Cohort profile: pathways to care among people with disorders of sex development (DSD).

PURPOSE: The 'DSD Pathways' study was initiated to assess health status and patterns of care among people enrolled in large integrated healthcare systems and diagnosed with conditions comprising the broad category of disorders (differences) of sex development (DSD). The objectives of this communication are to describe methods of cohort ascertainment for two specific DSD conditions-classic congenital adrenal hyperplasia with 46,XX karyotype (46,XX CAH) and complete androgen insensitivity syndrome (CAIS). PARTICIPANTS: Using electronic health records we developed an algorithm that combined diagnostic codes, clinical notes, laboratory data and pharmacy records to assign each cohort candidate a 'strength-of-evidence' score supporting the diagnosis of interest. A sample of cohort candidates underwent a review of the full medical record to determine the score cutoffs for final cohort validation. FINDINGS TO DATE: Among 5404 classic 46,XX CAH cohort candidates the strength-of-evidence scores ranged between 0 and 10. Based on sample validation, the eligibility cut-off for full review was set at the strength-of-evidence score of ≥7 among children under the age of 8 years and ≥8 among older cohort candidates. The final validation of all cohort candidates who met the cut-off criteria identified 115 persons with classic 46,XX CAH. The strength-of-evidence scores among 648 CAIS cohort candidates ranged from 2 to 10. There were no confirmed CAIS cases among cohort candidates with scores <6. The in-depth medical record review for candidates with scores ≥6 identified 61 confirmed cases of CAIS. FUTURE PLANS: As the first cohort of this type, the DSD Pathways study is well-positioned to fill existing knowledge gaps related to management and outcomes in this heterogeneous population. Analyses will examine diagnostic and referral patterns, adherence to care recommendations and physical and mental health morbidities examined through comparisons of DSD and reference populations and analyses of health status across DSD categories.

How Well Do ICD-9-CM Codes Predict True Congenital Heart Defects? A Centers for Disease Control and Prevention-Based Multisite Validation Project.

Background The Centers for Disease Control and Prevention's Surveillance of Congenital Heart Defects Across the Lifespan project uses large clinical and administrative databases at sites throughout the United States to understand population-based congenital heart defect (CHD) epidemiology and outcomes. These individual databases are also relied upon for accurate coding of CHD to estimate population prevalence. Methods and Results This validation project assessed a sample of 774 cases from 4 surveillance sites to determine the positive predictive value (PPV) for identifying a true CHD case and classifying CHD anatomic group accurately based on 57 International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. Chi-square tests assessed differences in PPV by CHD severity and age. Overall, PPV was 76.36% (591/774 [95% CI, 73.20-79.31]) for all sites and all CHD-related ICD-9-CM codes. Of patients with a code for complex CHD, 89.85% (177/197 [95% CI, 84.76-93.69]) had CHD; corresponding PPV estimates were 86.73% (170/196 [95% CI, 81.17-91.15]) for shunt, 82.99% (161/194 [95% CI, 76.95-87.99]) for valve, and 44.39% (83/187 [95% CI, 84.76-93.69]) for "Other" CHD anatomic group (X2=142.16, P<0.0001). ICD-9-CM codes had higher PPVs for having CHD in the 3 younger age groups compared with those >64 years of age, (X2=4.23, P<0.0001). Conclusions While CHD ICD-9-CM codes had acceptable PPV (86.54%) (508/587 [95% CI, 83.51-89.20]) for identifying whether a patient has CHD when excluding patients with ICD-9-CM codes for "Other" CHD and code 745.5, further evaluation and algorithm development may help inform and improve accurate identification of CHD in data sets across the CHD ICD-9-CM code groups.

An automated algorithm using free-text clinical notes to improve identification of transgender people.

Accurate identification of transgender persons is a critical first step in conducting transgender health studies. To develop an automated algorithm for identifying transgender individuals from electronic medical records (EMR) using free-text clinical notes. The development and validation of the algorithm was based on data from an integrated healthcare system that served as a participating site in the multicenter Study of Transition Outcomes and Gender. The training and test datasets each contained a total of 300 individuals identified between 2006 and 2014. Both datasets underwent a full medical record review by experienced research abstractors. The validated algorithm was then implemented to identify transgender individuals in the EMR using all clinical notes of patients that received care between January 1, 2015 and June 30, 2018. Validation of the algorithm against the full chart review demonstrated a high degree of accuracy with 97% sensitivity, 95% specificity, 94% positive predictive value, and 97% negative predictive value. The algorithm classified 7,409 individuals (3.5%) as "Definitely transgender" and 679 individuals (0.3%) as "Probably transgender" out of 212,138 candidates with a total of 378,641 clinical notes. The computerized NLP algorithm can support essential efforts to improve the health of transgender people.

