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.     

Efficacy and safety of adalimumab in Canadian patients with moderate to severe Crohn's disease: results of the Adalimumab in Canadian SubjeCts with ModErate to Severe Crohn's DiseaSe (ACCESS) trial

OBJECTIVE:

To evaluate open-label adalimumab therapy for clinical effectiveness, fistula healing, patient-reported outcomes and safety in Canadian patients with moderate to severe Crohn’s disease (CD) who were either naive to or previously exposed to antitumour necrosis factor (anti-TNF) therapy.

METHODS:

Patients with moderate to severe CD (CD activity index [CDAI] score of greater than 220, or Harvey-Bradshaw index [HBI] of 7 or greater) were eligible. Patients received open-label adalimumab as induction (160 mg and 80 mg subcutaneously [sc]) at weeks 0 and 2, respectively and maintenance (40 mg sc every other week) therapy. At or after eight weeks, patients with flare or nonresponse could have their dosage increased to 40 mg sc weekly. Patients were followed for a minimum of six months or until adalimumab was commercially available in Canada.

RESULTS:

Of the 304 patients enrolled, 160 were infliximab experienced, while 144 were anti-TNF naive. HBI remission (HBI score of 4 or lower) at week 24 was achieved by 53% of anti-TNF-naive and 36% of infliximab-experienced patients (P<0.01; P<0.001 for both groups for all visits versus baseline). Fistula healing rates at week 12 were 48% for anti-TNF-naive patients, and 26% for infliximab-experienced patients. At week 24, fistula healing rates were significantly greater for the anti-TNF-naive group (60% versus 28%; P<0.01). Improvements in quality of life and work productivity were sustained from week 4 to week 24 for all patients. Serious infections occurred in 2% of patients.

CONCLUSIONS:

Adalimumab therapy induced and sustained steroid-free remission in both infliximab-experienced and anti-TNF-naive patients with moderate to severe CD. Clinically meaningful rates of fistula healing were also observed. Improvements in patient-reported outcomes were sustained throughout the 24-week study period.     

Concordance of self- and program-reported rates of cardiac rehabilitation referral, enrollment and participation

BACKGROUND:

Despite potential bias, researchers often rely on patient self-reported data of health care use. However, the validity and accuracy of self-reported data on cardiac rehabilitation (CR) use are unknown.

OBJECTIVE:

To assess the concordance between patient self-report and site-verified CR referral, enrollment and participation.

METHODS:

A consecutive sample of 661 coronary artery disease inpatients (mean [± SD] age 61.27±1.31 years; 157 women [23.8%]) treated at three acute care sites was recruited (75% response rate) as part of a larger study comparing automatic with usual referral methods. CR referral, enrollment (attendance at intake assessment) and participation (percentage of program attended) were discerned in a mailed survey nine months following discharge (n=506; 84.3% retention). A total of 24 CR sites were contacted for verification.

RESULTS:

A total of 276 participants (54.5%) self-reported CR referral, and CR sites verified receipt of 262 referrals (51.8%) (Cohen’s kappa 0.899). A total of 232 participants (45.8%) self-reported CR enrollment, with site-verification for 208 participants (41.1%) (Cohen’s kappa 0.846). Self-reported data indicated that participants attended a mean of 81.78±25.84% of prescribed CR sessions, with CR sites reporting that participants completed 80.75±31.27% of the program (r=0.662; P<0.001). Equivalency testing revealed that the self-reported and site-verified rates of program participation were equivalent (z<1.96).

CONCLUSIONS:

The almost perfect agreement between the self-reported and site-verified use of CR services suggests that self-administered items are highly valid in this population.     

Renal effects of long-term treatment with 5-aminosalicylic acid

BACKGROUND:

A number of case reports link the use of 5-aminosalicylic acid (5-ASA) to interstitial nephritis in patients with inflammatory bowel disease (IBD).

OBJECTIVE:

To investigate whether the long-term use of 5-ASA has harmful effects on renal function in patients with IBD.

METHODS:

A retrospective analysis of 171 consecutive outpatients with Crohn’s disease or ulcerative colitis was conducted. Serum creati-nine levels and body weight were measured before and after treatment to calculate the creatinine clearance (CrCl) rate.

