Validation of HIV-infected cohort identification using automated clinical data in the Department of Veterans Affairs.

OBJECTIVES: The US Department of Veterans Affairs (VA) is the largest integrated health care provider for HIV-infected patients in the USA. VA data for HIV-specific clinical and quality improvement research are an important resource. We sought to determine the accuracy of using the VA Corporate Data Warehouse (CDW), a fully automated medical records database for all VA users nationally, to identify HIV-infected patients compared with a gold-standard VA HIV Clinical Case Registry (CCR). METHODS: We assessed the test performance characteristics of each of our CDW criteria-based algorithms (presence of one, two or all of the following: diagnostic codes for HIV, positive HIV laboratory tests, and prescription for HIV medication) by calculating their sensitivity (proportion of HIV-positive patients in the CCR accurately detected as HIV-positive by the CDW algorithm) and positive predictive value (PPV; the proportion of patients identified by the CDW algorithm who were classified as HIV-positive from the CCR). RESULTS: We found that using a CDW algorithm requiring two of three HIV diagnostic criteria yielded the highest sensitivity (95.2%) with very little trade-off in PPV (93.5%). CONCLUSIONS: A two diagnostic criteria-based algorithm can be utilized to accurately identify HIV-infected cohorts seen in the nationwide VA health care system.

Real-world effectiveness of elbasvir/grazoprevir In HCV-infected patients in the US veterans affairs healthcare system.

Elbasvir/grazoprevir (EBR/GZR) is an all-oral direct-acting antiviral agent (DAA) with high sustained virologic response (SVR) in clinical trials. This study's primary objective was to evaluate effectiveness of EBR/GZR among HCV-infected patients in a real-world clinical setting. We conducted a nationwide retrospective observational cohort study of HCV-infected patients in the US Department of Veterans Affairs (VA) using the VA Corporate Data Warehouse. The study population included patients with positive HCV RNA who initiated EBR/GZR from February 1 to August 1, 2016. We calculated the 95% confidence interval for binomial proportions for SVR overall and by demographic subgroups. Clinical and demographic characteristics were also evaluated. We included 2436 patients in the study cohort. Most were male (96.5%), African American (57.5%), with mean age of 63.5 (SD = 5.9) and 95.4% infected with genotype (GT) 1 [GT1a (34.7%), GT1b (58.6%)]. Other comorbidities included diabetes (53.2%), depression (57.2%) and HIV (3.0%). More than 50% had history of drug or alcohol abuse (53.9% and 60.5%, respectively). 33.2% of the cohort had cirrhosis. A total of 95.6% (2,328/2,436; 95% CI: 94.7%-96.4%) achieved SVR. The SVR rates by subgroups were: male, 95.5% (2245/2350); female, 96.5% (83/86); GT1a, 93.4%, GT1b, 96.6%, GT4, 96.9%, African American, 95.9% (1,342/1,400); treatment-experienced, 96.3% (310/322); cirrhosis, 95.6% (732/766); stage 4-5 CKD, 96.3% (392/407); and HIV, 98.6% (73/74). SVR rates were high overall and across patient subgroups regardless of gender, race/ethnicity, cirrhosis, renal impairment or HIV. This study provided important data regarding the effectiveness of EBR/GZR in a large clinical setting.

Validity of code based algorithms to identify primary open angle glaucoma (POAG) in Veterans Affairs (VA) administrative databases.

