mvlearnR and Shiny App for multiview learning.

Summary: The package mvlearnR and accompanying Shiny App is intended for integrating data from multiple sources or views or modalities (e.g. genomics, proteomics, clinical, and demographic data). Most existing software packages for multiview learning are decentralized and offer limited capabilities, making it difficult for users to perform comprehensive integrative analysis. The new package wraps statistical and machine learning methods and graphical tools, providing a convenient and easy data integration workflow. For users with limited programming language, we provide a Shiny Application to facilitate data integration anywhere and on any device. The methods have potential to offer deeper insights into complex disease mechanisms. Availability and implementation: mvlearnR is available from the following GitHub repository: https://github.com/lasandrall/mvlearnR. The web application is hosted on shinyapps.io and available at: https://multi-viewlearn.shinyapps.io/MultiView_Modeling/.

Practice Variation among Pediatric Endocrinologists in the Dosing of Glucocorticoids in Young Children with Congenital Adrenal Hyperplasia.

A Pediatric Endocrine Society (PES) Drugs and Therapeutics Committee workgroup sought to determine the prescribing practices of pediatric endocrinologists when treating children <10 years of age with congenital adrenal hyperplasia (CAH). Our workgroup administered a 32-question online survey to PES members. There were 187 respondents (88.9% attending physicians), mostly from university-affiliated clinics (~80%). Ninety-eight percent of respondents prescribed the short-acting glucocorticoid hydrocortisone to treat young children, as per the Endocrine Society CAH Guidelines, although respondents also prescribed long-acting glucocorticoids such as prednisolone suspension (12%), prednisone tablets (9%), and prednisone suspension (6%). Ninety-seven percent of respondents indicated that they were likely/very likely to prescribe hydrocortisone in a thrice-daily regimen, as per CAH Guidelines, although 19% were also likely to follow a twice-daily regimen. To achieve smaller doses, using a pill-cutter was the most frequent method recommended by providers to manipulate tablets (87.2%), followed by dissolving tablets in water (25.7%) to create a daily batch (43.7%) and/or dissolving a tablet for each dose (64.6%). Thirty-one percent of providers use pharmacy-compounded hydrocortisone suspension to achieve doses of <2.5 mg. Our survey shows that practices among providers in the dosing of young children with CAH vary greatly and sometimes fall outside of the CAH Guidelines-specifically when attempting to deliver lower, age-appropriate hydrocortisone doses.

Changes in adipose tissue distribution and relation to cardiometabolic risk factors after Roux-en-Y gastric bypass in adolescents.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) among adolescents with obesity results in significant weight loss; however, depot-specific changes have been understudied. OBJECTIVE: We hypothesized that visceral adipose tissue (VAT) reduction in adolescents undergoing RYGB would be greater than other depots and associated with improvement in cardiometabolic risk factors. SETTING: Three specialized treatment centers in Sweden. METHODS: Fifty-nine adolescents underwent dual x-ray absorptiometry before surgery and at 1, 2, and 5 years after RYGB. Changes in body composition in multiple depots (total fat, lean body, gynoid fat, android fat, subcutaneous adipose tissue, and VAT) and cardiometabolic risk factors were assessed using multiple linear regression analysis and generalized estimating equations adjusting for age, sex, and baseline risk factor levels. Data are presented as percent change (95% CI) with regression models showing slopes and estimated P values. RESULTS: At 1 year post-RYGB, a significant reduction was observed across all body composition measures (P < .001) with the greatest reduction observed in VAT (-65.1% [-68.7, -61.8]). From year 1 to 5 years post-RYGB, a regain was observed in all depots except lean body mass (1.2% [.3, 2.7], P = .105). A sex-specific difference in overall trajectories was only observed in lean body mass with males consistently having higher mean levels. Change in VAT at 1 year correlated with change in triglycerides (slope: .21 mg/dL/kg, P = .034) and fasting plasma insulin (slope: 44 pmol/L/kg, P = .027). CONCLUSIONS: Adiposity measures all decreased after RYGB but poorly predicted change in cardiometabolic risk. Despite significant reductions at 1 year, a steady regain was observed out to 5 years, with values still well below baseline. Further research should consider control group comparison and extended follow-up.

Comparable safety profile between neuro-oncology procedures involving stereotactic needle biopsy (SNB) followed by laser interstitial thermal therapy (LITT) and LITT alone procedures.

