations. The findings in the inverse probability treatment weighting-adjusted patient populations were confirmed in multiple sensitivity analyses. Our analyses of relapse risk suggest that natalizumab is more effective than fingolimod in the control of relapses in this population with high rates of new inflammatory activity, consistent with previous studies of natalizumab and fingolimod in adult-onset patients and POMS. In addition, both fingolimod and natalizumab were more effective than first-line injectable therapies. This study provides Class II evidence that patients with POMS treated with natalizumab had a lower risk of relapse than those with fingolimod.

The safety, feasibility and oncological outcomes of laparoscopic completion total gastrectomy for remnant gastric cancer: a prospective study with 3-year follow-up (FUGES-004 study).

The efficacy of laparoscopic completion total gastrectomy (LCTG) for remnant gastric cancer (RGC) remains controversial. The primary outcome was postoperative morbidity within 30 days after surgery. Secondary outcomes included 3-year disease-free survival (DFS), 3-year overall survival (OS), and recurrence. Inverse probability treatment weighted (IPTW) was used to balance the baseline between LCTG and OCTG. Final analysis included 46 patients with RGC who underwent LCTG at the FJMUUH between June 2016 and June 2020. The historical control group comprised of 160 patients who underwent open completion total gastrectomy (OCTG) in the six tertiary teaching hospitals from CRGC-01 study. After IPTW, no significant difference was observed between the LCTG and OCTG groups in terms of incidence (LCTG vs. OCTG: 28.0% vs. 35.0%, P=0.379) or severity of complications within 30 days after surgery. Compared with OCTG, LCTG resulted in better short-term outcomes and faster postoperative recovery. However, the textbook outcome rate was comparable between the two groups (45.9% vs. 32.8%, P=0.107). Additionally, the 3-year DFS and 3-year OS of LCTG were comparable to those of OCTG (DFS: log-rank P=0.173; OS: log-rank P=0.319). No significant differences in recurrence type, mean recurrence time, or 3-year cumulative hazard of recurrence were observed between the two groups (all P>0.05). Subgroup analyses and concurrent comparisons demonstrated similar trends. This prospective study suggested that LCTG was non-inferior to OCTG in both short- and long-term outcomes. In experienced centers, LCTG may be considered as a viable treatment option for RGC.

Rates of Recurrent Intestinal Metaplasia and Dysplasia After Successful Endoscopic Therapy of Barrett's Neoplasia by Endoscopic Mucosal Resection vs Endoscopic Submucosal Dissection and Ablation: A Large North American Multicenter Cohort.

Endoscopic eradication therapy (EET) combining endoscopic resection (ER) with endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) followed by ablation is the standard of care for the treatment of dysplastic Barrett's esophagus (BE). We have previously shown comparable rates of complete remission of intestinal metaplasia (CRIM) with both approaches. However, data comparing recurrence after CRIM are lacking. We compared rates of recurrence after CRIM with both techniques in a multicenter cohort. Patients undergoing EET achieving CRIM at 3 academic institutions were included. Demographic and clinical data were abstracted. Outcomes included rates and predictors of any BE and dysplastic BE recurrence in the 2 groups. Cox-proportional hazards models and inverse probability treatment weighting (IPTW) analysis were used for analysis. A total of 621 patients (514 EMR and 107 ESD) achieving CRIM were included in the recurrence analysis. The incidence of any BE (15.7, 5.7 per 100 patient-years) and dysplastic BE recurrence (7.3, 5.3 per 100 patient-years) were comparable in the EMR and ESD groups, respectively. On multivariable analyses, the chances of BE recurrence were not influenced by ER technique (hazard ratio 0.87; 95% confidence interval 0.51-1.49; P = 0.62), which was also confirmed by IPTW analysis (ESD vs EMR: hazard ratio 0.98; 95% confidence interval 0.56-1.73; P = 0.94). BE length, lesion size, and history of cigarette smoking were independent predictors of BE recurrence. Patients with BE dysplasia/neoplasia achieving CRIM, initially treated with EMR/ablation, had comparable recurrence rates to ESD/ablation. Randomized trials are needed to confirm these outcomes between the 2 ER techniques.