PURPOSE: The validity of the International Classification of Diseases, 9th revision, Clinical Modification (ICD-9) code for primary open angle glaucoma (POAG) in the Department of Veterans Affairs (VA) electronic medical record has not been examined. We determined the accuracy of the ICD-9 code for POAG and developed diagnostic algorithms for the detection of POAG. METHODS: We conducted a retrospective study of abstracted data from the Michael E. DeBakey VA Medical Center's medical records of 334 unique patients with at least one visit to the Eye Clinic between 1999 and 2013. Algorithms were developed to validly identify POAG using ICD-9 codes and pharmacy data. The positive predictive value (PPV), negative predictive value (NPV), sensitivity, specificity and percent agreement of the various algorithms were calculated. RESULTS: For the ICD-9 code 365.1x, the PPV was 65.9%, NPV was 95.2%, sensitivity was 100%, specificity was 82.6%, and percent agreement was 87.8%. The algorithm with the highest PPV was 76.3%, using pharmacy data in conjunction with two or more ICD-9 codes for POAG, but this algorithm also had the lowest NPV at 88.2%. CONCLUSIONS: Various algorithms for identifying POAG in the VA administrative databases have variable validity. Depending on the type of research being done, the ICD-9 code 365.1x can be used for epidemiologic or health services database research.

Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression.

The hypothesis that the S allele of the 5-HTTLPR serotonin transporter promoter region is associated with increased risk of depression, but only in individuals exposed to stressful situations, has generated much interest, research and controversy since first proposed in 2003. Multiple meta-analyses combining results from heterogeneous analyses have not settled the issue. To determine the magnitude of the interaction and the conditions under which it might be observed, we performed new analyses on 31 data sets containing 38 802 European ancestry subjects genotyped for 5-HTTLPR and assessed for depression and childhood maltreatment or other stressful life events, and meta-analysed the results. Analyses targeted two stressors (narrow, broad) and two depression outcomes (current, lifetime). All groups that published on this topic prior to the initiation of our study and met the assessment and sample size criteria were invited to participate. Additional groups, identified by consortium members or self-identified in response to our protocol (published prior to the start of analysis) with qualifying unpublished data, were also invited to participate. A uniform data analysis script implementing the protocol was executed by each of the consortium members. Our findings do not support the interaction hypothesis. We found no subgroups or variable definitions for which an interaction between stress and 5-HTTLPR genotype was statistically significant. In contrast, our findings for the main effects of life stressors (strong risk factor) and 5-HTTLPR genotype (no impact on risk) are strikingly consistent across our contributing studies, the original study reporting the interaction and subsequent meta-analyses. Our conclusion is that if an interaction exists in which the S allele of 5-HTTLPR increases risk of depression only in stressed individuals, then it is not broadly generalisable, but must be of modest effect size and only observable in limited situations.

Hepatitis C virus-related complications are increasing in women veterans: A national cohort study.

There are gender-specific variations in the epidemiology and clinical course of hepatitis C virus (HCV) infection. However, few long-term longitudinal studies have examined trends in the incidence and prevalence of serious liver complications among women compared with men with HCV infection. We used the Veterans Administration Corporate Data Warehouse to identify all veterans with positive HCV viraemia from January 2000 to December 2013. We calculated gender-specific annual incidence and prevalence rates of cirrhosis, decompensated cirrhosis and hepatocellular cancer (HCC) adjusting for age, diabetes, HIV and alcohol use. We also calculated the average annual per cent change (AAPC) for each outcome by gender using piecewise linear regression in the Joinpoint software. We identified 264 409 HCV-infected veterans during 2000-2013, of whom 7162 (2.7%) were women. There were statistically significant increases over time in the incidence rates of cirrhosis, decompensated cirrhosis and HCC for both men and women. The annual-adjusted incidence rates of cirrhosis, decompensated cirrhosis and HCC were higher in men than women for all study years. However, these complications increased at a similar rate in both groups. Specifically, the AAPC for cirrhosis was 13.1 and 15.2, while it was 15.6 and 16.9 for decompensated cirrhosis and 21.0 and 25.3 for HCC in men and women, respectively (all test of parallelism not significant). The results were similar in the prevalence analyses, although AAPCs were slightly smaller for each outcome. In conclusion, we found an ongoing upward trend in the incidence and prevalence of HCV complications in this cohort of HCV-infected women. This increase in cirrhosis complications in women with active HCV infection is similar to those in men. With cure from HCV now becoming a reality, most of the projected burden of HCV is potentially preventable. However, benefits of HCV treatment will need to extend to all patients in order to stem the rising tide of HCV complications.

