Citations

AbstractBackgroundBRCA1 methylation has been associated with homologous recombination deficiency, a biomarker of platinum sensitivity. Studies evaluating BRCA1-methylated tubal and ovarian cancer (OC) do not consistently support improved survival following platinum chemotherapy. We examine the characteristics of BRCA1-methylated OC in a meta-analysis of individual participant data.MethodsData of 2636 participants across 15 studies were analyzed. BRCA1-methylated tumors were defined according to their original study. Associations between BRCA1 methylation and clinicopathological characteristics were evaluated. The effects of methylation on overall survival (OS) and progression-free survival (PFS) were examined using mixed-effects models. All statistical tests were 2-sided.Results430 (16.3%) tumors were BRCA1-methylated. BRCA1 methylation was associated with younger age and advanced-stage, high-grade serous OC. There were no survival differences between BRCA1-methylated and non–BRCA1-methylated OC (median PFS = 20.0 vs 18.5 months, hazard ratio [HR] = 1.01, 95% CI = 0.87 to 1.16; P = .98; median OS = 46.6 vs 48.0 months, HR = 1.02, 95% CI = 0.87 to 1.18; P = .96). Where BRCA1/2 mutations were evaluated (n = 1248), BRCA1 methylation displayed no survival advantage over BRCA1/2-intact (BRCA1/2 wild-type non–BRCA1-methylated) OC. Studies used different methods to define BRCA1 methylation. Where BRCA1 methylation was determined using methylation-specific polymerase chain reaction and gel electrophoresis (n = 834), it was associated with improved survival (PFS: HR = 0.80, 95% CI = 0.66 to 0.97; P = .02; OS: HR = 0.80, 95% CI = 0.63 to 1.00; P = .05) on mixed-effects modeling.ConclusionBRCA1-methylated OC displays similar clinicopathological features to BRCA1-mutated OC but is not associated with survival. Heterogeneity within BRCA1 methylation assays influences associations. Refining these assays may better identify cases with silenced BRCA1 function and improved patient outcomes.

AbstractBackgroundGaps exist in our understanding of the clinical course of pouch-related disorders.MethodsWe evaluated baseline disease activity and longitudinal treatment patterns among patients with inflammatory conditions of the pouch.ResultsAmong 468 patients with an ileal pouch-anal anastomosis (IPAA), 94 (20%) had acute pouchitis, 96 (21%) had chronic pouchitis, and 192 (41%) had Crohn disease of the pouch. Following an IPAA, 38% of patients were treated with a biologic and 11% underwent inflammatory bowel disease- or bowel-related surgery.ConclusionsTreatment patterns after IPAA indicate that pouch-related disorders have a significant impact on individual patients and the healthcare system.

Abstract Aims To determine the extent of shared decision-making (SDM), during selection of oral anticoagulant (OAC) and rhythm control treatments, in patients with newly diagnosed atrial fibrillation (AF). Methods and results We evaluated survey data from 1006 patients with new-onset AF enrolled at 56 US sites participating in the SATELLITE substudy of the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT II). Patients completed surveys at enrolment and at 6-month follow-up. Patients were asked about who made their AF treatment decisions. Shared decision-making was classified as one that the patient felt was an autonomous decision or a shared decision with their healthcare provider (HCP). Approximately half of patients reported that their OAC treatment decisions were made entirely by their HCP. Compared with those reporting no SDM, patients reporting SDM for OAC were more often female (47.2% vs. 38.4%), while patients reporting SDM for rhythm control were more often male (62.2% vs. 57.6%). The most important factors cited by patients during decision-making for OAC were reducing stroke and bleeding risk, and their HCP’s recommendations. After adjustment, patients with self-reported understanding of OAC, and rhythm control options, had higher odds of having participated in SDM [odds ratio (OR) 2.54, confidence interval (CI): 1.75–3.68 and OR 2.36, CI: 1.50–3.71, both P ≤ 0.001, respectively]. Conclusion Shared decision-making is not widely implemented in contemporary AF practice. Patient understanding about available therapeutic options is associated with a more than a two-fold higher likelihood of SDM, and may be a potential target for future interventions.

