Assessment of socioeconomic and racial differences in patients undergoing concurrent gynecologic oncology and urogynecology surgeries: a National Inpatient Sample (NIS) database study.

OBJECTIVE: To assess social determinants of health impacting patients undergoing gynecologic oncology versus combined gynecologic oncology and urogynecology surgeries. METHODS: We identified patients who underwent gynecologic oncology surgeries from 2016 to 2019 in the National Inpatient Sample using the International Classification of Diseases-10 codes. Demographics, including race and insurance status, were compared for patients who underwent gynecologic oncology procedures only (Oncologic) and those who underwent concurrent incontinence or pelvic organ prolapse procedures (Urogynecologic-Oncologic). A logistic regression model assessed variables of interest after adjustment for other relevant variables. RESULTS: From 2016 to 2019 the National Inpatient Sample database contained 389 (1.14%) Urogynecologic-Oncologic cases and 33 796 (98.9%) Oncologic cases. Urogynecologic-Oncologic patients were less likely to be white (62.1% vs 68.8%, p=0.02) and were older (median 67 vs 62 years, p<0.001) than Oncologic patients. The Urogynecologic-Oncologic cohort was less likely to have private insurance as their primary insurance (31.9% vs 38.9%, p=0.01) and was more likely to have Medicare (52.2% vs 42.8%, p=0.01). After multivariable analysis, black (adjusted odds ratio (aOR) 1.41, 95% CI 1.05 to 1.89, p=0.02) and Hispanic patients (aOR 1.53, 95% CI 1.11 to 2.10, p=0.02) remained more likely to undergo Urogynecologic-Oncologic surgeries but the primary expected payer no longer differed significantly between the two groups (p=0.95). Age at admission, patient residence, and teaching location remained significantly different between the groups. CONCLUSIONS: In this analysis of a large inpatient database we identified notable racial and geographical differences between the cohorts of patients who underwent Urogynecologic-Oncologic and Oncologic procedures.

Extended-duration antibiotics are not associated with a reduction in surgical site infection in patients with ovarian cancer undergoing cytoreductive surgery with large bowel resection.

OBJECTIVE(S): To evaluate whether extended dosing of antibiotics (ABX) after cytoreductive surgery (CRS) with large bowel resection for advanced ovarian cancer is associated with reduced incidence of surgical site infection (SSI) compared to standard intra-operative dosing and evaluate predictors of SSI. METHODS: A retrospective single-institution cohort study was performed in patients with stage III/IV ovarian cancer who underwent CRS from 2009 to 2017. Patients were divided into two cohorts: 1) standard intra-operative dosing ABX and 2) extended post-operative ABX. All ABX dosing was at the surgeon's discretion. The impact of antibiotic duration on SSI and other postoperative outcomes was assessed using univariate and multivariable Cox regression models. RESULTS: In total, 277 patients underwent cytoreductive surgery (CRS) with large bowel resection between 2009 and 2017. Forty-nine percent (n = 137) received standard intra-operative ABX and 50.5% (n = 140) received extended post-operative ABX. Rectosigmoid resection was the most common large bowel resection in the standard ABX (89.9%, n = 124) and extended ABX groups (90.0%, n = 126), respectively. No significant differences existed between age, BMI, hereditary predisposition, or medical comorbidities (p > 0.05). No difference was appreciated in the development of superficial incisional SSI between the standard ABX and extended ABX cohorts (10.9% vs. 12.9%, p = 0.62). Of patients who underwent a transverse colectomy, a larger percentage of patients developed a superficial SSI versus no SSI (21% vs. 6%, p = 0.004). CONCLUSION(S): In this retrospective study of patients with advanced ovarian cancer undergoing CRS with LBR, extended post-operative ABX was not associated with reduced SSI, and prolonged administration of antibiotics should be avoided unless clinically indicated.

Bridging the Gap from Bench to Bedside: A Call for In Vivo Preclinical Models to Advance Endometrial Cancer and Cervical Cancer Immuno-Oncology Research.

