Heavy clinical and economic burden of osteoporotic fracture among elderly female Medicare beneficiaries.

We comprehensively described elderly Medicare women with an outpatient visit in 2011 and fracture within 2 years before. These women were at very high risk for subsequent fracture and high healthcare utilization and cost, especially those with vertebral or multiple fractures. However, rates of fracture prevention treatments were low. INTRODUCTION: Postmenopausal women with osteoporosis are stratified to high and very-high fracture risk categories, and this categorization drives algorithms for osteoporosis management in osteoporosis treatment guidelines. This study comprehensively describes a very-high-risk cohort. METHODS: This retrospective cohort study used the Medicare 20% database; elderly women with an outpatient visit in 2011 and fracture within 2 years before the visit were included. Outcomes included fracture risk, all-cause and fracture-related healthcare resource utilization and cost, and osteoporosis medication use in the 5 years after the visit. RESULTS: Overall, 43,193 patients were included. The 5-year probability was 0.36 for major fracture and 0.11 and 0.17 for hip fracture and vertebral fracture, respectively, much higher than the guidelines' 10-year probability thresholds for very-high-risk (0.3 for major fracture, 0.045 for hip fracture). Rates of hospitalizations, emergency department visits or observation stays, and skilled nursing facility stays in year 1 were 53.7, 57.0, and 18.8 per 100 patient-years, respectively, decreasing slightly in subsequent years. Mean healthcare cost was $23,700 in year 1, decreasing to $18,500 in year 5. About 29.1% of patients received osteoporosis medications in year 1, decreasing to 16.9% by year 5. Rates for all outcomes, especially fractures, were much higher among vertebral and multiple fracture cohorts. CONCLUSION: Elderly women with a fracture within last 2 years were at very-high-risk for subsequent fracture and high healthcare utilization and cost, especially those with vertebral or multiple fractures. However, rates of fracture prevention treatments were low. More effort is needed to identify and treat patients at very-high-risk for fracture.

Lipid-lowering treatment patterns in patients with new cardiovascular events - estimates from population-based register data in Sweden.

OBJECTIVES: The aim of this study was to assess treatment patterns of lipid-lowering therapy (LLT) in patients with hyperlipidaemia or prior cardiovascular (CV) events who experience new CV events. METHODS: A retrospective population-based cohort study was conducted using Swedish medical records and registers. Patients were included in the study based on a prescription of LLT or CV event history and followed up for up to 7 years for identification of new CV events and assessment of LLT treatment patterns. Patients were stratified into three cohorts based on CV risk level. All outcomes were assessed during the year following index (the date of first new CV event). Adherence was defined as medication possession ratio (MPR) > 0.80. Persistence was defined as no gaps > 60 days in supply of drug used at index. RESULTS: Of patients with major cardiovascular disease (CVD) history (n = 6881), 49% were not on LLT at index. Corresponding data for CV risk equivalent and low/unknown CV risk patients were 37% (n = 3226) and 38% (n = 2497) respectively. MPR for patients on LLT at index was similar across cohorts (0.74-0.75). The proportions of adherent (60-63%) and persistent patients (56-57%) were also similar across cohorts. Dose escalation from dose at index was seen within all cohorts and 2-3% of patients switched to a different LLT after index while 5-6% of patients augmented treatment by adding another LLT. CONCLUSIONS: Almost 50% of patients with major CVD history were not on any LLT, indicating a potential therapeutic gap. Medication adherence and persistence among patients on LLT were suboptimal.

Cardiovascular event rates and healthcare resource utilisation among high-risk adults with type 2 diabetes mellitus in a large population-based study.

