Surge and Mortality in ICUs in New York City's Public Healthcare System.

OBJECTIVES: To evaluate the impact of ICU surge on mortality and to explore clinical and sociodemographic predictors of mortality. DESIGN: Retrospective cohort analysis. SETTING: NYC Health + Hospitals ICUs. PATIENTS: Adult ICU patients with coronavirus disease 2019 admitted between March 24, and May 12, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Hospitals reported surge levels daily. Uni- and multivariable analyses were conducted to assess factors impacting in-hospital mortality. Mortality in Hispanic patients was higher for high/very high surge compared with low/medium surge (69.6% vs 56.4%; p = 0.0011). Patients 65 years old and older had similar mortality across surge levels. Mortality decreased from high/very high surge to low/medium surge in, patients 18-44 years old and 45-64 (18-44 yr: 46.4% vs 27.3%; p = 0.0017 and 45-64 yr: 64.9% vs 53.2%; p = 0.002), and for medium, high, and very high poverty neighborhoods (medium: 69.5% vs 60.7%; p = 0.019 and high: 71.2% vs 59.7%; p = 0.0078 and very high: 66.6% vs 50.7%; p = 0.0003). In the multivariable model high surge (high/very high vs low/medium odds ratio, 1.4; 95% CI, 1.2-1.8), race/ethnicity (Black vs White odds ratio, 1.5; 95% CI, 1.1-2.0 and Asian vs White odds ratio 1.5; 95% CI, 1.0-2.3; other vs White odds ratio 1.5, 95% CI, 1.0-2.3), age (45-64 vs 18-44 odds ratio, 2.0; 95% CI, 1.6-2.5 and 65-74 vs 18-44 odds ratio, 5.1; 95% CI, 3.3-8.0 and 75+ vs 18-44 odds ratio, 6.8; 95% CI, 4.7-10.1), payer type (uninsured vs commercial/other odds ratio, 1.7; 95% CI, 1.2-2.3; medicaid vs commercial/other odds ratio, 1.3; 95% CI, 1.1-1.5), neighborhood poverty (medium vs low odds ratio 1.6, 95% CI, 1.0-2.4 and high vs low odds ratio, 1.8; 95% CI, 1.3-2.5), comorbidities (diabetes odds ratio, 1.6; 95% CI, 1.2-2.0 and asthma odds ratio, 1.4; 95% CI, 1.1-1.8 and heart disease odds ratio, 2.5; 95% CI, 2.0-3.3), and interventions (mechanical ventilation odds ratio, 8.8; 95% CI, 6.1-12.9 and dialysis odds ratio, 3.0; 95% CI, 1.9-4.7) were significant predictors for mortality. CONCLUSIONS: Patients admitted to ICUs with higher surge scores were at greater risk of death. Impact of surge levels on mortality varied across sociodemographic groups.

Oestrogen replacement improves bone mineral density in oligo-amenorrhoeic athletes: a randomised clinical trial.

OBJECTIVE: Normal-weight oligo-amenorrhoeic athletes (OAA) are at risk for low bone mineral density (BMD). Data are lacking regarding the impact of oestrogen administration on bone outcomes in OAA. Our objective was to determine the effects of transdermal versus oral oestrogen administration on bone in OAA engaged in weight-bearing activity. METHODS: 121 patients with OAA aged 14-25 years were randomised to receive: (1) a 17ß-estradiol transdermal patch continuously with cyclic oral micronised progesterone (PATCH), (2) a combined ethinyl estradiol and desogestrel pill (PILL) or (3) no oestrogen/progesterone (NONE). All participants received calcium and vitamin D supplementation. Areal BMD was assessed at the lumbar spine, femoral neck, total hip and total body less head using dual-energy X-ray absorptiometry at baseline, 6 and 12 months. Intention-to-treat (ITT) and completers analyses were performed. RESULTS: Randomised groups did not differ for age, body mass index or BMD Z-scores at baseline. For ITT analysis, spine and femoral neck BMD Z-scores significantly increased in the PATCH versus PILL (p=0.011 and p=0.021, respectively) and NONE (p=0.021 and p=0.033, respectively) groups, and hip BMD Z-scores significantly increased in the PATCH versus PILL group (p=0.018). Similar findings were noted in completers analysis. CONCLUSION: Transdermal estradiol over 12 months improves BMD in young OAA, particularly compared with an ethinyl estradiol-containing contraceptive pill/oral contraceptives. TRIAL REGISTRATION NUMBER: NCT00946192; Pre-results.

