Adjustment for Renal Function Improves the Prognostic Performance of Urinary Thromboxane Metabolites.

BACKGROUND: Systemic thromboxane A2 generation, assessed by quantifying the concentration of stable thromboxane B2 metabolites (TXB2-M) in the urine adjusted for urinary creatinine, is strongly associated with mortality risk. We sought to define optimal TXB2-M cutpoints for aspirin users and nonusers and determine if adjusting TXB2-M for estimated glomerular filtration rate (eGFR) in addition to urinary creatinine improved mortality risk assessment. METHODS: Urinary TXB2-M were measured by competitive ELISA in 1363 aspirin users and 1681 nonusers participating in the Framingham Heart Study. Cutpoints were determined for TXB2-M and TXB2-M/eGFR using log-rank statistics and used to assess mortality risk by Cox proportional hazard modeling and restricted mean survival time. Multivariable models were compared using the Akaike Information Criterion (AIC). A cohort of 105 aspirin users with heart failure was used for external validation. RESULTS: Optimized cutpoints of TXB2-M were 1291 and 5609 pg/mg creatinine and of TXB2-M/eGFR were 16.6 and 62.1 filtered prostanoid units (defined as pg·min/creatinine·mL·1.73 m2), for aspirin users and nonusers, respectively. TXB2-M/eGFR cutpoints provided more robust all-cause mortality risk discrimination than TXB2-M cutpoints, with a larger unadjusted hazard ratio (2.88 vs 2.16, AIC P < 0.0001) and greater differences in restricted mean survival time between exposure groups (1.46 vs 1.10 years), findings that were confirmed in the external validation cohort of aspirin users. TXB2-M/eGFR cutpoints also provided better cardiovascular/stroke mortality risk discrimination than TXB2-M cutpoints (unadjusted hazard ratio 3.31 vs 2.13, AIC P < 0.0001). CONCLUSION: Adjustment for eGFR strengthens the association of urinary TXB2-M with long-term mortality risk irrespective of aspirin use.

Effect of Poloxamer 188 vs Placebo on Painful Vaso-Occlusive Episodes in Children and Adults With Sickle Cell Disease: A Randomized Clinical Trial.

Importance: Although effective agents are available to prevent painful vaso-occlusive episodes of sickle cell disease (SCD), there are no disease-modifying therapies for ongoing painful vaso-occlusive episodes; treatment remains supportive. A previous phase 3 trial of poloxamer 188 reported shortened duration of painful vaso-occlusive episodes in SCD, particularly in children and participants treated with hydroxyurea. Objective: To reassess the efficacy of poloxamer 188 for vaso-occlusive episodes. Design, Setting, and Participants: Phase 3, randomized, double-blind, placebo-controlled, multicenter, international trial conducted from May 2013 to February 2016 that included 66 hospitals in 12 countries and 60 cities; 388 individuals with SCD (hemoglobin SS, SC, S-ß0 thalassemia, or S-ß+ thalassemia disease) aged 4 to 65 years with acute moderate to severe pain typical of painful vaso-occlusive episodes requiring hospitalization were included. Interventions: A 1-hour 100-mg/kg loading dose of poloxamer 188 intravenously followed by a 12-hour to 48-hour 30-mg/kg/h continuous infusion (n = 194) or placebo (n = 194). Main Outcomes and Measures: Time in hours from randomization to the last dose of parenteral opioids among all participants and among those younger than 16 years as a separate subgroup. Results: Of 437 participants assessed for eligibility, 388 were randomized (mean age, 15.2 years; 176 [45.4%] female), the primary outcome was available for 384 (99.0%), 15-day follow-up contacts were available for 357 (92.0%), and 30-day follow-up contacts were available for 368 (94.8%). There was no significant difference between the groups for the mean time to last dose of parenteral opioids (81.8 h for the poloxamer 188 group vs 77.8 h for the placebo group; difference, 4.0 h [95% CI, -7.8 to 15.7]; geometric mean ratio, 1.2 [95% CI, 1.0-1.5]; P = .09). Based on a significant interaction of age and treatment (P = .01), there was a treatment difference in time from randomization to last administration of parenteral opioids for participants younger than 16 years (88.7 h in the poloxamer 188 group vs 71.9 h in the placebo group; difference, 16.8 h [95% CI, 1.7-32.0]; geometric mean ratio, 1.4 [95% CI, 1.1-1.8]; P = .008). Adverse events that were more common in the poloxamer 188 group than the placebo group included hyperbilirubinemia (12.7% vs 5.2%); those more common in the placebo group included hypoxia (12.0% vs 5.3%). Conclusions and Relevance: Among children and adults with SCD, poloxamer 188 did not significantly shorten time to last dose of parenteral opioids during vaso-occlusive episodes. These findings do not support the use of poloxamer 188 for vaso-occlusive episodes. Trial Registration: ClinicalTrials.gov Identifier: NCT01737814.