RESULTS:

In 171 patients (93 women, 78 men), the mean (± SD) dose of 5-ASA was 3.65±0.85 g/day with a cumulative dose of 11±7.7 kg over an interval of 8.4±5.9 years. Serum creatinine concentrations increased from 76.8 μmol/L to 88.7 μmol/L (n=171; P<0.0001) and the CrCl rate fell significantly from 104.6 mL/min to 93.1 mL/min (n=81; P<0.0001). There was one case of interstitial nephritis reported. Treatment groups included mesalamine (74.3%), sulfasalazine (15.2%) and combination (sulfalsalazine/mesalamine [10.5%]) with treatment durations of 7.2±4.5, 12.3±8.7 and 11.2±6.7 years, respectively. The duration of treatment was the most important covariate for change in CrCl and when analyzed by treatment group, those treated with sulfasazine had a strong correlation (r=−0.54, P=0.0145), while nonsignificant in the mesalamine group (r=0.06, P=0.7017). The decline in CrCl was negatively correlated with the pretreatment CrCl rate (r=−0.34; P=0.0024) and positively correlated with the mean daily dose of 5-ASA (r=0.32; P=0.0034).

CONCLUSION:

The present study is the first to demonstrate a significant dose- and treatment duration-dependant decline in CrCl. The risks need to be further evaluated because 5-ASA is widely used for long-term maintenance therapy in patients with IBD.     

Liver steatosis is associated with insulin resistance in skeletal muscle rather than in the liver in Japanese patients with non‐alcoholic fatty liver disease

Aims/Introduction

To examine the association between liver histological features and organ-specific insulin resistance indices calculated from 75-g oral glucose tolerance test data in patients with non-alcoholic fatty liver disease.

Materials and Methods

Liver biopsy specimens were obtained from 72 patients with non-alcoholic fatty liver disease, and were scored for steatosis, grade and stage. Hepatic and skeletal muscle insulin resistance indices (hepatic insulin resistance index and Matsuda index, respectively) were calculated from 75-g oral glucose tolerance test data, and metabolic clearance rate was measured using the euglycemic hyperinsulinemic clamp method.

Results

The degree of hepatic steatosis, and grade and stage of non-alcoholic steatohepatitis were significantly correlated with Matsuda index (steatosis r = −0.45, P < 0.001; grade r = −0.54, P < 0.001; stage r = −0.37, P < 0.01), but not with hepatic insulin resistance index. Multiple regression analyses adjusted for age, sex, body mass index and each histological score showed that the degree of hepatic steatosis (coefficient = −0.22, P < 0.05) and grade (coefficient = −0.40, P < 0.01) were associated with Matsuda index, whereas the association between stage and Matsuda index (coefficient = −0.07, P = 0.593) was no longer significant. A similar trend was observed for the association between steatosis and metabolic clearance rate (coefficient = −0.62, P = 0.059).

Conclusions

Liver steatosis is associated with insulin resistance in skeletal muscle rather than in the liver in patients with non-alcoholic fatty liver disease, suggesting a central role of fatty liver in the development of peripheral insulin resistance and the existence of a network between the liver and skeletal muscle.     

Cost-effectiveness of enoxaparin compared with unfractionated heparin in ST elevation myocardial infarction patients undergoing pharmacological reperfusion: A Canadian analysis of the Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment – Thrombolysis in Myocardial Infarction (ExTRACT-TIMI) 25 trial

OBJECTIVE:

To evaluate the cost-effectiveness of enoxaparin versus unfractionated heparin in conjunction with fibrinolysis in ST elevation myocardial infarction patients within Canada.

DESIGN:

Based on the Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment – Thrombolysis in Myocardial Infarction (ExTRACT-TIMI) 25 trial, a model was created to analyze the cost-effectiveness of enoxaparin compared with unfractionated heparin in conjunction with fibrinolysis among ST elevation myocardial infarction patients within Canada. Clinical outcomes were derived from published results of the main trial. Resource use costs were first assessed based on United States Diagnosis-Related Group values for hospitalizations and Current Procedural Terminology codes for outpatient visits and tests. Both were then converted using Canadian local costs. Survival and life expectancy were estimated from Framingham survival data. The incremental cost-effectiveness ratio was expressed as cost per life year gained.

