Benralizumab in severe eosinophilic asthma by previous biologic use and key clinical subgroups: real-world XALOC-1 programme.

BACKGROUND: Pivotal Phase 3 trials and real-world studies have demonstrated benralizumab's overall efficacy and safety in severe eosinophilic asthma (SEA). Additional large-cohort data are needed to confirm its real-world effectiveness in SEA according to previous biologic use and key baseline characteristics important for treatment selection. METHODS: XALOC-1 is a large, multinational, retrospective, observational, real-world study programme of benralizumab in adults with SEA. This 48-week integrated analysis assessed annualised exacerbation rate (AER), maintenance oral corticosteroid (mOCS) use, asthma symptom control and lung function during a 12-month baseline period and up to 48 weeks after benralizumab initiation. Subgroup analyses were based on previous biologic use and key baseline clinical characteristics (mOCS use, blood eosinophil count, exacerbation history, age at asthma diagnosis, fractional exhaled nitric oxide level and presence of atopy and chronic rhinosinusitis with nasal polyps). RESULTS: Of 1002 patients analysed, 380 were biologic-experienced. At Week 48, 71.3% were exacerbation-free (versus 17.2% at baseline); relative reduction in AER was 82.7% overall and 72.9% in biologic-experienced patients; rates were maintained across all key clinical characteristic subgroups. Of patients using mOCS at baseline (n=274), 47.4% (130/274) eliminated their use by Week 48; the mean reduction from baseline in daily dose was 51.2% and, notably, 34.9% in biologic-experienced patients (n=115). Clinically significant improvements in asthma symptom control and lung function were observed. CONCLUSION: In this large, real-world programme, SEA patients treated with benralizumab had substantial improvements in clinical outcomes irrespective of previous biologic use and key clinical characteristics important to therapeutic decision-making in clinical practice.

Prospective association of 25(OH)D with metabolic syndrome.

CONTEXT: Vitamin D may play a role in the aetiology of the metabolic syndrome (MetS), yet the majority of previous studies have been cross-sectional, and the limited number of prospective studies has yielded inconsistent results. OBJECTIVE: To examine the prospective association of vitamin D [25-hydroxyvitamin D, 25(OH)D] with MetS in a multi-ethnic cohort of adults in Ontario, Canada. DESIGN: Nondiabetic individuals with pre-existing MetS risk factors were recruited for participation in the PROspective Metabolism and ISlet cell Evaluation (PROMISE) cohort study, a longitudinal study of the determinants of insulin resistance and MetS. METHODS: Of the 654 participants enrolled at baseline, 489 attended a 3-year follow-up visit. There were 301 participants eligible for the analysis of 25(OH)D with incident MetS (age 49·2 ± 9·3 years old, 75·4% female), after excluding 188 (38·5%) prevalent MetS cases at baseline. Longitudinal change in MetS components was assessed in the entire follow-up cohort. RESULTS: There were 76 (15·5%) participants who developed MetS over the 3-years of follow-up. Multivariate logistic regression analyses indicated a decreased risk of MetS at follow-up per standard deviation increase in baseline 25(OH)D after adjustment for sociodemographics, season, baseline and change in supplement use and physical activity and insulin resistance (OR = 0·63, 95% CI 0·44-0·90). Multivariate linear regression analyses revealed a significant inverse association of baseline 25(OH)D with fasting glucose at follow-up (ß = -0·0005, P = 0·025). CONCLUSIONS: There was a significant inverse association of baseline 25(OH)D with incident MetS, which may be partly driven by its association with glucose homoeostasis.

Unfavorable Outcomes Associated With Glucocorticoid Use in Current Standard-of-Care Management of Systemic Lupus Erythematosus in Canada.

