Major Adverse Renal and Cardiovascular Events following Intra-Arterial Contrast Media Administration in Hospitalized Patients with Comorbid Conditions.

INTRODUCTION: Several clinical studies and meta-analyses have demonstrated lower incidence of adverse renal and cardiovascular outcomes associated with the use of iso-osmolar contrast media (IOCM) than low-osmolar contrast media (LOCM) in patients with variable risk profiles undergoing intra-arterial interventional procedures. However, the association of contrast-type and major adverse renal and cardiovascular events (MARCE) has not been studied via comprehensive and robust real-world data analyses in patients with comorbid conditions considered at risk for post-procedural acute kidney injury (AKI). The objective of this study was therefore to retrospectively assess the MARCE rates comparing IOCM with LOCM in at-risk patients receiving iodinated intra-arterial contrast media using a real-world inpatient data source. METHODS: Patients who underwent a diagnostic or treatment procedure with intra-arterial IOCM or LOCM administration were identified using the Premier Healthcare Database. Patient subgroups including those with diabetes, heart failure, chronic kidney disease (CKD) stages 1-4, CKD 3-4, or diagnosis of chronic total occlusion (CTO) were formed. Subgroups with combinations of diabetes and CKD 3-4 with and without CTO were also investigated. We compared the primary endpoint of MARCE (composite of AKI, AKI requiring dialysis, acute myocardial infarction, stroke/transient ischemic attack, stent occlusion/thrombosis, or death) after IOCM versus LOCM administration via adjusted multivariable regression analyses. RESULTS: A total of 536,013 inpatient visits met the primary inclusion and exclusion criteria (IOCM = 133,192; LOCM = 402,821). After multivariable modeling, the use of IOCM was associated with a significantly lower incidence of MARCE than LOCM in patients with CKD 1-4, CKD 3-4, diabetes, or heart failure, with greatest absolute risk reduction (ARR) of 2.4% (p < 0.0001) in CKD 3-4 patients (relative risk reduction [RRR] = 13.8%, number needed to treat [NNT] = 43). Additionally, ARR associated with IOCM increased to 3.5% (p < 0.0001) in patients with combined comorbidities of diabetes and CKD 3-4 (RRR = 19.1%, NNT = 29). Statistically significant risk reduction was also found for the use of IOCM among patients who underwent revascularization for CTO (ARR = 1.6% [p < 0.0001], RRR = 22.3%, NNT = 62). CONCLUSION: Intra-arterial administration using IOCM in at-risk patients is associated with lower rates of MARCE than the use of LOCM. This difference is especially apparent in patients with a combination of CKD 3-4 and diabetes and in patients with CTO, providing real-world data validation with meaningful NNT in favor of IOCM.

The Association Among Parental Bonding, Depression, Social Aggression, and Criminal Assault: Are There Gender Differences Between Male and Female Youth Offenders?

This research examined similarities and differences in gender regarding social aggression, criminal assault, depression, and familial factors. The participants were 251 youth offenders (158 males) who were arrested and incarcerated in a juvenile facility. The measures consisted of self-reported acts of social aggression, simple and aggravated assault, subtypes of depression, and self-reports on parental care and control. Our data demonstrate the importance of including gender, types of aggression/assault, subtypes of depression, and familial factors when examining their association. For example, less parental care predicted more social aggression for both males and females. However, neither did parental care predict aggravated assault for either gender, nor did parental care predict general depression or anhedonia. Parental control had different impact depending on gender. More parental control increased rates of social aggression and simple assault for females but not for males. Symptoms of general depression predicted committing simple assault for both males and females, but not anhedonia. However, general depressive symptoms and anhedonia were associated with committing aggravated assault for both genders. Policy implications were discussed.

Coinfection rates and clinical outcome data for cytomegalovirus and Epstein-Barr virus in post-transplant patients: A systematic review of the literature.