Advanced-stage endometrial and cervical cancers are associated with poor outcomes despite contemporary advances in surgical techniques and therapeutics. Recent clinical trial results have led to a shift in the treatment paradigm for both malignancies, where immunotherapy is now incorporated in the upfront setting for most patients with advanced endometrial and cervical cancers as the standard of care. Impressive response rates have been observed, but unfortunately, a subset of patients do not benefit from immunotherapy, and survival remains poor. Continued pre-clinical research and clinical trial development are crucial for our understanding of resistance mechanisms to immunotherapy and maximization of therapeutic efficacy. In this setting, syngeneic models are preferred over xenograft models as they allow for evaluation of the tumor-immune interaction in an immunocompetent host, most closely mimicking the tumor-immune interaction in human cancer patients. Unfortunately, significant disparities exist regarding syngeneic models in gynecologic malignancy, where queries from multiple large bioscience companies confirm no commercial availability of endometrial or cervical cancer syngeneic cell lines. Few published data exist regarding the recent development of several endometrial and cervical cancer syngeneic cell lines, warranting further investigation. Closing the disparity gap for pre-clinical models in endometrial and cervical cancer will support physician-scientists, basic and translational researchers, and clinical trialists who are dedicated to improving outcomes for our patients with advanced disease and poor prognosis.

Cost-effectiveness of chemotherapy and dostarlimab for advanced or recurrent endometrial cancer.

OBJECTIVE: The combination of dostarlimab with carboplatin and paclitaxel has demonstrated improved progression-free survival (PFS) and overall survival (OS) in primary advanced and recurrent endometrial cancer (EC). However, prior studies have not found immunotherapy to be cost-effective, or cost-effective only in specific subgroups, of recurrent endometrial cancer. This study aimed to determine the cost-effectiveness of combination therapy compared to chemotherapy alone. METHOD: A partitioned survival model was developed to compare the cost and effectiveness of dostarlimab in combination with chemotherapy compared to chemotherapy alone in primary advanced or recurrent endometrial cancer. Clinical data was derived from the RUBY trial and drug costs from average sale prices. The incremental cost-effectiveness ratio (ICER) was compared to a set willingness to pay (WTP) of $100,000/QALY to determine cost-effectiveness. One-way and probabilistic sensitivity analyses were performed. RESULTS: In the intention-to-treat (ITT) population, the dostarlimab combination incurred an additional cost of $308,430 but provided an additional 5.67 QALYs compared to chemotherapy alone. The ICER was $54,406/QALY. The dostarlimab combination was cost-effective compared to chemotherapy alone irrespective of MMR expression, with an ICER of $32,287/QALY for MMR deficient (MMRd) EC and $85,744/QALY for MMR proficient (MMRp) EC. Probabilistic sensitivity analysis demonstrated that the combination was cost-effective in 98.2% of iterations at the current WTP threshold. CONCLUSIONS: Despite the higher cost, adding dostarlimab to platinum chemotherapy significantly improves QALYs, rendering this regimen cost-effective relative to chemotherapy alone for treating primary advanced or recurrent EC. Combination therapy is a cost-effective approach for this patient population compared to chemotherapy alone.

Integration of Partner Notification Services at a Sexually Transmitted Infections Clinic.

OBJECTIVES: PNS is critical to prevent the spread of STIs. We evaluated the feasibility of integrating PNS into an STI clinic focused on MSM. DESIGN/METHODS: The RI STI Clinic, in partnership with the RIDOH, implemented a PNS program in 2019. Interviews with patients diagnosed with gonorrhea/ syphilis were conducted. RIDOH attempted outreach to partners identified. We utilized interview data among MSM diagnosed with gonorrhea/syphilis in clinic from 1/1/19-12/31/2021. Bivariate analyses/multivariable logistic regression were conducted. RESULTS: 341 MSM were diagnosed with gonorrhea/syphilis during the three-year period, and 233 (68%) interviews were completed. Partner information was provided in 173 (74%) interviews. At least one workable partner was provided in 110 (47%) interviews. No statistically significant associations between provision of workable partners and index patient age/race/ethnicity were found. CONCLUSIONS: PNS at an STI clinic was successful, but challenges led to suboptimal information. Research is needed to identify barriers to integrate/optimize PNS in STI clinics.

Pre-Exposure Prophylaxis Care Cascade Among Men Who Have Sex with Men Engaging in Partner Notification Services at a Sexually Transmitted Infections Clinic.

