Efficacy of Adalimumab in Korean Patients with Crohn’s Disease

Background/Aims

Adalimumab is effective for both remission induction and the maintenance of Crohn’s disease (CD) in Western countries. We evaluated the efficacy of adalim-umab in the conventional step-up treatment approach for CD in Korea.

Methods

We retrospectively reviewed 62 patients with CD who were treated with adalimumab. Their Crohn’s disease activity index (CDAI) was measured at weeks 4, 8, and 52. Clinical remission was defined as a CDAI score <150. Induction and maintenance outcomes were analyzed.

Results

Forty-one patients (66.1%) achieved a reduction of 70 CDAI points at week 8. Among them, 28 (45.2%) achieved clinical remission at week 8, 20 (32.3%) maintained remission at week 52. The absence of prior anti-tumor necrosis factor (TNF) therapy and Montreal classification L1 at baseline predicted clinical remission at week 8 in the multivariate logistic regression analysis. In the Cox proportional hazards model, the hazard ratio for the secondary loss of response during maintenance therapy after clinical remission induction was significantly higher in patients who showed initial mild CDAI severity or Montreal classification A3.

Conclusions

In our study, anti-TNF therapy-naive and Montreal classification L1 were associated with adalimumab efficacy as induction therapy in CD. Further studies are warranted to determine the prognostic factors for the long-term response after adalimumab therapy.     

A randomized controlled trial to assess the efficacy of tiotropium in Canadian patients with chronic obstructive pulmonary disease

BACKGROUND:

Patients with chronic obstructive pulmonary disease (COPD) who smoke have a greater annual rate of decline in forced expiratory volume in 1 s (FEV₁) than those patients who have stopped smoking.

OBJECTIVES:

To assess the effect of tiotropium on pre-dose (trough) FEV₁ in patients with COPD followed in Canada.

METHODS:

A total of 913 patients were randomly assigned to receive either tiotropium 18 μg once daily (n=608) or placebo (usual care minus inhaled anticholinergics) (n=305) for 48 weeks in the present randomized, double-blind, parallel-group study. The effect of tiotropium on measurements of lung function (FEV₁, FEV₆ and forced vital capacity), symptoms, health-related quality of life (St George’s Respiratory Questionnaire) and exacerbations were examined.

RESULTS:

Tiotropium improved trough FEV₁ in both current and ex-smokers compared with placebo. Baseline FEV₁ in smokers and ex-smokers was 1.03 L and 0.93 L, respectively (P<0.001). At week 48, the mean difference between the tiotropium and placebo groups was 0.14±0.04 L (P<0.001) in the smoker group and 0.08±0.02 L (P<0.0001) in the ex-smoker group. Tiotropium also significantly improved trough forced vital capacity and FEV₆ compared with placebo throughout the treatment period (P<0.05, for all). Furthermore, tiotropium significantly improved the St George’s Respiratory Questionnaire total score compared with placebo at week 48 (40.9 versus 43.7 units, P<0.005).

CONCLUSIONS:

Compared with the placebo group, tiotropium provides sustained improvements in lung function in patients with COPD, with improvements for smokers and ex-smokers.     

Effect of adalimumab on work productivity and indirect costs in moderate to severe Crohn's disease: a meta-analysis

OBJECTIVE:

To assess the effect of adalimumab on work productivity and indirect costs in patients with Crohn’s disease (CD) using a meta-analysis of clinical trials.

METHODS:

Study-level results were pooled from all clinical trials of adalimumab for moderate to severe CD in which work productivity outcomes were evaluated. Work Productivity and Activity Impairment Questionnaire outcomes (absenteeism, presenteeism and total work productivity impairment [TWPI]) were extracted from adalimumab trials. Meta-analyses were used to estimate pooled averages and 95% CIs of one-year accumulated reductions in work productivity impairment with adalimumab. Pooled averages were multiplied by the 2008 United States national average annual salary ($44,101) to estimate per-patient indirect cost savings during the year following adalimumab initiation.

RESULTS:

The four included trials (ACCESS, CARE, CHOICE and EXTEND) represented a total of 1202 employed adalimumab-treated patients at baseline. Each study followed patients for a minimum of 20 weeks. Pooled estimates (95% CIs) of one-year accumulated work productivity improvements were as follows: −9% (−10% to −7%) for absenteeism; −22% (−26% to −18%) for presenteeism; and −25% (−30% to −20%) for TWPI. Reductions in absenteeism and TWPI translated into per-patient indirect cost savings (95% CI) of $3,856 ($3,183 to $4,529) and $10,964 ($8,833 to $13,096), respectively.