Paramedian incisional complications after prophylactic laparoscopy-assisted gastropexy in 411 dogs.

OBJECTIVE: To determine the frequency and types of paramedian incisional complications after prophylactic laparoscopy-assisted gastropexy (LAG) in dogs and to evaluate potential risk factors for complications. STUDY DESIGN: Multi-institutional retrospective study. ANIMALS: Client-owned dogs (N = 411). METHODS: Records for dogs that underwent single-incision-port laparoscopy-assisted gastropexy (SIPLAG) or multiple-port laparoscopy-assisted gastropexy (MPLAG) at five veterinary referral hospitals were reviewed. Information regarding signalment, surgical procedures, perioperative care, and incisional complications was collected. Follow-up information was obtained by review of medical records and/or communication with owners. Potential risk factors for complications were examined statistically. RESULTS: Paramedian incisional complications were observed in 78 of 411 (19%) dogs. The most common complication was seroma formation, which occurred in 51 (12.4%) dogs. Surgical site infections were observed in 16 (3.9%) dogs, and dehiscence or development of excessive scar tissue at the incision site were each observed in nine (2.2%) dogs. Complications resolved with conservative treatment in 75 of 78 (96.2%) dogs and with surgical treatment in three of 78 (3.8%) dogs. The odds of complications were approximately twice as high in dogs undergoing SIPLAG than in dogs undergoing MPLAG (odds ratio, 2.03; P = .006). CONCLUSION: Minor paramedian incisional complications, particularly seroma formation, were frequently observed after LAG. Most complications were successfully managed conservatively. Single-incision-port laparoscopy-assisted gastropexy was associated with a higher complication rate compared with MPLAG. CLINICAL SIGNIFICANCE: Owners should be informed that there is a relatively high rate of minor paramedian incisional complications after LAG. The risk of complications appears to be higher for SIPLAG than for MPLAG.

Comparison of a computed tomographic pulmonary trunk to aorta diameter ratio with echocardiographic indices of pulmonary hypertension in dogs.

There are limited criteria for the detection of pulmonary hypertension in dogs undergoing computed tomography (CT) for pulmonary disease. This retrospective analytical exploratory study compared a CT pulmonary trunk to aorta ratio with echocardiographic estimates of pulmonary hypertension. Dogs having both a contrast thoracic CT and echocardiogram were selected and maximal pulmonary trunk and descending aorta diameters were measured by two observers on a single transverse CT image. Computed tomographic diameter ratios were compared with the echocardiographic parameters of tricuspid regurgitation gradient, right ventricular acceleration time-to-ejection time ratio, pulmonary insufficiency gradient, and pulmonary artery to aorta diameter. A total of 78 dogs were sampled, with 44 dogs having one or more finding suggestive of pulmonary hypertension. A moderate positive correlation was shown between tricuspid regurgitation gradient and CT pulmonary trunk to aorta ratio (r = 0.61, P-value < 0.0001). Mean CT pulmonary trunk to aorta ratio of dogs with moderate (P = 0.0132) and severe (P < 0.0003) pulmonary hypertension were significantly higher than normal dogs. There was no significant difference in mean CT pulmonary trunk to aorta ratio between normal and mild pulmonary hypertension dogs (P = 0.4244). The intraclass correlation coefficient (0.72) showed good reproducibility of the ratio. Findings indicated that CT pulmonary trunk to aorta ratio is a reproducible and potentially useful method to predict moderate and severe pulmonary hypertension in dogs, but not mild pulmonary hypertension. In dogs undergoing thoracic CT for pulmonary disease, an increased ratio should prompt follow up echocardiography.

Cortisol response to the Trier Social Stress Test in pregnant women at risk for postpartum depression.