BACKGROUND: In transplant recipients, cytomegalovirus (CMV) infection increases morbidity and mortality; furthermore, coinfection with other human herpesviruses like the Epstein-Barr virus (EBV) may complicate their management. This systematic literature review aimed to summarize rates of CMV-EBV coinfection and associated clinical outcomes among solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients. METHODS: An electronic literature search was performed using pre-specified search strategies (January 1, 2010-October 31, 2018) and following established/best practice methodology. Of 316 publications identified, 294 did not report CMV-EBV coinfection and were excluded. Studies meeting the inclusion criteria were further analyzed. Due to limited reporting/heterogeneity, data were not meta-analyzable. RESULTS: Nine studies (six SOT; three HSCT) reported CMV-EBV coinfection; rates of coinfection post transplantation varied between 2.6% and 32.7%. Two studies indicated CMV reactivation to be an independent variable associated with EBV reactivation. Among SOT studies, higher rates of graft dysfunction (47.4% vs 22.9%), rejection episodes (20.0% vs 8.9%), or acute rejection (50.0% vs 31.0%) were reported for patients with coinfection than without. In HSCT studies, patients with graft-vs-host disease were not reported separately for coinfection. Two studies described cases of post-transplant lymphoproliferative disorder (PTLD) in patients with CMV-EBV coinfection and reported rates of PTLD of 92% and 100%. CONCLUSION: The CMV-EBV coinfection rate in HSCT and SOT recipients varied and was associated with increased graft rejection and PTLD compared with patients without coinfection. Further research may improve understanding of the burden of CMV-EBV coinfection among transplant recipients.

Impact of mitral regurgitation on cardiovascular hospitalization and death in newly diagnosed heart failure patients.

AIMS: Heart failure (HF) carries a poor prognosis, and the impact of concomitant mitral regurgitation (MR) is not well understood. This analysis aimed to estimate the incremental effect of MR in patients newly diagnosed with HF. METHODS AND RESULTS: Data from the IBM® MarketScan® Research Databases were analysed. Included patients had at least one inpatient or two outpatient HF claims. A 6 month post-period after HF index was used to capture MR diagnosis and severity. HF patients were separated into three cohorts: without MR (no MR), not clinically significant MR (nsMR), and significant MR (sMR). Time-to-event analyses were modelled to estimate the clinical burden of disease. The primary outcome was a composite endpoint of death or cardiovascular (CV)-related admission. Secondary outcomes were death and CV hospitalization alone. All models controlled for baseline demographics and co-morbidities. Patients with sMR were at significantly higher risk of either death or CV admission compared with patients with no MR [hazard ratio (HR) 1.26; 95% confidence interval (CI) 1.15-1.39]. When evaluating death alone, patients with sMR had significantly higher risk of death (HR 1.24; 95% CI 1.08-1.43) compared with patients with no MR. When evaluating CV admission alone, patients with MR were at higher risk of hospital admission vs. patients with no MR, and the magnitude was dependent upon the MR severity: sMR (HR 1.55; 95% CI 1.38-1.74) and nsMR (HR 1.23; 95% CI 1.08-1.40). CONCLUSIONS: Evidence of MR in retrospective claims significantly increases the clinical burden of incident HF patients. Time to death and CV hospitalizations are increased when MR is clinically significant.

The economic impact of clinically significant tricuspid regurgitation in a large, administrative claims database.

Aim: This study aimed to quantify the healthcare burden of clinically significant tricuspid regurgitation (TR) in patients with and without heart failure (HF).Materials and Methods: Data were from the IBM MarketScan Research Databases from October 2011 to September 2016. Eligible patients met the following inclusion criteria: age ≥18 with a TR diagnosis, 12 months pre (baseline), and 6 months post (landmark) medical enrollment. The landmark period was used to categorize TR severity, defined as a record of pulmonary hypertension with ascites, lower extremity edema or hepatic insufficiency, or tricuspid valve surgery. Cohorts were defined based on TR etiology and severity: (1) no HF and no clinically significant TR; (2) HF with no clinically significant TR; (3) no HF with clinically significant TR; and (4) HF with clinically significant TR. Outcomes of interest were all-cause hospitalizations, hospital days, and expenditures. Multivariable models were fit for each of the annualized outcomes and adjusted for patient demographics, comorbidities, and other concomitant valve diseases.Results: There were 92,994 patients eligible for analysis. Patients with no HF and no clinically significant TR had the annualized healthcare burden of 0.20 all-cause hospitalizations (approximately one inpatient hospitalization every 5 years), 1.07 hospital days, and $17,478 in expenditures. The presence of clinically significant TR, alone or with HF, significantly increased healthcare utilization and expenditures. For patients with no HF with clinically significant TR, the annualized economic burden increased to 0.41 all-cause hospitalizations, 3.13 hospital days, and $29,985 in expenditures. For patients with HF and clinically significant TR, the annualized economic burden was even greater with 0.59 all-cause hospitalizations, 4.31 hospital days, and $42,255 in expenditures.Conclusion: The presence of clinically significant TR is associated with an increase in healthcare utilization and expenditures, irrespective of the presence of HF.