INTRODUCTION: Tissue diagnosis through stereotactic needle biopsy (SNB) is often needed prior to laser interstitial thermal therapy (LITT). Whether these procedures should be performed in the same surgery or in separate settings remain unclear. As a first step to address this question, we assess safety profile of procedures involving LITT alone versus SNB + LITT. METHODS: Using International Classification of Disease (ICD) codes, we queried the National Readmissions Database (NRD, 2010-2018) for malignant brain tumor patients who underwent either (1) LITT alone or (2) elective LITT in combination with SNB (SNB + LITT). Survey regression methods were utilized. Additionally, the procedural outcome of LITT or SNB + LITT performed by the senior surgeon (2014-2022) were reviewed. RESULTS: During the study period, an estimated 678 malignant brain tumor patients underwent LITT alone versus 373 patients that underwent SNB + LITT. Patients undergoing LITT and SNB + LITT exhibited statistically comparable median lengths of hospital stay (IQR; LITT = 2 day [1, 3]; SNB + LITT = 1 day [1, 3]; p = 0.405) and likelihood of routine discharge (LITT = 73.5%; SNB + LITT = 81.1%; p = 0.068). The odds of 30-day medical or neurological readmissions were comparable between LITT and SNB + LITT treated patients (all p ≥ 0.793). In the single surgeon experience of 218 procedures performed over an eight year period (2014-2022), the complications (LITT = 3.9%; SNB + LITT = 2.6%, p = 0.709), discharge within 48 h (LITT = 84.5%; SNB + LITT = 87.8%; p = 0.556), routine discharge (LITT = 91.3%; SNB + LITT = 93.9%; p = 0.604), and unplanned 30-day readmission (LITT = 3.9%; SNB + LITT = 1.7%; p = 0.423) were similarly comparable between LITT and SNB + LITT. CONCLUSION: The length of hospital stay, the likelihood of routine discharge, and 30-day readmission for malignant brain tumor patients who underwent LITT and SNB + LITT were comparable.

Development and Validation of a Hypertension Risk Calculator for Living Kidney Donors.

BACKGROUND: Ideally, when deciding whether to donate, kidney donor candidates would understand their long-term risks. Using single-center data (N = 4055; median [quartiles] follow-up: 18 [9-28] y), we developed a calculator for postdonation hypertension and validated it using long-term data from an external single-center cohort (N = 1189, median [quartiles] follow-up: 9 [5-17] y). METHODS: Risk factors considered were routinely obtained at evaluation from donor candidates. Two modeling approaches were evaluated: Cox proportional hazards and random survival forest models. Cross-validation prediction error and Harrell's concordance-index were used to compare accuracy for model development. Top-performing models were assessed in the validation cohort using the concordance-index and net reclassification improvement. RESULTS: In the development cohort, 34% reported hypertension at a median (quartiles) of 16 (8-24) y postdonation; and in the validation cohort, 29% reported hypertension after 17 (10-22) y postdonation. The most accurate model was a Cox proportional hazards model with age, sex, race, estimated glomerular filtration rate, systolic and diastolic blood pressure, body mass index, glucose, smoking history, family history of hypertension, relationship with recipient, and hyperlipidemia (concordance-index, 0.72 in the development cohort and 0.82 in the validation cohort). CONCLUSIONS: A postdonation hypertension calculator was developed and validated; it provides kidney donor candidates, their family, and care team a long-term projection of hypertension risk that can be incorporated into the informed consent process.

Health of Post-Institutionalized Haitian Children Adopted to the United States.

OBJECTIVES: Haiti remains a principal placement country for intercountry adoptees to the United States. This project reports the health status of children adopted from Haiti arriving to the U.S. and compares them to intercountry adoptees from other regions. METHODS: A retrospective chart review was conducted of adoptees placed in the U.S. from Haiti (n=87), age and sex matched with intercountry adoptees placed in the U.S. from Asia (n=87) and Latin America (n=87) between January 2010 and November 2019. Data on immunization status, contagious diseases, and nutrition and growth were analyzed via linear, logistic, and multinomial regression. RESULTS: After adjusting for age, sex, and standardized height, children adopted from Haiti, compared to adoptees from Latin America and Asia, demonstrated a lack of immunity to hepatitis B (OR=5.89;6.87), increased immunity to hepatitis A (OR=0.38;0.30), infection by two or more parasites (OR=8.43;38.48), high lead levels (OR=23.79;7.04), and anemia (OR=15.25;9.18). Unexpectedly, children adopted from Haiti had greater standardized height (-1.28 vs. -1.82 and -2.13) and standardized weight (-0.32 vs. -0.57 and -1.57) than their counterparts from Latin America and Asia. CONCLUSIONS: Children adopted from Haiti face complex medical challenges undoubtedly related to the country's low socioeconomic status (SES) and the impact of recurrent natural disasters and governmental neglect on public health infrastructure. Appropriate care is critical in preventing and avoiding transmission of infectious diseases in adoptees and family members. The high incidence of anemia and elevated lead levels may further exacerbate the developmental effects of early institutional deprivation.