Partner notification services (PNS) offers opportunities to discuss HIV pre-exposure prophylaxis (PrEP) and provide referrals. We evaluated the PrEP care cascade among men who have sex with men (MSM) engaging in PNS within a sexually transmitted infections clinic. Among 121 MSM eligible for PrEP during PNS, 21% subsequently initiated PrEP.

Diagnosis and management of gastric-type endocervical adenocarcinoma: A case report and review of the literature.

Gastric-type endocervical adenocarcinoma (GEA), a rare subtype of cervical cancer, has garnered increasing attention recently for its distinctive histopathological features, unique classification, genetic characteristics, and variable clinical outcomes compared to squamous cell and adenocarcinoma subtypes. Historically, GEA has evolved from a poorly understood entity to a distinct subtype of cervical adenocarcinoma, only recently recognized in the 2020 World Health Organization (WHO) classification. Accordingly, characteristic morphological features define GEA, shedding light on the diagnostic challenges and potential misclassification that can occur in clinical practice. Genetic alterations, including KRAS, ARID1A, and PIK3CA mutations, play a pivotal role in the development and progression of GEA. This article reviews a case of GEA and aims to provide a contemporary overview of the genetic mutations and molecular pathways implicated in GEA pathogenesis, highlighting potential therapeutic targets and the prospects of precision medicine in its management. Patients with GEA have variable clinical outcomes, with some exhibiting aggressive behavior while others follow a more indolent course. This review examines the factors contributing to this heterogeneity, including stage at diagnosis, histological grade, and genetic alterations, and their implications for patient prognoses. Treatment strategies for GEA remain a topic of debate and research. Here, we summarize the current therapeutic options, including surgery, radiation therapy, and chemotherapy, while also exploring emerging approaches, such as targeted therapies and immunotherapy. This article provides a comprehensive overview of GEA, synthesizing current knowledge from historical perspectives to contemporary insights, focusing on its classification, genetics, outcomes, and therapeutic strategies.

The Relationship Between Insertive Oral and Anal Sex and Select Measures of the Composition of the Urethral Microbiota Among Men Who Have Sex With Men.

BACKGROUND: Sexual behavior may influence the composition of the male urethral microbiota, but this hypothesis has not been tested in longitudinal studies of men who have sex with men (MSM). METHODS: From December 2014 to July 2018, we enrolled MSM with nongonococcal urethritis (NGU) attending a sexual health clinic. Men attended 5 in-clinic visits at 3-week intervals, collected weekly urine specimens at home, and reported daily antibiotics and sexual activity on weekly diaries. We applied broad-range 16S rRNA gene sequencing to urine. We used generalized estimating equations to estimate the association between urethral sexual exposures in the prior 7 days (insertive oral sex [IOS] only, condomless insertive anal intercourse [CIAI] only, IOS with CIAI [IOS + CIAI], or none) and Shannon index, number of species (observed, oral indicator, and rectal indicator), and specific taxa, adjusting for recent antibiotics, age, race/ethnicity, HIV, and preexposure prophylaxis. RESULTS: Ninety-six of 108 MSM with NGU attended ≥1 follow-up visit. They contributed 1140 person-weeks of behavioral data and 1006 urine specimens. Compared with those with no urethral sexual exposures, those with IOS only had higher Shannon index ( P = 0.03 ) but similar number of species and presence of specific taxa considered, adjusting for confounders; the exception was an association with Haemophilus parainfluenzae . CIAI only was not associated with measured aspects of the urethral microbiota. IOS + CIAI was only associated with presence of H. parainfluenzae and Haemophilus . CONCLUSIONS: Among MSM after NGU, IOS and CIAI did not seem to have a substantial influence on measured aspects of the composition of the urethral microbiota.

Laparoscopic predictability of minimally invasive interval debulking in advanced ovarian cancer: The MIID-SOC trial.