Antepartum depression and anxiety are risk factors for postpartum depression (PPD). Postpartum abnormalities in hypothalamic-pituitary-adrenal (HPA) reactivity are associated with PPD. It is not known if antepartum HPA abnormalities exist in women at risk for PPD (AR-PPD). We measured salivary cortisol response to the Trier Social Stress Test (TSST) in 44 (24 AR-PPD, 20 healthy comparison) pregnant women. Depression and anxiety were measured using the Edinburgh Postnatal Depression Scale (EPDS) and Spielberger State-Trait Anxiety Inventory-State (STAI-S). We analyzed longitudinal changes in cortisol using generalized estimating equation methods to control for the correlation within subjects at the six TSST time points. Group differences in area under the curve (AUC) were examined. A majority (70.8 %) of the AR-PPD had prior depression. EPDS total score was higher in AR-PPD vs. comparison women (mean EPDS = 9.8 ± 4.9 vs. mean EPDS = 2.4 ± 2.0 respectively, p < 0.001). Mean STAI-S total score was higher in AR-PPD vs. comparison women at all TSST time points and over time (z = 2.71, df = 1, p = 0.007). There was no significant difference in cortisol concentration over time between groups. We observed no detectable difference in cortisol response to psychosocial stress induced by the TSST despite clinically significant between-group differences in current/past depression and current symptomatology.

Prevalence and risk factors for postpartum depression symptoms among women with disabilities.

The adverse consequences of postpartum depression on the health of the mother and her child are well documented. However, there is little information on postpartum depression among mothers with disabilities. This study examines the patterns of depression and depressive symptoms before, during and after pregnancy and the association between depression before and during pregnancy and postpartum depression symptomatology (PPD) among women with and without disabilities. Data from the 2009-2011 Rhode Island Pregnancy Risk Assessment Monitoring System (PRAMS) were analyzed in 2013. Almost 30% (28.9%; 95% CI 22.8-35.8) of mothers with disabilities reported often or always feeling down, depressed or sad after childbirth compared to 10% of those without disabilities (95% CI 8.9-11.3). Compared to other women in the study, women with disabilities had a greater likelihood for PPD symptoms (RR 1.6, 95% CI 1.1-2.2) after accounting for sociodemographics, maternal characteristics related to PPD, and depression before and during pregnancy. Adjusting for other covariates, self-reported prenatal diagnosis of depression was not associated with symptoms of PPD and depression during pregnancy was marginally associated with PPD symptomatology for women with disabilities. Women with disabilities are at a greater risk of experiencing symptoms of postpartum depression than other women. Screening for PPD among new mothers with disabilities and timely referral of those with PPD diagnosis are vital to the health of mothers with disabilities and their children.

Evaluating progression of liver disease from repeat liver biopsies in children with chronic hepatitis C: a retrospective study.

UNLABELLED: Clinical and histologic progression of liver disease in untreated children with chronic hepatitis C virus (HCV) infection is poorly documented. The aim of this retrospective study was to characterize changes in liver histology over time in a cohort of HCV-infected children who had more than one liver biopsy separated by over 1 year. Forty-four untreated children without concurrent liver diseases, who had repeat liver biopsies at eight U.S.-based medical centers, were included. Biopsies were scored by a single pathologist for inflammation, fibrosis, and steatosis and were correlated with demographic data including age at biopsy, time from infection to biopsies, and laboratory values such as serum alanine aminotransferase (ALT). Mode of transmission was vertical in 25 (57%) and from transfusions in 17 children (39%). Genotype 1 was present in 30/35 (84%) children. The mean age at first and final biopsy was 8.6 and 14.5 years, respectively, and the mean interval between biopsies was 5.8 ± 3.5 years. Duration of infection to biopsy was 7.7 and 13.5 years, respectively. Laboratory values did not change significantly between the biopsies. Inflammation was minimal in about 50% at both timepoints. Fibrosis was absent in 16% in both biopsies, limited to portal/periportal in 73% in the first biopsy, and 64% in the final biopsy. Between the two biopsies, the proportion of patients with bridging fibrosis/cirrhosis increased from 11% to 20% (P = 0.005). CONCLUSION: Although in aggregate this cohort did not show significant histologic progression of liver disease over 5 years, 29.5% (n = 13) of children showed an increase in severity of fibrosis. These findings may have long-term implications for the timing of follow-up biopsies and treatment decisions.

Improved incident reporting following the implementation of a standardized emergency department peer review process.

