Beverley Adams-Huet

Relationship of psoriasis severity to obesity using same‐gender siblings as controls for obesity

Background.  Psoriasis is a multifactorial disease affected by both genetic and environmental factors. Several comorbid conditions, such as smoking, depression and obesity have been found to be associated with psoriasis. This study addressed the association of psoriasis and obesity using same‐gender full siblings as controls, correlating between body mass index (BMI) and severity of psoriasis as determined by body surface area (BSA) and the Physician’s Global Assessment (PGA).

Association of Hyperchloremia with Hospital Mortality in Critically Ill Septic Patients

Objectives:Hyperchloremia is frequently observed in critically ill patients in the ICU. Our study aimed to examine the association of serum chloride (Cl) levels with hospital mortality in septic ICU patients. Design:Retrospective cohort study. Setting:Urban academic medical center ICU. Patients:ICU adult patients with severe sepsis or septic shock who had Cl measured on ICU admission were included. Those with baseline estimated glomerular filtration rate less than 15 mL/min/1.73 m2 or chronic dialysis were excluded. Interventions:None. Measurements and Main Results:Of 1,940 patients included in the study, 615 patients (31.7%) had hyperchloremia (Cl ≥ 110 mEq/L) on ICU admission. All-cause hospital mortality was the dependent variable. Cl on ICU admission (Cl0), Cl at 72 hours (Cl72), and delta Cl (&Dgr;Cl = Cl72 – Cl0) were the independent variables. Those with Cl0 greater than or equal to 110 mEq/L were older and had higher cumulative fluid balance, base deficit, and Sequential Organ Failure Assessment scores. Multivariate analysis showed that higher Cl72 but not Cl0 was independently associated with hospital mortality in the subgroup of patients with hyperchloremia on ICU admission (adjusted odds ratio for Cl72 per 5 mEq/L increase = 1.27; 95% CI, 1.02–1.59; p = 0.03). For those who were hyperchloremic on ICU admission, every within-subject 5 mEq/L increment in Cl72 was independently associated with hospital mortality (adjusted odds ratio for &Dgr;Cl 5 mEq/L = 1.37; 95% CI, 1.11–1.69; p = 0.003). Conclusions:In critically ill septic patients manifesting hyperchloremia (Cl ≥ 110 mEq/L) on ICU admission, higher Cl levels and within-subject worsening hyperchloremia at 72 hours of ICU stay were associated with all-cause hospital mortality. These associations were independent of base deficit, cumulative fluid balance, acute kidney injury, and other critical illness parameters.

A multicentre, cross-sectional study on quality of life in patients with cutaneous lupus erythematosus.

Background  A study at the University of Pennsylvania (UPenn) Medical Center demonstrated that quality of life in patients with cutaneous lupus erythematosus (CLE) is negatively impacted. Whether patients with CLE in other geographic locations have similar quality of life is unknown.

Comparison of visceral fat mass measurement by dual-X-ray absorptiometry and magnetic resonance imaging in a multiethnic cohort: the Dallas Heart Study

Background/Objectives:Visceral adipose tissue (VAT) mass, a risk factor for cardiometabolic complications of obesity, is usually measured by magnetic resonance imaging (MRI) but this method is not practical in a clinical setting. In contrast, measurement of VAT by dual-x-ray absorptiometry (DXA) appears to circumvent the limitations of MRI. In this study, we compared measurements of VAT mass by MRI and DXA in the large, multiethnic cohort of the Dallas Heart Study (DHS).Subjects/Methods:About 2689 DHS participants underwent paired measurement of VAT by MRI and DXA. Sex-stratified analyses were performed to evaluate the correlation and agreement between DXA and MRI. Model validation was performed using bootstrapping and inter-reader variability was assessed.Results:Mean age of the cohort was 44 years, with 55% female, 48% Black and 75% overweight/obese participants. Regression analysis showed a linear relationship between DXA and MRI with R2=0.82 (95% confidence interval (CI) 0.81–0.84) for females and R2=0.86 (95% CI 0.85–0.88) for males. Mean difference between methods was 0.01 kg for females and 0.09 kg for males. Bland–Altman analysis showed that DXA tended to modestly underestimate VAT compared with MRI at lower VAT levels and overestimate it compared with MRI at higher VAT levels. Results were consistent in analyses stratified by race, body mass index status, waist girth and body fat. Inter-individual reader correlation among 50 randomly selected scans was excellent (inter-class correlation coefficient=0.997).Conclusions:VAT mass quantification by DXA was both accurate and valid among a large, multiethnic cohort within a wide range of body fatness. Further studies including repeat assessments over time will help determine its long-term applicability.