Long-term Outcomes Associated With Post-kidney Donation Pregnancy Complications.

BACKGROUND: Kidney donors have increased risk of postdonation gestational hypertension (gHTN) and preeclampsia. In the general population, pregnancy complications are associated with long-term maternal risk. However, little data exist on whether donors with postdonation pregnancy-related complications have similar increased long-term risks. We studied whether postdonation gHTN, preeclampsia/eclampsia, or gestational diabetes (gDM) was associated with increased risk of developing hypertension, DM, cardiovascular disease, or estimated glomerular filtration rate <45 mL/min/1.73 m 2 . METHODS: Postdonation pregnancies with complications were matched to pregnancies without complications based on time from donation. Incidence of outcomes was compared using sequential Cox regression with robust standard errors. Donors with predonation pregnancy complications were excluded. Models were adjusted for age at pregnancy, gravidity, year of donation, and family history of hypertension, DM, and heart disease. RESULTS: Of the 384 donors with postdonation pregnancies (median [quartiles] follow-up of 27.0 [14.2-36.2] y after donation), 39 experienced preeclampsia/eclampsia, 29 gHTN without preeclampsia, and 17 gDM. Median interval from donation to first pregnancy with preeclampsia was 5.1 (2.9-8.6) y; for gHTN, 3.7 (1.9-7.8) y; and for gDM, 7.3 (3.7-10.3) y. Preeclampsia/eclampsia (hazard ratio [HR] 2.70; 95% confidence interval [CI], 1.53-4.77) and gHTN (HR 2.39; 95% CI, 1.24-4.60) were associated with development of hypertension. Preeclampsia/eclampsia (HR 2.15; 95% CI, 1.11-4.16) and gDM (HR 5.60; 95% CI, 1.41-22.15) were associated with development of DM. Pregnancy-related complications were not associated with increased risk of cardiovascular disease or estimated glomerular filtration rate <45 mL/min/1.73 m 2 . CONCLUSIONS: In our single-center study, postdonation preeclampsia, gHTN, or gDM was associated with long-term risk of hypertension or DM.

Rates of operative intervention for infection after synthetic or autologous cranioplasty: a National Readmissions Database analysis.

OBJECTIVE: The aim of this study was to characterize the clinical utilization and associated charges of autologous bone flap (ABF) versus synthetic flap (SF) cranioplasty and to characterize the postoperative infection risk of SF versus ABF using the National Readmissions Database (NRD). METHODS: The authors used the publicly available NRD to identify index hospitalizations from October 2015 to December 2018 involving elective ABF or SF cranioplasty after traumatic brain injury (TBI) or stroke. Subsequent readmissions were further characterized if patients underwent neurosurgical intervention for treatment of infection or suspected infection. Survey Cox proportional hazards models were used to assess risk of readmission. RESULTS: An estimated 2295 SF and 2072 ABF cranioplasties were performed from October 2015 to December 2018 in the United States. While the total number of cranioplasty operations decreased during the study period, the proportion of cranioplasties utilizing SF increased (p < 0.001), particularly in male patients (p = 0.011) and those with TBI (vs stroke, p = 0.012). The median total hospital charge for SF cranioplasty was $31,200 more costly than ABF cranioplasty (p < 0.001). Of all first-time readmissions, 20% involved surgical treatment for infectious reasons. Overall, 122 SF patients (5.3%) underwent surgical treatment of infection compared with 70 ABF patients (3.4%) on readmission. After accounting for confounders using a multivariable Cox model, female patients (vs male, p = 0.003), those discharged nonroutinely (vs discharge to home or self-care, p < 0.001), and patients who underwent SF cranioplasty (vs ABF, p = 0.011) were more likely to be readmitted for reoperation. Patients undergoing cranioplasty during more recent years (e.g., 2018 vs 2015) were less likely to be readmitted for reoperation because of infection (p = 0.024). CONCLUSIONS: SFs are increasingly replacing ABFs as the material of choice for cranioplasty, despite their association with increased hospital charges. Female sex, nonroutine discharge, and SF cranioplasty are associated with increased risk for reoperation after cranioplasty.