The Economic Impact of Mitral Regurgitation on Patients With Medically Managed Heart Failure.

The objective of this study was to quantify the financial healthcare burden of mitral regurgitation (MR) on medically managed heart failure (HF) patients. Data from the Truven Health MarketScan Commercial Claims and Medicare Supplemental Databases were analyzed. Included patients had a minimum of 1 inpatient or 2 outpatient claims for HF with a 6-month preperiod (baseline). A 6-month postperiod (landmark) after HF index was used to capture MR diagnosis and severity. Following the landmark period, patients had to have 12 months of continuous medical and prescription drug plan enrollment with at least 2 records of HF medication refills. A therapeutic intensity score was calculated based on HF medication usage. Medically managed HF patients were separated into 3 cohorts: without MR (no MR), insignificant MR (iMR), and significant MR (sMR). Healthcare utilization and all-cause expenditures were modeled to quantify the burden of MR. All models controlled for baseline demographics, co-morbid conditions, and HF therapeutic intensity. Medically managed incident HF patients with sMR had significantly more hospital days (1.91 vs 1.72 days; p = 0.0096) and annual expenditures ($23,988 vs $21,530; p < 0.0001) compared with no MR patients. No differences were identified when comparing iMR and no MR. When evaluating HF admissions, sMR patients had an estimated 50% greater HF admissions rate (0.036 vs 0.024; p < 0.0001) compared with no MR patients. Additionally, HF admits for iMR were 23% more than those with no MR (0.029 vs 0.024; p = 0.0064). In conclusion, evidence of MR in retrospective claims significantly increases the healthcare impact of medically managed HF patients. Both utilization and financial burden is more pronounced when MR is clinically significant.

Relations Among Victimization, Witnessing, and Perpetration of Aggression: Impact of Gender Among Youth Offenders.

The participants included 251 (158 males; 93 females) youth offenders who were arrested and incarcerated in a juvenile facility in the Midwest United States. The aims were to assess (a) how often they were a victim, a witness, and/or a perpetrator of social aggression, simple assault, and aggravated assault during the past year; (b) to examine whether exposure (either witness or victim or both) predicted committing three types of aggressive behaviors; and (c) to assess the impact of gender among the youth offenders. Differential predictability models were utilized to assess gender differences. The findings revealed that gender was an important predictor. For example, females reported higher rates of being a witness, a victim, and a perpetrator of social aggression than did males. Moreover, female offenders committed simple assault more often than males and males committed aggravated assault more often than females. The general results suggest that it is important to examine the various forms of aggression, and exposure, as well as how gender affects these relationships.

Risk of renal events following intravenous iodinated contrast material administration among inpatients admitted with cancer a retrospective hospital claims analysis.

BACKGROUND: There is little published evidence examining the use of contrast material (CM) and the risk of acute renal adverse events (AEs) in individuals with increasingly common risk factors including cancer and chronic kidney disease (CKD). The objective of this study was to use real world hospital data to test the hypothesis that inpatients with cancer having CT procedures with iodinated CM would have higher rates of acute renal AEs in comparison to inpatients without cancer. METHODS: Inpatient hospital visits in the Premier Hospital Database from January 1, 2010 through September 30, 2015 were eligible for inclusion. The outcome of interest was a composite of acute renal AEs including: acute kidney injury, acute renal failure requiring dialysis, contrast induced-acute kidney injury and renal failure. Multivariable models, adjusted for differences in patient demographics and comorbid conditions, were used to estimate the incremental risk of acute renal AEs by CT (with or without iodinated CM), CKD stage and type of cancer. RESULTS: Among 29,850,475 inpatient visits across 611 hospitals, 7.4% had record of a CT scan, 5.9% had CKD, and 3.4% had the primary diagnosis of cancer. The baseline risk for an acute renal AE in patients without cancer or CKD and no CT or CM was 0.5%. The absolute risk increases from baseline by 0.2% with a CT and by 0.8% with iodinated CM. Patients with CKD having a CT scan with iodinated CM have an absolute risk of 4.1 to 9.7% depending on the stage of CKD. For patients with cancer, the absolute risk increases, varying from 0.3 to 2.3% depending on the type of cancer. CONCLUSIONS: Inpatients with cancer are at higher likelihood of developing acute renal AEs following CT with iodinated CM compared to those without a cancer. Understanding the underlying risks of acute renal AEs among complex inpatient admissions is an important consideration in treatment choices for oncology patients.