OBJECTIVE: Incident reporting is an important component of health care quality improvement. The objective of this investigation was to evaluate the effectiveness of an emergency department (ED) peer review process in promoting incident reporting. DESIGN: An observational, interrupted time-series analysis of health care provider (HCP) incident reporting to the ED during a 30-month study period prior to and following the peer review process implementation and a survey-based assessment of physician perceptions of the peer review process' educational value and its effectiveness in identifying errors. SETTING: Large, urban, academic ED. PARTICIPANTS AND INTERVENTIONS: HCPs were invited to participate in a standardized, non-punitive, non-anonymous peer review process that involved analysis and structured discussion of incident reports submitted to ED physician leadership. MAIN OUTCOME MEASURES: Monthly frequency of incident reporting by HCPs and physician perceptions of the peer review process. RESULTS: HCPs submitted 314 incident reports to the ED over the study period. Following the intervention, frequency of reporting by HCPs within the hospital increased over time. The frequencies of self-reporting, reporting by other ED practitioners and reporting by non-ED practitioners within the hospital increased compared with a control group of outside HCPs (P = 0.0019, P = 0.0025 and P < 0.0001). Physicians perceived the peer review process to be educational and highly effective in identifying errors. CONCLUSIONS: The implementation of a non-punitive peer review process that provides timely feedback and is perceived as being valuable for error identification and education can lead to increased incident reporting by HCPs.

Personal and parental weight misperception and self-reported attempted weight loss in US children and adolescents, National Health and Nutrition Examination Survey, 2007-2008 and 2009-2010.

INTRODUCTION: The objective of our study was to describe perceptions of child weight status among US children, adolescents, and their parents and to examine the extent to which accurate personal and parental perception of weight status is associated with self-reported attempted weight loss. METHODS: Our study sample comprised 2,613 participants aged 8 to 15 years in the National Health and Nutrition Examination Survey from the 2 most recent consecutive cycles (2007-2008 and 2009-2010). Categories of weight perception were developed by comparing measured to perceived weight status. Multivariable logistic regression analyses were used to examine the association between weight misperception and self-reported attempted weight loss. RESULTS: Among children and adolescents, 27.3% underestimated and 2.8% overestimated their weight status. Among parents, 25.2% underestimated and 1.1% overestimated their child's weight status. Logistic regression analyses showed that the odds of self-reported attempted weight loss was 9.5 times as high (95% confidence interval [CI]: 3.8-23.6) among healthy-weight children and adolescents who overestimated their weight status as among those who perceived their weight status accurately; the odds of self-reported attempted weight loss were 3.9 (95% CI, 2.4-6.4) and 2.9 (95% CI, 1.8-4.6) times as high among overweight and obese children and adolescents, respectively, who accurately perceived their weight status than among those who underestimated their weight status. Parental misperception of weight was not significantly associated with self-reported attempted weight loss among children and adolescents who were overweight or obese. CONCLUSION: Efforts to prevent childhood obesity should incorporate education for both children and parents regarding the proper identification and interpretation of actual weight status. Interventions for appropriate weight loss can target children directly because one of the major driving forces to lose weight comes from the child's perception of his or her weight status.

Proteomics identifies complement protein signatures in patients with alcohol-associated hepatitis.

Diagnostic challenges continue to impede development of effective therapies for successful management of alcohol-associated hepatitis (AH), creating an unmet need to identify noninvasive biomarkers for AH. In murine models, complement contributes to ethanol-induced liver injury. Therefore, we hypothesized that complement proteins could be rational diagnostic/prognostic biomarkers in AH. Here, we performed a comparative analysis of data derived from human hepatic and serum proteome to identify and characterize complement protein signatures in severe AH (sAH). The quantity of multiple complement proteins was perturbed in liver and serum proteome of patients with sAH. Multiple complement proteins differentiated patients with sAH from those with alcohol cirrhosis (AC) or alcohol use disorder (AUD) and healthy controls (HCs). Serum collectin 11 and C1q binding protein were strongly associated with sAH and exhibited good discriminatory performance among patients with sAH, AC, or AUD and HCs. Furthermore, complement component receptor 1-like protein was negatively associated with pro-inflammatory cytokines. Additionally, lower serum MBL associated serine protease 1 and coagulation factor II independently predicted 90-day mortality. In summary, meta-analysis of proteomic profiles from liver and circulation revealed complement protein signatures of sAH, highlighting a complex perturbation of complement and identifying potential diagnostic and prognostic biomarkers for patients with sAH.