Relationship of Endothelial Microparticles to Obesity and Cardiovascular Disease Risk in Children and Adolescents.

Background Microparticles and endothelial microparticles (EMPs) are implicated in accelerating cardiovascular disease (CVD); however, data in pediatrics are limited. We examined the relationship of microparticles and EMPs with adiposity and subclinical CVD risk measures in a pediatric population to determine their potential as biomarkers of CVD risk. Methods and Results A cross-sectional study of youth (n=280; ages 8-20 years) with a range of body mass index categories was used. Microparticles, EMPs, and activated EMPs were measured by flow cytometry. %Body fat and %visceral adipose tissue were measured by dual X-ray absorptiometry. Measures of arterial stiffness and vascular wall structure were obtained. Linear regression (with log-transformed outcomes) and logistic regression were used to evaluate associations and all results were exponentiated. Youth with overweight/obesity and severe obesity had 2.50 (95% CI, 1.56-4.01) and 3.42 (95% CI, 2.15-5.43) times the geometric means of the total number of microparticles, respectively, compared with those with normal weight. Youth with overweight/obesity and severe obesity had 1.97 (95% CI, 1.09-3.55) and 2.34 (95% CI, 1.31-4.19) times the geometric means of the total number of EMPs, respectively, compared with those with normal weight. There were positive associations between the levels of both microparticles and EMPs with higher adiposity measures and poor CVD risk measures. Youth with higher adiposity showed 1.84 times the odds of having high levels of activated EMPs (%) (odds ratio, 1.84; 95% CI, 1.08-3.14) compared with those with normal weight. Conclusions Levels of microparticles, EMPs, and activated EMPs were positively associated with adiposity and poor subclinical CVD risk in a pediatric population.

sJIVE: Supervised Joint and Individual Variation Explained.

Analyzing multi-source data, which are multiple views of data on the same subjects, has become increasingly common in molecular biomedical research. Recent methods have sought to uncover underlying structure and relationships within and/or between the data sources, and other methods have sought to build a predictive model for an outcome using all sources. However, existing methods that do both are presently limited because they either (1) only consider data structure shared by all datasets while ignoring structures unique to each source, or (2) they extract underlying structures first without consideration to the outcome. The proposed method, supervised joint and individual variation explained (sJIVE), can simultaneously (1) identify shared (joint) and source-specific (individual) underlying structure and (2) build a linear prediction model for an outcome using these structures. These two components are weighted to compromise between explaining variation in the multi-source data and in the outcome. Simulations show sJIVE to outperform existing methods when large amounts of noise are present in the multi-source data. An application to data from the COPDGene study explores gene expression and proteomic patterns associated with lung function.

Readmission risk of malignant brain tumor patients undergoing laser interstitial thermal therapy (LITT) and stereotactic needle biopsy (SNB): a covariate balancing weights analysis of the National Readmissions Database (NRD).

PURPOSE: Despite procedural similarities between laser interstitial thermal therapy (LITT) and stereotactic needle biopsy (SNB), LITT induces delayed, pro-inflammatory responses not associated with SNB that may increase the risk of readmission within 30- or 90- days. Here, we explore this hypothesis. METHODS: We queried the National Readmissions Database (NRD, 2010-18) for malignant brain tumor patients who underwent elective LITT or SNB using International Classification of Diseases codes. Readmissions were defined as non-elective inpatient hospitalizations. Survey regression methods and a weighted analysis were utilized to adjust for demographic and clinical differences between LITT and SNB cohorts. RESULTS: During the study period, an estimated 685 malignant brain patients underwent elective LITT and 15,177 underwent elective SNB. Patients undergoing LITT and SNB exhibited comparable median lengths of hospital stay [IQR; LITT = 2 (1, 3); SNB = 1 (1, 2); p = 0.820]. Likelihood of routine discharge was not significantly different between the two procedures (p = 0.263). No significant differences were observed in the odds of 30- or 90-day unplanned readmission between the LITT and SNB cohorts after multivariable adjustment (all p ≥ 0.177). The covariate balancing weighted analysis confirmed comparable 30 or 90-day readmission risk between LITT and SNB treated patients (all p ≥ 0.201). CONCLUSION: The likelihood of 30- and 90-day readmission for malignant brain tumor patients who underwent LITT or SNB are comparable, supporting the safety profile of LITT as therapy for malignant brain cancers.