Health Care Burden in Patients With Adrenal Insufficiency.

OBJECTIVE: This study aimed to estimate the annual health care burden for patients with adrenal insufficiency [AI; primary (PAI), secondary to pituitary disorder (PIT), and congenital adrenal hyperplasia (CAH)] using real-world data. METHODS: Using a US-based payer database comprising >108 million members, strict inclusion criteria with diagnostic codes and pharmacy records were used to identify 10,383 patients with AI. This included 1014 patients with PAI, 8818 with PIT, and 551 with CAH, followed for >12 months. Patients were matched 1:1 to controls, based on age (±5 years), sex, insurance, and region. Multivariable expenditure models were estimated for each AI cohort vs controls as well as subsets by glucocorticoid therapy (hydrocortisone, dexamethasone, prednisone, or multiple therapies). A separate multivariable model was estimated to assess the association between adherence and expenditures. RESULTS: Total annual health care expenditure estimates were significantly higher (P < 0.0001) in all AI cohorts compared with matched controls (PAI $18,624 vs $4320, PIT $32,218 vs $6956, CAH $7677 vs $4203). Patients with AI have more frequent inpatient hospital stays with up to eight to 10 times more days in the hospital per year than their matched controls. In each AI cohort, patients on multiple steroid therapies had higher expenditures in comparison with patients using hydrocortisone therapy alone. In PAI and PIT cohorts taking hydrocortisone only, fewer expenditures were found in higher adherence subsets. CONCLUSION: Patients with AI demonstrate a substantial annual health care burden. Expenditures vary by underlying cause and treatment and are reduced in patients with higher adherence to glucocorticoid replacement.

Adolescent Misconduct Behaviors: A Cross-Cultural Perspective of Adolescents and Their Parents.

The primary goal of the current study was to examine cultural differences in Chinese and U.S. adolescents' and parents' perceptions and evaluations of adolescent misconduct behaviors. A total of 395 U.S. and Chinese adolescents (ages 11-19 years) and 255 parents participated in this study. Each participant generated adolescent misconduct behaviors and rated each misconduct behavior as to the degree of wrongness. The misconduct behaviors were coded into 10 categories across three themes (moral offenses, drugs, and conventions). Results revealed significant cultural differences in a number of adolescent misconduct behaviors. For example, the United States generated more misconduct behaviors in weapon offenses and drug use than did China. These cultural differences were further complicated by an interaction between culture and generation. Chinese adolescents were more likely than U.S. adolescents to use categories of school, home, and social conventional violations, and considered these adolescent misconduct behaviors to be more wrong. However, it was the U.S. parents who considered adolescent misconduct behaviors in these categories to be more wrong than did Chinese parents.

Risk of major amputation or death among patients with critical limb ischemia initially treated with endovascular intervention, surgical bypass, minor amputation, or conservative management.

AIMS: Patients with critical limb ischemia (CLI) have an increased risk of major amputation. The initial treatment approach for CLI may significantly impact the subsequent risk of major amputation or death. The objective of this study was to describe the initial treatment approaches of patients with CLI and the limb outcomes associated with each approach. METHODS: Data from MarketScan Commercial and Medicare Supplemental Databases from January 2006-December 2014 was utilized. Cohorts of CLI patients were defined as follows: (1) peripheral vascular intervention (PVI); (2) peripheral vascular surgery (PVS); (3) minor amputation without concomitant PVI or PVS (MinAMP); and (4) Patients without PVI, PVS, or MinAMP (conservative therapy). The odds of major amputation or inpatient death were estimated using the Cox proportional hazards model. For those patients requiring a major amputation, the incremental expenditures per member per month (PMPM) were estimated using a gamma log-link model. RESULTS: Conservative therapy was associated with significantly higher odds of major amputation or inpatient death compared to patients who underwent minor amputation (1.59-times), PVI (2.08-times), or PVS (2.12-times). Patients treated with an initial strategy of minor amputation also had higher odds of major amputation or inpatient death compared to PVS (1.31-times) or PVI (1.33-times). The estimated incremental expenditures PMPM for patients with a major amputation was $5,165. CONCLUSIONS: Revascularization reduces the risk of a major amputation or inpatient death for patients with CLI when compared to conservative therapy. Major amputation is also associated with significantly higher healthcare expenditures.

