Dawn Peters

Dual-Energy X-Ray Absorptiometry for Quantification of Visceral Fat

Obesity is the major risk factor for metabolic syndrome and through it diabetes as well as cardiovascular disease. Visceral fat (VF) rather than subcutaneous fat (SF) is the major predictor of adverse events. Currently, the reference standard for measuring VF is abdominal X‐ray computed tomography (CT) or magnetic resonance imaging (MRI), requiring highly used clinical equipment. Dual‐energy X‐ray absorptiometry (DXA) can accurately measure body composition with high‐precision, low X‐ray exposure, and short‐scanning time. The purpose of this study was to validate a new fully automated method whereby abdominal VF can be measured by DXA. Furthermore, we explored the association between DXA‐derived abdominal VF and several other indices for obesity: BMI, waist circumference, waist‐to‐hip ratio, and DXA‐derived total abdominal fat (AF), and SF. We studied 124 adult men and women, aged 18–90 years, representing a wide range of BMI values (18.5–40 kg/m2) measured with both DXA and CT in a fasting state within a one hour interval. The coefficient of determination (r2) for regression of CT on DXA values was 0.959 for females, 0.949 for males, and 0.957 combined. The 95% confidence interval for r was 0.968 to 0.985 for the combined data. The 95% confidence interval for the mean of the differences between CT and DXA VF volume was −96.0 to −16.3 cm3. Bland‐Altman bias was +67 cm3 for females and +43 cm3 for males. The 95% limits of agreement were −339 to +472 cm3 for females and −379 to +465 cm3 for males. Combined, the bias was +56 cm3 with 95% limits of agreement of −355 to +468 cm3. The correlations between DXA‐derived VF and BMI, waist circumference, waist‐to‐hip ratio, and DXA‐derived AF and SF ranged from poor to modest. We conclude that DXA can measure abdominal VF precisely in both men and women. This simple noninvasive method with virtually no radiation can therefore be used to measure VF in individual patients and help define diabetes and cardiovascular risk.

Determinants of Prolonged QT Interval and Their Contribution to Sudden Death Risk in Coronary Artery Disease: The Oregon Sudden Unexpected Death Study

Background— In a recent cohort study, prolongation of the corrected QT interval (QTc) was associated with an independent increased risk of sudden cardiac death (SCD). We evaluated determinants of prolonged QTc and the relationship of prolonged QTc to SCD risk among patients with coronary artery disease in the general population. Methods and Results— A case-control design was used. Cases were SCD patients with coronary artery disease among a metropolitan area of 1 000 000 residents (2002 to 2006); controls were area residents with coronary artery disease but no history of SCD. All cases were required to have an ECG suitable for QTc analysis before and unrelated to the occurrence of SCD. A total of 373 cases and 309 controls met criteria for analysis. Mean QTc was significantly longer in cases than in controls (450±45 versus 433±37 ms; P<0.0001). In a multivariate model, gender, diabetes mellitus, and QTc-prolonging drugs were significant determinants of QTc prolongation in controls. In a logistic regression model predicting SCD, diabetes mellitus (odds ratio, 1.97; 95% confidence interval, 1.32 to 2.96) and use of QTc-prolonging drugs (odds ratio, 2.90; 95% confidence interval, 1.92 to 4.37) were significant predictors of SCD among subjects with normal or borderline QTc. However, abnormally prolonged QTc in the absence of diabetes and QT-prolonging medications was the strongest predictor of SCD (odds ratio, 5.53; 95% confidence interval, 3.20 to 9.57). Conclusions— Diabetes mellitus and QTc-affecting drugs determined QTc prolongation and were predictors of SCD in coronary artery disease. However, idiopathic abnormal QTc prolongation was associated with 5-fold increased odds of SCD. A continued search for novel determinants of QTc prolongation such as genomic factors is likely to enhance risk stratification for SCD in coronary artery disease.