BACKGROUND: We sought to create a laparoscopic-based model to predict the ability to perform a minimally invasive (MIS) cytoreductive surgery in advanced epithelial ovarian cancer patients who have received neoadjuvant chemotherapy (NACT). METHODS: Fifty women were enrolled in a multi-institutional prospective pilot study (NCT03378128). Each patient underwent laparoscopic evaluation of 43 abdominopelvic sites followed by surgeon dictated surgical approach, either continue MIS or laparotomically. However, if the procedure continued MIS, the placement of a hand-assist port for manual palpation was mandated to emulate a laparotomic approach and all 43 sites were re-evaluated. Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were calculated for each site to predict MIS resectability. Each parameter was assigned a numeric value based on the strength of statistical association and a total predictive index score (PIV) was assigned for each patient. Receiver operating characteristic curve analysis was used to assess the ability of the model to predict the MIS approach. RESULTS: Twenty-seven patients (61%) underwent MIS surgery. The following abdominopelvic sites were selected for inclusion in the model: gastrosplenic ligament, rectum, left mesocolon, transverse colon, right colon, cecum, appendix, liver capsule, intrahepatic fossa/gallbladder, ileum/jejunum. Using the PIV, a ROC was generated with an AUC = 0.695. In the final model, a PIV <2 identified patients able to undergo an optimal MIS cytoreductive surgery with an accuracy of 68.2%. The specificity, or the ability to identify patients who would not be able to undergo an optimal MIS interval cytoreductive surgery, was 66.7%. CONCLUSION: This predictive index model may help to guide future inclusion criteria in randomized studies evaluating the MIS approach in advanced epithelial ovarian cancer.

Does the choice of platinum doublet matter? A study to evaluate the impact of platinum doublet choice for treatment of platinum-sensitive ovarian cancer recurrence on the development of future PARP inhibitor and platinum resistance.

OBJECTIVES: The use of a platinum doublet for the treatment of platinum-sensitive epithelial ovarian cancer (EOC) recurrence is well established. The impact of the non­platinum chemotherapy used as part of a platinum doublet on PARP inhibitor (PARPi) and platinum sensitivity it not known. We aimed to describe oncologic outcomes in cases of recurrent EOC receiving PARPi as maintenance therapy based on preceding platinum doublet. METHODS: Retrospective study of patients with platinum-sensitive recurrent ovarian, fallopian tube or primary peritoneal cancer treated with platinum doublet followed by maintenance PARPi from 1/1/2015 and 1/1/2022. Comparisons were made between patients receiving carboplatin + pegylated liposomal doxorubicin (CD) versus other platinum doublets (OPDs). Descriptive statistics, Kaplan-Meier and univariate survival analyses were performed. RESULTS: 100 patients received PARPi maintenance following a platinum doublet chemotherapy regimen for platinum-sensitive recurrence. 25/100 (25%) received CD and 75/100 (75%) received OPDs. Comparing CD and OPDs, median progression-free survival was 8 versus 7 months (p = 0.26), median time to platinum resistance was 15 versus 13 months (p = 0.54), median OS was 64 versus 90 months (p = 0.28), and median OS from starting PARPi was 25 versus 26 months (p = 0.90), respectively. CONCLUSIONS: Using pegylated liposomal doxorubicin as part of a platinum doublet preceding maintenance PARPi for platinum-sensitive recurrence does not seem to hasten PARPi resistance or platinum resistance compared to OPDs. Although there was a non-significant trend towards increased OS among patients who received a platinum doublet other than CD prior to PARPi, the OS from PARPi start was similar between groups. Given the retrospective nature of this study and small study population, further research is needed to evaluate if the choice of platinum doublet preceding PARPi maintenance impacts PARPi resistance, platinum resistance and survival.

Prior Emergency Medical Services Utilization Among People Who Had an Accidental Opioid-Involved Fatal Drug Overdose-Rhode Island, 2018-2020.