Abstract Objectives The association of bipolar disorder with early and excessive cardiovascular disease was identified over a century ago. Nonetheless, the vascular‐bipolar link remains underrecognized, particularly with regard to how this link can contribute to our understanding of pathogenesis and treatment. Methods An international group of experts completed a selective review of the literature, distilling core themes, identifying limitations and gaps in the literature, and highlighting future directions to bridge these gaps. Results The association between bipolar disorder and vascular disease is large in magnitude, consistent across studies, and independent of confounding variables where assessed. The vascular‐bipolar link is multifactorial and is difficult to study given the latency between the onset of bipolar disorder, often in adolescence or early adulthood, and subsequent vascular disease, which usually occurs decades later. As a result, studies have often focused on risk factors for vascular disease or intermediate phenotypes, such as structural and functional vascular imaging measures. There is interest in identifying the most relevant mediators of this relationship, including lifestyle (eg, smoking, diet, exercise), medications, and systemic biological mediators (eg, inflammation). Nonetheless, there is a paucity of treatment studies that deliberately engage these mediators, and thus far no treatment studies have focused on engaging vascular imaging targets. Conclusions Further research focused on the vascular‐bipolar link holds promise for gleaning insights regarding the underlying causes of bipolar disorder, identifying novel treatment approaches, and mitigating disparities in cardiovascular outcomes for people with bipolar disorder.

Background: Hip arthroscopy has been previously demonstrated to be an effective treatment for adult mild hip dysplasia. There are many radiographic parameters used to classify hip dysplasia, but to date few studies have demonstrated which parameters are of most importance for predicting surgical outcomes. Purpose: To identify preoperative radiographic parameters that are associated with poor outcomes in the arthroscopic treatment of adult mild hip dysplasia. Study Design: Case-control study; Level of evidence, 3. Methods: Radiographic analysis was performed in patients with mild hip dysplasia who underwent arthroscopic surgery between 2009 and 2015. Preoperative radiographic measurements included lateral center edge angle, Tönnis angle, neck shaft angle, anterior center edge angle, alpha angle, femoral head extrusion index, and acetabular depth-to-width ratio. Failure was defined as failure to achieve the minimal clinically important difference (MCID) utilizing the modified Harris Hip Score or as the need for secondary operation. The equal variance t test was used to analyze radiographic parameters. Statistical significance was determined using a P value of .05. Results: A total of 373 hips underwent analysis with an average follow-up of 41 months (range, 24-102 months). Of these, 46 hips (12%) required secondary operation, and 95 (25%) failed to meet the MCID. The overall failure rate was 32.4%. There was no single measurement or combination thereof associated with failure to reach the MCID. Higher preoperative Tönnis angles were associated with secondary operation, with a mean of 6.7° (95% CI, 5.3°-8.1°) in the secondary operation group versus 4.8° (95% CI, 4.4°-5.3°) in the nonsecondary operation group ( P = .006). The odds ratio was 1.12 (95% CI, 1.0-1.2; P = .05) per degree increase in Tönnis angle for secondary operation. In patients with a Tönnis angle >10°, 84% required secondary operation. Conclusion: Higher Tönnis angles portend a higher risk for revision surgery. The probability of secondary operation was increased by a magnitude of 1.12 with each degree increase in the Tönnis angle. In patients with a Tönnis angle >10°, 84% required a secondary operation.