RESULTS:

Through 30 days after random assignment, the primary composite end point favoured the enoxaparin group over the unfractionated heparin group (death or recurrent myocardial infarction rate 9.9% versus 12.0%, P<0.001), and was associated with a modest increased cost of $169.50 ($8,757.00 versus $8,587.50, respectively). Life years gained as a result of treatment with enoxaparin was increased by 0.11 years (P<0.05). Enoxaparin was found to be cost-effective, as indicated by an incremental cost-effectiveness ratio of $4,930 with a 99% probability of costing less than $20,000.

CONCLUSIONS:

Although associated with modest increased direct medication costs, enoxaparin following fibrinolysis improved the clinical efficacy in STEMI patients and increased the life years gained.     

Can a self-management education program for patients with chronic obstructive pulmonary disease improve quality of life ?

OBJECTIVE:

To assess the effects of a self-management program on health-related quality of life (HRQoL) and morbidity commonly associated with chronic obstructive pulmonary disease (COPD).

METHODS:

A total of 57 outpatients with stable COPD received four weeks of self-management education, while 45 patients received usual care. Patients were evaluated at baseline, at three months and one year following the educational intervention. The primary outcome variable was HRQoL measured by the St George’s Respiratory Questionnaire (SGRQ). The secondary outcome variables were number of emergency room visits and hospitalizations for exacerbation.

RESULTS:

The intervention group’s HRQoL improved significantly at three months (total score A=−5.0 [P=0.006]) and 12 months (total score A=−6.7 [P<0.001]), as evidenced by decreased scores on the SGRQ. In contrast, the SGRQ scores increased significantly in the control group at three months (total score A=+3.7 [P= 0.022]) and 12 months (total score A=+3.4 [P=0.032]). Global impact appeared to be responsible for the change in the intervention group. Moreover, in the intervention group, the number of hospitalizations dropped from 0.7/person/year to 0.3/person/year (P=0.017), and emergency room visits dropped from 1.1 person/year to 0.2/person/year (P=0.002), while subjects in the control group did not experience any significant decreases in these parameters.

CONCLUSIONS:

A planned education program improved HRQoL while decreasing the number of emergency room visits and hospitalizations in patients with stable COPD; this improvement persisted at 12 months.     

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.     

Comparability of Internet and telephone data in a survey on the respiratory health of children

BACKGROUND:

Mixing survey administration modes has generated concern about the comparability of responses between modes.

OBJECTIVE:

To explore the differences in respondent profiles, and responses between Internet and telephone questionnaires in a survey on respiratory diseases.

METHODS:

The data were generated from a mixed Internet and telephone survey of respiratory diseases among children in Montreal (Quebec), in 2006. Comparison of 12 selected questions was performed after standardization for respondent education and income. Stratification of analysis on education and income categories was also performed for the questions with significantly divergent responses.

RESULTS:

Six questions showed significant differences in responses between modes after standardization. The largest differences among the closed-ended questions were observed for highly prevalent symptoms, dry cough during the night (difference of 9% for positive answer [P<0.01]) and symptoms of allergic rhinitis (difference of 7% for positive answer [P<0.01]). A large discrepancy was also found in the multiple choice question and with an open-ended response (ie, free answer). For the three potentially sensitive questions, a desirability bias was probably present in one question on smoking habits (difference of 2.6 % for positive answer [P<0.05]).

CONCLUSION:

The differences observed between Internet and telephone responses to selected questions were not completely explained by socioeconomic disparities among the respondents. In a mixed-mode survey (Internet and telephone), caution should be used when formulating sensitive, complex, open-ended and long-ended questions, and those related to highly prevalent and nonspecific symptoms.     

Inflammatory bowel disease: A Canadian burden of illness review

BACKGROUND:

Inflammatory bowel diseases (IBD) – Crohn’s disease (CD) and ulcerative colitis (UC) – significantly impact quality of life and account for substantial costs to the health care system and society.

OBJECTIVE:

To conduct a comprehensive review and summary of the burden of IBD that encompasses the epidemiology, direct medical costs, indirect costs and humanistic impact of these diseases in Canada.

