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.

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.

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.

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.

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.

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.

Left ventricular function in coronary artery disease. Evaluation of slope of end-systolic pressure-volume line (Emax) and ratio of peak systolic pressure to end-systolic volume (P/Ves).

Left ventricular function was assessed by measurement of systolic pressure-volume variables and ejection fraction in seven normal subjects (group I), five patients with coronary artery disease and normal symmetric left ventricular wall motion (group II) and eight patients with remote myocardial infarction and segmental akinesia (group III). Left ventricular volumes were obtained from right anterior oblique ventriculograms and pressures from catheter-tip micromanometer (14 patients) or fluid-filled catheters (6 patients) at two different systolic loads. P/Ves was calculated as the ratio of peak systolic pressure (P) to end-systolic volume (Ves) at rest, Emax as the slope of the end-systolic pressure volume line constructed at two systolic loads, and Vo as the volume axis intercept of this line. Emax was significantly (p less than 0.01) lower in patients with segmental akinesia (group III) (5.0 +/- 0.5) than in normal subjects (group I) (10.4 +/- 0.8) or patients with coronary artery disease and normal wall motion (group II) (9.9 +/- 0.8). In contrast, there was no significant difference in P/Ves among the three groups (6 +/- 1.0 in group I, 5 +/- 0.8 in group II, 3.7 +/- 0.5 in group III). Similarly, Ves and Vo failed to separate the three groups. Although ejection fraction was significantly (p less than 0.05) lower in group III (0.56 +/- 0.03) than in groups I and II (0.67 +/- 0.03 in both groups), there was considerable overlap of individual values in the three groups. In eight patients, measurements were repeated during isometric exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Young adults with coronary atherosclerosis: 10 year results of surgical myocardial revascularization.

This study reviews data on 107 patients, aged 35 years or younger, who underwent surgical coronary revascularization from 1971 to 1975. Early clinical events included one operative death and five nonfatal perioperative myocardial infarctions. Late follow-up (mean interval after operation 115 months) demonstrated actuarial survival rates of 94% at 5 years and 85% at 10 years. Fifteen late deaths, 23 nonfatal myocardial infarctions, 13 reoperations and return of severe angina in 10 patients were considered late clinical events. Actuarial survival free of early or late clinical events was 77% at 5 years and 53% at 10 postoperative years. Testing of clinical, angiographic and operative variables for influence on survival and event-free survival showed that survival was decreased by multivessel disease and impaired left ventricular function; event-free survival was decreased by a family history of coronary disease and cigarette smoking. Both survival and event-free survival were decreased by diabetes and elevated serum cholesterol. Postoperative cardiac catheterization (64 patients, mean postoperative interval 47 months) demonstrated that mammary artery graft patency (25 of 27, 93%) exceeded vein graft patency (49 of 88, 56%, p less than 0.01). The atherogenic diatheses of young adults may compromise the operative result, whereas use of internal mammary artery grafts may enhance the palliation of bypass surgery.

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.

Comparison of stress digital ventriculography, stress thallium scintigraphy, and digital fluoroscopy in the diagnosis of coronary artery disease in subjects without prior myocardial infarction.

Exercise thallium scintigraphy is often used for the diagnosis of coronary artery disease (CAD). Exercise digital subtraction ventriculography and digital subtraction fluoroscopy are new diagnostic procedures with roles that have not been determined. To compare the relative accuracies of the digital techniques with thallium scintigraphy, 97 consecutive patients without myocardial infarction underwent all 3 tests on the day before their scheduled coronary angiograms. Forty-two patients had CAD (more than 50% diameter narrowing of 1 major artery). A fixed or reversible perfusion defect defined an abnormal thallium test response and a segmental wall motion abnormality at rest or with exercise defined an abnormal digital ventriculographic response. Any visualized coronary calcific deposit defined an abnormal digital fluorographic response. The sensitivities of digital fluoroscopy (86%) and digital ventriculography (79%) were significantly higher than the sensitivity of thallium (62%) (p less than 0.05). The specificity of thallium (82%) was not significantly higher than that of either digital ventriculography (72%) or fluoroscopy (67%). The diagnostic accuracies of digital fluoroscopy, digital ventriculography, and thallium were 75%, 75% and 73%, respectively. A logistic regression model showed that thallium and digital fluoroscopy were more accurate in younger patients, whereas digital ventriculography was more sensitive in hypertensive persons and in those not taking beta-blocking drugs. The choice of test depends on disease prevalence, clinical variables (such as age and hypertension) and the importance of functional information obtained from stress testing.

Idiopathic hypertrophic subaortic stenosis and coronary atherosclerosis. Results of coronary artery bypass alone and myectomy combined with coronary artery bypass.