Prevalence of Colon Polyps Detected by Colonoscopy Screening in Asymptomatic Black and White Patients

CONTEXT Compared with white individuals, black men and women have a higher incidence and mortality from colorectal cancer and may develop cancer at a younger age. Colorectal cancer screening might be less effective in black individuals, if there are racial differences in the age-adjusted prevalence and location of cancer precursor lesions. OBJECTIVES To determine and compare the prevalence rates and location of polyps sized more than 9 mm in diameter in asymptomatic black and white individuals who received colonoscopy screening. DESIGN, SETTING, AND PATIENTS Colonoscopy data were prospectively collected from 67 adult gastrointestinal practice sites in the United States using a computerized endoscopic report generator between January 1, 2004, and December 31, 2005. Data were transmitted to a central data repository, where all asymptomatic white (n = 80 061) and black (n = 5464) patients who had received screening colonoscopy were identified. MAIN OUTCOME MEASURES Prevalence and location of polyps sized more than 9 mm, adjusted for age, sex, and family history of colorectal cancer in a multivariate analysis. RESULTS Both black men and women had a higher prevalence of polyps sized more than 9 mm in diameter compared with white men and women (422 [7.7%] vs 4964 [6.2%]; P < .001). Compared with white patients, the adjusted odds ratio (OR) for black men was 1.16 (95% confidence interval [CI], 1.01-1.34) and the adjusted OR for black women was 1.62 (95% CI, 1.39-1.89). Black and white patients had a similar risk of proximal polyps sized more than 9 mm (OR, 1.13;95% CI, 0.93-1.38). However, in a subanalysis of patients older than 60 years, proximal polyps sized more than 9 mm were more likely prevalent in black men (P = .03) and women (P < .001) compared with white men and women. CONCLUSION Compared with white individuals, black men and women undergoing screening colonoscopy have a higher risk of polyps sized more than 9 mm, and black individuals older than 60 years are more likely to have proximal polyps sized more than 9 mm.

Vitamin C Supplementation for Pregnant Smoking Women and Pulmonary Function in Their Newborn Infants: A Randomized Clinical Trial

IMPORTANCE Maternal smoking during pregnancy adversely affects offspring lung development, with lifelong decreases in pulmonary function and increased asthma risk. In a primate model, vitamin C blocked some of the in-utero effects of nicotine on lung development and offspring pulmonary function. OBJECTIVE To determine if newborns of pregnant smokers randomized to receive daily vitamin C would have improved results of pulmonary function tests (PFTs) and decreased wheezing compared with those randomized to placebo. DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind trial conducted in 3 sites in the Pacific Northwest between March 2007 and January 2011. One hundred fifty-nine newborns of randomized pregnant smokers (76 vitamin C treated and 83 placebo treated) and 76 newborns of pregnant nonsmokers were studied with newborn PFTs. Follow-up assessment including wheezing was assessed through age 1 year, and PFTs were performed at age 1 year. INTERVENTIONS Pregnant women were randomized to receive vitamin C (500 mg/d) (n = 89) or placebo (n = 90). MAIN OUTCOMES AND MEASURES The primary outcome was measurement of newborn pulmonary function (ratio of the time to peak tidal expiratory flow to expiratory time [TPTEF:TE] and passive respiratory compliance per kilogram [Crs/kg]) within 72 hours of age. Secondary outcomes included incidence of wheezing through age 1 year and PFT results at age 1 year. A subgroup of pregnant smokers and nonsmokers had genotyping performed. RESULTS Newborns of women randomized to vitamin C (n = 76), compared with those randomized to placebo (n = 83), had improved pulmonary function as measured by TPTEF:TE (0.383 vs 0.345 [adjusted 95% CI for difference, 0.011-0.062]; P = .006) and Crs/kg (1.32 vs 1.20 mL/cm H2O/kg [95% CI, 0.02-0.20]; P = .01). Offspring of women randomized to vitamin C had significantly decreased wheezing through age 1 year (15/70 [21%] vs 31/77 [40%]; relative risk, 0.56 [95% CI, 0.33-0.95]; P = .03). There were no significant differences in the 1-year PFT results between the vitamin C and placebo groups. The effect of maternal smoking on newborn lung function was associated with maternal genotype for the α5 nicotinic receptor (rs16969968) (P < .001 for interaction). CONCLUSIONS AND RELEVANCE Supplemental vitamin C taken by pregnant smokers improved newborn PFT results and decreased wheezing through 1 year in the offspring. Vitamin C in pregnant smokers may be an inexpensive and simple approach to decrease the effects of smoking in pregnancy on newborn pulmonary function and respiratory morbidities. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00632476.