CONCLUSION:

Adalimumab provided clinically meaningful improvements in work productivity among patients with moderate to severe CD, which may translate into substantial indirect cost savings from an employer’s perspective.     

Health care resource use and costs in Crohn's disease before and after infliximab therapy

BACKGROUND:

Infliximab therapy in patients with Crohn’s disease decreases resource use; however, the overall impact on health-related expenditures is unclear, especially beyond one year of study.

METHODS:

A retrospective analysis of economic data one and two years before and after infliximab therapy was performed using patients who served as their own controls. Total health care resource use and direct health care costs were compared for patients with or without fistulae.

RESULTS:

Patients with one (n=66) and two (n=39) years of economic data before and after infliximab treatment had their resource use and direct health care costs estimated. In the year following initiation of infliximab therapy, there were significant decreases in health care use, reflected in total hospital days (495 to 155 [P<0.05]), inpatient colonoscopies (46 to 24 [P<0.05]), outpatient colonoscopies (58 to 33 [P<0.05]) and major surgeries (10 to 2 [P<0.05]). Direct health care costs of inpatient costs for luminal (−$1,747 [P<0.05]) and fistulizing disease (−$2,530 [P<0.05]), major surgeries (−$1240 [P<0.05]) and outpatient colonoscopies (−$184 [P<0.05]) were also significantly reduced before and after infliximab therapy. Total direct health care costs, including the drug cost of infliximab, increased ($21,416 [P<0.05]). In general, the trends in health care costs analyzed over four consecutive years paralleled the two consecutive-year analysis.

CONCLUSIONS:

Infliximab therapy in patients with Crohn’s disease resulted in a significant decrease in both resource use and health care costs, but an increase in total direct health care costs once the cost of infliximab was added.     

Comparison of Canadian versus American emergency department visits for acute asthma

BACKGROUND:

Acute asthma is a common emergency department (ED) presentation in both Canada and the United States.

OBJECTIVE:

To compare ED asthma management and outcomes between Canada and the United States.

MEHODS:

A prospective cohort study of 69 American and eight Canadian EDs was conducted. Patients aged two to 54 years who presented with acute asthma underwent a structured ED interview and telephone follow-up two weeks later.

RESULTS:

A total of 3031 patients were enrolled. Canadian patients were more likely to be white (89% versus 22%; P<0.001), have health insurance (100% versus 69%; P<0.001) and identify a primary care provider (89% versus 64%; P<0.001) than American patients. In addition, Canadian patients were more likely to be using inhaled corticosteroids (63% versus 44%; P<0.001) and had higher initial peak expiratory flow (61% versus 48%; P<0.001). In the ED, Canadians received fewer beta-agonist (one versus two; P<0.001) and more anticholinergic (two versus one; P<0.001) treatments in the first hour; use of systemic corticosteroids was similar (60% versus 68%; P=0.13). Canadians were less likely to be hospitalized (11% versus 21%; P=0.02). Corticosteroids were prescribed similarly at discharge (60% versus 69%; P=0.13); however, Canadians were discharged more commonly on inhaled corticosteroids (63% versus 11%; P<0.001) and relapses were similar.

CONCLUSIONS:

Canadian patients with acute asthma have fewer barriers to primary care and are more likely to be on preventive medications, both before the ED visit and following discharge. Admissions rates are higher in the United States; however, relapse after discharge is similar between countries. These findings highlight the influences of preventive practices and heath care systems on ED visits for asthma.     

Effect of glucose-insulin-potassium infusion on oxidative stress in patients with dilated cardiomyopathy

OBJECTIVE

To investigate the effect of glucose-insulin-potassium (GIK) infusion on erythrocyte antioxidant enzyme activity levels during therapy and post-therapy in patients with dilated cardiomyopathy (DCM).