METHODS:

A literature search focused on Canadian data sources. Analyses were applied to the current 2012 Canadian population.

RESULTS:

There are approximately 233,000 Canadians living with IBD in 2012 (129,000 individuals with CD and 104,000 with UC), corresponding to a prevalence of 0.67%. Approximately 10,200 incident cases occur annually. IBD can be diagnosed at any age, with typical onset occurring in the second or third decade of life. There are approximately 5900 Canadian children <18 years of age with IBD. The economic costs of IBD are estimated to be $2.8 billion in 2012 (almost $12,000 per IBD patient). Direct medical costs exceed $1.2 billion per annum and are driven by cost of medications ($521 million), hospitalizations ($395 million) and physician visits ($132 million). Indirect costs (society and patient costs) total $1.6 billion and are dominated by long-term work losses of $979 million. Compared with the general population, the quality of life patients experience is low across all dimensions of health.

CONCLUSIONS:

The present review documents a high burden of illness from IBD due to its high prevalence in Canada combined with high per-patient costs. Canada has among the highest prevalence and incidence rates of IBD in the world. Individuals with IBD face challenges in the current environment including lack of awareness of IBD as a chronic disease, late or inappropriate diagnosis, inequitable access to health care services and expensive medications, diminished employment prospects and limited community-based support.     

Efficacy and safety of lixisenatide in Japanese patients with type 2 diabetes mellitus inadequately controlled by sulfonylurea with or without metformin: Subanalysis of GetGoal‐S

Aims/Introduction

This was a subanalysis of Japanese patients included in the glucagon-like peptide-1 receptor agonist AVE0010 in patients with type 2 diabetes mellitus for glycemic control and safety evaluation (GetGoal-S) study – a 24-week, randomized, placebo-controlled study of lixisenatide in patients with type 2 diabetes mellitus inadequately controlled by sulfonylurea with or without metformin.

Materials and Methods

In GetGoal-S, 127 Japanese patients received the once-daily prandial glucagon-like peptide-1 receptor agonist lixisenatide 20 μg/day or a matching placebo. The primary outcome was change in glycated hemoglobin.

Results

At week 24, lixisenatide significantly reduced mean glycated hemoglobin (least squares mean difference vs the placebo −1.1% [12 mmol/mol, P < 0.0001]), and significantly more lixisenatide patients reached glycated hemoglobin targets of <7% (53 mmol/mol) and ≤6.5% (48 mmol/mol) vs the placebo. Lixisenatide produced statistically significant reductions in 2-h postprandial plasma glucose (least squares mean difference vs the placebo −8.51 mmol/L, P < 0.0001) and glucose excursion vs the placebo, and significantly reduced fasting plasma glucose (least squares mean difference vs the placebo −0.65 mmol/L, P = 0.0454). Bodyweight decreased with both lixisenatide and the placebo (least squares mean change −1.12 kg for lixisenatide, −1.02 kg for placebo). The overall incidence of adverse events was similar for lixisenatide and the placebo (84.2 and 82.4%, respectively), the most frequent being gastrointestinal disorders (52.6% for lixisenatide vs 29.4% for placebo). The incidence of symptomatic hypoglycemia was higher with lixisenatide vs the placebo (17.1 and 9.8%, respectively), with no cases of severe symptomatic hypoglycemia in either group.

Conclusions

In the Japanese subpopulation of the GetGoal-S study, lixisenatide produced a significant and clinically relevant improvement in glycated hemoglobin, with a pronounced improvement in postprandial plasma glucose, and a good safety and tolerability profile.     

Patient Sharing Among Physicians and Costs of Care: A Network Analytic Approach to Care Coordination Using Claims Data

BACKGROUND

Improving care coordination is a national priority and a key focus of health care reforms. However, its measurement and ultimate achievement is challenging.

OBJECTIVE

To test whether patients whose providers frequently share patients with one another—what we term ‘care density’—tend to have lower costs of care and likelihood of hospitalization.