Physical activity and the risk of Barrett's esophagus.

Physical activity either directly or through influencing body fat may affect the risk of Barrett's esophagus (BE). However, the effect of physical activity on the risk of developing BE has not been examined. We conducted a case-control study among consecutive eligible patients either scheduled for elective endoscopy or recruited from primary care clinics to undergo a study endoscopy. Study participants completed the International Physical Activity Questionnaire (IPAQ) short form that measures physical activity during the past 7 days. We categorized level of physical activity by low, moderate, or high and estimated metabolic equivalent minutes per week (MET min/week). We calculated odds ratios (ORs) using logistic regression models and adjusted for age, sex, race, gastroesophageal reflux disease symptoms, Helicobacter pylori infection, body mass index, and waist-to-hip ratio. There were 307 cases with BE and 1724 controls (1262 from endoscopy and 462 from the primary care clinic) with IPAQ information. BE cases were more likely to be in the high-category physical activity category than controls (14.3% vs. 11.5% P = 0.08). However, there were no differences in the overall average MET min/week for walking between BE cases and controls (909 vs. 561; P = 0.16), with similar findings among those with moderate activity (1094 vs. 755, P = 0.18) or vigorous activity (784 vs. 826, P = 0.93). In multivariable logistic regression, physical activity level was not significantly associated with BE (OR = 1.19, 95% confidence interval: 0.82-1.73). Recent amount and intensity of physical activity are not associated with a reduction in the risk of BE. Studies are required to examine the long-term effects of physical activity.

Personal and family history of cancer and the risk of Barrett's esophagus in men.

The association between Barrett's esophagus (BE) and a personal or family history of cancer other than gastroesophageal remains unknown. To evaluate the effect of personal and family history of certain cancers and cancer treatments on the risk of BE, we analyzed data from a Veterans Affairs case-control study that included 264 men with definitive BE (cases) and 1486 men without BE (controls). Patients with history of esophageal or gastric cancer were excluded. Patients underwent elective esophagogastroduodenoscopy or a study esophagogastroduodenoscopy concurrently with screening colonoscopy to determine BE status. Personal and family history of several types of cancer was obtained from self-reported questionnaires, supplemented and verified by electronic medical-record reviews. We estimated the association between personal and family history of cancer or radiation/chemotherapy, and BE. Personal history of oropharyngeal cancer (1.5% vs. 0.4%) or prostate cancer (7.2% vs. 4.4%) was more frequently present in cases than controls. The association between BE and prostate cancer persisted in multivariable analyses (adjusted odds ratio 1.90; 95% confidence interval 1.07-3.38, P = 0.028) while that with oropharyngeal cancer (adjusted odds ratio 3.63; 95% confidence interval 0.92-14.29, P = 0.066) was attenuated after adjusting for retained covariates of age, race, gastroesophageal reflux disease, hiatal hernia, and proton pump inhibitor use. Within the subset of patients with cancer, prior treatment with radiation or chemotherapy was not associated with BE. There were no significant differences between cases and controls in the proportions of subjects with several specific malignancies in first- or second-degree relatives. In conclusion, the risk of BE in men may be elevated with prior personal history of oropharyngeal or prostate cancer. However, prior cancer treatments and family history of cancer were not associated with increased risk of BE. Further studies are needed to elucidate if there is a causative relationship or shared risk factors between prostate cancer and BE.

Poor sleep quality and obstructive sleep apnea in patients with GERD and Barrett's esophagus.

