The role of race/ethnicity and age in clinical trial knowledge among patients with gynecologic malignancy.

PURPOSE: To identify whether race/ethnicity plays a role in knowledge of clinical trials among patients with a gynecologic malignancy. PATIENTS AND METHODS: A cross-sectional survey was conducted at a tertiary medical center. Participants were adults (≥18 years old), with gynecologic malignancy, and literate in English, Spanish or Chinese. Participants completed a 9-item clinical trial knowledge assessment. Demographic characteristics were summarized using descriptive statistics. A multivariable model was employed to evaluate the relationship between race/ethnicity and clinical trial knowledge. RESULTS: 245 patients were approached, 25 (10.2%) declined. Among participants, 108 (50.2%) were white, and 107 (49.8%) were people of color. Significant differences were noted for age, education, birthplace, and income; no difference was observed for cancer type or stage. The median number of correct answers for the knowledge assessment was seven. 67 (62%) white vs 26 (24.3%) people of color had an above average clinical trial knowledge score (p < 0.001). Multivariable analysis showed white participants were 2.7 times more likely to have an above average clinical trial knowledge score. White participants overall utilized more resources. Elder adults (≥65 years old) had higher knowledge of clinical trials compared to non-elder adults (<65 years old); however, these findings were not significant. CONCLUSION: This study observed significant differences in clinical trial knowledge between white and people of color diagnosed with a gynecologic malignancy. White patients utilize more informational resources compared to people of color. Further studies need to develop resources and outreach mechanisms that will increase access and diversity in clinical trial participation.

Postoperative thrombotic events following major surgery in patients with a history of COVID-19: a retrospective cohort analysis of commercially insured beneficiaries in the USA.

PURPOSE: We sought to evaluate the synergistic risk of postoperative thrombosis in patients with a history of COVID-19 who undergo major surgery. Major surgery and SARS-CoV-2 infection are independently associated with an increased risk of thrombosis, but the magnitude of additional risk beyond surgery conferred by a COVID-19 history on the development of perioperative thrombotic events has not been clearly elucidated in the literature. METHODS: We conducted a retrospective cohort study among commercially insured adults in the USA from March 2020 to June 2021 using the Optum Labs Data Warehouse (OLDW), a longitudinal, real-world data asset containing deidentified administrative claims and electronic health records. We compared patients with prior COVID-19 who underwent surgery with control individuals who underwent surgery without a COVID-19 history and with control individuals who did not undergo surgery with and without a COVID-19 history. We assessed the interaction of surgery and previous COVID-19 on perioperative thrombotic events (venous thromboembolism and major adverse cardiovascular events) within 90 days using multivariable logistic regression and interaction analysis. RESULTS: Two million and two-hundred thousand eligible patients were identified from the OLDW. Patients in the surgical cohorts were older and more medically complex than nonsurgical population controls. After adjusting for confounders, only surgical exposure-not COVID-19 history-remained associated with perioperative thrombotic events (adjusted odds ratio [aOR], 4.07; 95% confidence interval [CI], 3.81 to 4.36). The multiplicative interaction term (aOR, 1.25; 95% CI, 0.96 to 1.61) and the synergy index (0.76; 95% CI, 0.56 to 1.04) suggest minimal effect modification of prior COVID-19 on surgery with regards to overall thrombotic risk. CONCLUSIONS: We found no evidence of synergistic thrombotic risk from previous COVID-19 in patients who underwent selected major surgery relative to the baseline thrombotic risk from surgery alone.