OBJECTIVE: This study ascertained the incidence and resource utilisation of non-fatal myocardial infarction (MI), stroke, coronary bypass surgery or angioplasty among adults with type 2 diabetes mellitus (T2DM) at high risk for cardiovascular disease (CVD) over 3 and 5 years. METHODS: Respondents from the US, population-based SHIELD study with T2DM and at cardiovascular risk were stratified into an established CVD cohort and a risk factors cohort. Proportion of respondents self-reporting a new MI, stroke or revascularisation was calculated. Multivariate discrete logistic hazards models were utilised. RESULTS: Incidence rate in the established CVD cohort (n = 1198) was 26.3% over 3 years (31.2%, 5 years) and in the risk factors cohort (n = 924) 18.8% over 3 years (26.0%, 5 years). Healthcare resource use was significantly greater among respondents who had a new CV event than among those not experiencing an event (p < 0.001). CONCLUSIONS: Individuals with T2DM at risk for CVD had a high incidence of CV events in this large US study, which represents a significant burden on the healthcare system.

Ischaemic cardiac events and use of strontium ranelate in postmenopausal osteoporosis: a nested case-control study in the CPRD.

UNLABELLED: We explored the cardiac safety of the osteoporosis treatment strontium ranelate in the UK Clinical Practice Research Datalink. While known cardiovascular risk factors like obesity and smoking were associated with increased cardiac risk, use of strontium ranelate was not associated with any increase in myocardial infarction or cardiovascular death. INTRODUCTION: It has been suggested that strontium ranelate may increase risk for cardiac events in postmenopausal osteoporosis. We set out to explore the cardiac safety of strontium ranelate in the Clinical Practice Research Datalink (CPRD) and linked datasets. METHODS: We performed a nested case-control study. Primary outcomes were first definite myocardial infarction, hospitalisation with myocardial infarction, and cardiovascular death. Cases and matched controls were nested in a cohort of women treated for osteoporosis. The association with exposure to strontium ranelate was analysed by multivariate conditional logistic regression. RESULTS: Of the 112,445 women with treated postmenopausal osteoporosis, 6,487 received strontium ranelate. Annual incidence rates for first definite myocardial infarction (1,352 cases), myocardial infarction with hospitalisation (1,465 cases), and cardiovascular death (3,619 cases) were 3.24, 6.13, and 14.66 per 1,000 patient-years, respectively. Obesity, smoking, and cardiovascular treatments were associated with significant increases in risk for cardiac events. Current or past use of strontium ranelate was not associated with increased risk for first definite myocardial infarction (odds ratio [OR] 1.05, 95 % confidence interval [CI] 0.68-1.61 and OR 1.12, 95 % CI 0.79-1.58, respectively), hospitalisation with myocardial infarction (OR 0.84, 95 % CI 0.54-1.30 and OR 1.17, 95 % CI 0.83-1.66), or cardiovascular death (OR 0.96, 95 % CI 0.76-1.21 and OR 1.16, 95 % CI 0.94-1.43) versus patients who had never used strontium ranelate. CONCLUSIONS: Analysis in the CPRD did not find evidence for a higher risk for cardiac events associated with the use of strontium ranelate in postmenopausal osteoporosis.

Health-related quality of life association with weight change in type 2 diabetes mellitus: perception vs. reality.

AIMS: This study compared health-related quality of life (HRQOL) in adults with type 2 diabetes mellitus (T2DM) who reported their perception of weight change vs. actual weight change. METHODS: Respondents to the US Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes (SHIELD) 2008 survey were asked if they had lost, maintained or gained weight compared with 1 year earlier (perception). Respondents also provided their actual weight and completed the SHIELD WQ-9 questionnaire to report how weight change affected 9 aspects of daily life. Perceived weight loss or gain was compared with measured weight change reported (2007 weight - 2008 weight) in those with T2DM. RESULTS: In respondents reporting weight loss (n = 762), 75.4% lost weight and 15.9% gained weight. For respondents reporting weight gain (n = 392), 70.2% gained weight and 19.6% lost weight. HRQOL did not differ between those who reported weight loss and actually lost weight vs. those who reported weight loss and actually gained weight (p > 0.05), except for self-esteem (p = 0.004). HRQOL was similar for those who reported weight gain and actually gained weight vs. those who reported weight gain, but actually lost weight (p > 0.20). Respondents who had perceived weight loss had significantly better HRQOL than those who perceived that they had gained weight. CONCLUSIONS: Perception of weight loss/gain may be as powerful as actual weight loss/gain in impacting HRQOL among adults with T2DM. Interventions that help individuals lose weight or perceive weight loss in addition to lowering glucose will assist in improving HRQOL.