METHODS

Forty-one patients with DCM were enrolled in the present study. GIK solution (50 U of insulin in 500 mL of 30% glucose, plus 60 mmol/L KCl), in addition to the standard treatment, was administered by 24 h infusion in 28 patients (GIK group). In the remaining 13 patients (control group), 0.9% NaCl solution was administered. Venous blood samples from all patients were collected at baseline, during therapy (2 h, 8 h, 12 h and 24 h after baseline) and after therapy (48 h after baseline). The activity levels of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSHP) were measured.

RESULTS

In the GIK group, SOD values showed a significant increase at 24 h and 48 h compared with baseline and 2 h values (P<0.05). An increasing trend in CAT activity was observed during and after GIK infusion compared with baseline (0 h) values. However, these differences were not statistically significant (P>0.05). With regard to GSHP activity, no significant change was found in the GIK group during follow-up (P>0.05). In the control group, SOD, CAT and GSHP activity levels measured during and after therapy were found to be similar to those measured at baseline (P>0.05).

CONCLUSION

Administration of GIK solution, in addition to standard therapy, in patients with DCM may improve the metabolic scope of the disease by reducing myocardial oxidative stress.     

Comparison of Canadian versus United States emergency department visits for chronic obstructive pulmonary disease exacerbation

INTRODUCTION:

Despite the frequency of emergency department (ED) visits for chronic obstructive pulmonary disease (COPD) exacerbation, little is known about practice variation in EDs.

OBJECTIVES:

To examine the differences between Canadian and United States (US) COPD patients, and the ED management they receive.

METHODS:

A prospective multicentre cohort study was conducted involving 29 EDs in the US and Canada. Using a standard protocol, consecutive ED patients with COPD exacerbations were interviewed, their charts reviewed and a two-week telephone follow-up completed. Comparisons between Canadian and US patients, as well as their treatment and outcomes, were made. Predictors of antibiotic use were determined by multivariate logistic regression.

RESULTS:

Of 584 patients who had physician-diagnosed COPD, 397 (68%) were enrolled. Of these, 63 patients (16%) were from Canada. Canadians were older (73 years versus 69 years; P=0.002), more often white (97% versus 65%; P<0.001), less educated (P=0.003) and more commonly insured (P<0.001) than the US patients. US patients more commonly used the ED for their usual COPD medications (17% versus 3%; P=0.005). Although Canadian patients had fewer pack-years of smoking (45 pack-years versus 53 pack-years; P=0.001), current COPD medications and comorbidities were similar. At ED presentation, Canadian patients were more often hypoxic and symptomatic. ED treatment with inhaled beta-agonists (approximately 90%) and systemic corticosteroids (approximately 65%) were similar; Canadians received more antibiotics (46% versus 25%; P<0.001) and other treatments (29% versus 11%; P=0.002). Admission rates were similar in both countries (approximately 65%), although Canadian patients remained in the ED longer than the US patients (10 h versus 5 h, respectively; P<0.001).

CONCLUSIONS:

Overall, patients with acute COPD in Canada and the US appear to have similar history, ED treatment and outcomes; however, Canadian patients are older and receive more aggressive treatment in the ED. In both countries, the prolonged length of stay and high admission rate contribute to the ED overcrowding crisis facing EDs.     

Opioid Use is Associated with Decreased Quality of Life in Patients with Crohn's Disease

Background/Aims:

Quality of life is an important consideration in the management of patients with Crohn''s disease. Previous studies suggest that Crohn''s disease patients using opioids may have decreased quality of life and increased risk of mortality. Our aim was to determine the association between health-related quality of life (HRQoL) and opioid use in patients with Crohn''s disease while controlling for disease severity.

Patients and Methods:

We conducted a cross-sectional study recruiting Crohn''s disease patients at our center. Disease activity was measured using the Harvey-Bradshaw Index (HBI), and HRQoL was measured using the Inflammatory Bowel Disease Questionnaire (IBDQ).

Results:

We enrolled 38 Crohn''s disease patients using opioids and 62 patients not using opioids. Patients using opioids had an increased duration of disease (median 18.5 vs. 9 years, P = 0.005), increased surgeries related to Crohn''s disease (median 3 vs. 0, P < 0.001), and increased prednisone use (29% vs. 11.3%, P = 0.03). Patients using opioids had increased disease activity (median HBI score 9.0 vs. 3.0, P < 0.001). Quality of life was lower in patients using opioids (mean IBDQ score 109.3 vs. 162.9, P < 0.001). This finding was significant when controlling for HBI scores, number of previous surgeries, and prednisone use (P = 0.003).