Memory and Executive Function in Adolescent and Young Adult Females with Moderate to Severe Obesity Before and After Weight Loss Surgery.

There is a global increase in the prevalence of severe obesity in females during adolescence, which is a critical period for neurocognitive development. An increasing number of adolescents and young adults are now undergoing weight loss surgery as a treatment strategy for obesity. In addition to metabolic complications, obesity has been linked to neurocognitive comorbidity, and studies exploring cognitive performance in adolescents with severe obesity and the impact of bariatric surgery on cognitive abilities are limited. Verbal memory and executive function were assessed cross-sectionally in 69 females with moderate to severe obesity and 24 females without obesity, 13-24 years old. In an exploratory analysis, cognitive changes were also assessed longitudinally over 12 months in a subset of 35 females with moderate to severe obesity following weight loss surgery (n = 21) or following usual care without surgery (n = 14). In cross-sectional analysis, females with moderate to severe obesity showed lower scores for short-term and long-term recall (verbal memory) and response inhibition and cognitive flexibility (executive function) than the comparison group, when adjusted for age and baseline intelligence. Females with moderate to severe obesity who underwent surgery showed significant weight loss but no improvement in verbal memory and executive function scores over 12 months compared with those who did not have surgery. Females with moderate to severe obesity demonstrate worse performance in tests of verbal memory and executive function than the comparison group without obesity. In addition, exploratory analyses provide no indication that weight loss surgery improves these observed cognitive decrements over a period of 12 months. Further studies are necessary to comprehensively evaluate changes in cognitive function following bariatric surgery.

Emerging Therapies for Advanced Clear Cell Renal Cell Carcinoma.

Multiple combinational regimens have recently been approved and are now considered the standard of care for patients with advanced clear cell renal cell carcinoma (RCC). Several additional combinational regimens are deep in clinical assessment and are likely to soon join the crowded front-line therapeutic landscape. Most of these regimens are combinations of agents already approved as single-agents in RCC including tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors. While these new front-line regimens are associated with reliably high response rates and prolonged survival, complete and durable remissions remain limited to a small subset of patients and the vast majority of patients continue to require subsequent therapy. The need for the continued development of novel agents in RCC persists and efforts have focused on agents targeting the molecular biology of clear cell RCC and novel immunotherapies including cytokines. In this review, we discuss the progress in the development of these novel therapies in the context of the evolving standard of care for patients with advanced clear cell RCC.

Depressive and anxiety symptoms and suicidality in adolescent and young adult females with moderate to severe obesity before and after weight loss surgery.

Data are conflicting regarding the impact of weight loss on mood and anxiety in adolescent and young adult females with moderate to severe obesity (OB), who are at increased risk for mood dysfunction compared with normal-weight females (NW). We examined depressive and anxiety symptoms in 94 females 13-21 years old: 39 in the NW group (body mass index [BMI]: 5th -85th percentiles) and 55 in the OB group (BMI >40 kg/m2 or >35 kg/m2 with comorbidities). Fifteen participants in the OB group who underwent bariatric surgery (gastric bypass or sleeve gastrectomy) and 15 getting routine care were re-assessed after 6 months. The Beck Depression Inventory-II (BDI-II) and State-Trait Anxiety Inventory (STAI) assessed depressive and anxiety symptoms, respectively. The OB group had higher BDI-II and STAI T-scores (P < .0001), a higher prevalence of clinical depression and anxiety (P < .001), and reported greater suicidal ideation (P = .02) vs the NW group. The bariatric surgery and non-surgical groups did not differ for changes in BDI-II and STAI T-Scores and suicidality over 6-month follow-up, despite greater weight loss in the former. Depressive and anxiety symptoms and suicidality were more frequently observed in the OB vs NW group. These symptoms did not improve following bariatric surgery despite significant weight loss, underscoring the need to investigate determinants of emergence and resolution of these symptoms in the OB group.