Pre-kidney Donation Pregnancy Complications and Long-term Outcomes.

BACKGROUND: Hypertension and diabetes are contraindications for living kidney donation in young candidates. However, little is known about the long-term outcomes of women who had these pregnancy-related complications and subsequently became donors. In the general population, gestational hypertension (GHtn), preeclampsia/eclampsia, and gestational diabetes (GDM) are associated with long-term risks. METHODS: Donors with the specified predonation complication were matched to contemporary control donors with pregnancies without the complication using nearest neighbor propensity score matching. Propensity scores were estimated using logistic regression with covariates for gravidity, blood pressure, glucose, body mass index, age, and creatinine at donation, donation year, race, relationship with recipient, and family history of disease. Long-term incidence of hypertension, diabetes, cardiovascular disease, and reduced renal function (estimated glomerular filtration rate [eGFR] <30, eGFR <45 mL/min/1.73 m 2 ) were compared between groups using proportional hazards models. RESULTS: Of 1862 donors with predonation pregnancies, 48 had preeclampsia/eclampsia, 49 had GHtn without preeclampsia, and 43 had GDM. Donors had a long interval between first pregnancy and donation (median, 18.5 y; interquartile range, 10.6-27.5) and a long postdonation follow-up time (median, 18.0; interquartile range, 9.2-27.7 y). GHtn was associated with the development of hypertension (hazard ratio, 1.89; 95% confidence interval, 1.26-2.83); GDM was associated with diabetes (hazard ratio, 3.04; 95% confidence interval, 1.33-6.99). Pregnancy complications were not associated with eGFR <30 or eGFR <45 mL/min/1.73 m 2 . CONCLUSIONS: Our data suggest that women with predonation pregnancy-related complications have long-term risks even with a normal donor evaluation. Donor candidates with a history of pregnancy-related complications should be counseled about these risks.

Persistent Racial Disparities in Deep Brain Stimulation for Parkinson's Disease.

We sought to determine whether racial and socioeconomic disparities in the utilization of deep brain stimulation (DBS) for Parkinson's disease (PD) have improved over time. We examined DBS utilization and analyzed factors associated with placement of DBS. The odds of DBS placement increased across the study period, whereas White patients with PD were 5 times more likely than Black patients to undergo DBS. Individuals, regardless of racial background, with 2 or more comorbidities were 14 times less likely to undergo DBS. Privately insured patients were 1.6 times more likely to undergo DBS. Despite increasing DBS utilization, significant disparities persist in access to DBS. ANN NEUROL 2022;92:246-254.

Anti-obesity medication prescriptions by race/ethnicity and use of an interpreter in a pediatric weight management clinic.

Background: Race/ethnicity and low English proficiency healthcare disparities are well established in the United States. We sought to determine if there are race/ethnicity differences in anti-obesity medication (AOM) prescription rates among youth with severe obesity treated in a pediatric weight management clinic and if, among youth from non-primary English speaking families, there are differences in prescriptions between those using interpreters during visits versus not. Methods: We reviewed electronic health records of 2- to 18-year-olds with severe obesity seen from 2012 to 2021. Race/ethnicity was self-report, and AOMs included topiramate, stimulants (e.g. phentermine, lisdexamfetamine), naltrexone (±bupropion), glucagon-like peptide-1 agonists, and orlistat. We used general linear regression models with log-link to compare incidence rate ratios (IRRs) within the first 1 and 3 years of being followed, controlling for age, percent of the 95th BMI percentile (%BMIp95), number of obesity-related comorbidities (e.g. insulin resistance, hypertension), median household income, and interpreter use. We repeated similar analyses among youth from non-primary English speaking families, comparing those using interpreters versus not. Results: 1,725 youth (mean age 11.5 years; %BMIp95 142%; 53% non-Hispanic White, 20% Hispanic/Latino, 16% non-Hispanic black; 6% used interpreters) were seen, of which 15% were prescribed AOMs within 1 year. The IRR for prescriptions was lower among Hispanic/Latino compared to non-Hispanic White youth at one (IRR 0.70; CI: 0.49-1.00; p = 0.047) but not 3 years. No other statistically significant differences by race/ethnicity were found. Among non-primary English speaking families, the IRR for prescriptions was higher at 1 year (IRR 2.49; CI: 1.32-4.70; p = 0.005) in those using interpreters versus not. Conclusions: Among youth seen in a pediatric weight management clinic, AOM prescription incidence rates were lower in Hispanics/Latinos compared to non-Hispanic Whites. Interpreter use was associated with higher prescription incidence rates among non-primary English speakers. Interventions to achieve equity in AOM prescriptions may help mitigate disparities in pediatric obesity.