OBJECTIVE: To help understand whether decreased emergency medical services (EMS) utilization due to the COVID-19 pandemic contributed to increased accidental fatal drug overdoses, we characterized recent EMS utilization history among people who had an accidental opioid-involved fatal drug overdose in Rhode Island. METHODS: We identified accidental opioid-involved fatal drug overdoses among Rhode Island residents that occurred from January 1, 2018, through December 31, 2020. We linked decedents by name and date of birth to the Rhode Island EMS Information System to obtain EMS utilization history. RESULTS: Among 763 people who had an accidental opioid-involved fatal overdose, 51% had any EMS run and 16% had any opioid overdose-related EMS run in the 2 years before death. Non-Hispanic White decedents were significantly more likely than decedents of other races and ethnicities to have any EMS run (P < .001) and any opioid overdose-related EMS run (P = .05) in the 2 years before death. Despite a 31% increase in fatal overdoses from 2019 through 2020, corresponding with the onset of the COVID-19 pandemic, EMS utilization in the prior 2 years, prior 180 days, or prior 90 days did not vary by time frame of death. CONCLUSION: In Rhode Island, decreased EMS utilization because of the COVID-19 pandemic was not a driving force behind the increase in overdose fatalities observed in 2020. However, with half of people who had an accidental opioid-involved fatal drug overdose having an EMS run in the 2 years before death, emergency care is a potential opportunity to link people to health care and social services.

Mental Health Status of Rhode Island Middle School and High School Students Before Versus During the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic negatively affected adolescent mental health due to school closures, isolation, family loss/hardships, and reduced health care access. METHODS: We compared adolescent mental health in Rhode Island before versus during the pandemic, separately among middle and high schoolers. This serial cross-sectional study used Youth Risk Behavior Survey data from 2019 and 2021 (N = 7403). Multivariable logistic regression models estimated the association between year and mental health status, adjusting for sociodemographics. RESULTS: Middle schoolers in 2021 had higher odds of ever seriously considering suicide (22.6% vs 16.7%) and ever attempting suicide (9.3% vs 6.1%) compared to 2019. Among high schoolers, those in 2021 had higher odds of experiencing persistent sadness/hopelessness in the past year (37.4% vs 32.0%). However, high schoolers in 2019 and 2021 had similar odds of considering suicide in the past year, while those in 2021 had lower odds of having attempted suicide in the past year (8.5% vs 14.6%). CONCLUSION: The COVID-19 pandemic may have worsened multiple aspects of adolescent mental health in Rhode Island, particularly among middle schoolers. IMPLICATIONS FOR SCHOOL HEALTH POLICY, PRACTICE, AND EQUITY: Promoting school connectedness, creating supportive environments, and diversifying the mental health workforce may help overcome adverse pandemic effects.

Association between comorbid chronic pain or prior hospitalization for mental illness and substance use treatment among a cohort at high risk of opioid overdose.

INTRODUCTION: Chronic pain and serious mental illness increase risk of opioid use, and opioid use can exacerbate both conditions. Substance use disorder (SUD) treatment can be lifesaving, but chronic pain and serious mental illness may make recovery challenging. We evaluated the association between current chronic pain and prior hospitalization for mental illness and 90-day SUD treatment engagement, among emergency department (ED) patients at high risk of opioid overdose. METHODS: We conducted a cohort analysis of 648 ED patients enrolled in a randomized controlled trial in Rhode Island. We linked baseline study data on chronic pain and prior hospitalization for mental illness to statewide administrative data on state-licensed treatment programs (including methadone) and buprenorphine treatment via prescription. We defined treatment engagement as initiation of a state-licensed treatment program, transfer between state-licensed programs/providers, or a buprenorphine prescription (re-)fill. We used modified Poisson models to estimate the association between each baseline comorbidity and treatment engagement within 90 days following the ED visit, adjusted for a priori potential confounders. In an exploratory analysis, models were stratified by baseline treatment status. RESULTS: The mean age of participants was 37 years; 439 (68 %) were male, and 446 (69 %) had been recently unhoused. Overall, 278 participants (43 %) engaged in treatment within 90 days of the ED visit. Participants with prior hospitalization for mental illness were more likely to engage in treatment than those without (adjusted risk ratio [ARR] = 1.24, 95 % confidence interval [CI] = 1.01-1.53), although this association was only among those already accessing treatment at baseline (ARR = 1.58, 95 % CI = 1.10-2.27). Chronic pain was not associated with 90-day treatment engagement overall (ARR = 1.12, 95 % CI = 0.91-1.38) or within baseline treatment subgroups. CONCLUSIONS: Among ED patients at high risk of opioid overdose and accessing treatment at baseline, those with prior hospitalization for mental illness (but not chronic pain) were more likely to engage in treatment following the ED visit, which may reflect disproportionate initiation of additional treatment programs, transfer between programs/providers, or ongoing buprenorphine treatment. Touchpoints within the medical system should be leveraged to ensure that everyone, including those with serious mental illness, can access high-quality SUD treatment at the desired intensity level.