RéSUMé: OBJECTIF: Nous avons cherché à évaluer le risque synergique de thrombose postopératoire chez les patient·es ayant des antécédents de COVID-19 qui bénéficient d'une intervention chirurgicale majeure. La chirurgie majeure et l'infection par le SRAS-CoV-2 sont indépendamment associées à un risque accru de thrombose, mais l'ampleur du risque supplémentaire d'apparition de complications thrombotiques périopératoires, au-delà de la chirurgie et conféré par des antécédents de COVID-19, n'a pas été clairement élucidée dans la littérature. MéTHODE: Nous avons mené une étude de cohorte rétrospective auprès d'adultes assuré·es commercialement aux États-Unis de mars 2020 à juin 2021 à l'aide de la base de données Optum Labs Data Warehouse (OLDW), un actif de données longitudinales du monde réel contenant des requêtes administratives anonymisées et des dossiers de santé électroniques. Nous avons comparé les patient·es ayant déjà souffert de COVID-19 et ayant bénéficié d'une intervention chirurgicale avec des personnes témoins ayant bénéficié d'une intervention chirurgicale sans antécédents de COVID-19 et avec des personnes témoins n'ayant pas bénéficié de chirurgie, avec et sans antécédents de COVID-19. Nous avons évalué l'interaction de la chirurgie et des antécédents de COVID-19 avec les complications thrombotiques périopératoires (thromboembolie veineuse et événements cardiovasculaires indésirables majeurs) dans les 90 jours à l'aide d'une régression logistique multivariée et d'une analyse des interactions. RéSULTATS: Deux millions deux cent mille personnes admissibles ont été identifiées à partir du registre OLDW. Les patient·es des cohortes chirurgicales étaient plus âgé·es et présentaient une plus grande complexité médicale que les personnes témoins de la population non chirurgicale. Après ajustement pour tenir compte des facteurs de confusion, seule l'exposition chirurgicale ­ et non les antécédents de COVID-19 ­ est restée associée aux complications thrombotiques périopératoires (rapport de cotes ajusté [RCa], 4,07; intervalle de confiance [IC] à 95 %, 3,81 à 4,36). Le terme d'interaction multiplicative (RCa, 1,25; IC 95 %, 0,96 à 1,61) et l'indice de synergie (0,76; IC 95 %, 0,56 à 1,04) suggèrent une modification minimale de l'effet d'un diagnostic antérieur de COVID-19 sur la chirurgie en matière de risque thrombotique global. CONCLUSION: Nous n'avons trouvé aucune preuve de risque thrombotique synergique lié à une COVID-19 antérieure chez les patient·es ayant bénéficié d'une intervention chirurgicale par rapport au risque thrombotique de base lié à la chirurgie seule.

High Risk of Substance Use Disorder-Related Outcomes in Veterans Released from Correctional Facilities in Mid to Late Life.

BACKGROUND: Veterans Affairs (VA) is likely to encounter a growing number of veterans returning to the community in mid to late life following incarceration (i.e., experiencing reentry). Yet, rates of negative health outcomes due to substance use disorders (SUDs) in this population are unknown. OBJECTIVE: To determine risk of and risk factors for SUD-related emergency department visits and inpatient hospitalizations (ED/IPH) and overdose death among older reentry veterans compared with never-incarcerated veterans. DESIGN: Retrospective cohort study using national VA and Medicare healthcare systems data. PARTICIPANTS: Veterans age ≥50, incarcerated for ≤5 consecutive years, and released between October 1, 2010, and September 30, 2017 (N = 18,803), were propensity score-matched 1:5 with never-incarcerated veterans (N = 94,015) on demographic characteristics, reason for Medicare eligibility, and SUD history. MAIN MEASURES: SUD-related ED/IPH (overall and substance-specific) were obtained from in-/outpatient VA health services and CMS data within the year following release date/index date (through September 30, 2018). Overdose death within 1 year was identified using the National Mortality Data Repository. Fine-Gray proportional hazards regression compared risk of SUD-related ED/IPH and overdose death between the two groups. RESULTS: The number of SUD-related ED/IPHs and overdose deaths was 2470 (13.1%) and 72 (0.38%) in the reentry sample versus 4402 (4.7%) and 198 (0.21%) in the never-incarcerated sample, respectively. Mid-to-late-life reentry was associated with higher risk of any SUD-related ED/IPH (13,136.2 vs. 2252.8 per 100,000/year; adjusted hazard ratio [AHR] = 2.19; 95% confidence interval [CI] = 2.08, 2.30) and overdose death (382.9 vs. 210.6 per 100,000/year; AHR = 2.24, 95% CI = 1.63, 3.08). CONCLUSIONS: Older reentry veterans have more than double the risk of experiencing SUD-related ED/IPH (overall and substance-specific) and overdose death, even after accounting for SUD history and other likely confounders. These findings highlight the vulnerability of this population. Improved knowledge regarding SUD-related negative health outcomes may help to tailor VA reentry programming.

High risk of complications after a "low risk" procedure: A national study of nursing home residents and older adults undergoing haemorrhoid surgery.

AIM: To evaluate 30-day complications and 1-year mortality for older adults undergoing haemorrhoid surgery. METHOD: This retrospective cohort study evaluated older adults (age 66+) undergoing haemorrhoid surgery using Medicare claims and the minimum data set (MDS). Long-stay nursing home residents were identified, and propensity score matched to community-dwelling older adults. Generalized estimating equation models were created to determine the adjusted relative risk of 30-day complications, length of stay (LOS), and 1-year mortality. Among nursing home residents, functional and cognitive status were evaluated using the MDS-activities of daily living (ADL) score and the Brief Instrument of Mental Status. Faecal continence status was evaluated among a subset of nursing home residents. RESULTS: A total of 3664 subjects underwent haemorrhoid surgery and were included in the analyses. Nursing home residents were at significantly higher risk for 30-day complications (52.3% vs. 32.9%, aRR 1.6 [95% CI: 1.5-1.7], p < 0.001), and 1-year mortality (24.9% vs. 16.1%, aRR 1.6 [95% CI: 1.3-1.8], p < 0.001). Functional and mental status showed an inflection point of decline around the time of the procedure, which did not recover to the baseline trajectory in the following year. Additionally, a subset of nursing home residents demonstrated worsening faecal incontinence. CONCLUSION: This study demonstrated high rates of 30-day complications and 1-year mortality among all older adults (yet significantly worse among nursing home residents). Ultimately, primary care providers and surgeons should carefully weigh the potential harms of haemorrhoid surgery in older adults living in a nursing home.