Conclusions:

Opioid use in Crohn''s disease patients appears to be associated with disease activity and severity. HRQoL is markedly decreased in patients using opioids and this association is significant even when controlling for variables reflecting disease severity. Our findings suggest that Crohn''s disease patients using opioids are likely to be significantly impacted by their disease.     

Cardiac and neuromuscular implications of left bundle branch block in left ventricular hypertrabeculation/noncompaction

BACKGROUND:

Left bundle branch block (LBB) is frequently found in left ventricular hypertrabeculation/noncompaction (LVHT).

OBJECTIVES:

To compare LVHT patients with and without LBB regarding LVHT location and extension, left ventricular function, symptoms, electrocardiographic findings, prevalence of neuromuscular disorders (NMDs) and mortality during follow-up.

METHODS:

The charts of patients who underwent transthoracic echocardiographic examination at the Krankenanstalt Rudolfstiftung (Wien, Austria) between June 1995 and November 2006 were examined.

RESULTS:

LVHT was diagnosed in 102 patients (30 women) with a mean (± SD) age of 53±16 years (range 14 to 94 years). A specific NMD was diagnosed in 21 patients and an NMD of unknown etiology was diagnosed in 47. The neurological investigation was normal in 14 patients and 20 patients refused the investigation. The 24 patients with LBB were older (61 versus 51 years of age; P<0.01), and suffered from exertional dyspnea (96% versus 59%; P<0.01) and heart failure (79% versus 46%; P<0.01) more often than patients without LBB. LBB patients had less frequent tall QRS complexes (8% versus 47%; P<0.01) and ST-T wave abnormalities (4% versus 50%; P<0.01) than patients without LBB. Patients with LBB had a larger left ventricular end-diastolic diameter (73 mm versus 61 mm; P<0.01), worse left ventricular fractional shortening (15% versus 26%; P<0.01) and more extensive LVHT (1.8 versus 1.5 ventricular segments; P<0.05). The prevalence of NMDs did not differ between patients with and without LBB. Survival did not differ between patients with and without LBB during follow-up.

CONCLUSIONS:

LBB is associated with increased age, decreased systolic function and increased extension of LVHT. Whether LBB is a prognostic factor in LVHT remains speculative.     

Blood pressure reactions to insulin treatment in patients with type 2 diabetes

BACKGROUND

The initiation of insulin therapy may be easy and uncomplicated in some patients with type 2 diabetes, but in others, mainly in obese patients, problems often arise (ie, poor compliance, worsening B-cell function and/or insulin resistance).

METHODS

As a substudy of a broader investigation concerning hemorheological effects of insulin treatment in insufficiently controlled type 2 diabetes, blood pressure was recorded in 12 patients at baseline, after two months and after four months on insulin.

RESULTS

After two months on insulin, analyses of triglycerides, high-density lipoprotein cholesterol and total cholesterol indicated metabolic improvement (P<0.05 to 0.001) and a surprisingly uniform increase of blood pressure values (P<0.05 to 0.01) was found. At the same time, the serum sodium concentration increased (P<0.01) and was positively correlated to both systolic and diastolic blood pressure (P<0.01). After four months on insulin, blood pressure returned to pretreatment values or lower (P<0.05 to 0.01). Serum sodium also decreased to pretreatment values. No significant changes of the flow behaviour of blood were seen after the initiation of insulin.

CONCLUSIONS

The number of patients was small and the study was not primarily designed to examine blood pressure. The preliminary conclusion from the present study, however, is that the initiation of insulin treatment in poorly controlled type 2 diabetes causes a temporary and possibly clinically significant elevation of blood pressure. A change in renal treatment of sodium caused by insulin may be one of several possible explanations of the results, but further studies are warranted to confirm the findings.     

Association between proximity to major roads and sputum cell counts

BACKGROUND:

Air pollution caused by motor vehicle emissions has been associated with exacerbations of obstructive airway diseases; however, the nature of the resulting bronchitis has not been quantified.

OBJECTIVE:

To examine whether proximity to major roads or highways is associated with an increase in sputum neutrophils or eosinophils, and to evaluate the effect of proximity to roads on spirometry and exacerbations in patients with asthma.