Dynamics of plasmid-mediated niche invasion, immunity to invasion, and pheromone-inducible conjugation in the murine gastrointestinal tract.

Microbial communities provide protection to their hosts by resisting pathogenic invasion. Microbial residents of a host often exclude subsequent colonizers, but this protection is not well understood. The Enterococcus faecalis plasmid pCF10, whose conjugative transfer functions are induced by a peptide pheromone, efficiently transfers in the intestinal tract of mice. Here we show that an invading donor strain established in the gastrointestinal tract of mice harboring resident recipients, resulting in a stable, mixed population comprised of approximately 10% donors and 90% recipients. We also show that the plasmid-encoded surface protein PrgB (Aggregation Substance), enhanced donor invasion of resident recipients, and resistance of resident donors to invasion by recipients. Imaging of the gastrointestinal mucosa of mice infected with differentially labeled recipients and donors revealed pheromone induction within microcolonies harboring both strains in close proximity, suggesting that adherent microcolonies on the mucosal surface of the intestine comprise an important niche for cell-cell signaling and plasmid transfer.

An evaluation of risk factors for Staphylococcus aureus colonization in a pre-surgical population.

Staphylococcus aureus (SA) colonization has significant implications in healthcare-associated infections. Here we describe a prospective study conducted in pre-surgical outpatients, done with the aim of identifying demographic and clinical risk factors for SA colonization. We found younger age to be a potential predictor of SA colonization.

Chronotropic index during 6-minute walk and acute respiratory events in COPDGene.

BACKGROUND: Lower heart rate (HR) increases during exercise and slower HR recovery (HRR) after exercise are markers of worse autonomic function that may be associated with risk of acute respiratory events (ARE). METHODS: Data from 6-min walk testing (6MWT) in COPDGene were used to calculate the chronotropic index (CI) [(HR immediately post 6MWT - resting HR)/((220 - age) - resting HR)] and HRR at 1 min after 6MWT completion. We used zero-inflated negative binomial regression to test associations of CI and HRR with rates of any ARE (requiring steroids and/or antibiotics) and severe ARE (requiring emergency department visit or hospitalization), among all participants and in spirometry subgroups (normal, chronic obstructive pulmonary disease [COPD], and preserved ratio with impaired spirometry). RESULTS: Among 4,484 participants, mean follow-up time was 4.1 years, and 1,966 had COPD. Among all participants, CI-6MWT was not associated with rate of any ARE [adjusted incidence rate ratio (aIRR) 0.98 (0.95-1.01)], but higher CI-6MWT was associated with lower rate of severe ARE [0.95 (0.92-0.99)]. Higher HRR was associated with a lower rate of both any ARE [0.97 (0.95-0.99)] and severe ARE [0.95 (0.92-0.98)]. Results were similar in the COPD spirometry subgroup. CONCLUSION: Heart rate measures derived from 6MWT tests may have utility in predicting risk of acute respiratory events and COPD exacerbations.

Bone Age Maturation and Growth Outcomes in Young Children with CAH Treated with Hydrocortisone Suspension.