Pegylated interferon for chronic hepatitis C in children affects growth and body composition: results from the pediatric study of hepatitis C (PEDS-C) trial.

UNLABELLED: Weight loss and changes in growth are noted in children treated with interferon alpha (IFN-α). The aim of this study was to prospectively determine changes in weight, height, body mass index (BMI), and body composition during and after treatment of children with hepatitis C virus (HCV). Children treated with pegylated interferon alpha-2a (Peg-IFN-α2a) ± ribavirin in the Pediatric Study of Hepatitis C (PEDS-C) trial underwent anthropometric measurements, dual-energy X-ray absorptiometry scan, as well as dietary and activity assessments during and after treatment. One hundred and fourteen (55% male) children, with a mean age of 11 ± 3 years, were randomized, and 107 received treatment for at least 24 weeks. Subjects were divided into three groups according to duration of treatment: 24 (N = 14), 48 (N = 82), or 72 (N = 11) weeks. Decrements of up to 0.50 z score were observed for weight, height, and BMI while on therapy among all groups (P ≤ 0.01, compared to baseline). In the group treated for 48 weeks, 29 (33%) subjects had greater than 0.5-unit decrement in height-for-age z (HAZ) score. Though weight-for-age and BMI z scores returned to baseline after cessation of therapy, mean HAZ score was slower to rebound, still lower than baseline at 96 weeks post-therapy for the long-treatment duration group (P = 0.03) and lower than baseline in most children treated for 48 weeks. Percent body fat, fat-free mass z scores, and triceps skinfold z scores decreased with therapy. Dietary energy intake and levels of physical activity did not change during treatment. CONCLUSIONS: Peg-IFN-α2a was associated with significant changes in body weight, linear growth, BMI, and body composition in children. These effects were generally reversible with cessation of therapy, although HAZ scores had not returned to baseline after 2 years of observation in many. Longer term growth data are needed among children treated for chronic HCV.

Autoantibodies and autoimmune disease during treatment of children with chronic hepatitis C.

OBJECTIVES: Autoantibodies were studied in a well-characterized cohort of children with chronic hepatitis C during treatment with pegylated interferon and ribavirin to assess the relation with treatment and development of autoimmune disease. METHODS: : A total of 114 children (5-17 years), screened for the presence of high-titer autoantibodies, were randomized to pegylated interferon with or without ribavirin. Anti-nuclear, anti-liver-kidney-microsomal, anti-thyroglobulin, anti-thyroid peroxidase, insulin, anti-glutamic acid decarboxylase (GAD) antibodies were measured after trial completion using frozen sera. RESULTS: At baseline, 19% had autoantibodies: anti-nuclear antibodies (8%), anti-liver-kidney-microsomal antibodies (4%), and glutamic acid decarboxylase antibodies (4%). At 24 and 72 weeks (24 weeks after treatment completion), 23% and 26% had autoantibodies (P=0.50, 0.48 compared with baseline). One child developed diabetes and 2 hypothyroidism during treatment; none developed autoimmune hepatitis. At 24 weeks, the incidence of flu-like symptoms, gastrointestinal symptoms, and headaches was 42%, 8% and 19% in those with autoantibodies versus 52%, 17%, and 26% in those without (P=0.18, 0.36, and 0.20, respectively). In children with negative hepatitis C virus polymerase chain reaction at 24 weeks, there was no difference in the rate of early virologic response/sustained virologic response, respectively, in those with autoantibodies 76%/69% vs 58%/65% in those without (P=0.48). CONCLUSIONS: Despite screening, we found autoantibodies commonly at baseline, during treatment for chronic hepatitis C and after. The presence of antibodies did not correlate with viral response, adverse effects, or autoimmune hepatitis. Neither screening nor archived samples assayed for thyroid and diabetes-related antibodies identified the 3 subjects who developed overt autoimmune disease, diabetes (1), and hypothyroidism (2).

A liposomal bupivacaine infiltrative block reduces rescue analgesia administration compared to a bupivacaine splash block after canine ovariohysterectomy in a teaching laboratory.