BACKGROUND: Gastroesophageal reflux disease (GERD) reduces sleep quality. Whether Barrett's esophagus (BE) affects sleep differently is unknown. Obstructive sleep apnea (OSA) often coexists with GERD and may disrupt sleep; whether GERD reduces sleep quality independently of OSA is unknown. Our aims were to compare the effect of GERD and BE on sleep quality, and assess the impact of OSA on this association. METHODS: Validated questionnaires for GERD symptoms, sleep quality, and OSA risk were prospectively administered to subjects undergoing upper endoscopy. GERD was defined by erosive esophagitis and/or reflux symptoms >1/week. BE was defined histologically. Controls had normal endoscopy and were asymptomatic. Poor sleep quality was defined by a Pittsburgh Sleep Quality Index score >5. Risk of OSA was defined by a positive Berlin Questionnaire. The risk poor sleep quality in GERD, BE, and controls was evaluated in multivariate models. KEY RESULTS: 83 GERD, 63 BE, and 75 controls were included. OSA and poor sleep quality were significantly more frequent in GERD (65% and 60%) but not BE (52% and 46%) compared with controls (48% and 39%). Controlling for age, race, gender, smoking, body mass index, and hypertension, the risk of poor sleep quality was significantly increased in GERD compared with controls (odds ratio [OR] = 2.79, 95% confidence interval [CI]: 1.08-6.80), significance was lost after adding OSA to the model (OR = 2.27, 95% CI: 0.87-5.85). CONCLUSIONS & INFERENCES: GERD but not BE increases the risk of poor sleep quality. This association is not independent of OSA.

Dietary consumption of meat, fat, animal products and advanced glycation end-products and the risk of Barrett's oesophagus.

BACKGROUND: Advanced glycation end-products (AGEs) are found in high quantity in high-fat foods and meat cooked at high temperature. AGEs have been shown to contribute to chronic inflammation and oxidative stress in humans. AIM: To investigate the associations between consumption of meat, fat and AGEs, and the risk of Barrett's oesophagus (BO). METHODS: We conducted a case-control study using data from the patients who were scheduled for elective esophagogastroduodenoscopy (EGD) and from a random sample of patients who were identified at primary care clinics. Daily consumption of meat, fat and Nε-(carboxymethyl) lysine (CML), a major type of AGEs, was derived from the food frequency questionnaire (FFQ). Multivariate logistic regression models were used to estimate the odds ratio (OR) and its 95% confidence interval (CI) for BO. RESULTS: A total of 151 cases with BO and 777 controls without BO completed the FFQ. The multivariate OR (95% CI) for BO was 1.91 (1.07-3.38) for total meat, 1.80 (1.02-3.16) for saturated fat and 1.63 (0.96-2.76) for CML-AGE, when the highest tertile of intake was compared with the lowest. The association for total meat was attenuated to 1.61 (0.82-3.16), and that for saturated fat to 1.54 (0.81-2.94) after adjusting for CML-AGE. CONCLUSIONS: Higher consumption of total meat, saturated fat or possibly CML-AGE was associated with an increased risk of Barrett's oesophagus. CML-AGE may partly explain the association between total meat and saturated fat consumption and the risk of Barrett's oesophagus.

The prevalence of oesophageal eosinophilia and eosinophilic oesophagitis: a prospective study in unselected patients presenting to endoscopy.

BACKGROUND: Oesophageal eosinophilia (EE) is encountered in clinical practice as oesophageal biopsies are being obtained in patients with GI symptoms other than classical symptoms of eosinophilic oesophagitis (EoE). The prevalence, determinants and clinical relevance of EE identified irrespective of symptoms are unclear. AIM: To determine the prevalence and risk factors of EE with or without EoE in a nonselected group of patients undergoing endoscopy and in primary care patients. METHODS: A cross-sectional study in a single VA centre in which we obtained at least one oesophageal biopsy from patients presenting to elective endoscopy, as well as a sample of patients eligible for screening colonoscopy recruited from primary care clinics. EE was defined by >15 eosinophils in a single HPF; and EoE was defined as definite, probable or none depending on the presence of EE, acid-suppressive therapy and oesophageal symptoms. RESULTS: EE was identified in 33 of 1357 patients (2.4%, 95% CI: 1.7-3.4); of whom 9 had definite EoE (0.66%, 95% CI: 0.23-1.10), 17 had probable EoE (1.25%), and the only 7 patients had EE without EoE. The prevalence of EE was 2.3% among patients undergoing elective endoscopy and 0.1% among patients eligible for screening colonoscopy. Seasonal allergies (adjusted OR: 2.78; 95% CI: 1.26-6.11) and oesophageal strictures (4.50; 0.90-22.40) were associated with EE. CONCLUSIONS: The prevalence of EE was 2.3% among unselected patients presenting to endoscopy most of whom have EoE. EE was present in 0.1% in primary care patients none of whom had EoE.