METHODS:

A retrospective study of 485 sputum cell counts from patients attending a tertiary chest clinic in Hamilton, Ontario, identified eosinophilic or neutrophilic bronchitis. Patients’ residences were geocoded to the street network of Hamilton using geographic information system software. Associations among bronchitis, lung function, and proximity to major roads and highways were examined using multinomial logistic and multivariate linear regression analyses adjusted for patient age, smoking status and corticosteroid medications.

RESULTS:

Patients living within 1000 m of highways showed an increased risk of bronchitis (OR 3.8 [95% CI 1.0 to 13.7]; P<0.05), particularly neutrophilic bronchitis (OR 4.7 [95% CI 1.2 to 18.7]; P<0.05) as well as an increased risk of an asthma diagnosis (OR 1.9 [95% CI 1.0 to 3.4]; P<0.05). Patients living within 300 m of a major road were at increased risk for an asthma exacerbation (OR 1.9 [95% CI 1.5 to 15.5]; P<0.01) and lower lung function, particularly in women (P=0.036).

CONCLUSION:

In patients with airway diseases, living close to a highway or major road was associated with neutrophilic bronchitis, an increased risk of asthma diagnosis, asthma exacerbations and lower lung function.     

HIV-related non-Hodgkin��s lymphoma in Calgary

OBJECTIVE:

To determine the incidence of human immunodeficiency virus (HIV) associated non-Hodgkin’s lymphoma (NHL) in a cohort of patients from a distinct geographic region (southern Alberta). The type and location of NHL as well as how it affected the survival of these patients was examined.

PATIENTS AND METHODS:

The Southern Alberta HIV Clinic in Calgary serves all of southern Alberta, which has an estimated population of one million. The clinic has provided primary care for 1086 patients from January 1983 to August 1995. Data were obtained by reviewing the clinic’s database and patients’ charts.

RESULTS:

Over a 12-year period, 39 cases of NHL were diagnosed in a group of 1086 HIV-infected patients. Presentation of NHL was at an extranodal site in all but four cases, with the most common sites being the bowel and central nervous system. The mean CD4 count on presentation with NHL was 143.4±37.4×10⁶/L (range 1 to 1219×10⁶/L). Mean survival was 1.25±0.25 years with a range from 0 (diagnosed on autopsy) to 6.45 years. Patients with a CD4 count of less than 200×10⁶/L and/or diagnosed with an AIDS-defining illness before development of NHL had significantly reduced survival (0.85 years versus 2.48 years, P<0.02 and 0.57 years versus 2.09 years, P<0.001, respectively). Patients who presented with NHL involving either nodes alone or central nervous system had significantly decreased survival (0.28 years and 0.29 years, respectively, P<0.05). Patients with NHL involving the gastrointestinal tract had a longer mean survival than those with NHL elsewhere (P<0.05). All but seven cases received therapy for NHL including chemotherapy, radiotherapy, surgery or combined therapy. Fifteen patients (47% of treated) achieved a complete response that led to improved survival (P<0.01). Patients tolerated surgery, chemotherapy and radiotherapy well and no deaths were due to NHL therapy.

CONCLUSIONS:

These data suggest that development of NHL in HIV is associated with reduced survival, and that survival is predominantly determined by CD4 count and site of involvement at the time of diagnosis of NHL.     

Measurement of von Willebrand factor as the marker of endothelial dysfunction in vascular diseases

BACKGROUND:

von Willebrand factor is a blood glycoprotein that is required for normal hemostasis. Its level can be increased by endothelial cell damage.

HYPOTHESIS:

von Willebrand factor is a suitable marker of endothelial dysfunction.

METHODS:

von Willebrand factor activity was determined by ELISA in patients with acute coronary syndromes, acute stroke and chronic vascular diseases, and was compared with the values of healthy controls.

RESULTS:

von Willebrand factor activity of patients in each group was significantly higher (P<0.001) than that of the control group. The values of patients with acute coronary syndrome and acute stroke were significantly higher (P<0.05 and P<0.01, respectively) than those of patients with chronic vascular diseases. von Willebrand factor activity was significantly higher in patients with acute coronary syndrome and acute stroke (P<0.05 and P<0.01, respectively) on the sixth day than on admission.