OBJECTIVE: This study aimed to determine whether an infiltrative block with liposomal bupivacaine was associated with less rescue analgesia administration and lower pain scores than a bupivacaine splash block after ovariohysterectomy in dogs. ANIMALS: Eligible dogs included those that were spayed as part of a veterinary teaching laboratory. Dogs were up to 7 years old and otherwise healthy. A total of 136 dogs were analyzed. METHODS: All dogs underwent ovariohysterectomy performed by veterinary students. Dogs received hydromorphone and acepromazine premedication, propofol induction, isoflurane maintenance, and an NSAID. Dogs were randomly allocated to receive either a splash block with standard bupivacaine or an infiltrative block with liposomal bupivacaine for incisional analgesia. Postoperatively, all dogs were assessed by a blinded evaluator using the Colorado State University-Canine Acute Pain Scale (CSU-CAPS) and Glasgow Composite Measures Pain Scale-Short Form (GCPS-SF). Dogs received rescue analgesia with buprenorphine if they scored ≥ 2 on the CSU-CAPS scale. RESULTS: Dogs that received liposomal bupivacaine had a significantly lower incidence of (P = .04) and longer time to (P = .03) administration of rescue analgesia. There was an overall time-averaged significant difference between groups for CSU-CAPS (P = .049) and GCPS-SF scores (P = .015), with dogs in the bupivacaine group being more likely to have an elevated pain score at some point for both scales. CLINICAL RELEVANCE: The use of liposomal bupivacaine in an infiltrative block may decrease the need for rescue analgesia in dogs undergoing ovariohysterectomy compared to a bupivacaine splash block.

Design of a multicenter randomized clinical trial for treatment of Alcohol-Associated Hepatitis.

Background: Mortality is high for severe alcohol-associated hepatitis (AH). Corticosteroids are the standard of care for patients without contraindications. Recent data showed that interleukin-1ß receptor antagonist anakinra attenuated inflammation and liver damage. We designed a multicenter, double-blind, randomized controlled trial to assess the safety and efficacy of anakinra compared to prednisone. Methods: Patients meeting the clinical and biochemical criteria for severe AH with MELD scores between 20 and 35 were recruited at eight clinical sites. Eligible patients enrolled in the study were randomized to anakinra, 100 mg subcutaneous injection for 14 days, plus zinc sulfate 220 mg for 90 days, vs. prednisone 40 mg PO daily for 30 days. Matching placebos for anakinra, zinc, and prednisone were provided to mask the treatment. Participants were followed for 180 days. The primary outcome was overall survival at 90 days. An unadjusted log-rank test was used to compare the survival of the two treatments in the first 90 days. Between July 10, 2020, and March 4, 2022, we screened 1082 patients with severe AH, and 147 eligible patients were enrolled and randomized. The average baseline MELD score was 25 [range 20-35], Maddrey discriminant function (MDF) was 59.4 [range 20.2-197.5]. The mean aspartate transaminase (AST)-to-alanine transaminase (ALT) ratio was 3.5. The baseline characteristics were not statistically different between the two treatment groups. Conclusions: The study provided a direct comparison of the survival benefits and safety profiles of anakinra plus zinc vs. prednisone in patients with severe AH.

Height, adiposity and body fat distribution and breast density in young women.

INTRODUCTION: Breast density is one of the strongest risk factors for breast cancer, but determinants of breast density in young women remain largely unknown. METHODS: Associations of height, adiposity and body fat distribution with percentage dense breast volume (%DBV) and absolute dense breast volume (ADBV) were evaluated in a cross-sectional study of 174 healthy women, 25 to 29 years old. Adiposity and body fat distribution were measured by anthropometry and dual-energy X-ray absorptiometry (DXA), while %DBV and ADBV were measured by magnetic resonance imaging. Associations were evaluated using linear mixed-effects models. All tests of statistical significance are two-sided. RESULTS: Height was significantly positively associated with %DBV but not ADBV; for each standard deviation (SD) increase in height, %DBV increased by 18.7% in adjusted models. In contrast, all measures of adiposity and body fat distribution were significantly inversely associated with %DBV; a SD increase in body mass index (BMI), percentage fat mass, waist circumference and the android:gynoid fat mass ratio (A:G ratio) was each associated significantly with a 44.4 to 47.0% decrease in %DBV after adjustment for childhood BMI and other covariates. Although associations were weaker than for %DBV, all measures of adiposity and body fat distribution also were significantly inversely associated with ADBV before adjustment for childhood BMI. After adjustment for childhood BMI, however, only the DXA measures of percentage fat mass and A:G ratio remained significant; a SD increase in each was associated with a 13.8 to 19.6% decrease in ADBV. In mutually adjusted analysis, the percentage fat mass and the A:G ratio remained significantly inversely associated with %DBV, but only the A:G ratio was significantly associated with ADBV; a SD increase in the A:G ratio was associated with an 18.5% decrease in ADBV. CONCLUSION: Total adiposity and body fat distribution are independently inversely associated with %DBV, whereas in mutually adjusted analysis only body fat distribution (A:G ratio) remained significantly inversely associated with ADBV in young women. Research is needed to identify biological mechanisms underlying these associations.