DESIGN

Cohort study

PARTICIPANTS

9,596 patients with congestive heart failure (CHF) and 52,688 with diabetes who received care during 2009. Patients were enrolled in five large, private insurance plans across the US covering employer-sponsored and Medicare Advantage enrollees

MAIN MEASURES

Costs of care, rates of hospitalizations

KEY RESULTS

The average total annual health care cost for patients with CHF was $29,456, and $14,921 for those with diabetes. In risk adjusted analyses, patients with the highest tertile of care density, indicating the highest level of overlap among a patient’s providers, had lower total costs compared to patients in the lowest tertile ($3,310 lower for CHF and $1,502 lower for diabetes, p < 0.001). Lower inpatient costs and rates of hospitalization were found for patients with CHF and diabetes with the highest care density. Additionally, lower outpatient costs and higher pharmacy costs were found for patients with diabetes with the highest care density.

CONCLUSION

Patients treated by sets of physicians who share high numbers of patients tend to have lower costs. Future work is necessary to validate care density as a tool to evaluate care coordination and track the performance of health care systems.

Electronic supplementary material

The online version of this article (doi:10.1007/s11606-012-2104-7) contains supplementary material, which is available to authorized users.KEY WORDS: care coordination, performance measure, provider social networks, care density     

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.     

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.     

Resource Use Study In COPD (RUSIC): A prospective study to quantify the effects of COPD exacerbations on health care resource use among COPD patients

BACKGROUND:

There is increasing interest in health care resource use (HRU) in Canada, particularly in resources associated with acute exacerbations of chronic obstructive pulmonary disease (COPD).

OBJECTIVE:

To identify HRU due to exacerbations of COPD.

METHODS:

A 52-week, multicentre, prospective, observational study of HRU due to exacerbations in patients with moderate to severe COPD was performed. Patients were recruited from primary care physicians and respirologists in urban and rural centres in Canada.

RESULTS:

In total, 524 subjects (59% men) completed the study. Their mean age was 68.2±9.4 years, with a forced expiratory volume in 1 s of 1.01±0.4 L. Patients had significant comorbidities. There were 691 acute exacerbations of COPD, which occurred in 53% of patients: 119 patients (23%) experienced one acute exacerbation, 70 patients (13%) had two acute exacerbations and 89 patients (17%) had three or more acute exacerbations. Seventy-five patients were admitted to hospital, with an average length of stay of 13.2 days. Fourteen of the patients spent time in an intensive care unit (average length of stay 5.6 days). Factors associated with acute exacerbations of COPD included lower forced expiratory volume in 1 s (P<0.001), high number of respiratory medications prescribed (P=0.037), regular use of oral corticosteroids (OCSs) (P=0.008) and presence of depression (P<0.001). Of the 75 patients hospitalized, only 53 received OCSs, four received referral for rehabilitation and 15 were referred for home care.

CONCLUSIONS:

The present study showed a high prevalence of COPD exacerbations, which likely impacted on HRU. There was evidence of a lack of appropriate management of exacerbations, especially with respect to use of OCSs, and referral for pulmonary rehabilitation and home care.     

Increased Cardiovascular Disease,Resource Use,and Costs Before the Clinical Diagnosis of Diabetes in Veterans in the Southeastern U.S.

Importance

Screening for diabetes might be more widespread if adverse associations with cardiovascular disease (CVD), resource use, and costs were known to occur earlier than conventional clinical diagnosis.

Objective

The purpose of this study was to determine whether adverse effects associated with diabetes begin prior to clinical diagnosis.

Design

Veterans with diabetes were matched 1:2 with controls by follow-up, age, race/ethnicity, gender, and VA facility. CVD was obtained from ICD-9 codes, and resource use and costs from VA datasets.

Setting

VA facilities in SC, GA, and AL.

Participants

Patients with and without diagnosed diabetes.

Main Outcome Measures

Diagnosed CVD, resource use, and costs.

Results

In this study, the 2,062 diabetic patients and 4,124 controls were 63 years old on average, 99 % male, and 29 % black; BMI was 30.8 in diabetic patients vs. 27.8 in controls (p<0.001). CVD prevalence was higher and there were more outpatient visits in Year −4 before diagnosis through Year +4 after diagnosis among diabetic vs. control patients (all p<0.01); in Year −2, CVD prevalence was 31 % vs. 24 %, and outpatient visits were 22 vs. 19 per year, respectively. Total VA costs/year/veteran were higher in diabetic than control patients from Year −4 ($4,083 vs. $2,754) through Year +5 ($8,347 vs. $5,700) (p<0.003) for each, reflecting underlying increases in outpatient, inpatient, and pharmacy costs (p<0.05 for each). Regression analysis showed that diabetes contributed an average of $1,748/year to costs, independent of CVD (p<0.001).