Cumulative Fluid Balance and Mortality in Septic Patients With or Without Acute Kidney Injury and Chronic Kidney Disease.

Objective:Incident acute kidney injury and prevalent chronic kidney disease are commonly encountered in septic patients. We examined the differential effect of acute kidney injury and chronic kidney disease on the association between cumulative fluid balance and hospital mortality in critically ill septic patients. Design:Retrospective cohort study. Setting:Urban academic medical center ICU. Patients:ICU adult patients with severe sepsis or septic shock and serum creatinine measured within 3 months prior to and 72 hours of ICU admission. Patients with estimated glomerular filtration rate less than 15 mL/min/1.73 m2 or receiving chronic dialysis were excluded. Interventions:None. Measurements and Main Results:A total of 2,632 patients, 1,211 with chronic kidney disease, were followed up until hospital death or discharge. Acute kidney injury occurred in 1,525 patients (57.9%), of whom 679 (44.5%) had chronic kidney disease. Hospital mortality occurred in 603 patients (22.9%). Every 1-L increase in cumulative fluid balance at 72 hours of ICU admission was independently associated with hospital mortality in all patients (adjusted odds ratio, 1.06 [95% CI] 1.04–1.08; p < 0.001), and in each acute kidney injury/chronic kidney disease subgroup (adjusted odds ratio, 1.06 [1.03–1.09] for acute kidney injury+/chronic kidney disease+; 1.09 [1.05–1.13] for acute kidney injury–/chronic kidney disease+; 1.05 [1.03–1.08] for acute kidney injury+/chronic kidney disease–; and 1.07 [1.02–1.11] for acute kidney injury–/chronic kidney disease–). There was a significant interaction between acute kidney injury and chronic kidney disease on cumulative fluid balance (p =0.005) such that different cumulative fluid balance cut-offs with the best prognostic accuracy for hospital mortality were identified: 5.9 L for acute kidney injury+/chronic kidney disease+; 3.8 L for acute kidney injury–/chronic kidney disease+; 4.3 L for acute kidney injury+/chronic kidney disease–; and 1.5 L for acute kidney injury–/chronic kidney disease–. The addition of cumulative fluid balance to the admission Sequential Organ Failure Assessment score had increased prognostic utility for hospital mortality when compared with Sequential Organ Failure Assessment alone, particularly in patients with acute kidney injury. Conclusions:Higher cumulative fluid balance at 72 hours of ICU admission was independently associated with hospital mortality regardless of acute kidney injury or chronic kidney disease presence. We characterized cumulative fluid balance cut-offs associated with hospital mortality based on acute kidney injury/chronic kidney disease status, underpinning the heterogeneity of fluid regulation in sepsis and kidney disease.

Premature coronary heart disease and autosomal dominant hypercholesterolemia: Increased risk in women with LDLR mutations.