The microbiome and gynecologic cancer: cellular mechanisms and clinical applications.

The microbiome plays a vital function in maintaining human health and homeostasis. Each microbiota has unique characteristics, including those of the gastrointestinal and female reproductive tract. Dysbiosis, or alterations to the composition of the microbial communities, impacts the microbiota-host relationship and is linked to diseases, including cancer. In addition, studies have demonstrated that the microbiota can contribute to a pro-carcinogenic state through altered host immunologic response, modulation of cell proliferation, signaling, gene expression, and dysregulated metabolism of nutrients and hormones.In recent years, the microbiota of the gut and female reproductive tracts have been linked to many diseases, including gynecologic cancers. Numerous pre-clinical and clinical studies have demonstrated that specific bacteria or microbial communities may contribute to the development of gynecologic cancers. Further, the microbiota may also impact the toxicity and efficacy of cancer therapies, including chemotherapy, immunotherapy, and radiation therapy in women with gynecologic malignancies. The microbiota is highly dynamic and may be altered through various mechanisms, including diet, exercise, medications, and fecal microbiota transplantation. This review provides an overview of the current literature detailing the relationship between gynecologic cancers and the microbiota of the female reproductive and gastrointestinal tracts, focusing on mechanisms of carcinogenesis and strategies for modulating the microbiota for cancer prevention and treatment. Advancing our understanding of the complex relationship between the microbiota and gynecologic cancer will provide a novel approach for prevention and therapeutic modulation in the future.

Long-term health care costs following COVID-19: implications for pandemic preparedness.

OBJECTIVES: To estimate excess health care costs in the 12 months following COVID-19 diagnosis. STUDY DESIGN: Retrospective cohort study using Blue Cross Blue Shield of Rhode Island claims incurred from January 1, 2019, to March 31, 2022, among commercial and Medicare Advantage members. METHODS: Difference-in-differences analyses were used to compare changes in health care spend between the 12 months before (baseline period) and the 12 months after (post period) COVID-19 diagnosis for COVID-19 cases and contemporaneous matched controls without COVID-19. RESULTS: Overall, there were 7224 commercial and 1630 Medicare Advantage members with a COVID-19 diagnosis on/before March 31, 2021, each with a matched control, yielding a sample of 14,448 commercial and 3260 Medicare Advantage members. Among commercial members, 51.9% were aged 25 to 54 years and 54.0% were female. Among Medicare Advantage members, 94.2% were 65 years or older and 62.0% were female. Among commercial members, from the baseline period to the post period, total health care spend increased $41.61 (7.7%) per member per month (PMPM) more among COVID-19 cases compared with their matched controls. Among Medicare Advantage members, the difference-in-differences was greater, with spend increasing $97.30 (13.1%) PMPM more among cases compared with controls. The difference-in-differences was greatest for outpatient and professional services (both populations) and prescription services (Medicare Advantage only). CONCLUSIONS: COVID-19 diagnosis was associated with excess health care spend PMPM over the subsequent 12 months, highlighting the importance of societal preparations to support individuals' long-term health care needs following COVID-19 and as a part of future pandemic preparedness.

Pandemic Preparedness and the Workforce: Employer Experiences with Long COVID.

BACKGROUND: Although viral infections, including SARS-CoV-2, can cause persistent symptoms and functional limitations, the impact of post-viral syndromes on workplaces is uncertain. METHODS: We conducted a cross-sectional study of workplaces in Rhode Island in the D&B Hoovers database (September-October 2022). Eligible workplaces had ≥1 contact with a valid email address and ≥2 paid employees. Participants completed a survey on the impact of Long COVID (post-viral syndrome of SARS-CoV-2) on their workplace. RESULTS: Of 6,149 eligible workplaces, 484 (8%) participated. Awareness of Long COVID among workplace leaders was limited. Overall, 28% of workplaces had any employees report having Long COVID. Of those, 14% had ≥1 employee discontinue employment, 45% had ≥1 employee reduce their workload, and 22% had ≥1 employee request an accommodation due to having Long COVID; 80% of employers reported improvement in employee productivity with accommodations. CONCLUSION: Pandemic preparations for the long-term impacts of post-viral syndromes should consider workplace settings.

