Persistence with cholinesterase inhibitor therapy in a population-based cohort of patients with Alzheimer's disease.

PURPOSE: To estimate the risk (and determinants) of discontinuing cholinesterase inhibitors (ChEIs) in a population-based sample of Alzheimer's disease (AD) patients. METHODS: This is a retrospective cohort study based on linked de-identified administrative health data from the province of Saskatchewan, Canada. The cohort included all AD patients receiving a ChEI prescription during the first year of provincial coverage (2000-2001). Persistence was defined as no gap of 60+ days between depletion and subsequent refill of a ChEI prescription. Kaplan-Meier analysis was used to estimate the risk of discontinuation over 40 months. Cox regression with time-varying covariates was used to assess risk factors for ChEI discontinuation. RESULTS: The sample included 1080 patients (64% female, average age 80 +/- 7 years). Baseline mean (SD) Mini-Mental State Examination (MMSE) and Functional Activities Questionnaire (FAQ) scores were 20.8 (4.4) and 17.5 (7.7), respectively. Over 40 months, 84% discontinued therapy. The 1-year risk of discontinuation was 66.4% (95%CI 63.5-69.3%). Discontinuation was significantly more likely for females (adjusted HR 1.34, 95%CI 1.16-1.55) and among those with lower MMSE scores (2.52, 2.01-3.17 if <15), not receiving social assistance (1.25, 1.07-1.45), and paying at least 65% of total prescription costs (1.51, 1.30-1.74). It was significantly less likely for patients with frequent physician visits (0.78, 0.66-0.93, for 7-19 vs. <7 visits), higher Chronic Disease Scores (0.74, 0.61-0.89, for 7+ vs. <4), and FAQ scores of 9+ (0.82, 0.69-0.99). CONCLUSION: The likelihood of discontinuing ChEI therapy was high in this real-world sample of AD patients. Significant predictors included clinical, socioeconomic, and practice factors.

The usefulness of the EQ-5D in differentiating among persons with major depressive episode and anxiety.

BACKGROUND: Major depressive episodes (MDE) and anxiety disorders are associated with significantly lower health-related quality of life (HRQL). The present study explores the ability of the EQ-5D HRQL measure to differentiate among those with a clinical diagnosis of MDE and/or anxiety disorders. METHODS: Data were collected as part of the Alberta Mental Health Survey (2003). MDE and anxiety were defined by DSM-IV using the Mini International Neuropsychiatric Interview (M.I.N.I). Descriptive and multivariate regression analyses were used to examine associations between EQ-5D scores and mental health diagnoses. RESULTS: The prevalence for diagnoses (and proportion within each group reporting problems on the Anxiety/Depression domain) were: MDE alone 2.6% (48.6%); anxiety disorders alone 11.2% (38.9%); MDE and anxiety 5.2% (81.1%); and neither 80.9% (8.2%), respectively. Adjusted mean EQ-Index and EQ-VAS scores were shown to be significantly lower among those with MDE and anxiety disorders (0.70, 64.2), followed by those with MDE alone (0.83, 70.8) and anxiety disorders alone (0.84, 76.7), when compared with subjects with none of these conditions. CONCLUSIONS: Reporting problems on the EQ-5D Anxiety/Depression domain was more common among subjects with MDE alone than anxiety disorders alone. Other domains of the EQ-5D did identify the burden of co-morbid mental health conditions, but not as well as the Anxiety/Depression domain.

Probiotics for pediatric antibiotic-associated diarrhea: a meta-analysis of randomized placebo-controlled trials.