Purpose To assess whether labral size is predictive of labral repair failure or shows an association with patient outcomes after hip arthroscopy. Methods We performed a retrospective chart review of patients who underwent arthroscopic hip labral repair. Labral size was measured in 4 quadrants with an arthroscopic probe. The average size across torn labral segments was assessed for failure as determined by the change in patient‐reported outcomes, the rate at which subjects achieved the minimal clinically important difference and patient acceptable symptomatic state, and the need for additional surgery. Outcomes were evaluated for any continuous correlation as well as significant differences between the middle 50% of labral sizes and classes of labral sizes derived from upper and lower quartile and decile ranges. Included hips were those from patients aged between 18 and 55 years with 2‐year postoperative follow‐up and lateral center‐edge angles between 25° and 40°. Results The study included 571 hips. Labral width did not show a significant difference between hips requiring revision and those not requiring revision ( P = .4054). No significant correlation was found between labral width and the change in the International Hip Outcome Tool 12 score ( R 2 = 0.05780), modified Harris Hip Score ( R 2 = 0.19826), or Nonarthritic Hip Score ( R 2 = 0.23543) from preoperatively to 2 years postoperatively. Hips with labral sizes in the upper decile of our cohort showed significantly decreased improvement in the International Hip Outcome Tool 12 score ( P = .0287) and Nonarthritic Hip Score ( P = .0490) compared with the middle 50% of labral sizes. No statistically significant difference was found in the rate at which the groups achieved the minimal clinically important difference or patient acceptable symptomatic state. Conclusions Hypertrophic labra in the largest 10th percentile showed lower postoperative outcome scores. However, no detectable clinical benefit was found in terms of patient‐perceived clinical difference or acceptable symptomatic state. For most patients, labral size does not appear to significantly alter patient outcomes or the need for arthroplasty. Level of Evidence Level IV, retrospective case series.

Background Past research in population health trends has shown that injuries form a substantial burden of population health loss. Regular updates to injury burden assessments are critical. We report Global Burden of Disease (GBD) 2017 Study estimates on morbidity and mortality for all injuries. Methods We reviewed results for injuries from the GBD 2017 study. GBD 2017 measured injury-specific mortality and years of life lost (YLLs) using the Cause of Death Ensemble model. To measure non-fatal injuries, GBD 2017 modelled injury-specific incidence and converted this to prevalence and years lived with disability (YLDs). YLLs and YLDs were summed to calculate disability-adjusted life years (DALYs). Findings In 1990, there were 4 260 493 (4 085 700 to 4 396 138) injury deaths, which increased to 4 484 722 (4 332 010 to 4 585 554) deaths in 2017, while age-standardised mortality decreased from 1079 (1073 to 1086) to 738 (730 to 745) per 100 000. In 1990, there were 354 064 302 (95% uncertainty interval: 338 174 876 to 371 610 802) new cases of injury globally, which increased to 520 710 288 (493 430 247 to 547 988 635) new cases in 2017. During this time, age-standardised incidence decreased non-significantly from 6824 (6534 to 7147) to 6763 (6412 to 7118) per 100 000. Between 1990 and 2017, age-standardised DALYs decreased from 4947 (4655 to 5233) per 100 000 to 3267 (3058 to 3505). Interpretation Injuries are an important cause of health loss globally, though mortality has declined between 1990 and 2017. Future research in injury burden should focus on prevention in high-burden populations, improving data collection and ensuring access to medical care.

Background Previous reports have described a leveling off of mortality from premature coronary artery disease (CAD). In recent years, the prevalence of cardiovascular risk factors has increased in rural communities and young adults. Methods and Results We extracted CAD mortality rates from the Centers for Disease Control and Prevention Wide‐Ranging Online Data for Epidemiologic Research (CDC WONDER) database from 1999 to 2017, focusing on mortality from premature CAD (defined as <65 years of age in women) and urban–rural differences. Variations in mortality rates over time, assessed with Joinpoint regression modeling, are expressed as estimated annual percentage change (95% CI) and stratified by urbanization, sex, age, and race. Age‐adjusted mortality rates decreased for women and men. Stratification by urbanization revealed that premature CAD mortality is stagnating among women in rural areas. However, this stagnation conceals a statistically significant increase in CAD mortality rates since 2009 in women aged 55 to 64 years (estimated annual percentage change: +1.4%; 95% CI, +0.3% to +2.5%) and since 1999 in women aged 45 to 54 years (estimated annual percentage change: +0.6%; 95% CI, +0.2% to 1.0%). Since 1999, mortality has been stagnating in the youngest group (aged 35–44 years; estimated annual percentage change: +0.2%; 95% CI, −0.4% to +0.8%). Stratification by race indicated an increase in mortality rates among white rural women. Premature CAD mortality remains consistently higher in the rural versus urban United States, regardless of sex, race, and age group. Conclusions Premature CAD mortality rates have declined over time. However, stratification by sex and urbanization reveals disparities that would otherwise remain concealed: CAD mortality rates have increased among women from rural areas since at least 2009.