Neville Suskin

Eosinophilic esophagitis in adults: distinguishing features from gastroesophageal reflux disease: a study of 41 patients

Eosinophilic esophagitis in adults is a recently described entity occurring in young males with dysphagia, in whom esophageal biopsies show eosinophilic infiltration. This study defines the clinical and histological features of patients with eosinophilic esophagitis, distinguishing it from gastroesophageal reflux disease. Esophageal biopsies from patients with dysphagia or esophagitis were reviewed blindly, and assessed for: epithelial eosinophil counts, presence of eosinophilic microabscesses, edema, basal zone hyperplasia, lamina propria papillae elongation, eosinophils and fibrosis. Clinical and endoscopic findings were obtained. Eosinophilic esophagitis was diagnosed with epithelial eosinophils ≥15 in ≥2 high-power fields (hpfs) or ≥25 in any hpf. Analysis was performed with Mann–Whitney, χ2 and ANOVA tests. Of 157 cases, 41 had eosinophilic esophagitis. Male gender (81%) and age ≤45 (54%) were commoner in patients with eosinophilic esophagitis (P=0.001, 0.010, respectively). Dysphagia was more common in eosinophilic esophagitis patients (63%, P<0.001); heartburn was more common in noneosinophilic esophagitis patients (53%, P<0.001). Endoscopic rings were more common in eosinophilic esophagitis patients (27%, P=0.023); hiatus hernia was more common in noneosinophilic esophagitis patients (11%, P=0.022). Eosinophils were more numerous in eosinophilic esophagitis biopsies (mean 39/hpf, P≤0.001). Only eosinophilic esophagitis biopsies had eosinophilic microabscesses (42%, P≤0.001). Edema, basal zone hyperplasia, lamina propria papillae elongation and lamina propria eosinophils were commoner in eosinophilic esophagitis (P=<0.001–0.002), while lamina propria fibrosis was specific for eosinophilic esophagitis (39%, P<0.001). Eosinophilic esophagitis is a disease with a predilection for young males with dysphagia and rings on endoscopy. Biopsies in eosinophilic esophagitis have high epithelial eosinophil counts, averaging nearly 40/hpf. Increased awareness of eosinophilic esophagitis is necessary, since treatment with allergen elimination or anti-inflammatory therapy may be more effective than acid suppression.

Contribution of patient and physician factors to cardiac rehabilitation enrollment: a prospective multilevel study.

Background Cardiac rehabilitation (CR) is an established means of reducing mortality, yet is grossly underutilized. This is due to both health system and patient-level factors; issues that have yet to be investigated concurrently. This study utilized a hierarchical design to examine physician and patient-level factors affecting verified CR enrollment. Design A prospective multisite study, using a multilevel design of 1490 coronary artery disease outpatients nested within 97 Ontario cardiology practices (mean 15 per cardiologist). Methods Cardiologists completed a survey regarding CR attitudes. Outpatients were surveyed prospectively to assess factors affecting CR enrollment. Patients were mailed a follow-up survey 9 months later to self-report CR enrollment This was verified with 40 CR sites. Results Five hundred and fifty (43.4%) outpatients were referred, and 469 (37.0%) enrolled in CR. In mixed logistic regression analyses, factors affecting verified CR enrollment were greater strength of physician endorsement (P = 0.005), shorter distance to CR (P = 0.001), being married (P = 0.01), and fewer perceived CR barriers (P = 0.03). Conclusion Both physician and patient factors play a part in CR enrollment. Patient CR barriers should be addressed during referral discussions, and reasons why physicians fail to uniformly endorse CR exploration. Although distance to CR was related to patient enrollment patterns, greater access to home-based CR services should be provided.