A systematic review and meta-analysis of cell-free DNA testing for detection of fetal sex chromosome aneuploidy.

OBJECTIVES: The aim was to determine the accuracy of cell-free DNA testing (cfDNA) for detecting sex chromosome aneuploidies (SCA) in singleton pregnancies. METHODS: A systematic review and meta-analysis was performed to assess cfDNA accuracy for prenatal detection of 45,X, 47,XXY, 47,XXX and 47,XYY. Inclusion was restricted to studies published between January 2010 and December 2021 reporting both cfDNA and confirmatory diagnostic test results. RESULTS: For 45,X, the sensitivity was 98.8% (95%CI 94.6%-100%), specificity 99.4% (95%CI 98.7%-99.9%) and positive predictive value (PPV) 14.5% (95%CI 7.0%-43.8%). For 47,XXY, the sensitivity was 100% (95%CI 99.6%-100%), specificity 100% (95%CI 99.9%-100%) and PPV 97.7% (95%CI 78.6%-100%). For 47,XXX, the sensitivity was 100% (95%CI 96.9%-100%), specificity 99.9% (95%CI 99.7%-100%) and PPV 61.6% (95%CI 37.6%-95.4%). For 47,XYY, the sensitivity was 100% (95%CI 91.3%-100%), specificity 100% (95% CI 100%-100%) and PPV 100% (95%CI 76.5%-100%). All four SCAs had estimated negative predictive values (NPV) exceeding 99.99%, though false negatives were reported. CONCLUSIONS: This analysis suggests that cfDNA is a reliable screening test for SCA, though both false negatives and false positives were reported. These estimates of test performance are derived from pregnancies at high pretest risk for aneuploidy, limiting the generalisability to average risk pregnancies.

Longitudinal Follow-Up of Participants With Tobacco Exposure and Preserved Spirometry.

Importance: People who smoked cigarettes may experience respiratory symptoms without spirometric airflow obstruction. These individuals are typically excluded from chronic obstructive pulmonary disease (COPD) trials and lack evidence-based therapies. Objective: To define the natural history of persons with tobacco exposure and preserved spirometry (TEPS) and symptoms (symptomatic TEPS). Design, Setting, and Participants: SPIROMICS II was an extension of SPIROMICS I, a multicenter study of persons aged 40 to 80 years who smoked cigarettes (>20 pack-years) with or without COPD and controls without tobacco exposure or airflow obstruction. Participants were enrolled in SPIROMICS I and II from November 10, 2010, through July 31, 2015, and followed up through July 31, 2021. Exposures: Participants in SPIROMICS I underwent spirometry, 6-minute walk distance testing, assessment of respiratory symptoms, and computed tomography of the chest at yearly visits for 3 to 4 years. Participants in SPIROMICS II had 1 additional in-person visit 5 to 7 years after enrollment in SPIROMICS I. Respiratory symptoms were assessed with the COPD Assessment Test (range, 0 to 40; higher scores indicate more severe symptoms). Participants with symptomatic TEPS had normal spirometry (postbronchodilator ratio of forced expiratory volume in the first second [FEV1] to forced vital capacity >0.70) and COPD Assessment Test scores of 10 or greater. Participants with asymptomatic TEPS had normal spirometry and COPD Assessment Test scores of less than 10. Patient-reported respiratory symptoms and exacerbations were assessed every 4 months via phone calls. Main Outcomes and Measures: The primary outcome was assessment for accelerated decline in lung function (FEV1) in participants with symptomatic TEPS vs asymptomatic TEPS. Secondary outcomes included development of COPD defined by spirometry, respiratory symptoms, rates of respiratory exacerbations, and progression of computed tomographic-defined airway wall thickening or emphysema. Results: Of 1397 study participants, 226 had symptomatic TEPS (mean age, 60.1 [SD, 9.8] years; 134 were women [59%]) and 269 had asymptomatic TEPS (mean age, 63.1 [SD, 9.1] years; 134 were women [50%]). At a median follow-up of 5.76 years, the decline in FEV1 was -31.3 mL/y for participants with symptomatic TEPS vs -38.8 mL/y for those with asymptomatic TEPS (between-group difference, -7.5 mL/y [95% CI, -16.6 to 1.6 mL/y]). The cumulative incidence of COPD was 33.0% among participants with symptomatic TEPS vs 31.6% among those with asymptomatic TEPS (hazard ratio, 1.05 [95% CI, 0.76 to 1.46]). Participants with symptomatic TEPS had significantly more respiratory exacerbations than those with asymptomatic TEPS (0.23 vs 0.08 exacerbations per person-year, respectively; rate ratio, 2.38 [95% CI, 1.71 to 3.31], P < .001). Conclusions and Relevance: Participants with symptomatic TEPS did not have accelerated rates of decline in FEV1 or increased incidence of COPD vs those with asymptomatic TEPS, but participants with symptomatic TEPS did experience significantly more respiratory exacerbations over a median follow-up of 5.8 years.