Predicting 30-day readmission after congenital heart surgery across the lifespan.

INTRODUCTION: Hospital readmission is an important driver of costs among patients with CHD. We assessed predictors of 30-day rehospitalisation following cardiac surgery in CHD patients across the lifespan. METHODS: This was a retrospective analysis of 981 patients with CHD who had cardiac surgery between January 2011 and December 2012. A multivariate logistic regression model was used to identify demographic, clinical, and surgical predictors of 30-day readmission. Receiver operating curves derived from multivariate logistic modelling were utilised to discriminate between patients who were readmitted and not-readmitted at 30 days. Model goodness of fit was assessed using the Hosmer-Lemeshow test statistic. RESULTS: Readmission in the 30 days following congenital heart surgery is common (14.0%). Among 981 patients risk factors associated with increased odds of 30-day readmission after congenital heart surgery through multivariate analysis included a history of previous cardiac surgery (p < 0.001), longer post-operative length of stay (p < 0.001), as well as nutritional (p < 0.001), haematologic (p < 0.02), and endocrine (p = 0.04) co-morbidities. Patients who underwent septal defect repair had reduced odds of readmission (p < 0.001), as did children (p = 0.04) and adult (p = 0.005) patients relative to neonates. CONCLUSION: Risk factors for readmission include a history of cardiac surgery, longer length of stay, and co-morbid conditions. This information may serve to guide efforts to prevent readmission and inform resource allocation in the transition of care to the outpatient setting. This study also demonstrated the feasibility of linking a national subspecialty registry to a clinical and administrative data repository to follow longitudinal outcomes of interest.

Health Care Transition Perceptions Among Parents of Adolescents with Congenital Heart Defects in Georgia and New York.

With increasing survival trends for children and adolescents with congenital heart defects (CHD), there is a growing need to focus on transition from pediatric to adult specialty cardiac care. To better understand parental perspectives on the transition process, a survey was distributed to 451 parents of adolescents with CHD who had recent contact with the healthcare system in Georgia (GA) and New York (NY). Among respondents, 90.7% reported excellent, very good or good health-related quality of life (HRQoL) for their adolescent. While the majority of parents (77.8%) had been told by a provider about their adolescent's need to transition to adult specialty cardiac care, most reported concerns about transitioning to adult care. Parents were most commonly concerned with replacing the strong relationship with pediatric providers (60.7%), locating an appropriate adult provider (48.7%), and accessing adult health insurance coverage (43.6%). These findings may offer insights into transition planning for adolescents with CHD.

Assessing Pregnancy, Gestational Complications, and Co-morbidities in Women With Congenital Heart Defects (Data from ICD-9-CM Codes in 3 US Surveillance Sites).

Improved treatment of congenital heart defects (CHDs) has resulted in women with CHDs living to childbearing age. However, no US population-based systems exist to estimate pregnancy frequency or complications among women with CHDs. Cases were identified in multiple data sources from 3 surveillance sites: Emory University (EU) whose catchment area included 5 metropolitan Atlanta counties; Massachusetts Department of Public Health (MA) whose catchment area was statewide; and New York State Department of Health (NY) whose catchment area included 11 counties. Cases were categorized into one of 5 mutually exclusive CHD severity groups collapsed to severe versus not severe; specific ICD-9-CM codes were used to capture pregnancy, gestational complications, and nongestational co-morbidities in women, age 11 to 50 years, with a CHD-related ICD-9-CM code. Pregnancy, CHD severity, demographics, gestational complications, co-morbidities, and insurance status were evaluated. ICD-9-CM codes identified 26,655 women with CHDs, of whom 5,672 (21.3%, range: 12.8% in NY to 22.5% in MA) had codes indicating a pregnancy. Over 3 years, age-adjusted proportion pregnancy rates among women with severe CHDs ranged from 10.0% to 24.6%, and 14.2% to 21.7% for women with nonsevere CHDs. Pregnant women with CHDs of any severity, compared with nonpregnant women with CHDs, reported more noncardiovascular co-morbidities. Insurance type varied by site and pregnancy status. These US population-based, multisite estimates of pregnancy among women with CHD indicate a substantial number of women with CHDs may be experiencing pregnancy and complications. In conclusion, given the growing adult population with CHDs, reproductive health of women with CHD is an important public health issue.

Lost in the system? Transfer to adult congenital heart disease care-Challenges and solutions.