Recurrent hepatocellular carcinoma after transplantation: Use of a pathological score on explanted livers to predict recurrence

Milan and University of California at San Francisco (UCSF) criteria are used to select patients with hepatocellular carcinoma (HCC) for liver transplantation (LT). Recurrent HCC is a significant cause of death. There is no widely accepted pathological assessment strategy to predict recurrent HCC after transplantation. This study compares the pathology of patients meeting Milan and UCSF criteria and develops a pathological score and nomogram to assess the risk of recurrent HCC after transplantation. All explanted livers with HCC from our center over the 18‐yr period 1985 to 2003 were assessed for multiple pathological features and relevant clinical data were recorded; multivariate analysis was performed to determine features associated with recurrent HCC. Using pathological variables that independently predicted recurrent HCC, a pathological score and nomogram were developed to determine the probability of recurrent HCC. Of 75 cases analyzed, 50 (67%) met Milan criteria, 9 (12%) met only UCSF criteria and 16 (21%) met neither criteria based on explant pathology. There were 20 cases of recurrent HCC and the mean follow‐up was 8 yr. Recurrent HCC was more common (67 vs. 12%; P < 0.001) and survival was lower (15 vs. 83% at 5 yr; 15 vs. 55% at 8 yr; P < 0.001) with those who met only UCSF criteria, compared to those who met Milan criteria. Cryptogenic cirrhosis (25 vs. 5%; P = 0.015), preoperative AFP >1,000 ng/mL (20 vs. 0%; P < 0.001) and postoperative OKT3 use (40 vs. 15%; P = 0.017) were more common among patients with recurrent HCC. While microvascular invasion was the strongest pathological predictor of recurrent HCC, tumor size ≥3 cm (P = 0.004; odds ratio [OR] = 7.42), nuclear grade (P = 0.044; OR = 3.25), microsatellitosis (P = 0.020; OR = 4.82), and giant/bizarre cells (P = 0.028; OR = 4.78) also predicted recurrent HCC independently from vascular invasion. The score and nomogram stratified the risk of recurrent HCC into 3 tiers: low (<5%), intermediate (40–65%), and high (>95%). In conclusion, compared to patients meeting Milan criteria, patients who meet only UCSF criteria have a worse survival and an increased rate of recurrent HCC with long‐term follow‐up, as well as more frequent occurrence of adverse histopathological features, such as microvascular invasion. Application of a pathological score and nomogram could help identify patients at increased risk for tumor recurrence, who may benefit from increased surveillance or adjuvant therapy. Liver Transpl, 2007.

Clinical and Pharmacogenetic Predictors of Circulating Atorvastatin and Rosuvastatin Concentrations in Routine Clinical Care

Background—A barrier to statin therapy is myopathy associated with elevated systemic drug exposure. Our objective was to examine the association between clinical and pharmacogenetic variables and statin concentrations in patients. Methods and Results—In total, 299 patients taking atorvastatin or rosuvastatin were prospectively recruited at an outpatient referral center. The contribution of clinical variables and transporter gene polymorphisms to statin concentration was assessed using multiple linear regression. We observed 45-fold variation in statin concentration among patients taking the same dose. After adjustment for sex, age, body mass index, ethnicity, dose, and time from last dose, SLCO1B1 c.521T>C (P<0.001) and ABCG2 c.421C>A (P<0.01) were important to rosuvastatin concentration (adjusted R2=0.56 for the final model). Atorvastatin concentration was associated with SLCO1B1 c.388A>G (P<0.01) and c.521T>C (P<0.05) and 4&bgr;-hydroxycholesterol, a CYP3A activity marker (adjusted R2=0.47). A second cohort of 579 patients from primary and specialty care databases were retrospectively genotyped. In this cohort, genotypes associated with statin concentration were not differently distributed among dosing groups, implying providers had not yet optimized each patient’s risk–benefit ratio. Nearly 50% of patients in routine practice taking the highest doses were predicted to have statin concentrations greater than the 90th percentile. Conclusions—Interindividual variability in statin exposure in patients is associated with uptake and efflux transporter polymorphisms. An algorithm incorporating genomic and clinical variables to avoid high atorvastatin and rosuvastatin levels is described; further study will determine whether this approach reduces incidence of statin myopathy.