BACKGROUND: Antibiotic treatment is known to disturb gastrointestinal microflora, which results in a range of clinical symptoms--most notably, diarrhea. This is especially important in children, for whom antibiotics are prescribed frequently. Although meta-analyses have been conducted to evaluate the ability of probiotics to prevent antibiotic-induced diarrhea in the general population, little is known about which probiotic strains and doses might be of most benefit to children. Our objective in this study was to assess the efficacy of probiotics (of any specified strain or dose) for the prevention of antibiotic-associated diarrhea in children and to assess adverse events associated with the use of probiotics when coadministered with antibiotics to children. METHODS: A comprehensive search was performed of the major electronic databases (e.g., CENTRAL, MEDLINE, EMBASE, CINAHL, AMED) from their inception to January 2005. We also contacted experts and searched registries and meeting abstracts for additional relevant articles. Randomized controlled trials that compared probiotic treatment with placebo or no treatment, involving pediatric subjects less than 19 years of age were included. Two reviewers independently applied eligibility criteria and assessed the studies for methodological quality. Data were independently extracted by 2 reviewers and analyzed via the standard Cochrane methodology. RESULTS: Six studies were included (total n = 707 patients). The combined results, analyzed with a per-protocol method that reported on the incidence of diarrhea during antibiotic treatment, showed significant benefit for the use of probiotics over placebo (relative risk [RR] 0.43, 95% confidence interval [CI] 0.25-0.75, Iota2 = 70.1%). In contrast, results from intention-to-treat analysis were nonsignificant overall (RR 1.01, 95% CI 0.64-1.61). Subgroup analysis on 4 studies that provided at least 5 billion single-strain colony-forming units (CFUs) daily (range 5.5-40 x 10(9) Lactobacillus GG, L. sporogens or Saccharomyces boulardii) showed strong evidence with narrow CIs for the preventative effects of probiotics for antibiotic-associated diarrhea (RR 0.36, 95% CI 0.25-0.53, Iota2 = 3.5%). No serious adverse events were reported. INTERPRETATION: The potential protective effects of probiotics to prevent antibiotic-associated diarrhea in children do not withstand intention-to-treat analysis. Before routine use is recommended, further studies (with limited losses of subjects to follow-up) are merited. Trials should involve those probiotic strains and doses with the most promising evidence (i.e., Lactobacillus GG, L. sporogens or S. boulardii at 5-40 x 10(9) CFUs daily).

Self-reported diagnoses of schizophrenia and psychotic disorders may be valuable for monitoring and surveillance.

OBJECTIVE: To examine whether a plausible estimate of the prevalence of schizophrenia can be obtained with a self-report item in a health survey. METHODS: We estimated a self-reported prevalence of schizophrenia, using a grouped variable for all people who reported schizophrenia or any other psychotic disorder in the Canadian Community Health Survey: Mental Health and Well-Being (n = 36,984). Estimates were stratified according to age, sex, and province of residence. RESULTS: Of survey respondents, 411 (1.1%) reported having schizophrenia or other psychosis, as diagnosed by a health professional; the weighted and adjusted estimate was 0.9% (0.7% to 1.0%). There was no statistical evidence that the prevalence estimates of schizophrenia and other psychosis varied by age, sex, or province of residence. CONCLUSIONS: Additional studies incorporating a gold standard diagnostic interview should be carried out to determine the validity of the approach. However, responses to 2 self-report survey items provide what appears to be a plausible epidemiologic pattern.

Misinterpretation with norm-based scoring of health status in adults with type 1 diabetes.