Abnormal Skeletal Muscle Capillary Recruitment During Exercise in Patients With Type 2 Diabetes Mellitus and Microvascular Complications

OBJECTIVES We sought to determine whether skeletal muscle capillary recruitment is impaired in type 2 diabetes mellitus (DM) with and without microvascular complications (MC). BACKGROUND Insulin and exercise each stimulate recruitment of skeletal muscle capillaries. Insulin-mediated recruitment is impaired in insulin-resistant humans and animals, but exercise-mediated recruitment has not been studied. METHODS We studied 20 control subjects, 22 patients with DM, and 8 patients with DM + MC. With the patients under fasting conditions, contrast-enhanced ultrasound perfusion imaging of the forearm flexor muscles was performed to evaluate capillary blood flow and blood volume at rest and during low- or high-intensity contractile exercise (25% and 80% maximal handgrip). Rheologic parameters of erythrocyte deformability and plasma viscosity were measured. RESULTS Muscle capillary responses to exercise were similar between the control and DM groups, but were reduced (p < 0.05) in those with DM + MC. The DM + MC group had a approximately 50% reduction in capillary recruitment and a approximately 60% to 70% reduction in capillary blood flow during both low- and high-intensity exercise compared with the control group. These abnormalities were independent of disease duration. Patients with DM + MC were more insulin resistant than DM patients and had an elevated whole blood viscosity that correlated with plasma glucose (p = 0.001) and C-reactive protein (p = 0.003). CONCLUSIONS Capillary recruitment during low- and high-intensity exercise is normal in uncomplicated type 2 DM but is impaired in those with microvascular complications. Abnormalities in capillary recruitment may be related to abnormal hemorheology, although larger trials are needed to establish this relation.

Prevalence of upper gastrointestinal tract findings in patients with noncardiac chest pain versus those with gastroesophageal reflux disease (GERD)-related symptoms: results from a national endoscopic database.

BACKGROUND:Available data on the prevalence of esophageal and upper gut findings in patients with noncardiac chest pain (NCCP) are scarce and limited to one centers experience.AIM:To determine the prevalence of esophageal and upper gut mucosal findings in patients undergoing upper endoscopy for NCCP only versus those with gastroesophageal reflux disease (GERD) symptoms only, using the national Clinical Outcomes Research Initiative (CORI) database.METHODS:During the study period, the CORI database received endoscopic reports from a network of 76 community, university, and Veteran Administration Health Care System (VAHCS)/military practice sites. All adult patients who underwent an upper endoscopy for NCCP only or GERD-related symptoms only were identified. Demographic characteristics and prevalence of endoscopic findings were compared between the two groups.RESULTS:A total of 3,688 consecutive patients undergoing an upper endoscopy for NCCP and 32,981 for GERD were identified. Normal upper endoscopy was noted in 44.1% of NCCP patients versus 38.8% of those with GERD (P < 0.0001). Of the NCCP group, 28.6% had a hiatal hernia (HH), 19.4% erosive esophagitis (EE), 4.4% Barretts esophagus (BE), and 3.6% stricture/stenosis. However, HH, EE, and BE were significantly more common in the GERD group as compared with the NCCP group (44.8%, 27.8%, and 9.1%, respectively, P < 0.0001). In univariate analysis of patients with NCCP, male gender was a risk factor for BE (OR 1.86, 95% CI 1.35–2.55, P = 0.0001) and being nonwhite was protective (OR 0.43, 95% CI 0.22–0.86, P = 0.02). In this group, male gender was also a risk factor for EE (OR 1.31, 95% CI 1.11–1.54, P = 0.001) and age ≥65 yr was protective (OR 0.73, 95% CI 0.6–0.89, P = 0.002). The NCCP group had a significantly higher prevalence of peptic ulcer in the upper gastrointestinal tract as compared with the GERD group (2.0% vs 1.5%, P = 0.01).CONCLUSIONS:In this endoscopic prevalence study, most of the endoscopic findings in NCCP were GERD related, but less common as compared with GERD patients.

Histologic and receptor analysis of primary and secondary vestibulodynia and controls: a prospective study

OBJECTIVE The objective of the study was to assess the association between hormone receptor densities, pain nerves, and inflammation in vestibulodynia patients. STUDY DESIGN In a prospective study, tender and nontender biopsies from 10 primary and 10 secondary vestibulodynia patients were compared with biopsies in 4 nontender controls. Hormone receptors were evaluated using immunohistochemistry for estrogen receptor-alpha and -beta, androgen, and progesterone receptors. Inflammation, nerves, and mast cells were assessed histologically. Statistical analysis was by Fishers exact test, analysis of variance, paired Student t test, and Wilcoxon rank test. RESULTS Tender sites from primary vestibulodynia had increased nerve density compared with secondary and control biopsies (P = .01). Tender sites in secondary vestibulodynia had more lymphocytes than tender primary sites and control biopsies (P < .0001). Mast cells were increased in tender sites compared with nontender and controls. There were no differences in hormone receptor expression. CONCLUSION Markers of inflammation differed between primary and secondary vestibulodynia and controls.

