Representation of women in clinical trials supporting FDA-approval of contemporary cancer therapies.

Contemporary anticancer therapies frequently have different efficacy and side effects in men and women. Yet, whether women are well-represented in pivotal trials supporting contemporary anticancer drugs is unknown. Leveraging the Drugs@FDA database, clinicaltrials.gov, MEDLINE, and publicly available FDA-drug-reviews, we identified all pivotal (phase II and III) non-sex specific trials supporting FDA-approval of anticancer drugs (1998-2018). Observed-enrollment-rates were compared to expected-population-rates derived from concurrent US-National-Cancer-Institute's Surveillance-Epidemiology-and-End-Results (SEER) reported rates and US-Census databases. Primary outcome was the proportional representation of women across trials, evaluated by a participation-to-prevalence ratio (PPR), according to cancer type. Secondary outcome was the report of any sex-specific analysis of efficacy and/or safety, irrespective of treatment-arm. Overall, there were 148 trials, enrolling 60,216 participants (60.5 ± 4.0 years, 40.7% female, 79.1% biologic, targeted, or immune-based therapies) evaluating 99 drugs. Sex was reported in 146 (98.6%) trials, wherein 40.7% (24,538) were women, compared to 59.3% (35,678) men (p < .01). Altogether, women were under-represented in 66.9% trials compared to the proportional incidence of cancers by respective disease type; weight-average PPR of 0.91 (relative difference: -9.1%, p < .01). Women were most under-represented in gastric (PPR = 0.63), liver (PPR = 0.71), and lung (PPR = .81) cancer trials. Sex-based safety data was reported in 4.0% trials. There was no association between adequate female enrollment and drug efficacy (HR: 0.616 vs. 0.613, p = .96). Over time, there was no difference in the percentage of women recruited into clinical trials. Among pivotal clinical trials supporting contemporary FDA-approved cancer drugs, women were frequently under-represented and sex-specific-efficacy and safety-outcomes were commonly not reported.

Database analysis comparing incidence and complication rates between inpatient and outpatient laminotomies for lumbar disc herniation.

Background: Lumbar disc herniation (LDH) is a common condition that can be characterized with disabling pain. While most patients recover without surgery, some still require operative intervention. The epidemiology and trends of laminotomy for LDH have not been recently studied, and current practice patterns might be different from historical norms. This study aimed to investigate the trends of inpatient and outpatient laminotomies for LDH and compare complication rates between these two sites of service. Methods: A large, national database was utilized to identify patients > 8 years old who underwent a laminotomy for LDH between 2009 and 2019. Two cohorts were created based on site of surgery: inpatient versus outpatient. The outpatient cohort was defined as patients who had a length of stay less than 1 day without any associated hospitalization. Epidemiologic analyses for these cohorts were performed by demographics. Patients in both groups were then 1:1 propensity-score matched based on age, sex, insurance type, geographic region, and comorbidities. Ninety-day postoperative complications were compared between cohorts utilizing multivariate logistic regressions. Results: The average incidence of laminotomy for LDH was 13.0 per 10,000 persons-years. Although the national trend in incidence had not changed from 2009 to 2019, the proportion of outpatient laminotomies significantly increased in this time period (p=.02). Outpatient laminotomies were more common among younger and healthier patients. Patients with inpatient laminotomies had significantly higher rates of surgical site infections (odds ratio [OR] 1.61, p<.001), venous thromboembolism (VTE) (OR 1.96, p<.001), hematoma (OR 1.71, p<.001), urinary tract infections (OR 1.41, p<.001), and acute kidney injuries (OR 1.75, p=.001), even when controlling for selected confounders. Conclusions: Our study demonstrated an increasing trend in the performance of laminotomy for LDH toward the outpatient setting. Even when controlling for certain confounders, patients requiring inpatient procedures had higher rates of postoperative complications. This study highlights the importance of carefully evaluating the advantages and disadvantages of performing these procedures in an outpatient versus inpatient setting.

Outcomes of Total Hip Arthroplasty in Patients Who Have Ehlers-Danlos Syndrome: A Matched Cohort Study.

INTRODUCTION: Total hip arthroplasty (THA) is an effective surgical treatment for severe osteoarthritis of the hip. While THA is considered a reliable and safe procedure, outcome data on patients who have Ehlers-Danlos syndrome (EDS) is limited. The purpose of this study was to compare rates of postoperative complications after primary THA in patients who have EDS against matched controls. METHODS: A large national database was searched to identify patients who underwent THA between 2009 and 2020. Patients younger than 18 years, who had a history of prior THA, and who were undergoing THA for a hip fracture were excluded from analysis. Propensity score matching was utilized to match patients who had EDS with patients who did not have EDS at a 1:4 ratio. Rates of medical and surgical complications at 90 days and 2 years were queried and compared between the cohorts using multivariable logistic regression. We identified 118 patients who had EDS and underwent primary THA, who were then matched with 418 controls. RESULTS: At 90 days, the EDS cohort had greater rates of dislocation (8.5 versus 3.8%, P = 0.038). At 2 years, the EDS cohort had greater odds of dislocation (OR [odds ratio] 2.47, P = 0.018), aseptic loosening (OR 6.91, P = 0.002), and aseptic revision (OR 2.66, P = 0.02). CONCLUSION: Patients who have EDS possess significantly higher odds of complications after THA compared to matched controls, including dislocation, aseptic loosening, and aseptic revision. Careful surgical planning in these patients should be made to prevent dislocation and potentially minimize the risk of other prosthesis-related complications leading to revision.

Outcomes of Total Knee Arthroplasty in Patients Who Have Ehlers-Danlos Syndrome: A Matched Cohort Study.

