Citations

Background TAILOR‐PCI (Tailored Antiplatelet Initiation to Lessen Outcomes due to decreased Clopidogrel Response After Percutaneous Coronary Intervention) studied genotype‐guided selection of antiplatelet therapy after percutaneous coronary intervention versus conventional therapy with clopidogrel. The presence of CYP2C19 loss‐of‐function alleles in patients treated with clopidogrel may be associated with increased risk for ischemic events. We report a prespecified sex‐specific analysis of genotyping and associated cardiovascular outcomes from this study. Methods and Results Associations between sex and major adverse cardiac events (MACE: cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia) and Bleeding Academic Research Consortium (BARC) bleeding at 12 months were analyzed using Cox proportional‐hazards models. Among 5276 randomized patients, loss‐of‐function carriers were observed in ≈36% of both sexes, and >80% of carriers were heterozygotes. At 12 months, after adjustment for baseline differences, risks of MACE (HR , 1.28 [0.97 to 1.68]; P =0.088) and BARC bleeding (hazard ratio [HR], 1.36 [0.91 to 2.05]; P =0.14) were comparable among women and men. There were no significant interactions between sex and treatment strategy for MACE interaction P value ( P int =0.59) or BARC bleeding ( P int =0.47) nor for sex and genotype (MACE P int =0.15, and BARC bleeding P int =0.60). Conclusions CYP2C19 loss‐of‐function alleles were present in ≈1 in 3 women and men. Women had similar adjusted risks of MACE and bleeding as men following percutaneous coronary intervention. Genotype‐guided therapy did not significantly reduce the risk of MACE or bleeding relative to conventional therapy for both sexes. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01742117.

Objective: This study is a follow-up to a study in 2020 that reviewed changes in the racial and ethnic composition of public health students, graduates, and faculty among Association of Schools and Programs of Public Health (ASPPH)–member institutions. In the current study, we evaluated how the racial and ethnic composition among biostatistics and epidemiology students, graduates, and faculty changed from 2010 to 2020. Methods: We analyzed data on race and ethnicity of enrolled graduate students, graduates (master’s and doctoral), and faculty at ASPPH-member institutions by using institutionally reported data from the ASPPH Data Center. We tabulated frequencies, percentages, and percentage-point changes by race and ethnicity. We measured differences between groups by using a test for difference in 2 proportions. Results: The number of enrolled students, graduates, and faculty in all departments increased during the study period, while the number of tenure-track faculty in biostatistics decreased. The percentage of enrolled Hispanic/Latino biostatistics graduate students increased from 5.6% in 2010 to 10.2% in 2020 ( P = .007), and the percentage of epidemiology graduates increased from 8.8% to 13.8% ( P = .008). We found no differences among other underrepresented racial and ethnic groups. Most biostatistics and epidemiology professors at all ranks were non-Hispanic White, despite substantial decreases. The percentage of underrepresented racial and ethnic minority biostatistics and epidemiology professors was constant across all ranks. Conclusion: Although more Hispanic/Latino students are enrolled in and graduating from biostatistics and epidemiology departments at ASPPH-member institutions, we found no change among faculty. More work is needed to recruit and retain other (American Indian/Alaska Native, Black or African American, Native Hawaiian/Other Pacific Islander) underrepresented students and faculty.

Abstract A discussion and debate on the American Medical Informatics Association’s (AMIA) Ethical, Legal, and Social Issues (ELSI) Working Group listserv in 2021 raised important issues related to a forthcoming conference in Texas. Texas had recently enacted a restrictive abortion law and restricted voting rights. Several AMIA members advocated for a boycott of the state and the scheduled conference. The discussion led the AMIA Board of Directors to request that the organization’s Ethics Committee provide general guidance for principle-based venue selection. This document recommends overarching principles for the venue selection for future AMIA events and conferences. Discussions by the AMIA Board, the Ethics Committee, and the ELSI Working Group informed these recommendations, and this document on guiding principles was approved by the AMIA Board of Directors in April 2022.

BACKGROUND: The Institute of Medicine best practice recommendation to review guidelines every 5 years is followed by the Congress of Neurological Surgeons Guidelines Committee. The aim of this work was to provide an updated literature review and evidence-based recommendations on the topic of diagnosis and treatment of patients with progressive glioblastoma (pGBM). OBJECTIVE: To review the literature published since the last guidelines on pGBM dated 2014, with literature search ending in June 2012. METHODS: PubMed, Embase, and Cochrane were searched for the period July 1, 2012, to March 31, 2019, using search terms and search strategies to identify pertinent abstracts. These were then screened using published exclusion/inclusion criteria to identify full-text review articles. Evidence tables were constructed using data derived from full-text reviews and recommendations made from the evidence derived. RESULTS: From the total 8786 abstracts identified by the search, 237 full-text articles met inclusion/exclusion criteria and were included in this update. Two new level II recommendations derived from this work. For the diagnosis of patients with GBM, the use of diffusion-weighted images is recommended to be included in the magnetic resonance images with and without contrast used for surveillance to detect pGBM. For the treatment of patients with pGBM, repeat cytoreductive surgery is recommended to improve overall survival. An additional 21 level III recommendations were provided. CONCLUSION: Recent published literature provides new recommendations for the diagnosis and treatment of pGBM. The Central Nervous System Guidelines Committee will continue to pursue timely updates to further improve the care of patients with diagnosis. https://www.cns.org/guidelines/browse-guidelines-detail/guidelines-management-of-progressive-glioblastoma