Influence of heating and acidification on the flavor of whey protein isolate.

Previous studies have established that whey protein manufacture unit operations influence the flavor of dried whey proteins. Additionally, manufacturers generally instantize whey protein isolate (WPI; ≥ 90% protein) by agglomeration with lecithin to increase solubility and wettability. Whey protein isolate is often subjected to additional postprocessing steps in beverage manufacturing, including acidification and heat treatment. These postprocessing treatments may further influence formation or release of flavors. The objective of the first study was to characterize the effect of 2 processing steps inherent to manufacturing of acidic protein beverages (acidification and heat treatment) on the flavor of non-instant WPI. The second study sought to determine the effect of lecithin agglomeration, a common form of instantized (INST) WPI used in beverage manufacturing, on the flavor of WPI after acidification and heat treatment. In the first experiment, commercial non-instantized (NI) WPI were rehydrated and evaluated as is (control); acidified to pH 3.2; heated to 85°C for 5 min in a benchtop high temperature, short time (HTST) pasteurizer; or acidified to 3.2 and heated to 85°C for 30s (AH-HTST). In the second experiment, INST and NI commercial WPI were subsequently evaluated as control, acidified, heated, or AH-HTST. All samples were evaluated by descriptive sensory analysis, solid-phase microextraction (SPME), and gas chromatography-mass spectrometry. Acidification of NI WPI produced higher concentrations of dimethyl disulfide (DMDS) and sensory detection of potato/brothy flavors, whereas heating increased cooked/sulfur flavors. Acidification and heating increased cardboard, potato/brothy, and malty flavors and produced higher concentrations of aldehydes, ketones, and sulfur compounds. Differences between INST and NI WPI existed before treatment; INST WPI displayed cucumber flavors not present in NI WPI. After acidification, INST WPI were distinguished by higher intensity of cucumber flavor and higher concentrations of E-2-nonenal. No perceivable differences were observed between INST and NI WPI after heating; sulfur and eggy flavors increased in both types of WPI. After treatment, AH-INST-HTST samples were differentiated from AH-NI-HTST by grassy/hay and grainy flavor and increased lipid oxidation products. Further processing of WPI in food applications has negative effects on the flavor contributions of WPI.

Rate and risk predictors for development of self-reported type-2 diabetes mellitus over a 5-year period: the SHIELD study.

AIMS: This investigation determined the proportion of adults newly diagnosed as having type-2 diabetes mellitus (T2DM), and ascertained risk predictors for development of self-reported T2DM. METHODS: The US Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes (SHIELD) survey was a 5-year longitudinal study of adults with and without diabetes mellitus. Adults completed a baseline health questionnaire in 2004 and ≥1 annual follow-up survey through 2009. Respondents with no self-reported diagnosis of diabetes at baseline were followed to measure rate of and assess risk factors for development of T2DM over 5 years. RESULTS: Among 8582 respondents without diabetes at baseline, 622 (7.2%) reported a diagnosis of T2DM over the subsequent 5 years. Increasing age, family history of T2DM, body mass index ≥30 kg/m(2), abdominal obesity, excessive thirst, asthma, gestational diabetes and 'high blood sugar without diabetes' significantly increased the risk of developing T2DM (p < 0.05 for each). Good to excellent health status and self-reported circulatory problems decreased the risk (p < 0.05 for each). CONCLUSIONS: Among this representative US adult population, the rate of developing T2DM was 7.2% over 5 years. Predictors of T2DM diagnosis identified in this analysis were readily obtainable via self-report.

Clinical synergy of perindopril and calcium-channel blocker in the prevention of cardiac events and mortality in patients with coronary artery disease. Post hoc analysis of the EUROPA study.