Clinical Outcomes in Critically Ill Coronavirus Disease 2019 Patients: A Unique New York City Public Hospital Experience.

To explore demographics, comorbidities, transfers, and mortality in critically ill patients with confirmed severe acute respiratory syndrome coronavirus 2. DESIGN: Retrospective cohort study. SETTING: Data were collected from a large tertiary care public hospital ICU that is part of the largest public healthcare network in the United States. PATIENTS: One-hundred thirty-seven adult (≥ 18 yr old) ICU patients admitted between March 10, 2020, and April 7, 2020, with follow-up collected through May 18, 2020. INTERVENTIONS: None. MEASUREMENTS: Demographic, clinical, laboratory, treatment, and outcome data extracted from electronic medical records. MAIN RESULTS: The majority of patients were male (99/137; 72.3%) and older than 50 years old (108/137; 78.9%). The most reported ethnicity and race were Hispanic (61/137; 44.5%) and Black (23/137; 16.7%). One-hundred six of 137 patients had at least one comorbidity (77.4%). One-hundred twenty-one of 137 (78.1%) required mechanical ventilation of whom 30 (24.8%) moved to tracheostomy and 46 of 137 (33.6%) required new onset renal replacement therapy. Eighty-two of 137 patients (59.9%) died after a median of 8 days (interquartile range 5-15 d) in the ICU. Male sex had a trend toward a higher hazard of death (hazard ratio, 2.1 [1.1-4.0]) in the multivariable Cox model. CONCLUSIONS: We report a mortality rate of 59.9% in a predominantly Hispanic and Black patient population. A significant association between comorbidities and mortality was not found in multivariable regression, and further research is needed to study factors that impact mortality in critical coronavirus disease 2019 patients. We also describe how a public hospital developed innovative approaches to safely manage a large volume of interhospital transfers and admitted patients.

Estrogen administration improves the trajectory of eating disorder pathology in oligo-amenorrheic athletes: A randomized controlled trial.

OBJECTIVE: Estrogen replacement prevents worsening body dissatisfaction with weight gain in adolescents with anorexia nervosa. However, the impact of estrogen administration on eating disorder (ED) pathology in normal-weight young women with exercise-induced amenorrhea is unknown. We hypothesized that (1) normal-weight oligo-amenorrheic athletes (OA) would show greater ED pathology than eumenorrheic athletes (EA) and non-athletes (NA), and (2) 12 months of estrogen replacement would improve those symptoms. TRIAL DESIGN: Randomized trial. METHODS: One hundred seventeen OA, 50 EA, and 41 NA completed the Eating Disorder Inventory-2 (EDI-2) for measures of Drive for Thinness (DT) and Body Dissatisfaction (BD) and the Three-Factor Eating Questionnaire-R18 (TFEQ-R18). OA were then randomized to receive 100 mcg transdermal 17ß-estradiol with cyclic progesterone (PATCH), an oral contraceptive pill (30 mcg ethinyl estradiol + 0.15 mg desogestrel) (PILL), or no estrogen (E-) for 12 months. Data are reported for the subset that completed questionnaires at 0 and 12 months between 11/2009 and 10/2016. RESULTS: OA showed higher EDI-2 DT and TFEQ-R18 Cognitive Restraint scores than EA and NA and higher EDI-2 BD scores than EA. Over 12 months, the E+ group (PATCH+PILL), compared to E-, showed improved trajectories for EDI-2 DT and BD scores. In 3-group comparisons, PATCH outperformed E- for decreases in EDI-2 DT and BD, and the PILL for TFEQ-R18 Uncontrolled Eating. CONCLUSION: In OA, 12 months of estrogen replacement improves ED pathology trajectories, emphasizing the broad importance of normalizing estrogen levels. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00946192.

Bone accrual in oligo-amenorrheic athletes, eumenorrheic athletes and non-athletes.