Acute Coronary Syndrome Revascularization Strategies With Multivessel Coronary Artery Disease

In acute coronary syndromes (ACS), revascularization is the standard of care. However, trials comparing contemporary coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) are limited. Optimal revascularization in patients with multi-vessel coronary artery disease (MV-CAD) presenting with ACS is unclear. This is a multi-centred, retrospective observational study from a large, hospital system in the United States. We abstracted data on patients with MV-CAD and ACS from 2018 to 2022 who underwent revascularization with PCI, CABG or medically managed (MM). We evaluated multivariate statistics comparing categorical variables and outcomes, including all-cause mortality (ACM) and myocardial infarction (MI) at 1 year. All logistic and Cox proportional-hazard models were balanced using inverse probability treatment weights accounting for age and sex. There were 295 CABG patients [median age 66 (IQR 59.7, 73.1); 73% male], 1,559 PCI patients [median age 68.3 (IQR 60, 76.6); 69.1% male], and 307 MM patients [median age 70 (60.9, 77.1) 74% male]. Patients revascularized with PCI had higher ACM at 1 year [14.1% vs. 5.1%; HR 2.4, CI (1.5, 3.8), p<0.001] and similar mortality to MM (13.4%). CABG also demonstrated reduced 1 year MI rate compared to PCI (1.7% vs 3.9%; HR 0.36, CI 0.21, 0.61, p=<0.001), with similar 1 year rate of MI to MM (3.9%). In conclusion, CABG, compared to PCI and MM, is associated with lower mortality, and repeat ACS events at 1 year in patients with ACS and MV-CAD.

Do end-of-life outcomes differ by assisted living memory-care designation?

Residential care/assisted living (RC/AL) is an increasingly common place of end-of-life care for persons with Alzheimer's disease and related dementia (ADRD), who have unique care needs as their health declines. Approximately 22% of RC/ALs provide specialized memory care (memory-care RC/AL). Understanding how end-of-life outcomes differ by memory care among residents with ADRD could facilitate aging/dying in place for this population. The objective of this paper is to examine if end-of-life outcomes (i.e., mortality, hospice use, and number of days receiving hospice in the last month of life) differ between residents with ADRD who moved to memory-care RC/AL, compared with residents with ADRD who moved to RC/AL without memory care (general RC/AL). Prospective cohort of 15,152 fee-for-service Medicare beneficiaries with ADRD who moved to large RC/AL (> = 25 beds) between 2016 and 2018. We used inverse probability treatment weighting to account for observable differences between memory-care and general RC/AL residents. Two-part models estimated the difference by memory care in the number of days receiving hospice care in the last months of life among RC/AL decedents. The unadjusted mortality rates were 13.4% in general RC/AL and 15.8% in memory-care RC/AL with an adjusted difference of 1.3 percentage points higher mortality among memory-care RC/AL residents (p = 0.04). Hospice use was 8% and 10.6% among general and memory-care RC/AL residents, respectively, with an adjusted difference of 1.4 percentage points (p = 0.01) higher in memory care. Two-part models showed that decedents in memory-care RC/AL spent about 1.4 more days receiving hospice care in the last month of life (p = 0.02). We find a higher mortality rate and higher rate of hospice use among memory-care RC/AL residents. These findings suggest that memory care may attract residents closer to the end of life and/or promote hospice use at the end of life.