Frailty Is Associated with an Increased Risk of Complications and Need for Repeat Procedures after Sling Surgery in Older Adults.

PURPOSE: Sling surgery is the gold standard treatment for stress urinary incontinence in women. While data support the use of sling surgery in younger and middle-aged women, outcomes in older, frail women are largely unknown. MATERIALS AND METHODS: Data were examined for all Medicare beneficiaries ≥65 years old who underwent sling surgery with or without concomitant prolapse repair from 2014 to 2016. Beneficiaries were stratified using the Claims-Based Frailty Index (CFI) into 4 categories: not frail (CFI <0.15), prefrail (0.15 ≤CFI <0.25), mildly frail (0.25 ≤CFI <0.35) and moderately to severely frail (CFI ≥0.35). Outcomes included rates and relative risk of 30-day complications, 1-year mortality and repeat procedures for persistent incontinence or obstructed voiding at 1 year. RESULTS: A total of 54,112 women underwent sling surgery during the study period, 5.2% of whom were mildly to moderately to severely frail. Compared to the not frail group, moderately to severely frail beneficiaries demonstrated an increased adjusted relative risk (aRR) of 30-day complications (56.5%; aRR 2.5, 95% CI: 2.2-2.9) and 1-year mortality (10.5%; aRR 6.7, 95% CI: 4.0-11.2). Additionally, there were higher rates of repeat procedures in mildly to severely frail beneficiaries (6.6%; aRR 1.4, 95% CI: 1.2-1.6) compared to beneficiaries who were not frail. CONCLUSIONS: As frailty increased, there was an increased relative risk of 30-day complications, 1-year mortality and need for repeat procedures for persistent incontinence or obstructed voiding at 1 year. While there were fewer sling surgeries in performed frail women, the observed increase in complication rates was significant. Frailty should be strongly considered before pursuing sling surgery in older women.

Geriatric conditions and healthcare utilisation in older adults living with HIV.

BACKGROUND: older HIV-positive adults experience a significant burden of geriatric conditions. However, little is known about the association between geriatric conditions and healthcare utilisation in this population. SETTING: outpatient safety-net HIV clinic in San Francisco. METHODS: in 2013, HIV-positive adults ≥50 years of age underwent geriatric assessment including functional impairment, fall(s)in past year, cognitive impairment (MOCA <26) and low social support (Lubben social network scale ≤12). We reviewed medical records from 2013 through 2017 to capture healthcare utilisation (emergency room (ER) visits and hospitalisations) and used Poisson models to examine the association between geriatric conditions and utilisation events over 4 years. RESULTS: among 192 participants, 81% were male, 51% were white, the median age was 56 (range 50-74), and the median CD4 count was 508 (IQR 338-688) cells/mm3. Sixteen percent of participants had ≥1 activities of daily living (ADL) dependency, 58% had ≥1 instrumental activities of daily living IADL dependency, 43% reported ≥1 falls, 31% had cognitive impairment, and 58% had low social support. Over 4 years, 90 participants (46%) had ≥1 ER visit (total of 289 ER visits), 39 (20%) had ≥1 hospitalisation (total of 68 hospitalisations), and 15 (8%) died. In unadjusted and adjusted analyses, IADL dependency and falls were associated with healthcare utilisation (adjusted incidence rate ratios IADL (95%CI): 1.73 (1.33-2.25); falls: 1.51 (1.21-1.87)). CONCLUSION: IADL dependency and history of falls were associated with healthcare utilisation among older HIV-positive adults. Although our results are limited by sample size, improved understanding of the association between geriatric conditions and healthcare utilisation could build support for geriatric HIV care models.

Predicting skin cancer in organ transplant recipients: development of the SUNTRAC screening tool using data from a multicenter cohort study.