BACKGROUND: Mechanical loading improves bone mineral density (BMD) and strength while decreasing fracture risk. Cross-sectional studies show that exercise advantage is lost in oligo-amenorrheic athletes (OA). Longitudinal studies examining the opposing effects of exercise and hypogonadism on bone are lacking in adolescents/young adults. OBJECTIVE: Evaluate differences in bone accrual over 12 months in OA, eumenorrheic athletes (EA) and non-athletes (NA). We hypothesized that bone accrual would be lower in OA than EA and NA, with differences most pronounced at non-weight bearing trabecular sites. METHODS: 27 OA, 29 EA, and 22 NA, 14-25 years old, completed 12-months of the prospective study. Athletes were weight-bearing endurance athletes. Subjects were assessed for areal BMD and bone mineral content (BMC) using DXA at the femoral neck, total hip, lumbar spine and whole body (WB). Failure load (a strength estimate) at the distal radius and tibia was assessed using microfinite element analysis of data obtained via high resolution peripheral quantitative computed tomography (HRpQCT). The primary analysis was a comparison of changes in areal BMD, BMC, and failure load across groups over 12-months at the respective sites. RESULTS: Groups did not differ for baseline age, height or BMI. Percent body fat was lower in both OA and EA compared to NA. OA attained menarche later than EA and NA. Over the follow-up period, OA gained 1.9 ±â€¯2.7 kg of weight compared to 0.5 ±â€¯2.4 kg and 0.8 ±â€¯2.3 kg in EA and NA respectively (p = 0.09); 39% of OA resumed menses. Changes in BMD, BMD Z-scores, and tibial failure load over 12-months did not differ among groups. At follow up, EA had higher femoral neck, hip and WB BMD Z-scores than NA, and higher hip BMD Z-scores than OA (p < 0.05) after adjusting for covariates. At follow-up, radial failure load was lower in OA vs. NA, and tibial failure load lower in OA and NA vs. EA (p ≤ 0.04 for all). Change in weight and fat mass were associated with changes in BMD measures at multiple sites. CONCLUSION: Despite weight gain and menses recovery in many OA during follow-up, residual deficits persist without catch-up raising concerns for suboptimal peak bone mass acquisition.

Comparison of Measured and Estimated Resting Energy Expenditure in Adolescents and Young Adults With Severe Obesity Before and 1 Year After Sleeve Gastrectomy.

Introduction: Resting energy expenditure (REE) is often evaluated in adults and adolescents with obesity to estimate caloric requirements when advising dietary changes. However, data are lacking regarding the accuracy of methods used to clinically assess REE in adolescents with severe obesity. Moreover, there are no data regarding the effects of sleeve gastrectomy (SG) on REE in adolescents. We evaluated the accuracy and error rate between estimated and measured REE in adolescents with severe obesity and changes in REE following (SG). Materials and Methods: Cross-sectional study (CSS): 64 adolescents and young adults, 14-22 years old, with moderate to severe obesity were enrolled. We measured REE (mREE) by indirect calorimetry and estimated REE (eREE) using Derumeaux (Deru), Mifflin-St Jeor (MS), Harris Benedict (HB), and World Health Organization (WHO) equations. DXA was used to determine body composition. Bland Altman analysis evaluated agreement between eREE and mREE. Longitudinal study: 12 subjects had repeat indirect calorimetry and DXA 1 year after SG. Longitudinal analysis was used to assess changes in REE and body composition. Results: CSS: Median BMI was 45.2 kg/m2 and median age was 18.0 (16.3-19.9) years. mREE correlated strongly with eREE . Bland Altman analysis demonstrated that only a few points were beyond the 1.96 SD limit of disagreement. However, there was considerable overestimation of mREE by most equations. Longitudinal Study: In the subset that underwent SG, after 12-months, absolute REE decreased from 1709 (1567.7-2234) to 1580.5 (1326-1862.5) Calories (p = 0.002); however, the ratio of REE/Total Body Weight (TBW) increased from 13.5 ± 2.3 at baseline to 15.5 ± 2.2 at 1 year (p = 0.043). When evaluating parameters affecting % total weight loss, we found that it correlated positively with REE/TBW at 12 months (R = 0.625; p = 0.03) and negatively with % fat mass at 12 months (R = -0.669; p = 0.024). Discussion: In adolescents with moderate-severe obesity, despite a correlation between mREE using indirect calorimetry and eREE using the Deru, MS, HB, and WHO equations, there is significant over-estimation of REE at the individual level, challenging their clinical utility. One year after SG, REE/TBW increased and strongly correlated with % total weight loss in adolescents.