Impact of neoadjuvant chemotherapy on short-term outcomes after simple and complex minimally invasive minor hepatectomy for colorectal liver metastases: A propensity-score matched and coarsened exact matched study

BackgroundIn the last three decades, minimally invasive liver resection has been replacing conventional open approach in liver surgery. More recently, developments in neoadjuvant chemotherapy have led to increased multidisciplinary management of colorectal liver metastases with both medical and surgical treatment modalities. However, the impact of neoadjuvant chemotherapy on the surgical outcomes of minimally invasive liver resections remains poorly understood. MethodsA multicenter, international, database of 4998 minimally invasive minor hepatectomy for colorectal liver metastases was used to compare surgical outcomes in patients who received neoadjuvant chemotherapy with surgery alone. To correct for baseline imbalance, propensity score matching, coarsened exact matching and inverse probability treatment weighting were performed. Results2546 patients met the inclusion criteria. After propensity score matching there were 759 patients in both groups and 383 patients in both groups after coarsened exact matching. Baseline characteristics were equal after both matching strategies. Neoadjuvant chemotherapy was not associated with statistically significant worse surgical outcomes of minimally invasive minor hepatectomy. ConclusionNeoadjuvant chemotherapy had no statistically significant impact on short-term surgical outcomes after simple and complex minimally invasive minor hepatectomy for colorectal liver metastases.

Assessing the effectiveness and safety of surufatinib versus everolimus or sunitinib in advanced neuroendocrine neoplasms: insights from a real-world, retrospective cohort study using propensity score and inverse probability treatment weighting analysis.

While surufatinib, sunitinib, and everolimus have shown efficacy for advanced neuroendocrine neoplasms (NENs) in randomized controlled trials (RCTs), direct comparisons in a real-world setting remain unexplored. This gap highlights the clinical need to understand their comparative effectiveness and safety within the diverse Chinese population. Addressing this, our study provides insights into the real-world performance of these therapies, aiming to inform treatment selection and improve patient outcomes. A retrospective, observational study was conducted at Fudan University Shanghai Cancer Center, including patients with advanced NENs treated with surufatinib, sunitinib, or everolimus between July 2020 and April 2023. Eligibility criteria focused on histologically confirmed, locally advanced, unresectable, or metastatic NENs, with patients having received at least one month of targeted therapy. We employed inverse probability weighting (IPW) with the propensity score (PS) matching to adjust for the bias of baseline characteristics. The assessment of covariates included age, sex, performance status, primary tumor site, functional status, genetic mutations, tumor differentiation, Ki67 index, tumor grade, metastasis site, and previous therapies. The primary outcome was progression-free survival (PFS), and secondary outcomes included objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). The study enrolled 123, 56, and 68 locally advanced or metastatic NEN patients treated with surufatinib, sunitinib, and everolimus, respectively. Before adjusting for confounding factors, surufatinib was used less frequently as a first-line treatment compared to sunitinib and everolimus in pancreatic NENs (pNENs) (11.1% vs. 22.1%, P=0.057). Significant differences were noted in prior treatments and tumor characteristics between surufatinib and everolimus groups in extrapancreatic NENs (epNENs) (P<0.05). Post-IPW, these disparities were resolved (P>0.05). Surufatinib demonstrated superior median PFS (mPFS) in both pancreatic [8.30 vs. 6.33 months, hazard ratio (HR) 0.592, P<0.001] and epNENs (8.73 vs. 3.70 months, HR 0.608, P<0.001) compared to everolimus or sunitinib. Notably, male gender (HR 1.75, P=0.001), functional status (HR 2.09, P=0.01), Ki67 index >20% (HR 12.7, P=0.004), previous somatostatin analogue (SSA) treatment (HR 1.73, P=0.001), germline mutation (HR 5.62, P<0.001), poor differentiation (HR 7.45, P<0.001), liver metastasis (HR 1.72, P=0.001) and multiple treatment lines (HR 1.62 for 2nd line, P=0.04; HR 1.88 for ≥3rd line, P=0.01) were identified as negative prognostic factors for PFS. Conversely, dose adjustment (HR 0.63, P=0.009) and treatment with surufatinib (HR 0.58 for pNEN, P<0.001; HR 0.62 for epNEN, P=0.002) were correlated with longer PFS. In a real-world Chinese cohort, surufatinib significantly outperformed sunitinib and everolimus in prolonging PFS among advanced NEN patients, with identifiable clinical features impacting survival, and conclusions regarding superiority should be interpreted with caution due to the retrospective design. Our findings underscore the need for prospective studies to further validate these results and explore additional predictive biomarkers for personalized treatment strategies.