Objective: Studies on low-grade serous ovarian cancer (LGSC) are limited by a low number of cases. The aim of this study was to define the prognostic significance of age, stage, and CA-125 levels on survival in a multi-institutional cohort of women with pathologically confirmed LGSC. Methods: Women with LGSC were identified from the collaborative Ovarian Cancer Association Consortium (OCAC). Cases of newly diagnosed primary LGSC were included if peri-operative CA-125 levels were available. Age at diagnosis, FIGO stage, pre- and post-treatment CA-125 levels, residual disease, adjuvant chemotherapy, disease recurrence, and vital status were collected by the participating institutions. Progression-free (PFS) and overall survival (OS) were calculated. Multivariable (MVA) Cox proportional hazard models were used and hazard ratios (HR) calculated. Results: A total of 176 women with LGSC were included in this study; 82% had stage III/IV disease. The median PFS was 2.3 years and the median OS was 6.4 years. Age at diagnosis was not significantly associated with worse PFS (p = 0.23) or OS (p = 0.3) (HR per year: 0.99; 95%CI, 0.96–1.01 and 0.98; 95%CI 0.95–1.01). FIGO stage III/IV was independently associated with PFS (HR 4.26, 95%CI 1.43–12.73) and OS (HR 1.69, 95%CI 0.56–5.05). Elevated CA-125 (≥35 U/mL) at diagnosis was not significantly associated with worse PFS (p = 0.87) or OS (p = 0.78) in MVA. Elevated CA-125 (≥35 U/mL) after completion of primary treatment was independently associated with worse PFS (HR 2.81, 95%CI 1.36–5.81) and OS (HR 6.62, 95%CI 2.45–17.92). In the MVA, residual disease was independently associated with PFS (0.022), but not OS (0.85). Conclusion: Advanced LGSC was associated with poor long-term prognosis. FIGO stage and abnormal post-treatment CA-125 level are key prognostic factors inversely associated with PFS and OS. Highlights: 1. Through a multi-center collaborative effort, data from 176 women with low-grade serous ovarian cancer were analyzed. 2. Although low-grade serous ovarian cancer is often considered indolent, the progression-free and overall survival are poor. 3. Elevated post-treatment CA-125 levels are independently associated with poor survival.

Abstract Background Lactate hydrogenase (LDH) is a common biomarker utilized in the detection and monitoring of left ventricular assist device (LVAD) hemolysis and thrombosis. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are common laboratory tests that can be used to calculate the De Ritis ratio and the De Ritis adjusted AST. Methods A retrospective review of LVAD patients was performed to identify three cohorts of patients: those with confirmed pump thrombosis after device exchange, those with LVAD‐related hemolysis who were medically managed without pump exchange, and those who did not meet these criteria and served as the control cohort. Evaluation of AST, AST/ALT ratio (referred to as the De Ritis ratio) as well as AST x (AST/ALT) or the De Ritis‐adjusted AST (DRA) was performed. Results There were 29 patients who underwent device exchange for thrombosis, 25 patients who were diagnosed with hemolysis and treated medically (clopidogrel ( N = 6), heparin ( N = 13), tirofiban ( N = 8), eptifibatide ( N = 2), and some received more than one of these treatments), and 425 control patients. A qualitatively comparable relative and absolute rise in DRA and LDH were found in both surgically managed pump thrombosis and suspected device‐related hemolysis. Conclusions Both AST and LDH as well DRA are significantly associated with pump thrombosis ( p < 0.0001 for each). DRA is a potential screening biomarker for hemolysis and device thrombosis in stable left ventricular assist device patients.

Background: Ischemic event rates are low after percutaneous coronary intervention (PCI), conversely second generation P2Y12 inhibitors increase bleeding therefore identifying patients at risk to enable precision in prescribing dual anti-platelet therapy (DAPT) is of clinical interest. Prior machine-learning predictive analyses have been limited by use of older generation stents and lack of genetic data. We utilized clinical and genetic data of patients with new generation stents enrolled in TAILOR-PCI, a 40-center international trial to predict ischemic events after PCI. Methods: There were 4398 eligible post PCI patients with acute coronary syndromes or stable coronary artery disease who were randomly split into training (n=3299) and validation (n=1099) cohorts. The primary endpoint comprising of cardiovascular death, myocardial infarction, stroke, or stent thrombosis within 12 months of PCI was predicted with patient characteristics prior to hospital discharge. First, random forests were used for feature selection with 1,000 bootstraps comprising equal numbers of those with and without ischemic events to minimize the bias of sample imbalance. Features were selected by a consensus on variable-importance over bootstraps. Second, using these features in the training cohort, support vector machines (SVM) with a polynomial kernel was trained with repeated 5-fold cross validation to choose a model with highest area under the receiver operating characteristic curve (AUC) which was then used to predict ischemic events in the validation cohort. Results: The primary endpoint occurred in 2.4% of patients. Using 89 clinical and genetic variables in the random-forest feature selection step, variable importance-based consensus identified 50 top predictors. These 50 predictors achieved AUC=0.703 in the SVM training cohort and AUC=0.744 (specificity=0.84; sensitivity =0.43) in the SVM validation cohort. Conclusions: Machine learning methods using baseline clinical and genetic data enables prediction of infrequent ischemic events in post PCI patients receiving new generation stents. The role of such artificial intelligence algorithms in individualization of DAPT by identifying high or low risk patients needs to be explored.