Skin cancer is a common post-transplant complication. In this study, the Skin and Ultraviolet Neoplasia Transplant Risk Assessment Calculator (SUNTRAC) was developed to stratify patients into risk groups for post-transplant skin cancer. Data for this study were obtained from the Transplant Skin Cancer Network (TSCN), which conducted a multicenter study across 26 transplant centers in the United States. In total, 6340 patients, transplanted from 2003 and 2008, were included. Weighted point values were assigned for each risk factor based on beta coefficients from multivariable modeling: white race (9 points), pretransplant history of skin cancer (6 points), age ≥ 50 years (4 points), male sex (2 points), and thoracic transplant (1 point). Good prognostic discrimination (optimism-corrected c statistic of 0.74) occurred with a 4-tier system: 0-6 points indicating low risk, 7-13 points indicating medium risk, 14-17 points indicating high risk, and 18-22 points indicating very high risk. The 5-year cumulative incidence of development of skin cancer was 1.01%, 6.15%, 15.14%, and 44.75%, for Low, Medium, High, and Very High SUNTRAC categories, respectively. Based on the skin cancer risk in different groups, the authors propose skin cancer screening guidelines based on this risk model.

The impact of frailty on treatment for overactive bladder in older adults.

AIMS: To examine the impact of frailty on treatment outcomes for overactive bladder (OAB) in older adults starting pharmacotherapy, onabotulinumtoxinA, and sacral neuromodulation. METHODS: This is a prospective study of men and women age ≥60 years starting pharmacotherapy, onabotulinumtoxinA, or sacral neuromodulation. Subjects were administered questionnaires at baseline and again at 1- and 3-months. Frailty was assessed at baseline using the timed up and go test (TUGT), whereby a TUGT time of ≥12 seconds was considered to be slow, or frail. Response to treatment was assessed using the overactive bladder symptom score (OABSS) and the OAB-q SF (both Bother and HRQOL subscales). Information on side effects/adverse events was also collected. Mixed effects linear modeling was used to model changes in outcomes over time both within and between groups. RESULTS: A total of 45 subjects enrolled in the study, 40% (N = 18) of whom had a TUGT ≥12 seconds. Both TUGT groups demonstrated improvement in OAB symptoms over time and there were no statistically significant differences in these responses per group (all P-values >.05). Similar trends were found for both OAB-q SF Bother and OAB-q SF HRQOL questionnaire responses. Side effects and adverse events were not significantly different between groups (all P's >.05). CONCLUSIONS: Adults ≥60 years of age starting second- and third-line treatments for OAB, regardless of TUGT time, demonstrated improvement in OAB symptoms at 3 months. These findings suggest that frail older adults may receive comparable benefit and similar rates of side effects compared with less frail older individuals.

All-cause mortality in patients with basal and squamous cell carcinoma: A systematic review and meta-analysis.

BACKGROUND: There are varying reports of the association of basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (SCC) with mortality. OBJECTIVE: To synthesize the available information on all-cause mortality after a diagnosis of BCC or SCC in the general population. METHODS: We searched PubMed (1966-present), Web of Science (1898-present), and Embase (1947-present) and hand-searched to identify additional records. All English articles that reported all-cause mortality in patients with BCC or SCC were eligible. We excluded case reports, case series, and studies in subpopulations of patients. Random effects model meta-analyses were performed separately for BCC and SCC. RESULTS: The searches yielded 6538 articles, and 156 were assessed in a full-text review. Twelve studies met the inclusion criteria, and 4 were included in the meta-analysis (encompassing 464,230 patients with BCC and with 175,849 SCC), yielding summary relative mortalities of 0.92 (95% confidence interval, 0.83-1.02) in BCC and 1.25 (95% confidence interval, 1.17-1.32) in SCC. LIMITATIONS: Only a minority of studies controlled for comorbidities. There was significant heterogeneity in meta-analysis (χ2P < .001, I2 > 98%), but studies of SCC were qualitatively concordant: all showed statistically significant increased relative mortality. CONCLUSIONS: We found that patients with SCC are at higher risk for death from any cause compared with the general population.

Impact of frailty on complications in patients undergoing common urological procedures: a study from the American College of Surgeons National Surgical Quality Improvement database.

OBJECTIVES: To evaluate the association of frailty, a measure of diminished physiological reserve, with both major and minor surgical complications among patients undergoing urological surgery. MATERIALS AND METHODS: Using data from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) from 2007 to 2013, we identified all urological cases that appeared > 1000 times in the dataset among patients aged ≥40 years. Frailty was measured using the NSQIP frailty index (FI), a validated measure that includes 11 impairments, such as decreased functional status and impaired sensorium. We created multivariable logistic regression models using the NSQIP FI to assess major and minor complications after surgery. RESULTS: We identified 95 108 urological cases representing 21 urological procedures. The average frequency of complications per individual was 11.7%, with the most common complications being hospital readmission (6.2%), blood transfusion (4.6%) and urinary tract infection (3.1%). Major and minor complications increased with increasing NSQIP FI. Frailty remained strongly associated with complications after adjustment for year, age, race, smoking status and method of anaesthesia (adjusted odds ratio 1.74 [95% confidence interval 1.64, 1.85] for an NSQIP FI ≥0.18). Increasing NSQIP FI was associated with increasing frequency of complications within age groups (by decade) up to age 81 years and across most procedures. CONCLUSION: Frailty strongly correlates with risk of postoperative complications among patients undergoing urological surgery. This finding is true within most age groups and across most urological procedures.