OBJECTIVE: Our objective was to describe the administration of glucocorticoids (GCs) and characterize its association with organ damage in a longitudinal systemic lupus erythematosus (SLE) cohort over a time period spanning the introduction of biologics in Canada. METHODS: A retrospective observational study was conducted using data from a large SLE cohort in Canada, including adults without lupus nephritis or central nervous system lupus. Patients were observed from time of entry into the cohort to the last available clinic visit (up to December 31, 2020), with a minimum of 24 months of follow-up. Demographic and clinical characteristics, including average disease activity, treatment administration, and prevalence of organ damage, were examined. Organ damage was stratified by GC administration. RESULTS: A total of 1,255 patients were included. The mean follow-up duration was 10.5 (SD 8.6) years. One hundred eighty-two (15%) patients had organ damage at baseline. More than 80% of patients were prescribed GCs over the follow-up period, almost all patients had long-term GC treatment, and only 5% of patients took any biologics. Organ damage was more frequent in patients with a higher average GC dose and greater years of GC exposure. CONCLUSION: In this large cohort of patients with SLE, the majority of patients continue to rely on GC for SLE symptom management, with limited administration of biologics. GC administration was correlated with increased irreversible organ damage. Access to novel GC-sparing treatment options is critical to improve long-term outcomes for patients with SLE, especially given the continued reliance on GC despite the introduction of biologics.

Comparative effectiveness of cladribine tablets versus fingolimod in the treatment of highly active multiple sclerosis: A real-world study.

BACKGROUND: Cladribine tablets and fingolimod have similar marketing authorisations in Europe for the treatment of patients with highly active relapsing multiple sclerosis (HA-RMS). In the absence of direct head-to-head studies, real-world data are important to assess the comparative effectiveness of these oral disease-modifying therapies (DMTs). The primary objective of the present study was to compare relapse rates between patients who received either cladribine tablets or fingolimod. METHODS: This multicentre retrospective study conducted in the United Kingdom and Germany assessed non-inferiority in relapse rates of cladribine tablets versus fingolimod in HA-RMS patients over a 12-month period. Eligible patients who initiated treatment with cladribine tablets or fingolimod at least 12 months prior to the screening date were sampled consecutively until the target sample size was reached. Patients were censored at discontinuation of study treatment, commencement of another DMT, death, loss to follow-up, or at 12 months post-baseline, whichever happened earliest. The primary analytic timeframe for physician-confirmed relapse outcomes was the study effectiveness period (nine months of follow-up after an initial 12 weeks of treatment). Propensity score analysis was applied based on the inverse probability of treatment weighting approach. RESULTS: The primary analytic cohort consisted of 1,095 HA-RMS patients: 610 (55.7%) receiving cladribine tablets and 485 (44.3%) receiving fingolimod. Fewer patients discontinued cladribine tablets and/or switched to another DMT compared with fingolimod (0.2% versus 3.5%, respectively). The primary endpoint, adjusted annualised relapse rate (ARR), was 0.10 (95% confidence interval [CI]: 0.07-0.14) for cladribine tablets and 0.14 (95% CI: 0.10-0.20) for fingolimod. The adjusted ARR ratio of cladribine tablets versus fingolimod was 0.68 (95% CI: 0.42-1.11). Given the entire 95% CI was less than the non-inferiority margin of 1.2, cladribine tablets was non-inferior to fingolimod. CONCLUSIONS: In this real-world retrospective cohort study, cladribine tablets demonstrated comparable effectiveness to fingolimod at one year following treatment initiation. The full treatment dosage of cladribine tablets is completed over two years and so these results may be conservative.

Real-world effectiveness of immunotherapies in pre-treated, advanced non-small cell lung cancer Patients: A systematic literature review.