The impact of antibiotic and proton pump inhibitor use at the time of adjuvant platinum-based chemotherapy on survival in patients with endometrial cancer.

OBJECTIVE: We sought to assess the impact of antibiotic (ABX) and proton-pump inhibitor (PPI) use on progression-free (PFS) and overall survival (OS) in patients treated with adjuvant platinum-based chemotherapy (PC) for endometrial cancer (EC). METHODS: A retrospective, single-institution cohort study of EC patients treated with ≥four cycles of adjuvant PC following surgical staging from 2014 to 2020. Demographics and clinicopathologic features, including ABX and PPI use, were compared using χ2 and Fisher's exact tests. Univariate and multivariable analyses were performed, and survival outcomes were compared using the log-rank test. RESULTS: Of 325 patients, 95 (29%) received ABX, and 80 (24.6%) received PPI. ABX were associated with decreased 3-year PFS (49.9% vs. 66%; p = 0.0237) but not 3-year OS (68.9% vs. 79.9%; p = 0.0649). ABX targeting gram-positive bacteria were associated with decreased 3-year PFS (21.2% vs. 66.0% vs. 55.4%; p = 0.0038) and 3-year OS (36.5% vs. 79.9% vs. 75.6%; p = 0.0014) compared to no ABX and other ABX, respectively. PPI use was associated with decreased 3-year PFS (46.9% vs. 66.0%; p = 0.0001) and 3-year OS (60.7% vs. 81.9%; p = 0.0041) compared to no PPI. On multivariable regression analysis controlling for confounders including stage, histology, grade, radiation, and co-morbidities, PPI use was independently associated with worse PFS (HR 1.96, 95% CI 1.25-3.08; p = 0.0041) and OS (HR 2.06, 95% CI 1.01-4.18, p = 0.04). CONCLUSION: In this retrospective cohort study, we demonstrate that PPI use is independently associated with worse PFS and OS in patients with EC treated with PC. ABX use was associated with worse PFS on univariate analysis only. There is an unmet need to understand how PPI, ABX, and, potentially, the microbiome impact the effectiveness of chemotherapy in EC patients.

Buprenorphine Dose and Time to Discontinuation Among Patients With Opioid Use Disorder in the Era of Fentanyl.

Importance: Buprenorphine treatment for opioid use disorder (OUD) has more than doubled since 2009. However, current US Food and Drug Administration buprenorphine dosing guidelines are based on studies among people using heroin, prior to the emergence of fentanyl in the illicit drug supply. Objective: To estimate the association between buprenorphine dose and time to treatment discontinuation during a period of widespread fentanyl availability. Design, Setting, and Participants: This retrospective cohort study used statewide Rhode Island Prescription Drug Monitoring Program data. Participants were Rhode Island residents initiating buprenorphine treatment for OUD between October 1, 2016, and September 30, 2020. Data analysis was performed from December 9, 2022, to August 10, 2023. Exposure: Daily dose of buprenorphine (16 mg and 24 mg) defined starting on the day of initiation based on total quantity and days' supply dispensed. Patients were censored on any dose change. Main Outcomes and Measures: Buprenorphine treatment discontinuation in the 180 days following initiation, defined as a gap in treatment of more than 27 days based on prescription fill dates and days' supply. Kaplan-Meier and Cox regression survival analyses were conducted to estimate the association between buprenorphine dose and time to treatment discontinuation, controlling for potential informative censoring and measured potential confounders. Results: Among 6499 patients initiating buprenorphine treatment for OUD, most were aged 25 to 44 years (57%; n = 3682), were male (61%; n = 3950), and had private (47%; n = 3025) or Medicaid (33%; n = 2153) insurance. More than half of patients were prescribed a daily dose of interest at initiation (16 mg: 50%; n = 3264; 24 mg: 10%; n = 668). In Kaplan-Meier analyses, 58% of patients discontinued buprenorphine treatment within 180 days (16 mg: 59% vs 24 mg: 53%; log-rank test P = .005). In Cox regression analyses, patients prescribed a dose of 16 mg had a greater risk of treatment discontinuation than those prescribed 24 mg (adjusted hazard ratio, 1.20; 95% CI, 1.06-1.37). Conclusions and Relevance: In this cohort study of patients initiating buprenorphine treatment from 2016 to 2020, patients prescribed a 24 mg dose of buprenorphine remained in treatment longer than those prescribed 16 mg. The value of higher buprenorphine doses than currently recommended needs to be considered for improving retention in treatment.