A PROSPECTIVE COMPARISON OF CARDIAC REHABILITATION ENROLLMENT FOLLOWING AUTOMATIC VS USUAL REFERRAL

OBJECTIVE Cardiac rehabilitation remains grossly under-utilized despite its proven benefits. This study prospectively compared verified cardiac rehabilitation enrollment following automatic vs usual referral, postulating that automatic referral would result in significantly greater enrollment for cardiac rehabilitation. DESIGN Prospective controlled multi-center study. PATIENTS AND METHODS A consecutive sample of 661 patients with acute coronary syndrome treated at 2 acute care centers (75% response rate) were recruited, one site with automatic referral via a computerized prompt and the other with a usual referral strategy at the physicians discretion. Cardiac rehabilitation referral was discerned in a mailed survey 9 months later (n = 506; 84% retention), and verified with 24 cardiac rehabilitation sites to which participants were referred. RESULTS A total of 124 (52%) participants enrolled in cardiac rehabilitation following automatic referral, vs 84 (32%) following usual referral (p < 0.001). Automatically referred participants were more likely to be referred from an in- patient unit (p < 0.01), and to be referred in a shorter time period (p < 0.001). Logistic regression analyses revealed that, after controlling for sociodemographic characteristics and case-mix, automatically referred participants were significantly more likely to enroll in cardiac rehabilitation (odds ratio = 2.1; 95% confidence interval 1.4-3.3) than controls. CONCLUSION Automatic referral resulted in over 50% verified cardiac rehabilitation enrollment; 2 times more than usual referral. It also significantly reduced utilization delays to less than one month.

A Multisite Examination of Sex Differences in Cardiac Rehabilitation Barriers by Participation Status

BACKGROUND Despite its proven benefits and need, women are significantly less likely than men to participate in and complete cardiac rehabilitation (CR). The purpose of this study was to quantitatively investigate sex differences in CR barriers by participation status. METHODS Cardiac outpatients (1496, 430 female, 28.7%) of 97 cardiologists completed a mailed survey to discern CR participation. Respondents were asked to rate 19 CR barriers on a 5-point Likert scale. RESULTS Five hundred twenty-nine (43%) respondents self-reported participating in CR, with men being more likely to participate (p < 0.05). There was no significant sex difference in total number of CR barriers, but differences in individual barriers were found. For CR participants, t tests revealed significant sex differences in the perception of exercise as tiring or painful (p = 0.042) and work responsibilities (p = 0.013). For CR nonparticipants, women rated the following barriers as greater than men: transportation (p = 0.025), family responsibilities (p = 0.039), lack of CR awareness (p = 0.036), experiencing exercise as tiring or painful (p = 0.002), and comorbidities (p = 0.009). CONCLUSIONS Overall, women do not perceive greater barriers to CR participation than men, but the nature of their barriers differs, particularly among nonparticipants. Beliefs about the value of CR, awareness, and exercise parameters are all modifiable barriers that should be addressed among women.

Changes in exercise capacity and lipids after clinic versus home-based aerobic training in coronary artery bypass graft surgery patients.

PURPOSE Despite the documented benefits of participating in rehabilitation programs, access to cardiac rehabilitation is limited for a large number of people with coronary artery disease (CAD). There is potential to increase participation in exercise training if home-based exercise were a viable option. METHODS We conducted a retrospective database review of 1,042 patients who took part in exercise rehabilitation following coronary artery bypass graft surgery (CABGS) between 1992 and 1998. Of these, 713 patients took part in supervised exercise, and 329 were in an unsupervised, home-based group. All exercise protocols were based upon American College of Sports Medicine guidelines, and patients in both groups received exercise prescriptions that were similar in intensity, frequency, and duration. RESULTS There were no differences between groups at baseline. Following 6 months of exercise training, there were substantial improvements in peak VO2, peak workload, and peak MET levels in both the supervised and unsupervised groups (P < 0.0001). Patients in the supervised group had significant improvements in both LDL and HDL-cholesterol, whereas the home-based group showed improvement in HDL-cholesterol only. When analyzed by sex, men performed better than women for all measures of exercise capacity; however, women in both groups showed approximate 20% improvements (P < 0.05) in exercise capacity as well as improvements in HDL-cholesterol. CONCLUSION Stable post CABGS patients who receive a detailed exercise prescription to follow at home do as well as those in supervised rehabilitation.