BACKGROUND: Clinical trials have shown immunotherapy (IO) to be more effective than chemotherapy in pre-treated, advanced non-small cell lung cancer (NSCLC). However, there is a lack of understanding of its effectiveness in clinical practice, and among patient groups that are often underrepresented in trials. We aimed to summarize the existing real-world evidence (RWE) on the survival outcomes of IO in second- or higher line in advanced NSCLC. METHODS: We conducted a systematic review of real-world observational studies that reported overall survival (OS) estimates with IO, primarily nivolumab, pembrolizumab or atezolizumab, in adult, previously treated advanced or recurrent NSCLC patients. Meta-analysis was conducted using random-effect models to pool 1- and 2-year OS rates across studies. Additional subgroups were examined among patients treated with IO, including the elderly, those with poor performance status (PS) and those exhibiting metastasis. RESULTS: In total, 66 studies were included, of which 46 (70%) included a nivolumab-specific study arm. Pooled 1-year and 2-year OS rates with nivolumab monotherapy were 45.6% (95% CI; 43.4-47.8) and 28.0% (95% CI; 24.8-31.4), respectively, compared to 43.9% (95% CI; 39.1-48.8) and 20.4% (95% CI; 14.7-27.6) in the mixed immune checkpoint inhibitors (ICI) group. OS rates with nivolumab were slightly lower in elderly compared to non-elderly populations. Poor PS was associated with worse survival rates, with a pooled one-year OS estimate of 27.1% in PS ≥ 2 vs 51.6% in PS < 2. The pooled 2-year OS rate with nivolumab in patients with and without brain metastases was 22.1% and 26.1% respectively, and this difference was significant in 36% of individual studies. CONCLUSIONS: While the OS benefits of IO seen in real-world studies among pre-treated, advanced NSCLC patients are consistent with pivotal clinical trials, these tend to vary for the more vulnerable patient groups, such as patients with poor PS, which are often excluded from trials. Further research is needed to investigate findings in patients with brain and liver metastases.

Understanding celiac disease monitoring patterns and outcomes after diagnosis: A multinational, retrospective chart review study.

BACKGROUND: Long-term outcomes and monitoring patterns in real-world practice are largely unknown among patients with celiac disease. AIM: To understand patterns of follow-up and management of patients with celiac disease, and to characterize symptoms and villous atrophy after diagnosis. METHODS: A retrospective chart review study was performed using medical chart data of patients diagnosed with celiac disease. Three gastroenterology referral centers, with substantial expertise in celiac disease, participated in the United Kingdom, United States, and Norway. Demographic and clinical data were collected from medical charts. Descriptive analyses were conducted on patients with biopsy-confirmed celiac disease, diagnosed between 2008 and 2012, with at least one follow-up visit before December 31, 2017. Patient demographic and clinical characteristics, biopsy/serology tests and results, symptoms, and comorbidities were captured at diagnosis and for each clinic visit occurring within the study period (i.e., before the study end date of December 31, 2017). RESULTS: A total of 300 patients were included in this study [72% female; mean age at diagnosis: 38.9 years, standard deviation (SD) 17.2]. Patients were followed-up for a mean of 29.9 mo (SD 22.1) and there were, on average, three follow-up visits per patient during the study period. Over two-thirds (68.4%) of patients were recorded as having ongoing gastrointestinal symptoms and 11.0% had ongoing symptoms and enteropathy during follow-up. Approximately 80% of patients were referred to a dietician at least once during the follow-up period. Half (50.0%) of the patients underwent at least one follow-up duodenal biopsy and 36.6% had continued villous atrophy. Patterns of monitoring varied between sites. Biopsies were conducted more frequently in Norway and patients in the United States had a longer follow-up duration. CONCLUSION: This real-world study demonstrates variable follow-up of patients with celiac disease despite most patients continuing to have abnormal histology and symptoms after diagnosis.

Degree and correlates of cardiac knowledge and awareness among cardiac inpatients.

OBJECTIVE: To investigate the degree of CHD awareness as well as symptom, risk factor, and treatment knowledge in a broad sample of cardiac inpatients, and to examine its sociodemographic, clinical and psychosocial correlates. METHODS: 1308 CHD inpatients (351 [27.0%] female), recruited from 11 acute care sites in Ontario, participated in this cross-sectional study. Participants were provided with a survey which included a knowledge questionnaire among other measures, and clinical data were extracted from medical charts. RESULTS: 855 (68.8%) respondents cited heart disease as the leading cause of death in men, versus only 458 (37.0%) in women. Participants with less than high school education (p<.001), an annual family income less than $50,000CAD (p=.022), low functional capacity (p=.042), who were currently smoking (p=.022), who had no family history of heart disease (p<.001), and who had a perception of low personal control (p=.033) had significantly lower CHD knowledge. CONCLUSIONS: Awareness of CHD is not optimal, especially among women, South Asians, and those of low socioeconomic status. CHD patients have a moderate level of disease knowledge overall, but greater education is needed. PRACTICE IMPLICATIONS: Tailored educational approaches may be necessary for those of low socioeconomic status, particularly with regard to the nature of CHD, tests and treatments.