The combination of ribavirin and peginterferon is superior to peginterferon and placebo for children and adolescents with chronic hepatitis C.

BACKGROUND & AIMS: Although randomized trials of adults infected with hepatitis C virus (HCV) have shown that ribavirin increases the efficacy of pegylated interferon (PEG), such trials have not been performed in children. We conducted a randomized controlled trial of PEG and ribavirin, compared with PEG and placebo, in children 5 to 17 years old with chronic hepatitis C. METHODS: HCV RNA-positive children from 11 university medical centers were randomly assigned to receive either PEG alfa-2a (PEG-2a; 180 µg/1.73 m(2) body surface area, subcutaneously each week; n = 55) and ribavirin (15 mg/kg orally in 2 doses daily) or PEG-2a and placebo (n = 59) for 48 weeks. The primary end point was sustained virologic response (SVR; lack of detectable HCV RNA at least 24 weeks after stopping therapy). RESULTS: SVR was achieved in 53% of children treated with PEG-2a and ribavirin, compared with 21% of children who received PEG-2a and placebo (P < .001). Early virologic response (HCV RNA reduction >2 log(10) IU at 12 weeks) had a negative predictive value of only 0.89 in children with genotype 1, indicating that these children might benefit from 24 weeks of therapy before stopping treatment. Side effects, especially neutropenia, led to dose modification in 40% of children. Eighty-two percent of the PEG/ribavirin and 86% of the PEG/placebo group were in compliance with the year 2 follow-up visit; the durability of virologic response was 100% in both groups. CONCLUSIONS: The combination of PEG and ribavirin is superior to PEG and placebo as therapy for chronic hepatitis C in children and adolescents.

Self-reported adherence with the use of a device in a clinical trial as validated by electronic monitors: the VIBES study.

BACKGROUND: Adherences to treatments that require a behavioral action often rely on self-reported recall, yet it is vital to determine whether real time self reporting of adherence using a simple logbook accurately captures adherence. The purpose of this study was to determine whether real time self-reported adherence is an accurate measurement of device usage during a clinical trial by comparing it to electronic recording. METHODS: Using data collected from older adult men and women (N=135, mean age 82.3 yrs; range 66 to 98 yrs) participating in a clinical trial evaluating a vibrating platform for the treatment of osteoporosis, daily adherence to platform treatment was monitored using both self-reported written logs and electronically recorded radio-frequency identification card usage, enabling a direct comparison of the two methods over one year. Agreement between methods was also evaluated after stratification by age, gender, time in study, and cognition status. RESULTS: The two methods were in high agreement (overall intraclass correlation coefficient = 0.96). The agreement between the two methods did not differ between age groups, sex, time in study and cognitive function. CONCLUSIONS: Using a log book to report adherence to a daily intervention requiring a behavioral action in older adults is an accurate and simple approach to use in clinical trials, as evidenced by the high degree of concordance with an electronic monitor.

Ergocalciferol in New-onset Type 1 Diabetes: A Randomized Controlled Trial.

CONTEXT: The effect of the anti-inflammatory and immunomodulatory actions of vitamin D on the duration of partial clinical remission (PR) in youth with type 1 diabetes (T1D) is unclear. OBJECTIVE: This work aimed to determine the effect of adjunctive ergocalciferol on residual ß-cell function (RBCF) and PR in youth with newly diagnosed T1D who were maintained on a standardized insulin treatment protocol. The hypothesis was that ergocalciferol supplementation increases RBCF and prolongs PR. METHODS: A 12-month, randomized, double-blind, placebo-controlled trial was conducted of 50 000 IU of ergocalciferol per week for 2 months, and then once every 2 weeks for 10 months, vs placebo in 36 individuals aged 10 to 21 years, with T1D of less than 3 months and a stimulated C-peptide (SCP) level greater than or equal to 0.2 nmol/L (≥ 0.6 ng/mL). The ergocalciferol group had 18 randomly assigned participants (10 male/8 female), mean age 13.3 ±â€…2.8 years, while the control group had 18 participants (14 male/4 female), aged 14.3 ±â€…2.9 years. RESULTS: The ergocalciferol treatment group had statistically significantly higher serum 25-hydroxyvitamin D at 6 months (P = .01) and 9 months (P = .02) than the placebo group. At 12 months, the ergocalciferol group had a statistically significantly lower serum tumor necrosis factor α (TNF-α) concentration (P = .03). There were no statistically significant differences between the groups at each time point from baseline to 12 months for SCP concentration (P = .08), glycated hemoglobin A1c (HbA1c) (P = .09), insulin dose-adjusted A1c (IDAA1c), or total daily dose of insulin. Temporal trends for rising HbA1c (P = .04) and IDAA1c (P = .02) were statistically significantly blunted in the ergocalciferol group. CONCLUSION: Ergocalciferol statistically significantly reduced serum TNF-α concentration and the rates of increase both in A1c and IDAA1c, suggesting a protection of RBCF and PR in youth with newly diagnosed T1D.