BACKGROUND For patients with autosomal dominant hypercholesterolemia (ADH), it remains unclear whether differences exist in the risk of premature coronary heart disease (CHD) between patients with confirmed mutations in low-density lipoprotein receptor (LDLR) vs those without detectable mutations. OBJECTIVE This study sought to assess the risk of premature CHD in ADH patients with mutations in LDLR (referred to as familial hypercholesterolemia [FH]) vs those without detectable mutations (unexplained ADH), stratified by sex. METHODS Comparative study of premature CHD in a multiethnic cohort of 111 men and 165 women meeting adult Simon-Broome criteria for ADH. RESULTS Women with FH (n = 51) had an increased risk of premature CHD compared with unexplained ADH women (n = 111; hazard ratio [HR], 2.74; 95% confidence interval, 1.40-5.34; P = .003) even after adjustment for lipid levels and traditional CHD risk factors (HR, 2.53 [1.10-5.83]; P = .005). Men with FH (n = 42), in contrast, had a similar risk of premature CHD when compared with unexplained ADH men (n = 66; unadjusted: HR, 1.48 [0.84-2.63]; P = .18; adjusted: HR, 1.04 [0.46-2.37]; P = .72). To address whether mutation status provides additional information beyond LDL-cholesterol level, we analyzed premature CHD risk for FH vs unexplained ADH at various percentiles of LDL-cholesterol: the risk ratios were significant for women at 25th percentile (HR, 4.90 [1.69-14.19]) and 50th percentile (HR, 3.44 [1.42-8.32]) but not at 75th percentile (HR, 1.99 [0.95-4.17]), and were not significant for men at any percentile. CONCLUSIONS Our findings suggest that genetic confirmation of ADH may be important to identify patients risk of CHD, especially for female LDLR mutation carriers.

Effect Modification of Chronic Kidney Disease on the Association of Circulating and Imaging Cardiac Biomarkers With Outcomes

Background Cardiac troponin T and brain natriuretic peptide (BNP) are elevated in >50% of dialysis patients and are associated with poor outcomes. Few data investigated these associations in earlier chronic kidney disease (CKD). Methods and Results We studied whether CKD modified associations of elevated BNP, N‐terminal‐pro‐BNP, high‐sensitivity cardiac troponin T, coronary artery calcification, and left ventricular hypertrophy with all‐cause death and cardiovascular death/events in 3218 multiethnic individuals followed for 12.5 years, and whether biomarkers added prognostic information to traditional cardiovascular risk factors in CKD. Of the cohort, 279 (9%) had CKD. There were 296 deaths and 218 cardiovascular deaths/events. Of non‐CKD individuals, 7% died and 6% had cardiovascular death/event versus 32% and 30% of CKD participants, P<0.001 for both. The interaction between BNP and CKD on death was significant (P=0.01): the adjusted hazard ratio in CKD was 2.05, 95% CI (1.34, 3.14), but not significant in non‐CKD, 1.04 (0.76, 1.41). CKD modified the association of high‐sensitivity cardiac troponin T with cardiovascular death/event, adjusted hazard ratio 3.34 (1.56, 7.18) in CKD versus 1.65 (1.16, 2.35) in non‐CKD, interaction P=0.09. There was an interaction between N‐terminal‐pro‐BNP and CKD for death in those without prior cardiovascular disease. Addition of each biomarker to traditional risk factors improved risk prediction, except coronary artery calcification was not discriminatory for cardiovascular death/event in CKD. Conclusions Cardiac biomarkers, with the exception of coronary artery calcification, prognosticated outcomes in early‐stage CKD as well as, if not better than, in non‐CKD individuals, even after controlling for estimated glomerular filtration rate, and added to information obtained from traditional cardiovascular risk factors alone.

Effect of Adding Liraglutide vs Placebo to a High-Dose lnsulin Regimen in Patients With Type 2 Diabetes: A Randomized Clinical Trial