A randomized controlled trial to evaluate the safety and efficacy of cardiac contractility modulation in patients with moderately reduced left ventricular ejection fraction and a narrow QRS duration: study rationale and design.

Cardiac contractility modulation (CCM) signals are nonexcitatory electrical signals delivered during the cardiac absolute refractory period that enhance the strength of cardiac muscular contraction. The FIX-HF-5 study was a prospective randomized study comparing CCM plus optimal medical therapy (OMT) to OMT alone that included 428 New York Heart Association (NYHA) functional class III or IV heart failure patients with ejection fraction (EF) ≤45% according to core laboratory assessment. The study met its primary safety end point, but did not reach its primary efficacy end point: a responders analysis of changes in ventilatory anaerobic threshold (VAT). However, in a prespecified subgroup analysis, significant improvements in primary and secondary end points, including the responder VAT end point, were observed in patients with EFs ranging from 25% to 45%, who constituted about one-half of the study subjects. We therefore designed a new study to prospectively confirm the efficacy of CCM in this population. A hierarchic bayesian statistical analysis plan was developed to take advantage of the data already available from the first study. In addition, based on technical difficulties encountered in reliably quantifying VAT and the relatively large amount of nonquantifiable studies, the primary efficacy end point was changed to peak VO2, with significant measures incorporated to minimize the influence of placebo effect. In this paper, we provide the details and rationale of the FIX-HF-5C study design to study CCM plus OMT compared with OMT alone in subjects with normal QRS duration, NYHA functional class III or IV, and EF 25%-45%. This study is registered on www.clinicaltrials.gov with identifier no. NCT01381172.

Second malignant neoplasms among children, adolescents and young adults with Wilms tumor.

BACKGROUND: The goal of this study was to describe the incidence, characteristics, and outcomes of secondary malignant neoplasms (SMN) in survivors of Wilms tumor. PROCEDURES: Patients who were 0-20 years of age at time of primary diagnosis with Wilms tumor and reported to the Surveillance, Epidemiology, and End Results [SEER] program between 1973 and 2011 were eligible for inclusion in the cohort. We used competing risks methods to estimate the cumulative incidence of SMNs and assess contributing factors for developing SMN. We estimated standardized incidence ratios (SIR), absolute excess risk and overall survival after SMN using standard methods. RESULTS: Within the SEER database, 2,851 patients were diagnosed with Wilms tumor as their first malignancy. Of these, 34 patients were reported to have a SMN. Cumulative incidence of for a secondary malignancy was 0.6% (95% confidence interval [95% CI] 0.3-1.0%) at 10 years, 1.6% (95% CI 1.0-2.3%) at 20 years, and 3.8% (95% CI 2.4-5.9%) at 30 years. Median time from primary diagnosis to SMN diagnosis was 12.5 years. SIR for SMN for survivors of Wilms tumor was 3.4 (95% CI 2.2-4.9) with an absolute excess risk of 7.6 per 10,000 persons per year. Exposure to radiation did not significantly increase risk for development of second malignancy. Overall survival for patients with SMN was 64.5% at 5 years. CONCLUSION: Survivors of Wilms tumor are at an increased risk of SMN compared to the general population, but the added risk is relatively small compared to other pediatric cancers.

Breastfeeding Initiation in People With Hepatitis C Virus Infection in the United States.