Patients' intuitive judgments about surveillance endoscopy in Barrett's esophagus: a review and application to models of decision-making.

Adherence to practice guidelines for endoscopic surveillance of Barrett's esophagus is equivocal with evidence of underutilization and overutilization. While physicians report strong agreement with and adherence to recommended surveillance endoscopy (esophagogastroduodenoscopy [EGD]) guidelines, less is known about modifiable barriers and facilitators shaping patients' adherence behaviors. The aim of this study is to conduct a structured literature review of studies exploring patients' perspectives regarding surveillance EGD and to place these results within a conceptual framework. A structured literature review of PubMed, Cochrane, and Google Scholar databases with qualitative thematic analysis was performed. Six studies met eligibility criteria. Analysis of results identified five distinct themes. First, patients' objective cancer risk estimates are consistent with subjective risk perceptions, but neither is associated with EGD surveillance. Second, patients have strong beliefs in the benefits of cancer screening and surveillance and trust in their doctors. Third, anxiety and depression symptoms are related to risk perceptions and outcome expectancies of surveillance. Fourth, endoscopic surveillance itself has affective and physical consequences. Finally, health services and system variables are related to risk perception and EGD surveillance. These themes coherently fit within an integrated model of intuitive decision-making and health behaviors. Studies meeting eligibility criteria were heterogeneous in terms of their study objectives and findings. Quantitative meta-analyses of study findings could not be performed. To improve adherence, endoscopic surveillance programs should consider how patients intuitively frame risks and benefits and patients' emotional reactions to the endoscopy procedure, and focus on how physicians communicate recommendations.

Myelosuppression monitoring after immunomodulator initiation in veterans with inflammatory bowel disease: a national practice audit.

BACKGROUND: Immunomodulator medications (IMM) play a vital role in the care of patients with inflammatory bowel disease (IBD). IBD practice guidelines recommend myelosuppression monitoring after initiation of IMM. AIM: To identify adherence rates and predictors of myelosuppression monitoring after IMM initiation in a large practice setting. METHODS: We identified a national cohort of VA users with IBD for the fiscal years 2003-2009 using the Veterans Affairs administrative datasets. Subjects with filled prescriptions for IMM were included. The primary endpoint was the proportion of subjects who had a white blood cell (WBC) test completed within 90 days of the IMM index date. Determinants of myelosuppression monitoring were identified by univariate and multivariate analyses. RESULTS: A total of 6045 unique IBD patients were identified with filled IMM prescriptions. Overall, only 57% of subjects completed a WBC test within 90 days of IMM index date. Monitoring rates increased over time, from 48% in 2003 to 75% in 2009. There was variability of monitoring rates by facility, ranging from 0 to 83%. In multivariate analyses, older age at IMM index date was associated with a lower rate of monitoring. Frequency of VA encounters and IMM index date were associated with increased rates of myelosuppression monitoring. CONCLUSIONS: Monitoring for myelosuppression among veterans with inflammatory bowel disease after immunomodulator medications initiation is low with wide variability based on facility. This may reflect a low quality of care among veterans with IBD. Provider- and system-wide interventions are needed to improve adherence and reduce variability of immunomodulator medications monitoring across facilities.

Hepatitis vaccination in patients with hepatitis C: practice and validation of codes at a large Veterans Administration Medical Centre.