Efficacy and safety of first-line carboplatin-versus cisplatin-based chemotherapy for non-small cell lung cancer: A meta-analysis.

OBJECTIVES: Platinum-based chemotherapy is the mainstay of first-line (1L) therapy for advanced non-small cell cancer (NSCLC). The objective of this study was to evaluate the relative efficacy, safety, and health-related quality of life (HRQoL) of carboplatin- versus cisplatin-based chemotherapy in 1L NSCLC. MATERIALS AND METHODS: A meta-analysis by the Cochrane group (2013) was updated. Systematic searches of CENTRAL, Medline, Embase, Latin American and Caribbean Health Sciences database, clinicaltrials.gov and conference proceedings were conducted to include randomized controlled trials (RCTs) published between 2013-January 2018 which compared carboplatin and cisplatin combined with: gemcitabine, vinorelbine, docetaxel, paclitaxel, irinotecan, or pemetrexed. Endpoints included overall survival (OS), one-year OS, objective response rate (ORR), grade 3/4 drug-related toxicities, and HRQoL. RESULTS: Twelve RCTs (2,048 patients) were identified from 4,139 records for inclusion in the meta-analysis. There were no significant differences in OS (hazards ratio [HR]: 1.08, 95% confidence interval [CI]: 0.96, 1.21) and one-year OS (relative risk [RR]: 0.97, CI: 0.89, 1.07) between carboplatin- and cisplatin-based chemotherapy. A small effect on ORR favouring cisplatin was detected (RR = 0.88; CI: 0.78, 0.99). Differences in drug-related toxicities were observed between carboplatin- and cisplatin-based chemotherapy for thrombocytopenia, anaemia, neurotoxicity, and the risk of nausea/vomiting. Three RCTs comparing HRQoL between carboplatin- and cisplatin-based chemotherapy found no significant differences. CONCLUSIONS: This updated evidence base corroborates findings of previous meta-analyses showing no difference in OS between carboplatin- and cisplatin-based chemotherapy, despite a slight benefit in ORR for cisplatin. Toxicity profiles should be considered alongside patients' comorbidities in the choice of therapy.

A Network Meta-analysis Comparing Exenatide Once Weekly with Other GLP-1 Receptor Agonists for the Treatment of Type 2 Diabetes Mellitus.

INTRODUCTION: Exenatide is a glucagon-like peptide-1 receptor agonist (GLP-1 RA), approved for treatment of type 2 diabetes mellitus (T2DM). There is limited direct evidence comparing the efficacy and tolerability of exenatide 2 mg once weekly (QW) to other GLP-1 RAs. A network meta-analysis (NMA) was conducted to estimate the relative efficacy and tolerability of exenatide QW versus other GLP-1 RAs for the treatment of adults with T2DM inadequately controlled on metformin monotherapy. METHODS: A systematic literature review was conducted to identify randomized controlled trials (RCTs) that investigated GLP-1 RAs (albiglutide, dulaglutide, exenatide, liraglutide, and lixisenatide) at approved doses in the United States/Europe, added on to metformin only and of 24 ± 6 weeks treatment duration. A Bayesian NMA was conducted. RESULTS: Fourteen RCTs were included in the NMA. Exenatide QW obtained a statistically significant reduction in glycated hemoglobin (HbA1c) relative to lixisenatide 20 µg once daily. No other comparisons of exenatide QW to other GLP-1 RAs were statistically significant for change in HbA1c. No statistically significant differences in change in weight, systolic blood pressure, risk of nausea or discontinuation due to adverse events were observed for exenatide QW versus other GLP-1 RAs. CONCLUSION: Exenatide QW demonstrated similar effectiveness and tolerability compared to other GLP-1 RAs, for the treatment of T2DM in adults inadequately controlled on metformin alone.

Traditional foods and 25(OH)D concentrations in a subarctic First Nations community.