Cost consequence analysis of adding semaglutide to treatment regimen for patients with Type II diabetes in Saudi Arabia

IntroductionSemaglutide, a Glucagon-like Peptide-1 Receptor Agonist (GLP-1 RA), is often prescribed for managing type 2 diabetes, particularly in cases unresponsive to other hypoglycemic agents. Despite its popularity, the real-world efficacy and cost-effectiveness of Semaglutide relative to other treatments remain understudied. ObjectiveThis study aimed to examine the direct medical cost and consequences of adding Semaglutide to the treatment regimen for patients with type 2 diabetes in Saudi Arabia. MethodsWe conducted a single-center, retrospective review of Electronic Medical Records (EMRs) for adults with type 2 diabetes. Patients who had been on Semaglutide for at least three months were matched with those receiving alternative hypoglycemic therapies. Exclusions were made for patients with cancer, incomplete EMRs, or lacking prescription data. Investigated outcomes included changes in HbA1C levels and weight, and the direct costs comprised medications, clinic visits, and emergency care. Baseline adjustments were made through inverse probability treatment weighting, and uncertainty was assessed via bootstrapping with 10,000 replications. ResultsOut of 350 patients meeting the criteria, 116 were on Semaglutide. Predominantly females (62%), the cohort had an average age of 60 and a disease duration of 22 years. The difference in HbA1C (%) reductions between Semaglutide and non-Semaglutide users over 3,6, and 12 months were 0.154 (95% CI: –0.452-0.483), –0.031(95% CI: –0.754-0.239), –0.16(95% CI: –1.425-0.840), respectively. Semaglutide users did experience modest weight reductions ranging from 0.42 kg to 1.16 kg. The annual additional direct medical cost for Semaglutide was USD 4,086.82 (95% CI: $3,710.85 - $4,294.99). ConclusionAlthough Semaglutide induced modest weight reductions, it did not offer significant advantages in lowering HbA1C levels compared to other hypoglycemic treatments. These findings suggest the need for further research involving larger and more diverse cohorts to corroborate these findings.

Propofol vs etomidate for induction prior to invasive mechanical ventilation in patients with acute myocardial infarction

BackgroundPatients with acute myocardial infarction (AMI) requiring invasive mechanical ventilation (IMV) have a high mortality. However, little is known regarding the impact of induction agents, used prior to IMV, on clinical outcomes in this population. We assessed for the association between induction agent and mortality in patients with AMI requiring IMV. MethodsWe compared clinical outcomes between those receiving propofol compared to etomidate for induction among adults with AMI between October 2015 and December 2019 using the Vizient® Clinical Data Base, a multicenter, US national database. We used inverse probability treatment weighting (IPTW) to assess for the association between induction agent and in-hospital mortality. ResultsWe identified 5,147 patients, 1,386 (26.9%) of received propofol and 3,761 (73.1%) received etomidate for IMV induction. The mean (SD) age was 66.1 (12.4) years, 33.0% were women, and 51.6% and 39.8% presented with STEMI and cardiogenic shock, respectively. Patients in the propofol group were more likely to require preintubation vasoactive medication and mechanical circulatory support (both, P < .05). Utilization of propofol was associated with lower mortality compared to etomidate (32.3% vs 36.1%, P = .01). After propensity weighting, propofol use remained associated with lower mortality (weighted mean difference −4.7%; 95% confidence interval: −7.6% to −1.8%, P = .002). Total cost, ventilator days, and length of stay were higher in the propofol group (all, P < .001). ConclusionsInduction with propofol, compared with etomidate, was associated with lower mortality for patients with AMI requiring IMV. Randomized trials are needed to determine the optimal induction agent for this critically ill patient population.