BACKGROUND: Hepatitis vaccination is recommended in patients with chronic liver disease. AIM: To validate Current Procedural Terminology (CPT) codes and drug codes for hepatitis vaccination in administrative databases and determine vaccination rates in hepatitis C virus (HCV)-infected patients in a single large Veterans Administration Medical Center. METHODS: We calculated predictive values for hepatitis vaccination codes in a validation set of 168 patients. We then conducted a retrospective cohort study of 243 HCV-infected patients to determine rates of hepatitis vaccination and serological testing. RESULTS: The presence of CPT or drug codes for hepatitis A vaccine yielded a positive predictive value (PPV) and negative predictive value (NPV) of 93.2% and 94.0%. The presence of hepatitis B vaccine codes yielded a PPV of 98.0% and an NPV of 94.0%. Among patients diagnosed with HCV between 2000 and 2005, receipt of hepatitis vaccination was documented in approximately 8% overall and 7% in patients with cirrhosis. Half of the patients without hepatitis vaccinations were either not tested for immunity or had negative serology. CONCLUSIONS: Current Procedural Terminology or drug codes for hepatitis vaccinations in administrative data are highly predictive of the presence of vaccinations in medical records. Our data suggest that there is significant under-utilization of vaccination in patients with HCV.

Lagtimes in diagnosis and treatment of colorectal cancer: determinants and association with cancer stage and survival.

BACKGROUND: Lagtimes to diagnostic colonoscopy have been used as practice performance measures. AIM: To evaluate the duration, determinants and outcomes of lagtimes between referral for endoscopic evaluation and colorectal cancer (CRC) diagnosis. METHODS: We examined the medical records of 289 patients with CRC and evaluated lagtimes, their potential determinants and their association with CRC stage at diagnosis as well as overall survival. RESULTS: Median lag between referral and CRC diagnosis was 41 days (41.5% > 60 days, 30.1% > 90 days). The only significant predictor of lagtime was the initiating event for referral: abnormal symptom, laboratory test or imaging study was associated with shortest and presence of family history was associated with longest lagtimes respectively. Longer lagtimes were associated with lower mortality risk, but this was completely explained by earlier CRC stage. An analysis restricted to 100 patients referred for abnormal CRC screening tests found no association between duration of lag and CRC stage or mortality. CONCLUSIONS: There seems to be no meaningful association between mortality in patients with CRC and lagtimes between referral for colonoscopy and CRC diagnosis for periods up to 2-3 months. On the contrary, longer lagtimes were inversely associated with CRC stage at the time of diagnosis.

The validity of viral hepatitis and chronic liver disease diagnoses in Veterans Affairs administrative databases.

BACKGROUND: The validity of International Classification of Diseases-9 codes for liver disease has not been determined. AIM: To examine the accuracy of International Classification of Diseases-9 codes for cirrhosis with hepatitis C virus or alcoholic liver disease and HIV or hepatitis B virus coinfection with hepatitis C virus in Veterans Affairs data. METHODS: We conducted a retrospective study comparing the Veterans Affairs administrative data with abstracted data from the Michael E. DeBakey VA Medical Center's medical records. We calculated the positive predictive value, negative predictive value, per cent agreement and kappa. RESULTS: For cirrhosis codes, the positive predictive value (probability that cirrhosis is present among those with a code) and negative predictive value (probability that cirrhosis is absent among those without a code) were 90% and 87% with 88% agreement and kappa = 0.70. For hepatitis C virus codes, the positive predictive value and negative predictive value were 93% and 92%, yielding 92% agreement and kappa = 0.78. For alcoholic liver disease codes, the positive predictive value and negative predictive value were 71% and 98%, with 89% agreement and kappa = 0.74. All parameters for HIV coinfection with hepatitis C virus were >89%; however, the codes for hepatitis B virus coinfection had a positive predictive value of 43-67%. CONCLUSION: These diagnostic codes (except hepatitis B virus) in Veterans Affairs administrative data are highly predictive of the presence of these conditions in medical records and can be reliably used for research.

The association of body mass index with Barrett's oesophagus.