BACKGROUND: Sub-optimal vitamin D status is common worldwide and the condition may be associated with increased risk for various chronic diseases. In particular, low vitamin D status is highly prevalent in indigenous communities in Canada, although limited data are available on the determinants of serum 25-hydroxyvitamin D (25(OH)D) concentrations in this population. The relationship between traditional food consumption and vitamin D status has not been well documented. OBJECTIVE: To investigate the determinants of serum 25(OH)D status in a First Nations community in Ontario, Canada, with a focus on the role of traditional food consumption and activities. METHODS: A cross-sectional analysis was conducted within the Sandy Lake Health and Diabetes Project (2003-2005). A total of 445 participants (>12 years of age) were assessed for serum 25(OH)D status, anthropometric and lifestyle variables, including traditional and non-traditional dietary practices and activities. Diet patterns were identified using factor analysis, and multivariate linear regression analysis was used to analyse the determinants of 25(OH)D concentrations. RESULTS: Mean serum 25(OH)D concentrations were 22.1 nmol/L (16.9, 29.9 nmol/L) in men and 20.5 nmol/L (16.0, 27.3 nmol/L) in women. Multivariate determinants of higher serum 25(OH)D included higher consumption of traditional and healthier market foods, higher wild fish consumption, male gender, spring/summer season of blood collection and more frequent physical activity. Significant negative determinants included hours of TV/day, higher BMI and higher consumption of unhealthy market foods. CONCLUSIONS: Traditional food consumption contributed independently to higher 25(OH)D concentrations in a First Nations community with a high prevalence of sub-optimal vitamin D status.

Associations of circulating 25(OH)D with cardiometabolic disorders underlying type 2 diabetes mellitus in an Aboriginal Canadian community.

AIMS: To investigate the associations of 25-hydroxyvitamin D (25(OH)D) with insulin resistance (IR), beta-cell function and metabolic syndrome (MetS) in a First Nations population. METHODS: We conducted a cross-sectional analysis using data from the Sandy Lake Health and Diabetes Project (2003-2005). A total of 390 participants (>12 y) were assessed for 25(OH)D, fasting glucose, insulin, lipids, blood pressure, inflammatory markers, anthropometric and lifestyle variables and a 75-g oral glucose tolerance test was administered. IR was calculated using the Matsuda insulin sensitivity index (ISOGTT) and the computational homeostasis model assessment of IR (HOMA2-IR). Beta-cell function was calculated using the insulinogenic index (IGI) divided by HOMA-IR (IGI/IR) and the insulin secretion sensitivity index-2 (ISSI-2). The 2009 harmonized criteria were used to define MetS. RESULTS: Higher 25(OH)D was associated with a decreased prevalence of dysglycemia (OR = 0.71 95% CI, 0.51-0.97 per SD increase). In addition, there were significant associations of 25(OH)D with measures of insulin action (ISOGTT; beta=0.31; 95% CI, 0.12, 0.49; HOMA2-IR; beta = -29; 95% CI -0.46, -0.11 and beta-cell function (ISSI-2; beta = 0.15; 95% CI, 0.02, 0.28). The prevalence of MetS was 41%. There was a decreased risk (OR=0.73, 95% CI 0.56, 0.94) of MetS per SD increase in baseline 25(OH)D. Finally, there was a significant positive association of 25(OH)D with adiponectin (beta = 0.16; 95% CI = 0.01, 0.31). CONCLUSIONS: These results support a potential role for vitamin D metabolism in the natural history of T2DM among Aboriginal Canadians, although carefully designed randomized trials will be required to establish causality.

Peripheral Neuropathy and Nerve Dysfunction in Individuals at High Risk for Type 2 Diabetes: The PROMISE Cohort.