BACKGROUND: The purposes of the study were to determine the effects of addition of perindopril to long-term continuous treatment with calcium-channel blocker (CCB) on cardiac outcomes in the stable coronary artery disease (CAD) population of EUROPA and to explore the presence of synergy between perindopril and CCB in secondary prevention. METHODS: We identified participants receiving CCB at every visit during the 4.2-year follow-up and analyzed the effect of addition of perindopril (n = 1,022 perindopril/CCB vs n = 1,100 placebo/CCB). RESULTS: Addition of perindopril to CCB significantly reduced total mortality by 46% (P < .01 vs placebo) and primary end point (a composite of cardiovascular mortality, nonfatal myocardial infarction, and resuscitated cardiac arrest) by 35% (P < .05 vs placebo). There were 41%, 54%, and 28% reductions in cardiovascular mortality, hospitalization for heart failure, and myocardial infarction, respectively. Comparison of hazard ratios suggests the presence of a clinical synergy between perindopril and CCB, with a greater effect than addition of individual effects. CONCLUSION: Addition of perindopril to CCB in stable CAD patients had a significant supplementary impact on cardiac outcomes and mortality.

Long-term follow-up of the first patients to undergo transcatheter alcohol septal ablation.

We describe the 10-year outcome of the first-in-human series of 12 patients with hypertrophic cardiomyopathy treated with alcohol septal ablation. There was no 30-day mortality. Survival free of death, internal cardiac defibrillator discharge for treatment of ventricular fibrillation or tachycardia, severe New York Heart Association (NYHA) class III/IV and/or Canadian Cardiovascular Society class III/IV symptoms and the need for surgical myectomy in this cohort was 91% at 1 year and 73% at 10 years. The reduction in outflow tract gradient was maintained over the 10 years, from a mean preoperative gradient of 70 mm Hg to a median of 3 mm Hg at 126 months of follow-up (p < 0.01). Two patients (16%) underwent a further ablation procedure. Two patients (16%) suffered sudden cardiac death, 91 and 102 months after the procedure. Long-term symptom benefit was experienced by all patients, with a reduction in mean NYHA class from 2.7 +/- 0.6 before the procedure to 1 after the procedure at the last follow-up (p < 0.01). This historic small cohort study demonstrates that septal ablation can provide long-term haemodynamic and symptomatic benefit.

Underutilisation of cardiovascular medications among at-risk individuals.

AIMS: Guidelines recommend antihypertensive, lipid-lowering and/or antiplatelet therapy for prevention of cardiovascular disease (CVD). This study examined the utilisation of cardiovascular therapies among individuals at CVD risk to assess adherence to guidelines. METHODS: Respondents to the SHIELD study were classified based on National Cholesterol Education Program Adult Treatment Panel III risk categories. High coronary heart disease (CHD) risk (n = 7510) was defined as self-reported diagnosis of heart disease/heart attack, narrow or blocked arteries, stroke or diabetes; moderate risk (n = 4823) included respondents with > or = 2 risk factors (i.e., men > 45 years, women > 55 years, hypertension, low high-density lipoprotein cholesterol, smoking and family history of CHD); and low risk (n = 5307) was 0-1 risk factor. Respondents reporting a myocardial infarction, stroke or revascularisation at baseline (prior CVD event) (n = 3777), those reporting a new CVD event during 2 years of follow up (n = 953), and those with type 2 diabetes mellitus (n = 3937) were evaluated. The proportion of respondents reporting treatment with lipid-lowering, antiplatelet or antihypertensive agents was calculated. RESULTS: Utilisation of lipid-lowering therapy was low (< or = 25%) in each group. Prescription antithrombotic therapy was minimal among respondents with prior CVD events, but 47% received antihypertensive medication. No use before or after a new CVD event was reported by 36% of respondents for lipid-lowering, 32% for antithrombotic and > 50% for antihypertensive medications. CONCLUSIONS: More than 50% of at-risk respondents and > 33% of respondents with new CVD events were not taking CVD therapy as recommended by guidelines.