Systematic Review and Meta-Analysis of Neuropsychiatric Symptoms and Executive Functioning in Adults With Phenylketonuria.

This systematic review and meta-analysis (MA) investigates the impact of elevated blood phenylalanine (Phe) on neuropsychiatric symptoms in adults with phenylketonuria (PKU). The meta-analysis of PKU is challenging because high-quality evidence is lacking due to the limited number of affected individuals and few placebo-controlled, double-blind studies of adults with high and low blood Phe. Neuropsychiatric symptoms associated with PKU exceed general population estimates for inattention, hyperactivity, depression, and anxiety. High Phe is associated with an increased prevalence of neuropsychiatric symptoms and executive functioning deficits whereas low Phe is associated with improved neurological performance. Findings support lifelong maintenance of low blood Phe.

Hormone changes in peripubertal girls.

CONTEXT: Studies of hormone changes in the peripubertal period note increases in adrenal hormones prior to increases in sex steroids. It is unclear how these processes are related to each other, except through this temporal relationship. OBJECTIVE: Examine relationships in adrenal and sex hormones in 252 peripubertal girls. SETTING AND DESIGN: Longitudinal observation study. School districts, at the Cincinnati site of the Breast Cancer and the Environment Research Centers, between 2004-2010. Participants were recruited between ages 6 and 7 years of age and were seen every 6 months. Main outcome measures included height, weight, maturation status, and fasting blood specimen. Serum was analyzed for selected hormones every six months, beginning 30 months prior to, and extending to 6 months after, breast development. Androstenedione, estradiol, estrone, and T were measured by high-performance liquid chromatography (HPLC) with tandem mass spectrometry. Dehydroepiandrosterone-sulfate (DHEA-S) and SHBG also were measured. RESULTS: DHEA-S concentrations increased 24 months before breast development; androstenedione and estrone between 12 to 18 months before breast development; whereas estradiol and T increased, and SHBG fell between 6 and 12 months before breast development. Girls with greater body mass index had lower estradiol concentrations at onset of breast development as well as 6 months after pubertal onset. CONCLUSIONS: Serum estrone and DHEA-S increased prior to estradiol concentrations, and the increase in estradiol occurred prior to breast development. Heavier peripubertal girls have lower estradiol levels at puberty, suggesting peripheral conversion of adrenal androgens to estrone.

Understanding preferences for disclosure of individual biomarker results among participants in a longitudinal birth cohort.

BACKGROUND: To describe the preferences for disclosure of individual biomarker results among mothers participating in a longitudinal birth cohort. METHODS: We surveyed 343 mothers that participated in the Health Outcomes and Measures of the Environment Study about their biomarker disclosure preferences. Participants were told that the study was measuring pesticide metabolites in their biological specimens, and that the health effects of these low levels of exposure are unknown. Participants were asked whether they wanted to receive their results and their child's results. In addition, they were asked about their preferred method (letter vs in person) and format (more complex vs less complex) for disclosure of results. RESULTS: Almost all of the study participants wanted to receive their individual results (340/343) as well as their child's results (342/343). However, preferences for receiving results differed by education level. Mothers with less than a college degree preferred in-person disclosure of results more often than mothers with some college education or a college degree (34.3% vs 17.4% vs 7.9%, p<0.001). Similarly, mothers with less than a college education preferred a less complex disclosure format than mothers with some college education or a college degree (59.7% vs 79.1% vs 86.3%, p<0.0001). CONCLUSION: While almost all study participants preferred to receive results of their individual biomarker tests, level of education was a key factor in predicting preferences for disclosure of biomarker results. To ensure effective communication of this information, disclosure of biomarker results should be tailored to the education level of the study participants.