BACKGROUND: Total knee arthroplasty (TKA) is an excellent surgical option for patients who have end-stage knee osteoarthritis. While rates of major postoperative complications have steadily decreased with modern implants and operative techniques, contemporary outcome data for patients who have Ehlers-Danlos syndrome (EDS) are scarce. The goal of this study was to compare complication rates after primary TKA in patients who have EDS versus matched controls. METHODS: A large administrative database was used to identify patients who underwent primary TKA from 2009 to 2020. Patients who had a diagnosis of EDS were identified by International Classification of Diseases Coding. Propensity scores were utilized to match these patients with controls at a 1:4 ratio based on age, sex, and various comorbidities. Multivariable logistic regression analysis was used to compare the rates of medical and surgical complications at 90 days and 2 years. A total of 188 patients who had EDS and 752 controls were included in this study. RESULTS: After univariate analysis, Ehlers-Danlos patients exhibited significantly higher rates of wound complications (4.8 versus 0.9%, P = .001) at 90 days. When adjusted for comorbidities, Ehlers-Danlos patients still exhibited significantly increased odds of developing wound complications (odds ratio: 7.06; P < .001). CONCLUSIONS: Patients who have EDS undergoing TKA exhibited significantly higher rates of wound complications within 90 days postoperatively compared to matched controls. Rates of instability, manipulation under anesthesia, periprosthetic joint infection, aseptic loosening, and aseptic revision arthroplasty did not significantly differ between the cohorts. This study found generally favorable short-term outcomes of TKA in this population; however, the inability to control for implant type and other confounding variables may have influenced the lack of difference in complication rates at 2 years. Surgeons should monitor for the potentially increased risk of wound complications and consider the possible need for increased constraint in this population during preoperative planning.

Early Versus Late Periprosthetic Joint Infection After Total Knee Arthroplasty: Do Patient Differences Exist?

BACKGROUND: Periprosthetic joint infection (PJI) is a devastating complication following total knee arthroplasty (TKA). Little evidence exists comparing those with early versus late PJI. The purpose of the study was to determine comorbidity profile differences between patients developing early and late PJI. METHODS: There were 72,659 patients undergoing primary TKA from 2009 to 2021, who were identified from a commercial claims and encounters database. Subjects diagnosed with PJI were categorized as either 'early' (within 90 days of index procedure) or 'late' (> 2 years after index arthroplasty). Non-infected patients within these periods served as control groups following 4:1 propensity score matching on other extraneous variables. Logistic regression analyses were performed comparing comorbidities between groups. RESULTS: Patients were significantly younger in the late compared to the early infection group (58.1 versus 62.4 years, P < .001). When compared to those with early PJI, patients who had chronic kidney disease (13.3 versus 4.1%; OR [odds ratio] 5.17, P = .002), malignancy (20.4 versus 10.5%; OR 2.53, P = .009), uncomplicated diabetes (40.8 versus 30.6%; OR 2.00, P = .01), rheumatoid arthritis (9.2 versus 3.3%; OR 2.66, P = .046), and hypertension (88.8 versus 81.6%; OR 2.17, P = .04), were all significant predictors of developing a late PJI. CONCLUSIONS: When compared to patients diagnosed with early PJI following primary TKA, the presence of chronic kidney disease, malignancy, uncomplicated diabetes, rheumatoid arthritis, and hypertension, were independent risk factors for the development of late PJI. Younger patients who have these comorbidities may be targets for preoperative optimization interventions that minimize the risk of PJI.

General surgery textbooks and surgical disparities.

INTRODUCTION: Some academic textbooks have previously disseminated simplistic or even incorrect conceptions of race. Propagation of such ideas in General Surgery could contribute to gaps in quality of care received by minority patients. This study aims to determine whether General Surgery textbooks provide a thorough understanding of racial disparities. METHODS: General Surgery texts were drawn from Doody's list, an industry-standard list of textbooks for medical education. Technical guides, atlases, and books for non-General Surgery professionals were excluded. Passages mentioning medical differences amongst racial and ethnic groups were extracted. Six binary classifications were made, based on whether passages (a) described interventions to alleviate difference; (b) addressed environmental mediators of difference; (c) described the contribution of racism or discrimination; (d) used causal language to connect race to difference; (e) referred to known, heritable genetic mechanisms; and (f) directly provided a reference. Types of intervention were also extracted. A heuristic scale was calculated granting one point each for classifications a-c and losing one point for classification d. Three authors performed classifications, and raw agreement and Cohen's kappa were used to assess inter-rater reliability. RESULTS: Thirteen textbooks from Doody's list contained 511 passages discussing medical differences among racial/ethnic groups. Among passages, 25% discussed white people, 22% Black people/African Americans, 19% Asians, 9% Latinos, 4% Jewish/Ashkenazi people, 3% Native Americans, and 18% other. Fifteen passages (2.9%) used language indicating race was the cause of medical difference, and only two explicitly discussed racism or discrimination. Most passages (370, 72.3%) received a scale of 0. 120 (23.5%) received a scale of 1, eight (1.2%) received a scale of 2, and zero received a scale of 3. The mean passage scale was 0.24 and is not changing with time (regression coefficient -0.006/year, p = 0.538). Agreement was 91.2% across all categories and overall Kappa was 0.62. CONCLUSIONS: General Surgery textbooks do not provide readers with scientifically thorough understanding of health disparities. Teaching more comprehensive conceptions, including systemic causes and the role of racism, may prevent reflexive association of minority patients with poor outcomes. Future editions should include these details where disparities are discussed in an independent, comprehensive section.