Association of Thromboxane Generation With Survival in Aspirin Users and Nonusers.

BACKGROUND: Persistent systemic thromboxane generation, predominantly from nonplatelet sources, in aspirin (ASA) users with cardiovascular disease (CVD) is a mortality risk factor. OBJECTIVES: This study sought to determine the mortality risk associated with systemic thromboxane generation in an unselected population irrespective of ASA use. METHODS: Stable thromboxane B2 metabolites (TXB2-M) were measured by enzyme-linked immunosorbent assay in banked urine from 3,044 participants (mean age 66 ± 9 years, 53.8% women) in the Framingham Heart Study. The association of TXB2-M to survival over a median observation period of 11.9 years (IQR: 10.6-12.7 years) was determined by multivariable modeling. RESULTS: In 1,363 (44.8%) participants taking ASA at the index examination, median TXB2-M were lower than in ASA nonusers (1,147 pg/mg creatinine vs 4,179 pg/mg creatinine; P < 0.0001). TXB2-M were significantly associated with all-cause and cardiovascular mortality irrespective of ASA use (HR: 1.96 and 2.41, respectively; P < 0.0001 for both) for TXB2-M in the highest quartile based on ASA use compared with lower quartiles, and remained significant after adjustment for mortality risk factors for similarly aged individuals (HR: 1.49 and 1.82, respectively; P ≤ 0.005 for both). In 2,353 participants without CVD, TXB2-M were associated with cardiovascular mortality in ASA nonusers (adjusted HR: 3.04; 95% CI: 1.29-7.16) but not in ASA users, while ASA use was associated with all-cause mortality in those with low (adjusted HR: 1.46; 95% CI: 1.14-1.87) but not elevated TXB2-M. CONCLUSIONS: Systemic thromboxane generation is an independent risk factor for all-cause and cardiovascular mortality irrespective of ASA use, and its measurement may be useful for therapy modification, particularly in those without CVD.

Epidemiological and clinical features of Panton-Valentine Leukocidin positive Staphylococcus aureus bacteremia: A case-control study.

BACKGROUND: Panton-Valentine Leukocidin (PVL) toxin in Staphylococcus aureus has been associated with both severe pneumonia and skin and soft tissue infections. However, there are only limited data on how this virulence factor may influence the clinical course or complications of bacteremic S. aureus infections. METHODS: Between September 2016 and March 2018, S. aureus isolates from clinical cultures from hospitals in an academic medical center underwent comprehensive genomic sequencing. Four hundred sixty-nine (29%) of 1681 S. aureus sequenced isolates were identified as containing the genes that encode for PVL. Case patients with one or more positive blood cultures for PVL were randomly matched with control patients having positive blood cultures with lukF/lukS-PV negative (PVL strains from a retrospective chart review). RESULTS: 51 case and 56 control patients were analyzed. Case patients were more likely to have a history of injection drug use, while controls more likely to undergo hemodialysis. Isolates from 78.4% of case patients were methicillin resistant as compared to 28.6% from control patients. Case patients had a higher incidence of pneumonia and skin and soft tissue infection and longer duration of fever without differences in length of bacteremia. Clinical cure or expiration was comparable. CONCLUSIONS: These results are consistent with prior observations associating the PVL toxin with both community-acquired MRSA strains as well as severe staphylococcal pneumonia. The presence of the PVL toxin does not appear to otherwise influence the natural history of bacteremic S. aureus disease other than in prolonging the duration of fever.