BACKGROUND: Interpretations of profile and preference based measure scores can differ. Profile measures often use a norm-based scoring algorithm where each scale is scored to have a standardized mean and standard deviation, relative to the general population scores/norms (i.e., norm-based). Preference-based index measures generate an overall scores on the conventional scale in which 0.00 is assigned to dead and 1.00 is assigned to perfect health. Our objective was to investigate the interpretation of norm-based scoring of generic health status measures in a population of adults with type 1 diabetes by comparing norm-based health status scores and preference-based health-related quality of life (HRQL) scores. METHODS: Data were collected through self-complete questionnaires sent to patients with type 1 diabetes. The RAND-36 and the Health Utilities Index Mark 3 (HUI3) were included. RESULTS: A total of 216 (61%) questionnaires were returned. The respondent sample was predominantly female (58.8%); had a mean (SD) age of 37.1 (14.3) years and a mean duration of diabetes of 20.9 (12.4) years. Mean (SD) health status scores were: RAND-36 PHC 47.9 (9.4), RAND-36 MHC 47.2 (11.8), and HUI3 0.78 (0.23). Histograms of these scores show substantial left skew. HUI3 scores were similar to those previously reported for diabetes in the general Canadian population. Physical and mental health summary scores of the RAND-36 suggest that this population is as healthy as the general adult population. CONCLUSION: In this sample, a preference-based measure indicated poorer health, consistent with clinical evidence, whereas a norm-based measure indicated health similar to the average for the general population. Norm-based scoring measure may provide misleading interpretations in populations when health status is not normally distributed.

Treatment gaps for hypertension management in rural Canadian patients with type 2 diabetes mellitus.

BACKGROUND: There were a reported 2.2 million Canadians living with diabetes mellitus (DM) in 2002, of whom 1.98 million (90.0%) had type 2 DM. In addition, there are approximately 60,000 new cases of type 2 DM diagnosed in Canada each year. However, the research shows that evidence and guidelines for management of hypertension in DM are not always translated into clinical practice. In rural areas, factors affecting implementation of recommendations and/or guidelines are less well understood, although some studies suggest that urban practices provide higher quality of care overall than rural areas. OBJECTIVE: The goal of this study was to describe the patterns of medication use for hypertension for patients with type 2 DM in rural northern Alberta, Canada. We also tried to identify treatment gaps and opportunities for prescribing antihypertensives relative to the Canadian Diabetes Association's 1998 Clinical Practice Guidelines for the Management of Diabetes in Canada and the Canadian Hypertension Society Recommendations Working Group's 2003 Canadian Recommendations for the Management of Hypertension: Therapy. METHODS: This study was conducted at the Institute of Health Economics and the University of Alberta (Edmonton, Alberta, Canada). We collected information from a cohort of patients aged >or =20 years with type 2 DM living in 2 adjacent rural regions of northern Alberta, Canada, at the time of enrollment in a diabetes care quality-improvement program as part of the Diabetes Outreach Van Enhancement (DOVE) study. Treatment gaps were determined by comparing antihypertensive pharmacotherapy with a blood pressure (BP) target of < or =130/< or =85 mm Hg. We used multivariate regression analyses to determine the associations between sociodemographic and clinical characteristics and treatment gaps. RESULTS: A total of 392 patients (229 women, 164 men; mean [SD] age, 62.3 [12.5] years) with type 2 DM were included in this analysis. Patients had a mean (SD) duration of diabetes of 8.3 (8.5) years. A total of 75.8% (297/392) of the study population had hypertension, and most (236/392[60.2%]) were receiving some pharmacotherapy. Treatment gaps were present; 42.7% (n = 67) of patients not receiving pharmacotherapy for hypertension were above the established BP targets. For patients receiving monotherapy, 70% were not at BP targets. For patients receiving dual, triple, and > or =4 medications, 65%, 66%, and 46%, respectively, were not at BP targets. After controlling for systolic blood pressure, male sex (adjusted odds ratio [aOR], 2.17; 95% CI, 1.17-4.03), older age (aOR, 1.80 per decade; 95% CI, 1.51-2.09), lower self-reported physical health (aOR, 0.68; 95% CI, 0.41-0.96), higher body mass index (aOR, 1.05; 95% CI, 1.01-1.10), and past/current smoking (aOR, 1.95; 95% CI, 1.01-3.76) were all significantly associated with a lack of treatment for hypertension. CONCLUSIONS: Treatment maps in the management of hypertension exist in these rural Canadian patients with type 2 DM. Cardiovascular risk may be underestimated in these patients, particularly among younger patients and women, and those with multiple non-DM risk factors. These are patient subgroups that should be targeted as opportunities to improve hypertension management at the population level.