BACKGROUND: Obesity has been linked to gastro-oesophageal reflux disease symptoms and oesophageal adenocarcinoma; however, there is no published evidence for an association with Barrett's oesophagus. AIM: To investigate the association between obesity and Barrett's oesophagus. METHODS: We conducted a retrospective cross-sectional study of patients who underwent upper endoscopy at the Southern Arizona Veteran's Affairs Healthcare System between 1998 and 2004. We examined male patients without malignancy, with available information on weight and height. Based on endoscopic and histological findings, patients were classified as cases with Barrett's oesophagus or non-cases without Barrett's oesophagus. Multivariable logistic regression analysis was conducted to examine the association of body mass index and obesity with Barrett's oesophagus and Barrett's oesophagus length while adjusting for age and race. RESULTS: There were 65 cases with Barrett's oesophagus and 385 non-cases without Barrett's oesophagus. The mean body mass index was significantly higher in cases than in non-cases (29.8 vs. 28.0, P = 0.03). Cases had significantly greater mean weight than controls (206 lb vs. 190,P = 0.005). The proportions of cases with body mass index 25-30 and body mass index > or =30 were greater than those in non-cases (44.6% vs. 37.7%) and (40.0% vs. 33.5%), respectively (P = 0.08). In the multivariable logistic regression model adjusting for race and age, when compared with body mass index < 25, the odds ratio was 2.43 (95% confidence interval: 1.12-5.31) for body mass index 25-30 and 2.46 (1.11-5.44) for body mass index > or =30. When examined as a continuous variable the adjusted odd ratio for each five-point increase in body mass index was 1.35 (95% confidence interval: 1.06-1.71, P = 0.01). The association between weight and Barrett's oesophagus was also statistically significant (adjusted odd ratio for each 10 pound increase = 1.10, 1.03-1.17, P =0.002). Among the 65 cases of Barrett's oesophagus, there was no correlation between the length of Barrett's oesophagus at the time of diagnosis and the body mass index (correlation coefficient = 0.03, P = 0.79). CONCLUSION: This retrospective cross-sectional study in male veterans shows that overweight is associated with a two-and-half-fold increased risk of Barrett's oesophagus. Larger studies of the underlying mechanism are warranted to better understand how and why obese patients are at greater risk for Barrett's oesophagus.

Developmental sequence from disruptive behavior diagnosis to adolescent alcohol dependence.

OBJECTIVE: The authors sought to clinically describe the relationship of disruptive behavior disorders with both alcohol dependence and the use of a variety of substances. METHOD: The Child Semi-Structured Assessment for the Genetics of Alcoholism was used to collect data on 54 adolescents with a diagnosis of alcohol dependence. The frequency and age at onset of the disruptive behavior disorder diagnoses were examined as well as age at first use of alcohol, tobacco, marijuana, and other street drugs. RESULTS: Nearly three-quarters of the alcohol-dependent adolescents had at least one disruptive behavior disorder diagnosis. Attention deficit hyperactivity disorder (ADHD) typically occurred first, followed by conduct disorder. Substance use began with alcohol or tobacco, followed by marijuana and then other street drugs. Alcohol dependence began significantly later than the onset of either ADHD or conduct disorder and significantly later than the first use of tobacco. CONCLUSIONS: Disruptive behavior diagnoses, particularly conduct disorder, typically precede the initiation of use of a variety of substances that, in turn, precede the diagnosis of alcohol dependence in adolescents.

Raman microspectroscopy of human coronary atherosclerosis: biochemical assessment of cellular and extracellular morphologic structures in situ.