BACKGROUND: Young children with congenital adrenal hyperplasia (CAH) require small doses (0.1-1.25 mg) of hydrocortisone (HC) to control excess androgen production and avoid the negative effects of overtreatment. The smallest commercially available HC formulation, before the recent US Food and Drug Administration approval of HC granules, was a scored 5-mg tablet. The options to achieve small doses were limited to using a pharmacy-compounded suspension, which the CAH Clinical Practice Guidelines recommended against, or splitting tablets into quarters or eighths, or dissolving tablets into water. METHODS: Cross-sectional chart review of 130 children with classic CAH treated with tablets vs a pharmacy-compounded alcohol-free hydrocortisone suspension to compare growth, weight, skeletal maturation, total daily HC dose, and exposure over the first 4 years of life. RESULTS: No significant differences were found in height, weight, or body mass index z-scores at 4 years, and in predicted adult height, before or after adjusting for age at diagnosis and sex. Bone age z-scores averaged 2.8 SDs lower for patients on HC suspension compared with HC tablets (P < 0.001) after adjusting for age at diagnosis and sex. The suspension group received 30.4% lower (P > 0.001) average cumulative HC doses by their fourth birthday. CONCLUSIONS: Our data indicate that treatment with alcohol-free HC suspension decreased androgen exposure as shown by lower bone age z-scores, allowed lower average and cumulative daily HC dose compared to HC tablets, and generated no significant differences in SDS in growth parameters in children with CAH at 4 years of age. Longitudinal studies of treating with smaller HC doses during childhood are needed.

BMI metrics and their association with adiposity, cardiometabolic risk factors, and biomarkers in children and adolescents.

BACKGROUND: There are limited data comparing the relative associations of various BMI metrics with adiposity and cardiometabolic risk factors in youth. OBJECTIVE: Examine correlations of 7 different BMI metrics with adiposity, cardiometabolic risk factors, and biomarkers (i.e. blood pressure, waist circumference, cholesterol, leptin, insulin, high molecular weight adiponectin, high-sensitivity c-reactive protein (hsCRP)). METHODS: This was a cross-sectional analysis of youth in all BMI categories. BMI metrics: BMI z-score (BMIz), extended BMIz (ext.BMIz), BMI percentile (BMIp), percent of the BMI 95th percentile (%BMIp95), percent of the BMI median (%BMIp50), triponderal mass index (TMI), and BMI (BMI). Correlations between these BMI metrics and adiposity, visceral adiposity, cardiometabolic risk factors and biomarkers were summarized using Pearson's correlations. RESULTS: Data from 371 children and adolescents ages 8-21 years old were included in our analysis: 52% were female; 20.2% with Class I obesity, 20.5% with Class II, and 14.3% with Class III obesity. BMIp consistently demonstrated lower correlations with adiposity, risk factors, and biomarkers (r = 0.190-0.768) than other BMI metrics. The %BMIp95 and %BMIp50 were marginally more strongly correlated with measures of adiposity as compared to other BMI metrics. The ext.BMIz did not meaningfully outperform BMIz. CONCLUSION: Out of all the BMI metrics evaluated, %BMIp95 and %BMIp50 were the most strongly correlated with measures of adiposity. %BMIp95 has the benefit of being used currently to define obesity and severe obesity in both clinical and research settings. BMIp consistently had the lowest correlations. Future research should evaluate the longitudinal stability of various BMI metrics and their relative associations with medium to long-term changes in adiposity and cardiometabolic outcomes in the context of intervention trials.

Recent Trends in Admission Diagnosis and Related Mortality in the Medically Critically Ill.

PURPOSE: With decades of declining ICU mortality, we hypothesized that the outcomes and distribution of diseases cared for in the ICU have changed and we aimed to further characterize them. STUDY DESIGN AND METHODS: A retrospective cohort analysis of 287,154 nonsurgical-critically ill adults, from 237 U.S. ICUs, using the manually abstracted Cerner APACHE Outcomes database from 2008 to 2016 was performed. Surgical patients, rare admission diagnoses (<100 occurrences), and low volume hospitals (<100 total admissions) were excluded. Diagnoses were distributed into mutually exclusive organ system/disease-based categories based on admission diagnosis. Multi-level mixed-effects negative binomial regression was used to assess temporal trends in admission, in-hospital mortality, and length of stay (LOS). RESULTS: The number of ICU admissions remained unchanged (IRR 0.99, 0.98-1.003) while certain organ system/disease groups increased (toxicology [25%], hematologic/oncologic [55%] while others decreased (gastrointestinal [31%], pulmonary [24%]). Overall risk-adjusted in-hospital mortality was unchanged (IRR 0.98, 0.96-1.0004). Risk-adjusted ICU LOS (Estimate -0.06 days/year, -0.07 to -0.04) decreased. Risk-adjusted mortality varied significantly by disease. CONCLUSION: Risk-adjusted ICU mortality rate did not change over the study period, but there was evidence of shifting disease burden across the critical care population. Our data provides useful information regarding future ICU personnel and resource needs.