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of lymphoproliferative disorders arising from mature T cells, accounting for about 10% of non-Hodgkin lymphomas. PTCL-not otherwise specified is the most common subtype, followed by angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma, anaplastic lymphoma kinase–positive, anaplastic large cell lymphoma, anaplastic lymphoma kinase–negative, and enteropathy-associated T-cell lymphoma. This discussion section focuses on the diagnosis and treatment of PTCLs as outlined in the NCCN Guidelines for T-Cell Lymphomas.

OBJECTIVE Combinations of certain social risk factors of race, sex, education, socioeconomic status (SES), insurance, education, employment, and one’s housing situation have been associated with poorer pain and disability outcomes after lumbar spine surgery. To date, an exploration of such factors in patients with cervical spine surgery has not been conducted. The objective of the current work was to 1) define the social risk phenotypes of individuals who have undergone cervical spine surgery for myelopathy and 2) analyze their predictive capacity toward disability, pain, quality of life, and patient satisfaction–based outcomes. METHODS The Cervical Myelopathy Quality Outcomes Database was queried for the period from January 2016 to December 2018. Race/ethnicity, educational attainment, SES, insurance payer, and employment status were modeled into unique social phenotypes using latent class analyses. Proportions of social groups were analyzed for demonstrating a minimal clinically important difference (MCID) of 30% from baseline for disability, neck and arm pain, quality of life, and patient satisfaction at the 3-month and 1-year follow-ups. RESULTS A total of 730 individuals who had undergone cervical myelopathy surgery were included in the final cohort. Latent class analysis identified 2 subgroups: 1) high risk (non-White race and ethnicity, lower educational attainment, not working, poor insurance, and predominantly lower SES), n = 268, 36.7% (class 1); and 2) low risk (White, employed with good insurance, and higher education and SES), n = 462, 63.3% (class 2). For both 3-month and 1-year outcomes, the high-risk group (class 1) had decreased odds (all p < 0.05) of attaining an MCID score in disability, neck/arm pain, and health-related quality of life. Being in the low-risk group (class 2) resulted in an increased odds of attaining an MCID score in disability, neck/arm pain, and health-related quality of life. Neither group had increased or decreased odds of being satisfied with surgery. CONCLUSIONS Although 2 groups underwent similar surgical approaches, the social phenotype involving non-White race/ethnicity, poor insurance, lower SES, and poor employment did not meet MCIDs for a variety of outcome measures. This finding should prompt surgeons to proactively incorporate socially conscience care pathways within healthcare systems, as well as to optimize community-based resources to improve outcomes and personalize care for populations at social risk.

Background In TAILOR‐PCI, genotype‐guided selection of P2Y 12 inhibitors after percutaneous coronary intervention did not significantly reduce the risk of ischemic events at 12 months. The Age, Body Mass Index, Chronic Kidney Disease, Diabetes, and Genotyping (ABCD‐GENE) score identifies patients with high platelet reactivity on clopidogrel at increased risk of ischemic events. The aim of this study was to investigate the value of the ABCD‐GENE score for tailoring P2Y 12 inhibitor selection after percutaneous coronary intervention. Methods and Results In a post hoc analysis of the TAILOR‐PCI, outcomes were analyzed by ABCD‐GENE score and allocation to genotype‐guided or conventional P2Y 12 inhibitor selection. Primary (death, myocardial infarction, or stroke) and secondary (cardiovascular death, myocardial infarction, stroke, stent thrombosis, or severe recurrent ischemia) outcomes were assessed. Among 3883 patients discharged on clopidogrel in the genotype‐guided and conventional therapy groups, 15.8% and 84.2% had high (≥10 points) or low (<10) ABCD‐GENE scores, respectively. At 12 months, both the primary (5.2% versus 2.6%, P <0.001) and secondary outcomes (7.7% versus 4.6%, P =0.001) were significantly increased in patients with high ABCD‐GENE score. Among 4714 patients allocated to genotype‐guided or conventional therapy, the former did not significantly reduce the 12‐month risk of the primary and secondary outcomes in both the high and low ABCD‐GENE score groups (p interaction =0.48 and 0.27, respectively). Conclusions Among patients with percutaneous coronary intervention on clopidogrel, the ABCD‐GENE score was helpful in identifying those at higher risk. The ABCD‐GENE score may potentially enhance the precision of tailored selection of P2Y 12 inhibitors, which needs to be confirmed in prospective investigations. Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique Identifier: NCT01742117.