BACKGROUND: We have previously shown that Raman spectroscopy can be used for chemical analysis of intact human coronary artery atherosclerotic lesions ex vivo without tissue homogenization or extraction. Here, we report the chemical analysis of individual cellular and extracellular components of atherosclerotic lesions in different stages of disease progression in situ using Raman microspectroscopy. METHODS: Thirty-five coronary artery samples were taken from 16 explanted transplant recipient hearts, and thin sections were prepared. Using a high-resolution confocal Raman microspectrometer system with an 830-nm laser light, high signal-to-noise Raman spectra were obtained from the following morphologic structures: internal and external elastic lamina, collagen fibers, fat, foam cells, smooth muscle cells, necrotic core, beta-carotene, cholesterol crystals, and calcium mineralizations. Their Raman spectra were modeled by using a linear combination of basis Raman spectra from the major biochemicals present in arterial tissue, including collagen, elastin, actin, myosin, tropomyosin, cholesterol monohydrate, cholesterol linoleate, phosphatidyl choline, triolein, calcium hydroxyapatite, calcium carbonate, and beta-carotene. RESULTS: The results show that the various morphologic structures have characteristic Raman spectra, which vary little from structure to structure and from artery to artery. The biochemical model described the spectrum of each morphologic structure quite well, indicating that the most essential biochemical components were included in the model. Furthermore, the biochemical composition of each structure, indicated by the fit contributions of the biochemical basis spectra of the morphologic structure spectrum, was very consistent. CONCLUSIONS: The Raman spectra of various morphologic structures in normal and atherosclerotic coronary artery may be used as basis spectra in a linear combination model to analyze the morphologic composition of atherosclerotic coronary artery lesions.

Diagnosis of human coronary atherosclerosis by morphology-based Raman spectroscopy.

BACKGROUND: Recent studies have shown that chemical composition and morphology, rather than anatomy (degree of stenosis), determine atherosclerotic plaque instability and predict disease progression. Current clinical diagnostic techniques provide accurate assessment of plaque anatomy, but have limited capability to assess plaque morphology in vivo. Here we describe a technique for a morphology-based diagnosis of atherosclerosis in the coronary arteries using Raman spectroscopy that can potentially be performed in vivo using optical fiber technology. METHODS: Raman tissue spectra were collected from normal and atherosclerotic coronary artery samples in different stages of disease progression (n=165) from explanted transplant recipient hearts (n=16). Raman spectra from the elastic laminae (EL), collagen fibers (CF), smooth muscle cells (SMC), adventitial adipocytes (AA) or fat cells, foam cells (FC), necrotic core (NC), cholesterol crystals (CC), beta-carotene containing crystals (beta-C), and calcium mineralizations (CM) were used as basis spectra in a linear least squares-minimization (LSM) model to calculate the contribution of these morphologic structures to the coronary artery tissue spectra. RESULTS: We developed a diagnostic algorithm that used the fit-contributions of the various morphologic structures to classify 97 coronary artery samples in an initial calibration data set as either nonatherosclerotic, calcified plaque, or noncalcified atheromatous plaque. The algorithm was subsequently tested prospectively in a second validation data set, and correctly classified 64 (94%) of 68 coronary artery samples. CONCLUSIONS: Raman spectroscopy provides information about the morphologic composition of intact human coronary artery without the need for excision and microscopic examination. In the future, it may be possible to use this technique to analyze the morphologic composition of atherosclerotic coronary artery lesions and assess plaque instability and disease progression in vivo.

Risk domains associated with an adolescent alcohol dependence diagnosis.

AIMS: To determine the contribution of familial, interpersonal, academic and early substance use factors to relative risk for an alcohol dependence (AD) diagnosis in adolescents. METHODS: Information on 619 adolescents and their 390 sets of biological parents was obtained using the adolescent version of the Child Semi-Structured Assessment for the Genetics of Alcoholism (C-SSAGA) and the adult counterpart of this instrument, the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA). The C-SSAGA elicits a wide range of environmental, social, and psychiatric diagnostic information. Specific domain scale scores associated with an adolescent AD were computed, and generalized estimating equations (GEE) modeling was used to determine the odds ratio (relative risk) of the specified risk domains for an alcohol dependence diagnosis. FINDINGS: Risk factors for a DSM-III-R AD diagnosis included being at least 16 years of age, as well as negative parent-child interactions, school and personal-related difficulties (including the presence of an externalizing or internalizing DSM-III-R non-alcohol-related diagnosis), and early experimentations with a variety of substances. CONCLUSIONS: An array of familial, interpersonal, academic and early substance use factors were strongly associated with adolescent AD. Given the findings of this study, further research to determine temporal relationships that might influence the onset of adolescent alcohol dependence is warranted.