A qualitative examination of the effects of international counter-drug interdictions.

BACKGROUND: The purpose of this study is to utilize unique qualitative data to determine the effects of sporadic international drug interdictions on drug trafficking, and to assess whether the responses of drug traffickers align with rational choice theory. METHODS: Qualitative data obtained from 23 high-level United States Drug Enforcement Administration (DEA) informants, who are embedded in international drug trafficking groups, are examined to identify common responses to drug interdiction operations. RESULTS: The findings indicate that sporadic counter-drug interdictions do not a have permanent deterrent effect on transnational drug smuggling operations. However, these types of law enforcement operations produce temporary alterations in drug trafficking, as traffickers adopted a variety of methods to thwart the efforts of law enforcement-often by relying on information acquired from corrupt local law enforcement. The results also indicate that while interdiction operations displaced trafficking activities (temporally, spatially, and methodological), there is little evidence that drug traffickers responded to such operations by moving into new areas (i.e., malign spatial displacement). CONCLUSION: Sporadic international drug interdiction programs do little to deter drug trafficking organizations (DTOs) from engaging in their illicit trade. Instead, DTOs adjust in a calculating manner to these operations to ensure that their illegal products reach consumer marketplaces, which is congruent with the rational choice theoretical perspective.

Racial Disparities in Obesity Treatment.

PURPOSE OF REVIEW: Obesity rates in the USA have reached pandemic levels with one third of the population with obesity in 2015-2016 (39.8% of adults and 18.5% of youth). It is a major public health concern, and it is prudent to understand the factors which contribute. Racial and ethnic disparities are pronounced in both the prevalence and treatment of obesity and must be addressed in the efforts to combat obesity. RECENT FINDINGS: Disparities in prevalence of obesity in racial/ethnic minorities are apparent as early as the preschool years and factors including genetics, diet, physical activity, psychological factors, stress, income, and discrimination, among others, must be taken into consideration. A multidisciplinary team optimizes lifestyle and behavioral interventions, pharmacologic therapy, and access to bariatric surgery to develop the most beneficial and equitable treatment plans. The reviewed studies outline disparities that exist and the impact that race/ethnicity have on disease prevalence and treatment response. Higher prevalence and reduced treatment response to lifestyle, behavior, pharmacotherapy, and surgery, are observed in racial and ethnic minorities. Increased research, diagnosis, and access to treatment in the pediatric and adult populations of racial and ethnic minorities are proposed to combat the burgeoning obesity epidemic and to prevent increasing disparity.

Weight Loss Medications in Older Adults After Bariatric Surgery for Weight Regain or Inadequate Weight Loss: A Multicenter Study.

Weight loss medications are effective to confer additional weight loss after bariatric surgery in the general population, but they have not been evaluated in adults 60 years of age and older. We performed a retrospective study identifying 35 patients who were ≥60 years old and had undergone Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) from 2000 to 2014, and were subsequently prescribed weight loss medications. Linear regression analyses were performed to determine beta coefficients of certain predictor variables being associated with weight loss. Patients lost weight on medications with an average body mass index (BMI) change of -2.74 kg/m2, standard deviation = 2.6 kg/m2. RYGB patients lost a greater percentage of BMI on medication than SG (SG; -1.38 ± 1.49 kg/m2 and RYGB; -3.37 ± 2.83 kg/m2, p = 0.0372). Patients with hypertension were less likely to lose weight on medications (ß = 16.76, p = 0.004, and 95% confidence interval = 5.85-27.67). Weight loss medications are a useful treatment to confer additional weight loss in adults 60 years of age and older after RYGB and SG.