Twenty-one patients with combined coronary artery disease and idiopathic hypertrophic subaortic stenosis (IHSS) have had coronary artery bypass grafting alone (Group I, n = 7) or in combination with left ventricular septal myectomy (Group II, n = 14). Patients ranged in age from 46 to 73 years (mean 59 years). There were no operative deaths, but one Group I patient died 16 months after operation. Patients in Group I have had continuing symptoms after the operation, whereas Group II patients have had consistent relief of symptoms. Patients with documented IHSS and coronary atherosclerosis should undergo combined coronary bypass and septal myectomy if symptoms recur with medical management.

Vein graft disease: the clinical impact of stenoses in saphenous vein bypass grafts to coronary arteries.

The influence of coronary artery stenoses on patient survival and event-free survival is known, but no studies have reported the long-term outcome of patients with stenoses in saphenous vein bypass grafts. We retrospectively studied 723 patients who underwent a postoperative angiographic study that documented a stenosis of 20% to 99% in at least one saphenous vein graft and who did not undergo reoperation or percutaneous transluminal coronary angioplasty within 1 year after that catheterization. The mean follow-up interval was 83 months (range 1 to 237 months). For comparison, a group of 573 patients who underwent a postoperative catheterization that did not show any vein graft stenosis were also followed up. Cox regression analyses were used to identify predictors of late survival, reoperation-free survival, and event-free survival. For the entire group of patients with stenotic vein grafts, moderate or severe impairment of left ventricular function (p less than 0.001), interval between operation and catheterization (p less than 0.001), older age (p = 0.001), triple-vessel or left main coronary artery disease (p = 0.004), and stenosis of the vein graft to the left anterior descending coronary artery (p = 0.09) were associated with decreased late survival. Patients with an operation-to-catheterization interval greater than or equal to 5 years were at particularly high risk, and multivariate analyses of that subgroup confirmed that a stenotic graft to the left anterior descending artery was a strong predictor of decreased survival (p less than 0.001), decreased reoperation-free survival (p less than 0.001), and decreased event-free survival (p less than 0.001). Patients greater than or equal to 5 years postoperatively with greater than or equal to 50% stenosis of vein grafts to the left anterior descending artery had survival of 70% and 50% at 2 and 5 years after catheterization, compared with 97% and 80% for those with greater than or equal to 50% stenosis of the native left anterior descending artery (p = 0.002). Late vein graft stenoses are more dangerous than native coronary stenoses. Late stenoses in saphenous vein grafts to the left anterior descending coronary artery predict a high rate of death and cardiac events and are an indication for reoperation.

Late clinical and arteriographic results in 500 coronary artery reoperations.

The incidence of coronary artery reoperations averaged 2.7% from 1967 through 1979. In a mean interval of 51 months between operations, three-vessel disease increased from 24% to 63%, and 31% of these 500 consecutive patients lost previously normal left ventricular function. Three angiographic indication groups were identified: (1) progressive coronary atherosclerosis, 247 (51%); (2) graft failure, 147 (29%); and (3) a combination of progressive coronary atherosclerosis and graft failure, 96 (19%). Angina recurred earlier in patient with graft failure, mean 17 months compared with a mean of 37 months for the other groups. Twenty (4%) operative deaths occurred. The series is divided into 387 patients operated upon under normothermic anoxic arrest and 113 with systemic hypothermia and cold cardioplegia. In the cardioplegia group, perioperative myocardial infarction was 2.7% in comparison with 7.8% for patients with anoxic arrest (p = 0.055). The number of grafts per patient increased from 1.0 to 1.9 and blood usage decreased from 11 units to 2.7 units. After a mean follow-up of 42 months, angina was relieved or improved in 86%. Recatheterization of 104 patients after a mean interval of 19 months showed a 79% vein graft patency rate and a 97% mammary artery graft patency rate. Grafting performed for graft failure (47) yielded an 85% patency rate. Actuarial 5 year survival was 87.4% for those with progressive atherosclerosis, 89.4% for patients with graft failure, and 91.5% for the combined indication group. Clinical improvement, graft patency, and long-term survival are nearly equal among the indication groups. Palliation derived from these reoperations approaches that achieved after primary revascularization.

Removal of surgically induced fibrous arterial plaques by argon ion laser angiosurgery using a multifiber delivery system. An experimental study in the dog.

Removal of intravascular atherosclerotic obstructions by laser irradiation has gained the attention of many investigators, but has proven to be considerably more difficult to accomplish than initially envisioned. We tested, in an animal model, an argon ion laser delivery system that permits control of (1) laser power, (2) exposure time, and (3) laser beam spot size. The study was conducted on surgically, induced focal fibrous plaques in the carotid arteries of nine dogs. Plaque removal, vessel patency, and healing were evaluated angiographically and by light and electron microscopy at intervals up to 60 days after treatment. Results showed that intravascular obstructions could be removed, healing occurred, and vessels remained patent for up to 60 days.

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.