OBJECTIVE: Transfer of congenital heart disease care from the pediatric to adult setting has been identified as a priority and is associated with better outcomes. Our objective is to determine what percentage of patients with congenital heart disease transferred to adult congenital cardiac care. DESIGN: A retrospective cohort study. SETTING: Referrals to a tertiary referral center for adult congenital heart disease patients from its pediatric referral base. PATIENTS: This resulted in 1514 patients age 16-30, seen at least once in three pediatric Georgia health care systems during 2008-2010. INTERVENTIONS: We analyzed for protective factors associated with age-appropriate care, including distance from referral center, age, timing of transfer, gender, severity of adult congenital heart disease, and comorbidities. OUTCOME MEASURES: We analyzed initial care by age among patients under pediatric care from 2008 to 2010 and if patients under pediatric care subsequently transferred to an adult congenital cardiologist in this separate pediatric and adult health system during 2008-2015. RESULTS: Among 1514 initial patients (39% severe complexity), 24% were beyond the recommended transfer age of 21 years. Overall, only 12.1% transferred care to the referral affiliated adult hospital. 90% of these adults that successfully transferred were seen by an adult congenital cardiologist, with an average of 33.9 months between last pediatric visit and first adult visit. Distance to referral center contributed to delayed transfer to adult care. Those with severe congenital heart disease were more likely to transfer (18.7% vs 6.2% for not severe). CONCLUSION: Patients with severe disease are more likely to transfer to adult congenital heart disease care than nonsevere disease. Most congenital heart disease patients do not transfer to adult congenital cardiology care with distance to referral center being a contributing factor. Both pediatric and adult care providers need to understand and address barriers in order to improve successful transfer.

Surveillance of Congenital Heart Defects among Adolescents at Three U.S. Sites.

The prevalence, co-morbidities, and healthcare utilization in adolescents with congenital heart defects (CHDs) is not well understood. Adolescents (11 to 19 years old) with a healthcare encounter between January 1, 2008 (January 1, 2009 for MA) and December 31, 2010 with a CHD diagnosis code were identified from multiple administrative data sources compiled at 3 US sites: Emory University, Atlanta, Georgia (EU); Massachusetts Department of Public Health (MA); and New York State Department of Health (NY). The estimated prevalence for any CHD was 4.77 (EU), 17.29 (MA), and 4.22 (NY) and for severe CHDs was 1.34 (EU), 3.04 (MA), and 0.88 (NY) per 1,000 adolescents. Private or commercial insurance was the most common insurance type for EU and NY, and Medicaid for MA. Inpatient encounters were more frequent in severe CHDs. Cardiac co-morbidities included rhythm and conduction disorders at 20% (EU), 46% (MA), and 9% (NY) as well as heart failure at 3% (EU), 15% (MA), and 2% (NY). Leading noncardiac co-morbidities were respiratory/pulmonary (22% EU, 34% MA, 16% NY), infectious disease (17% EU, 22% MA, 20% NY), non-CHD birth defects (12% EU, 23% MA, 14% NY), gastrointestinal (10% EU, 28% MA, 13% NY), musculoskeletal (10% EU, 32% MA, 11% NY), and mental health (9% EU, 30% MA, 11% NY). In conclusion, this study used a novel approach of uniform CHD definition and variable selection across administrative data sources in 3 sites for the first population-based CHD surveillance of adolescents in the United States. High resource utilization and co-morbidities illustrate ongoing significant burden of disease in this vulnerable population.

AMPA-induced dark cell degeneration is associated with activation of caspases in pyramidal neurons of the rat hippocampus.

Various neurons in the central nervous system (CNS) exhibit selective vulnerability to AMPA-induced delayed neurotoxicity known as dark cell degeneration. Hippocampal pyramidal neurons in the CA1 and CA3 regions display such vulnerability that encompasses morphological changes including cytoplasmic and nuclear condensation, neuronal shrinkage, formation of cytoplasmic vacuoles, and general failure of physiology. The present study was undertaken to ascertain the potential involvement of initiator (caspase-9) and executor (caspase-3) caspases in AMPA-receptor-induced dark cell degeneration in pyramidal neurons. Immunohistochemical analyses revealed that immunoreactivity of the active form of caspase-9 and -3 was increased in pyramidal neurons in CA1 and CA3 regions of the hippocampus following AMPA (100 microM). Elevated levels of active caspase-9 immunoreactivity generally preceded elevations in active caspase-3 immunoreactivity. The pan caspase inhibitor FK011 effectively attenuated AMPA-induced dark cell degeneration in both CA1 and CA3 regions. Collectively, the data suggest a role for these caspases in mediating AMPA-induced toxicity in pyramidal neurons of the rat hippocampus.