Differential associations between appendicular and axial marrow adipose tissue with bone microarchitecture in adolescents and young adults with obesity.

Marrow adipose tissue (MAT) in humans is distributed differentially across age and skeletal site. We have shown impaired microarchitecture and reduced bone strength at appendicular sites in conditions associated with high MAT of the axial skeleton in adults (including conditions of over- and undernutrition). Data are lacking regarding differences in MAT content of the appendicular versus the axial skeleton, and its relationship with bone microarchitecture and strength. Furthermore, data are conspicuously lacking in adolescents, a time when hematopoietic marrow is progressively converted to fatty marrow. The purpose of our study was to examine differential associations between appendicular (distal tibia) and axial (lumbar spine) MAT and bone microarchitecture and strength estimates of the distal tibia in adolescents with obesity. We hypothesized that compared to MAT of the axial skeleton (lumbar spine), MAT of the appendicular skeleton (distal tibia) would show stronger associations with bone microarchitecture and strength estimates of the appendicular skeleton (distal tibia). We evaluated 32 adolescents and young adults (27 females) with obesity; with a mean age of 17.8 ±â€¯2.1 years and median body mass index (BMI) of 41.34 kg/m2, who underwent dual energy X-ray absorptiometry (DXA) for total fat mass, proton MR spectroscopy (1H-MRS) of the distal tibia and 4th lumbar vertebra for MAT, high resolution peripheral quantitative computed tomography (HR-pQCT) of the distal tibia for volumetric bone mineral density (vBMD) and microarchitecture, and micro finite element analysis (FEA) for distal tibial strength estimates. Linear correlations between bone parameters and MAT were determined using the Spearman or Pearson methods, depending on data distribution. Lumbar spine MAT was inversely associated with age (r = -0.36; p = 0.037). Total and trabecular vBMD and trabecular number at the distal tibia were inversely associated with MAT at the distal tibia (r = -0.39, p = 0.025; r = -0.51, p = 0.003; r = -0.42, p = 0.015 respectively) but not with lumbar spine MAT (r = -0.19, p = 0.27; r = -0.18, p = 0.3; r = 0.005, p = 0.97 respectively). In adolescents and young adults with obesity, the associations between MAT and appendicular bone parameters differ depending on the site of MAT assessment i.e. axial vs. appendicular. Studies evaluating these endpoints in adolescents and young adults with obesity should take the site of MAT assessment into consideration.

Weight Loss Medications in Young Adults after Bariatric Surgery for Weight Regain or Inadequate Weight Loss: A Multi-Center Study.

This paper presents a retrospective cohort study of weight loss medications in young adults aged 21 to 30 following Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) between November 2000 and June 2014. Data were collected from patients who used topiramate, phentermine, and/or metformin postoperatively. Percentage of patients achieving ≥5%, ≥10%, or ≥15% weight loss on medications was determined and percent weight change on each medication was compared to percent weight change of the rest of the cohort. Our results showed that 54.1% of study patients lost ≥5% of their postsurgical weight; 34.3% and 22.9% lost ≥10% and ≥15%, respectively. RYGB had higher median percent weight loss (-8.1%) than SG (-3.3%) (p = 0.0515). No difference was found in median percent weight loss with medications started at weight plateau (-6.0%) versus after weight regain (-5.4%) (p = 0.5304). Patients taking medications at weight loss plateau lost 41.2% of total body weight from before surgery versus 27.1% after weight regain (p = 0.076). Median percent weight change on metformin was -2.9% compared to the rest of the cohort at -7.7% (p = 0.0241). No difference from the rest of the cohort was found for phentermine (p = 0.2018) or topiramate (p = 0.3187). Topiramate, phentermine, and metformin are promising weight loss medications for 21 to 30 year olds. RYGB patients achieve more weight loss on medications but both RYGB and SG benefit. Median total body weight loss from pre-surgical weight may be higher in patients that start medication at postsurgical nadir weight. Participants on metformin lost significantly smaller percentages of weight on medications, which could be the result of underlying medical conditions.