OBJECTIVE: Emerging evidence suggests that peripheral neuropathy begins in the early stages of diabetes pathogenesis. Our objective was to describe the prevalence of peripheral neuropathy and nerve dysfunction according to glucose tolerance and metabolic syndrome status and examine how these conditions are associated with neurological changes in individuals at risk for type 2 diabetes. RESEARCH DESIGN AND METHODS: We studied 467 individuals in the longitudinal PROMISE (Prospective Metabolism and Islet Cell Evaluation) cohort. Peripheral neuropathy was defined by Michigan Neuropathy Screening Instrument (MNSI) scores (>2), and the severity of nerve dysfunction was measured objectively by vibration perception thresholds (VPTs) using a neurothesiometer. Metabolic syndrome was defined using the International Diabetes Federation/American Heart Association harmonized criteria. RESULTS: The prevalence of peripheral neuropathy was 29%, 49%, and 50% for normal glycemia, prediabetes, and new-onset diabetes, respectively (P < 0.001 for trend). The mean VPT was 6.5 V for normal glycemia, 7.9 V for prediabetes, and 7.6 V for new-onset diabetes (P = 0.024 for trend). Prediabetes was associated with higher MNSI scores (P = 0.01) and VPTs (P = 0.004) versus normal glycemia, independent of known risk factors. Additionally, progression of glucose intolerance over 3 years predicted a higher risk of peripheral neuropathy (P = 0.007) and nerve dysfunction (P = 0.002). Metabolic syndrome was not independently associated with MNSI scores or VPTs. CONCLUSIONS: In individuals with multiple risk factors for diabetes, prediabetes was associated with similar risks of peripheral neuropathy and severity of nerve dysfunction as new-onset diabetes. Prediabetes, but not metabolic syndrome, was independently associated with both the presence of peripheral neuropathy and the severity of nerve dysfunction.

Association of 25(OH)D and PTH with metabolic syndrome and its traditional and nontraditional components.

CONTEXT: Emerging evidence suggests that 25-hydroxy vitamin D [25(OH)D] and PTH may play a role in the etiology of the metabolic syndrome (MetS). However, evidence to date is limited and inconsistent, and few studies have examined associations with nontraditional MetS components. OBJECTIVE: The objective of the study was to examine the association of vitamin D and PTH with MetS and its traditional and nontraditional components in a large multiethnic sample. DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, we examined 654 participants from London and Toronto, Ontario, Canada, aged 30 yr and older with risk factors for type 2 diabetes. MAIN OUTCOME MEASURES: Presence of MetS and its traditional and nontraditional components was measured. RESULTS: Approximately 43% of the study participants were classified as having MetS. Higher 25(OH)D was significantly associated with a reduced presence of MetS after adjustment for age, sex, season, ethnicity, supplement use, physical activity, and PTH (odds ratio 0.76, 95% confidence interval 0.62-0.93). PTH was not associated with the presence of MetS after multivariate adjustment. Multivariate linear regression analyses indicated significant adjusted inverse associations of 25(OH)D with waist circumference, triglyceride level, fasting insulin, and alanine transaminase (P < 0.041). Elevated PTH was positively associated with waist circumference and high-density lipoprotein cholesterol (P < 0.04). Other associations between PTH and MetS components were attenuated after adjustment for adiposity. CONCLUSIONS: Serum 25(OH)D, but not PTH, was significantly associated with MetS as well as a number of MetS components after multivariate adjustment. These results suggest that low 25(OH)D may play a role in the etiology of the MetS.

Prospective associations of vitamin D with ß-cell function and glycemia: the PROspective Metabolism and ISlet cell Evaluation (PROMISE) cohort study.