PROACTIVE SCREENING ALGORITHM FOR EARLY-ONSET PNEUMONIA IN PATIENTS WITH OUT-OF-HOSPITAL CARDIAC ARREST: A BEFORE-AFTER IMPLEMENTATION STUDY.

Introduction : Early-onset pneumonia (EOP) occurs in around 50% of critically ill patients with out-of-hospital cardiac arrest (OHCA) and is associated with increased morbidity. Prompt diagnosis of EOP in these patients is difficult because of targeted temperature management and the postcardiac arrest syndrome. We hypothesized that an algorithm for proactive screening of EOP would improve patient outcomes. Methods : We conducted a single-center observational study comparing the outcomes of mechanically ventilated adult patients with OHCA, before (study period 1) and after (study period 2) implementation of an algorithm for proactive diagnosis of EOP, including an early distal pulmonary specimen. An inverse probability treatment weighted multivariable regression was performed to identify independent parameters associated with duration of mechanical ventilation. A subgroup analysis was conducted in patients alive on day 5 after intensive care unit admission. Results : Over the 4-year study period, 190 patients (99 and 91 for study periods 1 and 2, respectively) were enrolled. The overall incidence of EOP was 57.4% and was similar between both study periods. Although there was no difference in the time interval to antibiotic initiation, study period 2 was independently associated with higher SpO 2 /FiO 2 ratios on days 3 and 4. We also observed a decrease in mechanical ventilation time in study period 2 (4.5 [1-11.3] vs. 3 [2-5.8] days; P = 0.07), and this reached statistical significance in the subgroup analysis of patients alive at day 5 (10 [5-17] vs. 5 [3-9] days, P = 0.01). Conclusion: In critically ill patients with OHCA, proactive diagnosis of EOP was not associated with a significant change in the time to antibiotic initiation. Further research is warranted to better define optimal diagnosis and management of EOP in this setting.

Association between change in cardiorespiratory fitness and prostate cancer incidence and mortality in 57 652 Swedish men

ObjectivesTo examine the associations between changes in cardiorespiratory fitness (CRF) in adulthood and prostate cancer incidence and mortality.MethodsIn this prospective study, men who completed an occupational health profile assessment including...

Association between tranexamic acid administration and mortality based on the trauma phenotype: a retrospective analysis of a nationwide trauma registry in Japan

BackgroundIn trauma systems, criteria for individualised and optimised administration of tranexamic acid (TXA), an antifibrinolytic, are yet to be established. This study used nationwide cohort data from Japan to evaluate the association between TXA and in-hospital mortality among all patients with blunt trauma based on clinical phenotypes (trauma phenotypes).MethodsA retrospective analysis was conducted using data from the Japan Trauma Data Bank (JTDB) spanning 2019 to 2021.ResultsOf 80,463 patients with trauma registered in the JTDB, 53,703 met the inclusion criteria, and 8046 (15.0%) received TXA treatment. The patients were categorised into eight trauma phenotypes. After adjusting with inverse probability treatment weighting, in-hospital mortality of the following trauma phenotypes significantly reduced with TXA administration: trauma phenotype 1 (odds ratio [OR] 0.68 [95% confidence interval [CI] 0.57–0.81]), trauma phenotype 2 (OR 0.73 [0.66–0.81]), trauma phenotype 6 (OR 0.52 [0.39–0.70]), and trauma phenotype 8 (OR 0.67 [0.60–0.75]). Conversely, trauma phenotypes 3 (OR 2.62 [1.98–3.47]) and 4 (OR 1.39 [1.11–1.74]) exhibited a significant increase in in-hospital mortality.ConclusionsThis is the first study to evaluate the association between TXA administration and survival outcomes based on clinical phenotypes. We found an association between trauma phenotypes and in-hospital mortality, indicating that treatment with TXA could potentially influence this relationship. Further studies are needed to assess the usefulness of these phenotypes.Graphical abstract