IMPORTANCE An increasing number of patients with type 2 diabetes are treated with high doses of insulin. Such treatment is associated with weight gain, hypoglycemia, and high treatment burden. OBJECTIVE To assess the effectiveness and safety of adding a glucagon-like peptide 1 receptor agonist to the treatment regimen of patients with type 2 diabetes requiring therapy with high-dose insulin. DESIGN, SETTING, AND PARTICIPANTS This clinical trial was a double-blind, placebo-controlled, randomized (1:1) study with 6 months of follow-up, conducted from August 13, 2012, to February 9, 2015, at ambulatory clinics at the University of Texas Southwestern Medical Center and Parkland Hospital. Participants were 71 patients with uncontrolled type 2 diabetes (glycated hemoglobin level, 7.5%-11.0%) using more than 1.5 U/kg/d of insulin. INTERVENTIONS Subcutaneous injection of liraglutide (1.8 mg/d) or matching placebo for 6 months. MAIN OUTCOMES AND MEASURES The primary outcome was the change in glycated hemoglobin level. Secondary outcomes were changes in weight, hypoglycemia rate, insulin dosage, and quality-of-life measures. RESULTS Among 71 patients, 45 (63%) were female. The mean (SD) age of patients was 54.2 (7.4) years, with a mean (SD) type 2 diabetes duration of 17.9 (8.4) years and a mean (SD) total daily dose of insulin of 247.0 (95.1) U. Ninety-three percent (66 of 71) of participants completed all scheduled visits. The glycated hemoglobin level improved from a mean (SD) of 9.0% (1.2%) to 7.9% (1.1%) in the liraglutide group (P < .001) and remained unchanged (8.9%) in the placebo group, with an estimated treatment difference of 0.9% (95% CI, -1.5 to -0.4) (P = .002). Weight decreased from a mean (SD) of 114.6 (21.4) kg to 113.6 (20.8) kg in the liraglutide group vs a mean (SD) increase from 116.1 (26.6) kg to 117.2 (27.2) kg in the placebo group, with a treatment difference of -2.3 kg (95% CI, -4.3 to -0.4 kg) (P = .02). The total daily dose of insulin decreased 11.5% (95% CI, -21.8% to -1.1%) in the liraglutide group (P = .20). The hypoglycemia rate was higher in the first month after initiation of liraglutide compared with placebo (2.30 vs 0.91 events per person-month, P = .01), while the overall hypoglycemia rate over the entire follow-up was similar between groups (P = .11). Glycemia control perception, satisfaction with insulin treatment, and willingness to continue insulin use improved more in the liraglutide group. CONCLUSIONS AND RELEVANCE Liraglutide added to high-dose insulin therapy improved glycemic control, decreased body weight, and enhanced treatment satisfaction in this difficult-to-treat patient population with high-dose insulin requirements. Further studies are warranted to confirm these findings and evaluate the long-term risk and benefit of this treatment option. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01505673.

Respiratory modulation of human autonomic function on Earth

We studied healthy supine astronauts on Earth with electrocardiogram, non‐invasive arterial pressure, respiratory carbon dioxide concentrations, breathing depth and sympathetic nerve recordings. The null hypotheses were that heart beat interval fluctuations at usual breathing frequencies are baroreflex mediated, that they persist during apnoea, and that autonomic responses to apnoea result from changes of chemoreceptor, baroreceptor or lung stretch receptor inputs. R‐R interval fluctuations at usual breathing frequencies are unlikely to be baroreflex mediated, and disappear during apnoea. The subjects’ responses to apnoea could not be attributed to changes of central chemoreceptor activity (hypocapnia prevailed); altered arterial baroreceptor input (vagal baroreflex gain declined and muscle sympathetic nerve burst areas, frequencies and probabilities increased, even as arterial pressure climbed to new levels); or altered pulmonary stretch receptor activity (major breathing frequency and tidal volume changes did not alter vagal tone or sympathetic activity). Apnoea responses of healthy subjects may result from changes of central respiratory motoneurone activity.

Respiratory modulation of human autonomic function: long‐term neuroplasticity in space

We studied healthy astronauts before, during and after the Neurolab Space Shuttle mission with controlled breathing and apnoea, to identify autonomic changes that might contribute to postflight orthostatic intolerance. Measurements included the electrocardiogram, finger photoplethysmographic arterial pressure, respiratory carbon dioxide levels, tidal volume and peroneal nerve muscle sympathetic activity. Arterial pressure fell and then rose in space, and drifted back to preflight levels after return to Earth. Vagal metrics changed in opposite directions: vagal baroreflex gain and two indices of vagal fluctuations rose and then fell in space, and descended to preflight levels upon return to Earth. Sympathetic burst frequencies (but not areas) were greater than preflight in space and on landing day, and astronauts’ abilities to modulate both burst areas and frequencies during apnoea were sharply diminished. Spaceflight triggers long‐term neuroplastic changes reflected by reciptocal sympathetic and vagal motoneurone responsiveness to breathing changes.