Comprehensive Cardiac Rehabilitation for Secondary Prevention After Transient Ischemic Attack or Mild Stroke I: Feasibility and Risk Factors

Background and Purpose— Comprehensive cardiac rehabilitation (CCR), which integrates structured lifestyle interventions and medications, reduces morbidity and mortality among cardiac patients. CCR has not typically been used with cerebrovascular populations, despite important commonalities with heart patients. We tested feasibility and effectiveness of 6-month outpatient CCR for secondary prevention after transient ischemic attack or mild, nondisabling stroke. This article presents risk factors. A future article will discuss psychological outcomes. Methods— Consecutive consenting subjects having sustained a transient ischemic attack or mild, nondisabling stroke within the previous 12 months (mean, 11.5 weeks; event-to-CCR entry) with ≥1 vascular risk factor, were recruited from a stroke prevention clinic providing usual care. We measured 6-month CCR outcomes following a prospective cohort design. Results— Of 110 subjects recruited from January 2005 to April 2006, 100 subjects (mean age, 64.9 years; 46 women) entered and 80 subjects completed CCR. We obtained favorable, significant intake-to-exit changes in: aerobic capacity (+31.4%; P<0.001), total cholesterol (−0.30 mmol/L; P=0.008), total cholesterol/high-density lipoprotein (−11.6%; P<0.001), triglycerides (−0.27 mmol/L; P=0.003), waist circumference (−2.44 cm; P<0.001), body mass index (−0.53 kg/m2; P=0.003), and body weight (−1.43 kg; P=0.001). Low-density lipoprotein (−0.24 mmol/L), high-density lipoprotein (+0.06 mmol/L), systolic (−3.21 mm Hg) and diastolic (−2.34 mm Hg) blood pressure changed favorably, but nonsignificantly. A significant shift toward nonsmoking occurred (P=0.008). Compared with intake, 11 more individuals (25.6% increase) finished CCR in the lowest-mortality risk category of the Duke Treadmill Score (P<0.001). Conclusions— CCR is feasible and effective for secondary prevention after transient ischemic attack or mild, nondisabling stroke, offering a promising model for vascular protection across chronic disease entities. We know of no similar previous investigation, and are now conducting a randomized trial.

Randomized trial of an internet-based computer-tailored expert system for physical activity in patients with heart disease

Background: The CardioFit internet-based expert system was designed to promote physical activity in patients with coronary heart disease (CHD) who were not participating in cardiac rehabilitation. Design: This randomized controlled trial compared CardioFit to usual care to assess its effects on physical activity following hospitalization for acute coronary syndromes. Methods: A total of 223 participants were recruited at the University of Ottawa Heart Institute or London Health Sciences Centre and randomly assigned to either CardioFit (n = 115) or usual care (n = 108). The CardioFit group received a personally tailored physical-activity plan upon discharge from the hospital and access to a secure website for activity planning and tracking. They completed five online tutorials over a 6-month period and were in email contact with an exercise specialist. Usual care consisted of physical activity guidance from an attending cardiologist. Physical activity was measured by pedometer and self-reported over a 7-day period, 6 and 12 months after randomization. Results: The CardioFit internet-based physical activity expert system significantly increased objectively measured (p = 0.023) and self-reported physical activity (p = 0.047) compared to usual care. Emotional (p = 0.038) and physical (p = 0.031) dimensions of heart disease health-related quality of life were also higher with CardioFit compared to usual care. Conclusions: Patients with CHD using an internet-based activity prescription with online coaching were more physically active at follow up than those receiving usual care. Use of the CardioFit program could extend the reach of rehabilitation and secondary-prevention services.

Barriers to Cardiac Rehabilitation: Does Age Make a Difference?

PURPOSE To quantitatively investigate age differences in barriers to cardiac rehabilitation (CR) enrollment and participation. METHODS Cardiac outpatients (N = 1,273, mean age = 65.9 ± 11.2) completed a mailed survey to discern barriers to CR enrollment and participation. Both enrollees and nonenrollees were asked to rate 18 CR barriers on a 5-point Likert scale. RESULTS Of the respondents, 535 (43%) reported participating in CR at 1 of 40 sites, with younger patients being more likely to participate (P = .002). Older age was positively related to total CR barriers (P < .001). Older patients more strongly endorsed the following CR barriers: already exercising at home (P = .001), confidence in ability to self-manage their condition (P = .003), perception of exercise as tiring or painful (P = .001), not knowing about CR (P = .001), lack of physician encouragement (P < .001), comorbidities (P < .001), and perception that CR would not improve their health (P < .001). CONCLUSION Given that the benefits of CR are achieved in older patients as well as the young, interventions to overcome these modifiable barriers to enrollment and participation are needed.