The impact of polysubstance use patterns on engagement of substance use disorder treatment among emergency department patients at high risk of opioid overdose.

Background: Substance use patterns are diverse, and multiple substances are often involved in fatal and nonfatal overdoses. Additionally, polysubstance use is associated with greater difficulty accessing and remaining in substance use disorder (SUD) treatment. The aim of this study was to identify substance use patterns and determine their association with SUD treatment engagement among emergency department (ED) patients at risk of opioid overdose. Methods: This was a sub-analysis of a randomized controlled trial comparing two behavioral interventions for individuals at two EDs in Rhode Island from 2018 to 2021. Past six-month substance use frequency for eight substances plus injection drug use was self-reported at trial enrollment, and SUD treatment engagement within 90 days after enrollment was obtained using administrative data linkages. Latent class analysis identified substance use patterns and multivariable log-binomial models estimated the association with SUD treatment engagement. Results: Among 607 participants, there were four substance use patterns: 1) low reported use (n = 295), 2) frequent injection and heroin use (n = 131), 3) high frequency broad polysubstance use (n = 62), and 4) low frequency broad polysubstance use (n = 119). Compared to participants with the low reported use pattern, those with the frequent injection and heroin pattern had a greater likelihood of SUD treatment engagement (adjusted risk ratio = 1.28; 95% confidence interval = 1.02-1.61). Conclusions: Distinct and meaningful polysubstance use patterns showed differential SUD treatment engagement after ED discharge. Nuanced relationships between substance use patterns and treatment highlight the necessity for tailored harm reduction, treatment, and recovery services.

Association of Clinical Trial Participation With Improved Overall Survival for Recurrent, Platinum-Resistant Ovarian Cancer.

OBJECTIVE: To investigate whether clinical trial participation is associated with overall survival in patients with platinum-resistant ovarian cancer. METHODS: An IRB-approved, retrospective, single-institution cohort study was performed in patients with platinum-resistant ovarian cancer from January 1, 2009, to December 31, 2017. Platinum resistance was defined as progression within 6 months after completion of platinum chemotherapy. Patients were divided into two cohorts: 1) clinical trial participants for platinum-resistant ovarian cancer or 2) standard of care. The association of trial participation with overall survival from the date of platinum resistance was assessed with univariate and multivariable models. RESULTS: Of 305 eligible patients with recurrent platinum-resistant ovarian cancer, 46 (15.1%) were clinical trial participants. There were no significant differences in age (61.2 years vs 63.3 years, P =.21), body mass index (27.5 vs 27.6, P =.90), race ( P =.61), medical comorbidities ( P >.05), or performance status ( P =.07) for clinical trial participants compared with those receiving standard of care. The majority underwent primary cytoreduction (76.1% vs 69.1%, P =.34) with no differences in residual disease ( P =.43) for clinical trial participants compared with those receiving standard of care. There was no difference in poly-ADP-ribose polymerase inhibitor (21.7% vs 15.1%, P =.26) or bevacizumab (22.2% vs 32.1%, P =.31) use for clinical trial participants compared with those receiving standard of care. On multivariable analysis controlling for comorbidities, stage, and germline mutational status, clinical trial participation was associated with significantly improved overall survival from the date of platinum resistance compared with standard of care (13.8 months vs 10.5 months, adjusted hazard ratio 1.46, 95% CI 1.04-2.05, P =.028). CONCLUSIONS: In this retrospective cohort of patients with platinum-resistant ovarian cancer, clinical trial participation was associated with improved overall survival compared with standard of care therapies. Availability and participation in clinical trials should be prioritized in patients with recurrent, platinum-resistant ovarian cancer.