Conclusions and Relevance

VA costs per veteran are higher—over $1,000/year before and $2,000/year after diagnosis of diabetes—due to underlying increases in outpatient, inpatient, and pharmacy costs, greater number of outpatient visits, and increased CVD. Moreover, adverse associations with veterans’ health and the VA healthcare system occur early in the natural history of the disease, several years before diabetes is diagnosed. Since adverse associations begin before diabetes is recognized, greater consideration should be given to systematic screening in order to permit earlier detection and initiation of preventive management. Keeping frequency of CVD and marginal costs in line with those of patients before diabetes is currently diagnosed has the potential to save up to $2 billion a year.

Electronic supplementary material

The online version of this article (doi:10.1007/s11606-014-3075-7) contains supplementary material, which is available to authorized users.Key words: diabetes, health care cost, cardiovascular disease, prediabetes     

Improvement in health-related quality of life after lung transplantation

BACKGROUND/OBJECTIVE:

Traditional survival outcomes do not reflect the effects on the health-related quality of life (HRQL) of patients. HRQL following lung transplantation has not been studied systematically. The Health Utilities Index (HUI) is a family (HUI2 and HUI3) of measures of HRQL that has not been previously used to assess HRQL in lung transplantation. The objective of the present study was to assess the impact of lung transplantation on patient’s HRQL using the HUI.

METHODS:

A total of 43 patients completed a battery of questionnaires before lung transplantation, and at three months and six months after lung transplantation. The 15-item questionnaire (HUI2 and HUI3) was used. Overall scores were based on a conventional scale (0.00 = dead, 1.00 = perfect health). Mental health was assessed by the Hospital Anxiety and Depression Scale. Adherence to medication and exercise were assessed by Morisky’s and Godin’s questionnaires, respectively.

RESULTS:

Sixty-five per cent of the patients were men, with a mean age of 53 years (range 18 to 67 years). The mean overall HUI3 score for the lung transplant candidates (0.57) was much lower than for the lung transplant recipients (0.82) at six months post-transplantation. This difference was clinically important and statistically significant (P<0.05 [paired ttest, degrees of freedom (df) = 35]). Differences in mean Hospital Anxiety and Depression Scale scores after transplantation were statistically significant (P<0.05 [paired t test, df=35]). After six months, transplant recipients were more adherent to medication (P<0.05 [χ² test, df=1]). Recipients were able to increase the duration of exercise at all levels of intensity.

CONCLUSION:

Lung transplantation improved the patients’ HRQL and adherence to medication. Anxiety levels persisted six months after transplantation but depression levels had decreased significantly.     

Association of matrix Gla protein gene allelic polymorphisms (G?7→A,T?138→C and Thr83→Ala) with acute coronary syndrome in the Ukrainian population

BACKGROUND:

Several allelic variants of matrix γ-carboxyglutamic acid protein (MGP) can differentially affect the development of certain forms of ischemic heart disease depending on specific characteristics of each population.

OBJECTIVE:

To study the distribution of allelic variants of MGP promoter T⁻¹³⁸→C (rs1800802) and G⁻⁷→A (rs1800801), and Thr₈₃→Ala exon 4 (rs4236) polymorphisms in a Ukrainian population of patients with acute coronary syndrome (ACS).

METHODS:

Polymerase chain reaction and restriction fragment length polymorphism (RFLP) analysis were used to detect the above-mentioned variants of the MGP gene in 115 patients with ACS and in 140 essentially healthy individuals.