OBJECTIVE: To evaluate breastfeeding initiation rates among people living with and without hepatitis C virus (HCV) infection during pregnancy and to identify characteristics associated with breastfeeding initiation. METHODS: We conducted a cross-sectional analysis of individuals who had a live birth in the United States from 2016 to 2021 using the National Center for Health Statistics birth certificate data. We grouped participants by whether they had HCV infection during pregnancy. Using propensity-score matching, we assessed the association between breastfeeding initiation before hospital discharge , defined as neonates receiving any parental breast milk or colostrum, and HCV infection during pregnancy in a logistic regression model. We also assessed factors associated with breastfeeding initiation among those with HCV infection. RESULTS: There were 96,896 reported cases (0.5%) of HCV infection among 19.0 million births that met inclusion criteria during the study period. Using propensity-score matching, we matched 87,761 individuals with HCV infection during pregnancy with 87,761 individuals without HCV infection. People with HCV infection during pregnancy were less likely to initiate breastfeeding compared with those without HCV infection (51.5% vs 64.2%, respectively; odds ratio 0.59, 95% CI, 0.58-0.60, P <.001). Characteristics associated with higher rates of breastfeeding initiation among individuals with HCV infection included a college degree (adjusted odds ratio [aOR] 1.22, 95% CI, 1.21-1.24); self-identified race or ethnicity as Native Hawaiian or Pacific Islander (aOR 1.22, 95% CI, 1.06-1.40), Asian (aOR 1.09, 95% CI, 1.06-1.13), or Hispanic (aOR 1.09, 95% CI, 1.08-1.11); private insurance (aOR 1.07, 95% CI, 1.06-1.08); nulliparity (aOR 1.09, 95% CI, 1.08-1.10), and being married (aOR 1.08, 95% CI, 1.07-1.09). Characteristics associated with not breastfeeding before hospital discharge included receiving no prenatal care (aOR 0.81, 95% CI, 0.79-0.82), smoking during pregnancy (aOR 0.88, 95% CI, 0.88-0.89), and neonatal intensive care unit admission (aOR 0.92, 95% CI, 0.91-0.93). CONCLUSION: Despite leading health organizations' support for people living with HCV infection to breastfeed, our study demonstrates low breastfeeding initiation rates in this population. Our findings highlight the need for tailored breastfeeding support for people with HCV infection and for understanding the additional effects of human immunodeficiency virus (HIV) co-infection, HCV treatment, and concurrent substance use disorders on breastfeeding initiation.

Use of Muscle Relaxants After Surgery in Traditional Medicare Part D Enrollees.

BACKGROUND: Surgeons have come under increased scrutiny for postoperative pain management, particularly for opioid prescribing. To decrease opioid use but still provide pain control, nonopioid medications such as muscle relaxants are being used, which can be harmful in older adults. However, the prevalence of muscle relaxant prescribing, trends in use over time, and risk of prolonged use are unknown. STUDY DESIGN: Using a 20% representative Medicare sample, we conducted a retrospective analysis of muscle relaxant prescribing to patients ≥ 65 years of age. We merged patient data from Medicare Carrier, MedPAR, and Outpatient Files with Medicare Part D for the years 2013-2018. A total of 14 surgical procedures were included to represent a wide range of anatomic regions and specialties. RESULTS: The study cohort included 543,929 patients. Of the cohort, 8111 (1.5%) received a new muscle relaxant prescription at discharge. Spine procedures accounted for 12% of all procedures but 56% of postoperative prescribing. Overall, the rate of prescribing increased over the time period (1.4-2.0%, p < 0.001), with increases in prescribing primarily in the spine (7-9.6%, p < 0.0001) and orthopedic procedure groups (0.9-1.4%, p < 0.0001). Of patients discharged with a new muscle relaxant prescription, 10.7% had prolonged use. CONCLUSIONS: The use of muscle relaxants in the postoperative period for older adults is low, but increasing over time, especially in ortho and spine procedures. While pain control after surgery is crucial, surgeons should carefully consider the risks of muscle relaxant use, especially for older adults who are at higher risk for medication-related problems.

Attitudes on participation in clinical drug trials: A nationally representative survey of older adults with multimorbidity.

BACKGROUND: Older adults with multimorbidity are under-represented in clinical drug trials. Their inclusion will not increase unless they are willing and able to participate. Data on motivators and barriers to participation in trials of new medications of older adults with multimorbidity are needed. METHODS: Cross-sectional internet and telephone survey of a nationally representative sample of adults ≥65 years with ≥3 chronic conditions (NORC University of Chicago Amerispeak Panel) conducted from March-April, 2023 to determine motivators and barriers to drug trial participation, described graphically and using statistics. RESULTS: Surveyed 1318 (1142 Internet, 176 phone) with mean age 72.3 ± 6.3 (SD), 52% women; race: 83% White, 10% Black or African American, 5% Hispanic or Latino, 1.1% Asian; 4.4 ± 1.9 chronic conditions (of 16 queried), taking 7.5 ± 3.3 medications. Barriers included fear of side effects (48%), taking too many medications (44%), placebo (44%), mobility (33%), bathroom needs (25%), hearing (19%), eyesight (15%), video visits (33%; higher in women, Black or African-American respondents, and those ≥80 years). Sixty-five percent would join all in-person trials, 49% would join all-video trials. Travel >1 h was difficult for 66%, most difficult for women. Trust was a concern in 25% of Black respondents. Caregiving responsibilities or lack of time were not obstacles. Participants were most likely to consider a drug trial for a problem they have (63%) versus prevention (44%) and if invited by a physician (80%) or University healthcare system (58%). Getting better care was ranked very important (79%) followed by helping others (57%). CONCLUSIONS: Major concerns of older patients with multimorbidity about participation in drug trials are potential side effects, taking too many medicines, and video visits. Physicians have the greatest influence on decisions and in-person visits are preferred. Proposed changes in trial design to increase enrollment of under-represented older adults may not align with patient-reported preferences.