CONCLUSIONS:

By measuring von Willebrand factor activity, a considerable, significant difference could be found between healthy people and chronic and acute vascular patients. The routine measurement of von Willebrand factor activity in vascular patients as an index of endothelial dysfunction may have clinical importance, because detection of this marker can be a noninvasive way of assisting diagnosis and indicating disease progression.     

Efficacy and Safety of Adalimumab in Moderately to Severely Active Cases of Ulcerative Colitis: A Meta-Analysis of Published Placebo-Controlled Trials

Background/Aims

To evaluate the efficacy and safety of adalimumab (ADA) in moderately to severely active ulcerative colitis (UC) patients who are unresponsive to traditional therapy.

Methods

Electronic databases, including the PubMed, Embase, and Cochrane databases, were searched to April 20, 2014. UC-related randomized controlled trials (RCTs) that compared ADA with placebo were eligible. Review Manager 5.1 was used for data analysis.

Results

This meta-analysis included three RCTs. ADA was considerably more effective compared with a placebo, and it increased the ratio of patients with clinical remission, clinical responses, mucosal healing and inflammatory bowel disease questionnaire responses in the induction and maintenance phases (p<0.05), as well as patients with steroid-free remission (p<0.05) during the maintenance phase. Clinical remission was achieved in a greater number of UC cases in the ADA 160/80/40 mg groups (0/2/4 week, every other week) compared with the placebo group at week 8 (p=0.006) and week 52 (p=0.0002), whereas the week 8 clinical remission rate was equivalent between the ADA 80/40 mg groups and the placebo group. Among the patients who received immunomodulators (IMM) at baseline, ADA was superior to the placebo in terms of inducing clinical remission (p=0.01). Between-group differences were not observed in terms of serious adverse events (p=0.61).

Conclusions

ADA, particularly at doses of 160/80/40 mg (0/2/4 week, every other week), is effective and safe in patients with moderate-to-severe UC who are unresponsive to traditional treatment. Concomitant IMM therapy may improve the short-term therapeutic efficacy of ADA.     

Impact of the metabolic syndrome on aortic pulse pressure and ascending aortic pulsatility in patients with angiographically normal coronary arteries

BACKGROUND:

Large artery stiffness is a major determinant of pulse pressure (PP), and PP at baseline has been associated with future coronary events.

OBJECTIVE:

To evaluate the impact of the metabolic syndrome on aortic PP and ascending aortic pulsatility (AP) in patients with angiographically normal coronary arteries.

METHODS:

Forty-two patients with the metabolic syndrome and 40 age-matched control subjects without the metabolic syndrome were included in the study. All subjects had normal coronary arteries. Diagnosis of the metabolic syndrome was based on the International Diabetes Federation guidelines published in 2005. Ascending AP was estimated as the ratio of aortic PP to mean blood pressure.

RESULTS:

Aortic PP (59±12 mmHg versus 43±10 mmHg; P<0.001) and ascending AP (0.54±0.10 versus 0.48±0.10; P<0.001) were significantly higher in the metabolic syndrome group. Multiple regression analysis revealed statistically independent relationships between ascending AP and fasting blood glucose, waist circumference and systolic blood pressure (model R²=0.408; P<0.001). The metabolic syndrome, as a whole, was also independently associated with both ascending AP (P<0.01) and aortic PP (P<0.01).

CONCLUSION:

The data showed that the metabolic syndrome is independently associated with increased aortic PP and ascending AP in patients with normal coronary arteries, suggesting aortic stiffness as one of the possible mechanisms underlying the excess cardiovascular risk associated with the metabolic syndrome.     

The effect of place of residence on access to invasive cardiac services following acute myocardial infarction

BACKGROUND:

The Canadian health care system is mandated to provide reasonable access to health care for all Canadians regardless of age, sex, race, socioeconomic status or place of residence. In the present study, the impact of place of residence in Nova Scotia on access to cardiac catheterization and long-term outcomes following an acute myocardial infarction (MI) were examined.

METHODS:

All patients with an acute MI who were hospitalized between April 1998 and December 2001 were identified. Place of residence was defined by postal code and separated into three categories: metropolitan area (MA); nonmetropolitan urban area (UA); and rural area (RA). Rates of and waiting times for cardiac catheterization were determined, as were risk-adjusted long-term rates of mortality and readmission to the hospital.