Respiratory compliance in preterm infants after a single rescue course of antenatal steroids: a randomized controlled trial

OBJECTIVE To compare respiratory compliance and functional residual capacity in infants randomized to a rescue course of antenatal steroids vs placebo. STUDY DESIGN Randomized, double-blinded trial. Pregnant women > or =14 days after initial antenatal steroids were randomized to rescue antenatal steroids or placebo. The primary outcomes were measurements of respiratory compliance and functional residual capacity. This study is registered with clinicaltrials.gov (NCT00669383). RESULTS Forty-four mothers (56 infants) received rescue antenatal steroids and 41 mothers (57 infants) received placebo. There was no significant difference in birthweight, or head circumference. Infants in the rescue group had an increased respiratory compliance (1.21 vs 1.01 mL/cm H(2)O/kg; adjusted 95% confidence interval, 0.01-0.49; P = .0433) compared with placebo. 13% in the rescue vs 29% in the placebo group required > or =30% oxygen (P < .05). Patients delivered at < or =34 weeks had greater pulmonary benefits. CONCLUSION Infants randomized to rescue antenatal steroids have a significantly increased respiratory compliance compared with placebo.

Differences in Primary Compared With Secondary Vestibulodynia by Immunohistochemistry

OBJECTIVE: To assess whether primary and secondary vestibulodynia represent different pathologic pathways. METHODS: This was an analysis of archived vestibulectomy specimens from 88 premenopausal women with vestibulodynia (2002–2008). Patient records were reviewed to classify the type of vestibulodynia, duration of symptoms, and hormone status. Histologic sections were stained for hematoxylin and eosin to grade inflammation, S100 to highlight nerves, CD117 for mast cells, estrogen receptor &agr;, and progesterone receptor. Differences between primary and secondary vestibulodynia were tested by t tests, chi-square analysis, and linear and logistic regression. RESULTS: Primary vestibulodynia showed significant neural hypertrophy and hyperplasia (P=.02, adjusted odds ratio [OR] 3.01, 95% confidence interval [CI] 1.2–7.6) and increased progesterone receptor nuclear immunostaining (P=.004, adjusted OR 3.94, CI 1.6–9.9) compared with secondary vestibulodynia. Estrogen receptor &agr; expression was also greater in primary vestibulodynia when symptom diagnosis was less than 5 years (P=.004, adjusted OR 5.53 CI 1.71–17.91). CONCLUSION: Primary and secondary vestibulodynia have significantly different histologic features, suggesting that they may have separate mechanistic pathways. Clinically, this may mean the discovery of distinct conditions. LEVEL OF EVIDENCE: II

Identifying and distinguishing cases of parkinsonism and Parkinson's disease using ICD-9 CM codes and pharmacy data

Administrative databases have the potential to assess quality and cost of care for parkinsonism and Parkinsons disease. However, the validity of findings is limited by our understanding of how cases are identified. Patient records listing International Classification of Diseases, Version 9, Clinical Modification (ICD‐9 CM) codes for parkinsonism (n = 2,076) and dopaminergic medications (n = 2,798) were pulled from fiscal years 1999 to 2001 for patients in the Pacific Northwest Veterans Administration. Samples of these records (n = 397) and records without these ICD‐9 CM codes (n = 500) were reviewed, and clinical data were extracted. The accuracy of administrative data to identify and distinguish between Parkinsons disease and parkinsonism was calculated. A total of 37.9% of parkinsonism cases were detected using pharmacy data and ICD‐9 CM codes compared to 18.7% by using ICD‐9 CM codes alone. The ICD‐9 CM code for paralysis agitans (332.0) did not distinguish between probable Parkinsons disease and other causes of parkinsonism, whereas the ICD‐9 CM code for degenerative basal ganglia disorder (333.0) predicted having secondary parkinsonism (odds ratio [OR] = 5.0) as well as dopa‐responsiveness in patients without secondary parkinsonism (OR = 4.5). Administrative data are limited in the ability to identify parkinsonism. The ICD‐9 CM code, 332.0, which is generally considered the code to identify Parkinsons disease, did not distinguish between parkinsonism and Parkinsons disease.