RESULTS:

The distribution of homozygous carriers of a major allelic variant, and heterozygous and homozygous minor allele variants of the T⁻¹³⁸→C MGP promoter polymorphism in patients with ACS were 59.8%, 32.7% and 7.5%, respectively. The corresponding distributions of variants in the control group were 54.0%, 41.0% and 5.0%, respectively (P>0.05 [χ² test]). With respect to the G⁻⁷→A polymorphism, the respective distributions were 42.1%, 45.6% and 12.3%, compared with 50.7%, 45.0% and 4.3% in the control group, respectively (P<0.05). Finally, the respective distributions according to the Thr₈₃→Ala exon 4 polymorphism were 42.6%, 43.5% and 13.9%, respectively, compared with 45.3%, 43.0% and 11.7% in the control group. Using logistic regression analysis, it was estimated that the A/A genotype (G⁻⁷→A polymorphism) was significantly (P=0.02) associated with ACS (OR 4.302 [95% CI 1.262 to 14.673]).

CONCLUSION:

The allelic A/A promoter variant of MGP G⁻⁷→A polymorphism can be considered a risk factor for ACS in the Ukrainian population.     

Prenatal exposure to carbon monoxide temporarily impairs maturation of rat cardiomyocytes: Electrophysiological evidence

BACKGROUND:

Maternal smoking is an independent risk factor for sudden infant death syndrome. Carbon monoxide (CO) is a major component of cigarette smoke. No information is available concerning the effect of CO and/or smoking on postnatal maturation of the heart.

OBJECTIVES:

To investigate the effect of prenatal exposure to CO on cellular electrophysiological maturation in male Wistar rats.

METHODS:

The patch-clamp technique was used to measure the action potential and ionic currents (transient outward current and long-lasting type Ca²⁺ current) from rat ventricular myocytes.

RESULTS:

During growth, action potential duration (APD) measurements at −20 mV and −50 mV (APD₋₂₀ and APD₋₅₀) progressively decreased in both groups. APD was significantly delayed in rats prenatally exposed to 150 parts per million CO: at four weeks APD₋₂₀ and APD₋₅₀ were 90 ms and 148 ms, respectively, in CO-exposed rats (n=13), and 36 ms and 78 ms, respectively, in control rats (n=14; P<0.01 and P<0.05, respectively); this normalized at eight weeks. After four weeks, the density of long-lasting type Ca²⁺ current increased by 34% and the density of transient outward current decreased by 37% in CO-exposed versus control rats; this normalized at eight weeks.

CONCLUSIONS:

Prenatal CO exposure affects the physiological shortening of APD in neonatal rats. It is speculated that prolonged myocyte repolarization induced by prenatal exposure to smoke may establish a period of vulnerability for life-threatening arrhythmias during infancy.     

Ulcerative colitis-associated hospitalization costs: A population-based study

BACKGROUND:

Hospitalization costs for ulcerative colitis (UC) following the introduction of infliximab have not been evaluated.

OBJECTIVE:

To study predictors of costs for UC patients who were hospitalized for a flare or colectomy.

METHODS:

Population-based surveillance identified adults (≥18 years of age) admitted to hospital for UC flare or colectomy between 2001 and 2009 in the Calgary Health Zone (Alberta). Medical charts were reviewed and patients stratified into three admission types: responsive to inpatient medical therapy (n=307); emergent colectomy (n=227); and elective colectomy (n=208). The annual median cost with interquartile range (IQR) was calculated. Linear regression determined the effect of admission type on hospital charges after adjusting for age, sex, smoking, comorbidities, disease extent, medication use (eg, infliximab) and year. The adjusted cost increase was presented as the percent increase with 95% CIs. Joinpoint analysis assessed for an inflection point in hospital cost after the introduction of infliximab.

RESULTS:

Median hospitalization cost for UC flare, emergent colectomy and elective colectomy, respectively, were: $5,499 (IQR $3,374 to $8,904), $23,698 (IQR $17,981 to $32,385) and $14,316 (IQR $11,932 to $18,331). Adjusted hospitalization costs increased approximately 6.0% annually (95% CI 4.5% to 7.5%). Adjusted costs were higher for patients who underwent an elective colectomy (percent increase cost 179.8% [95% CI 151.6% to 211.1%]) or an emergent colectomy (percent increase cost 211.1% [95% CI 183.2% to 241.6%]) than medically responsive patients. Infliximab in hospital was an independent predictor of increased costs (percent increase cost 69.5% [95% CI 49.2% to 92.5%]). No inflection points were identified.

CONCLUSION:

Hospitalization costs for UC increased due to colectomy and infliximab.