RESULTS:

A total of 7351 patients were hospitalized with an acute MI during the study period. Rates of cardiac catheterization differed across the three groups (MA 45.6%, UA 37.3%, RA 37.3%; P<0.0001), as did mean waiting times (MA 15.0 days, UA 32.1 days, RA 28.7 days) (P<0.0001). After adjusting for differences among patients, residence in either UA or RA emerged as an independent predictor of lower rates of cardiac catheterization (UA: hazard ratio [HR] 0.77, P<0.0001; RA: HR 0.75, P<0.0001), greater waiting times (UA: an additional 14.1 days, P<0.0001; RA: an additional 10.8 days, P<0.0001) and increased long-term rates of readmission (UA: HR 1.24, P=0.0001; RA: HR 1.12, P=0.04).

CONCLUSION:

In patients admitted with an acute MI, residence outside of an MA was associated with diminished rates of cardiac catheterization, longer waiting times and increased rates of readmission. Despite universal health care coverage, Canadians are subject to significant geographical barriers to cardiac catheterization with associated poorer outcomes.     

Predictive factors for an effective beta-blocker therapy in Chinese patients with congenital long QT syndrome: A multivariate regression analysis

OBJECTIVE:

To investigate the factors that may predict the effectiveness of beta-blocker therapy for congenital long QT syndrome (LQTS) in a Chinese patient population.

METHODS:

Twenty-six LQTS patients were treated with oral propranolol (n=16) or metoprolol tartrate (n=10) for 38 months. Clinical symptoms, heart rate, corrected QT interval (QTc) and left ventricular ejection fraction were assessed before and after the therapy.

RESULTS:

Cardiac events were reduced by more than 50% in 22 patients with beta-blocker therapy. The average number of syncopes/patient and the average frequency of syncopes/patient/year in the responders were reduced from 16.2±5.1 to 1.1±0.9 (P<0.01) and from 4.5+1.2 to 0.7+0.6 (p<0.01), respectively. The QTc was also reduced from 0.56±0.06 s to 0.50±0.03 s. There was no significant difference in the reduction of syncopes and QTc in patients treated with propranolol and metoprolol tartrate. Multivariate regression analysis showed no correlation between the reduction in syncopal attacks and patients’ age, sex, heart rate or left ventricular function (P>0.05). QTc reduction was the only independent predictive factor for syncope control (R=0.81, P<0.001).

CONCLUSIONS:

Oral beta-blockers are an effective therapy for Chinese patients with LQTS. A significant reduction in QTc is highly indicative of treatment success with beta-blockers.     

Temporal trends in the use of invasive cardiac procedures for non-ST segment elevation acute coronary syndromes according to initial risk stratification

BACKGROUND:

Current guidelines support an early invasive strategy in the management of high-risk non-ST elevation acute coronary syndromes (NSTE-ACS). Although studies in the 1990s suggested that high-risk patients received less aggressive treatment, there are limited data on the contemporary management patterns of NSTE-ACS in Canada.

OBJECTIVE:

To examine the in-hospital use of coronary angiography and revascularization in relation to risk among less selected patients with NSTE-ACS.

METHODS:

Data from the prospective, multicentre Global Registry of Acute Coronary Events (main GRACE and expanded GRACE²) were used. Between June 1999 and September 2007, 7131 patients from across Canada with a final diagnosis of NSTE-ACS were included the study. The study population was stratified into low-, intermediate- and high-risk groups, based on their calculated GRACE risk score (a validated predictor of in-hospital mortality) and according to time of enrollment.

RESULTS:

While rates of in-hospital death and reinfarction were significantly (P<0.001) greater in higher-risk patients, the in-hospital use of cardiac catheterization in low- (64.7%), intermediate- (60.3%) and high-risk (42.3%) patients showed an inverse relationship (P<0.001). This trend persisted despite the increase in the overall rates of cardiac catheterization over time (47.9% in 1999 to 2003 versus 51.6% in 2004 to 2005 versus 63.8% in 2006 to 2007; P<0.001). After adjusting for confounders, intermediate-risk (adjusted OR 0.80 [95% CI 0.70 to 0.92], P=0.002) and high-risk (adjusted OR 0.38 [95% CI 0.29 to 0.48], P<0.001) patients remained less likely to undergo in-hospital cardiac catheterization.