Resilience, Survival, and Functional Independence in Older Adults Facing Critical Illness.

BACKGROUND: Older adults surviving critical illness often experience new or worsening functional impairments. Modifiable positive psychological constructs such as resilience may mitigate post-intensive care morbidity. RESEARCH QUESTION: Is pre-ICU resilience associated with: (1) post-ICU survival; (2) the drop in functional independence during the ICU stay; or (3) the trend in predicted independence before vs after the ICU stay? STUDY DESIGN AND METHODS: This retrospective cohort study was performed by using Medicare-linked Health and Retirement Study surveys from 2006 to 2018. Older adults aged ≥ 65 years admitted to an ICU were included. Resilience was calculated prior to ICU admission. The resilience measure was defined from the Simplified Resilience Score, which was previously adapted and validated for the Health and Retirement Study. Resilience was scored by using the Leave-Behind survey normalized to a scale from 0 (lowest resilience) to 12 (highest resilience). Outcomes were survival and probability of functional independence. Survival was modeled by using Gompertz models and independence using joint survival models adjusting for sociodemographic and clinical variables. Average marginal effects were estimated to determine independence probabilities. RESULTS: Across 3,409 patients aged ≥ 65 years old admitted to ICUs, preexisting frailty (30.5%) and cognitive impairment (24.3%) were common. Most patients were previously independent (82.7%). Mechanical ventilation occurred in 14.8% and sepsis in 43.2%. Those in the highest resilience group (vs lowest resilience) had a lower risk of post-ICU mortality (adjusted hazard ratio, 0.81; 95% CI, 0.70-0.94). Higher resilience was associated with greater likelihood of post-ICU functional independence (estimated probability of functional independence 5 years after ICU discharge in highest-to-lowest resilience groups (adjusted hazard ratio [95% CI]): 0.53 (0.33-0.74), 0.47 (0.26-0.68), 0.49 (0.28-0.70), and 0.36 (0.17-0.55); P < .01. Resilience was not associated with a difference in the drop in independence during the ICU stay or a difference in the pre-ICU vs post-ICU trend in predicted independence . INTERPRETATION: ICU survivors with higher resilience had increased rates of survival and functional independence, although the slope of functional decline before vs after the ICU stay did not differ according to resilience group.

Estimating Vitamin K Antagonist Anticoagulation Benefit in People With Atrial Fibrillation Accounting for Competing Risks: Evidence From 12 Randomized Trials.

BACKGROUND: Patients with atrial fibrillation have a high mortality rate that is only partially attributable to vascular outcomes. The competing risk of death may affect the expected anticoagulant benefit. We determined if competing risks materially affect the guideline-endorsed estimate of anticoagulant benefit. METHODS: We conducted a secondary analysis of 12 randomized controlled trials that randomized patients with atrial fibrillation to vitamin K antagonists (VKAs) or either placebo or antiplatelets. For each participant, we estimated the absolute risk reduction (ARR) of VKAs to prevent stroke or systemic embolism using 2 methods-first using a guideline-endorsed model (CHA2DS2-VASc) and then again using a competing risk model that uses the same inputs as CHA2DS2-VASc but accounts for the competing risk of death and allows for nonlinear growth in benefit. We compared the absolute and relative differences in estimated benefit and whether the differences varied by life expectancy. RESULTS: A total of 7933 participants (median age, 73 years, 36% women) had a median life expectancy of 8 years (interquartile range, 6-12), determined by comorbidity-adjusted life tables and 43% were randomized to VKAs. The CHA2DS2-VASc model estimated a larger ARR than the competing risk model (median ARR at 3 years, 6.9% [interquartile range, 4.7%-10.0%] versus 5.2% [interquartile range, 3.5%-7.4%]; P<0.001). ARR differences varied by life expectancies: for those with life expectancies in the highest decile, 3-year ARR difference (CHA2DS2-VASc model - competing risk model 3-year risk) was -1.3% (95% CI, -1.3% to -1.2%); for those with life expectancies in the lowest decile, 3-year ARR difference was 4.7% (95% CI, 4.5%-5.0%). CONCLUSIONS: VKA anticoagulants were exceptionally effective at reducing stroke risk. However, VKA benefits were misestimated with CHA2DS2-VASc, which does not account for the competing risk of death nor decelerating treatment benefit over time. Overestimation was most pronounced when life expectancy was low and when the benefit was estimated over a multiyear horizon.