OBJECTIVE: To examine the prospective associations of baseline vitamin D [25-hydroxyvitamin D; 25(OH)D] with insulin resistance (IR), ß-cell function, and glucose homeostasis in subjects at risk for type 2 diabetes. RESEARCH DESIGN AND METHODS: We followed 489 subjects, aged 50 ± 10 years, for 3 years. At baseline and follow-up, 75-g oral glucose tolerance tests (OGTTs) were administered. IR was measured using the Matsuda index (IS(OGTT)) and the homeostasis model assessment of IR (HOMA-IR), ß-cell function was determined using both the insulinogenic index divided by HOMA-IR (IGI/IR) and the insulin secretion sensitivity index-2 (ISSI-2), and glycemia was assessed using the area under the glucose curve (AUC(glucose)). Regression models were adjusted for age, sex, ethnicity, season, and baseline value of the outcome variable, as well as baseline and change in physical activity, vitamin D supplement use, and BMI. RESULTS: Multivariate linear regression analyses indicated no significant association of baseline 25(OH)D with follow-up IS(OGTT) or HOMA-IR. There were, however, significant positive associations of baseline 25(OH)D with follow-up IGI/IR (ß = 0.005, P = 0.015) and ISSI-2 (ß = 0.002, P = 0.023) and a significant inverse association of baseline 25(OH)D with follow-up AUC(glucose) (ß = -0.001, P = 0.007). Progression to dysglycemia (impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes) occurred in 116 subjects. Logistic regression analyses indicated a significant reduced risk of progression with higher baseline 25(OH)D (adjusted odds ratio 0.69 [95% CI 0.53-0.89]), but this association was not significant after additional adjustment for baseline and change in BMI (0.78 [0.59-1.02]). CONCLUSIONS: Higher baseline 25(OH)D independently predicted better ß-cell function and lower AUC(glucose) at follow-up, supporting a potential role for vitamin D in type 2 diabetes etiology.

Association of vitamin D with insulin resistance and beta-cell dysfunction in subjects at risk for type 2 diabetes.

OBJECTIVE: To examine cross-sectional associations of serum vitamin D [25-hydroxyvitamin D, 25(OH)D] concentration with insulin resistance (IR) and beta-cell dysfunction in 712 subjects at risk for type 2 diabetes. RESEARCH DESIGN AND METHODS: Serum 25(OH)D was determined using a chemiluminescence immunoassay. Insulin sensitivity/resistance were measured using the Matsuda insulin sensitivity index for oral glucose tolerance tests (IS(OGTT)) and homeostasis model assessment of insulin resistance HOMA-IR. beta-Cell function was determined using both the insulinogenic index (IGI) divided by HOMA-IR (IGI/IR) and the insulin secretion sensitivity index-2 (ISSI-2). RESULTS Linear regression analyses indicated independent associations of 25(OH)D with IS(OGTT) and HOMA-IR (beta = 0.004, P = 0.0003, and beta = -0.003, P = 0.0072, respectively) and with IGI/IR and ISSI-2 (beta = 0.004, P = 0.0286, and beta = 0.003, P = 0.0011, respectively) after adjusting for sociodemographics, physical activity, supplement use, parathyroid hormone, and BMI. CONCLUSIONS: Vitamin D may play a role in the pathogenesis of type 2 diabetes, as 25(OH)D concentration was independently associated with both insulin sensitivity and beta-cell function among individuals at risk of type 2 diabetes.

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.

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.

Degree and correlates of patient trust in their cardiologist.

RATIONALE AND OBJECTIVES: Trust in one's doctor has been associated with increased treatment adherence, patient satisfaction and improved health status. This study investigated the level and correlates of patient trust in their cardiac specialist. METHODS: All 386 urban cardiologists in Southern Ontario (95 participating, response rate = 30%) were approached to recruit a sample of their coronary artery disease outpatients. A total of 1111 recent and consecutive patients consented to participate (approximately 13 patients per cardiologist, 317 female (26.7%); response rate = 60%), and clinical data were extracted from their medical charts. Participants completed a mailed survey including the Trust in Physicians scale, in addition to an assessment of socio-demographic, clinical and psychosocial correlates. RESULTS: The mean trust score was equivalent to that reported in studies of primary care patients. Results of the significant multivariate model (F = 7.631, P < 0.001) revealed that less education (P < 0.001), higher systolic blood pressure (P = 0.022), less perceived cyclical/unpredictable illness timeline (P = 0.007) and greater perceived personal control over their heart condition (P = 0.004), were significant correlates of greater trust in cardiologist care. CONCLUSIONS: The significance of education is corroborated by findings of lower satisfaction with cardiac care among those of higher socio-economic status, despite having generally greater access to care in Ontario. Moreover, the relationship between hypertension and greater trust may suggest that such perceptions are not based on doctor competence. Future studies should further investigate the correlates of trust, as well as the impact of trust on cardiac health outcomes.