CONCLUSION:

Despite the temporal increase in the use of invasive cardiac procedures, they remain paradoxically targeted toward low-risk patients with NSTE-ACS in contemporary practice. This treatment-risk paradox needs to be further addressed to maximize the benefits of invasive therapies in Canada.     

Loss of neutral endopeptidase activity contributes to neutrophil activation and cardiac dysfunction during chronic hypomagnesemia: Protection by substance P receptor blockade

BACKGROUND/OBJECTIVE:

Hypomagnesemia (Hypo-Mg) in rodents leads to neurogenic inflammation associated with substance P (SP) elevations; neutral endopeptidase (NEP) is a principle cell surface proteolytic enzyme, which degrades SP. The effects of chronic Hypo-Mg on neutrophil NEP activity, cell activation and the associated cardiac dysfunction were examined.

METHODS/RESULTS:

Male Sprague-Dawley rats (180 g) were fed Mg-sufficient or Mg-deficient (Hypo-Mg) diets for five weeks. Enriched blood neutrophils were isolated at the end of one, three and five weeks by step gradient centrifugation. NEP enzymatic activity decreased by 20% (P value was nonsignificant), 50% (P<0.025) and 57% (P<0.01), respectively, for week 1, 3 and 5 Hypo-Mg rats. In association, neutrophil basal superoxide (•O₂⁻)-generating activities were elevated: 30% at week 1 (P value was nonsignificant), and fourfold to sevenfold for weeks 3 to 5 (P<0.01). Maximal phorbol myristate acetate-stimulated •O₂⁻ production by Hypo-Mg neutrophils increased twofold at week 5. Also, plasma 8-isoprostane levels were elevated twofold to threefold, and red blood cell glutathione decreased by 50% (P<0.01) after three to five weeks of chronic Hypo-Mg. When Hypo-Mg rats were treated with the SP receptor blocker (L-703,606), neutrophil NEP activities were retained at 75% (week 3) and 77% (week 5) (P<0.05); activation of neutrophil •O₂⁻ and other oxidative indexes were also significantly (P<0.05) attenuated. After five weeks, histochemical (hematoxylin and eosin) staining of Hypo-Mg-treated rat ventricles revealed significant white blood cell infiltration, which was substantially reduced by L-703,606. Echocardiography after three weeks of Hypo-Mg only showed modest diastolic impairment, but five weeks resulted in significant (P<0.05) depression in both left ventricular systolic and diastolic functions; changes in these functional parameters were attenuated by L-703,606.

CONCLUSION:

NEP activity regulates neutrophil •O₂⁻ formation by controlling SP bioavailability. When oxidative inactivation of NEP is prevented by SP receptor blockade, partial protection is afforded against cardiac contractile dysfunction.     

Success in pulmonary rehabilitation in patients with chronic obstructive pulmonary disease

BACKGROUND:

Pulmonary rehabilitation (PR) is beneficial for some, but not all, patients with chronic lung disease.

OBJECTIVES:

To determine the success rate of a comprehensive PR program for patients with chronic obstructive pulmonary disease (COPD) and to characterize the differences between responders and nonresponders.

METHODS:

A chart review was performed on patients with a clinical diagnosis of COPD who were referred for PR. Success was defined according to clinically important changes in St George’s Respiratory Questionnaire scores and/or 6 min walk test distance.

RESULTS:

The majority of subjects were men (58%) with a mean (± SD) age of 69±10 years (n=177). Sixty-two per cent of participants had a successful outcome with PR, with proportionally more responders noting subjective improvement than objective improvement on a 6 min walk test (73% versus 51%). Subjects with poor baseline St George’s Respiratory Questionnaire scores tended to improve the most (P=0.011 [ANOVA]). Successful participants had a greater forced expired volume in 1 s (1.1 L versus 0.9 L; P<0.05) and a lower BODE index (body mass index, airflow obstruction, dyspnea, and exercise capacity index) at baseline (9.6 versus 10.3; P<0.05). Success of PR was not correlated with age, sex, chronic hypoxemic respiratory failure or other chronic conditions. Successful participants were more likely to be compliant and to experience fewer adverse events (P≤0.001).

CONCLUSIONS:

Our study reinforced the belief that the majority of participants with COPD benefit from PR. Few baseline characteristics were predictive of success. Subjectively measured improvement occurred more frequently than objectively measured improvement and was greatest in those with the poorest baseline values.