Vibrio cholerae non-O1 infection in cirrhotics: case report and literature review.

Vibrio species are ubiquitous in the marine environment and can cause severe infections in cirrhotic patients. Patients with liver disease should be warned about the potential dangers of consuming raw or undercooked seafood, and avoiding exposure of wounds to seawater. We report a case of severe sepsis from Vibrio cholerae non-O1 in a patient with cirrhosis awaiting orthotopic liver transplant. This case is aimed to advise clinicians about the importance of V. cholerae subtypes, and non-cholera Vibrio species infections in cirrhotic patients, highlighting the need to educate these patients to stay away from undercooked seafood.

Self-reported diagnosis of heart disease: results from the SHIELD study.

OBJECTIVE: This study evaluated the self-reported method of diagnosis of heart disease (HD) to elucidate whether diagnosis is occurring at early, presymptomatic stages as recommended by the prevention guidelines. METHODS: Respondents to the 2006 survey in the US population-based Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes (SHIELD) reported whether a physician told them that they had HD, including heart attack, angina, heart failure, angioplasty or heart bypass surgery. Self-report of age at diagnosis, specialty of physician who made the diagnosis and whether the diagnosis was made after having symptoms, during routine screening or while being treated for another health problem were assessed. Year of diagnosis was categorised into 3-year intervals from 1985 to 2006. Individuals with HD diagnosis with and without type 2 diabetes mellitus (T2DM) were compared using chi-square tests. RESULTS: Of 1573 respondents reporting a diagnosis of HD, > 87% were white, > 49% were men and 38% had T2DM. Approximately 19% of respondents reported that their HD diagnosis was made during routine screening. A significantly greater percentage of HD respondents with T2DM reported the diagnosis being made based on symptoms (54%) and while being treated for another health problem (22%) compared with respondents without diabetes (48% symptoms and 15% other health problem, p > 0.05). HD was diagnosed primarily by cardiologists (> 60%) and family doctors (> 25%). CONCLUSION: There remains a missed opportunity to diagnose HD at earlier stages through routine screening or during treatment of other health conditions such as diabetes, as many individuals were not diagnosed until they were symptomatic.

Quality of life and depression of people living with type 2 diabetes mellitus and those at low and high risk for type 2 diabetes: findings from the Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes (SHIELD).

OBJECTIVES: This study compared health-related quality of life (HRQoL) and depression among individuals with type 2 diabetes mellitus (T2D) and those at low or high risk for T2D. METHODS: Respondents in a population-based US 2004 survey reported whether they had T2D (n = 3530) or risk factors for T2D [abdominal obesity, body mass index (BMI) >/= 28 kg/m(2), dyslipidaemia, hypertension and history of cardiovascular disease]. Respondents without T2D were stratified into low risk (0-2 risk factors, n = 5335) and high risk (3-5 risk factors, n = 5051). SF-12 version 2 (SF-12) and Patient Health Questionnaire (PHQ)-9 were used to measure HRQoL and depression. Mean scores were compared across the three groups using analysis of variance. Linear regression identified factors associated with SF-12 Physical and Mental Component Summary scores (PCS and MCS), adjusting for age, gender, race, income, geographic region, household size, BMI and group. RESULTS: Respondents were mostly women (60%) with mean age of 54 years. Mean PCS scores for T2D and high risk (39.5 and 41.7, respectively) were significantly lower than for low risk (50.6, p < 0.001). After adjustment, high-risk and T2D groups were associated with lower PCS and MCS scores compared with low risk group (p < 0.05). Mean PHQ-9 scores and per cent with moderate-to-severe depression were significantly higher for T2D and high risk than for low risk (p < 0.01). CONCLUSIONS: Health-related quality of life and depression scores in T2D were similar to those at high risk, and indicated significant decrements in physical health and greater depression compared with low-risk respondents.

Self-reported prevalence and awareness of metabolic syndrome: findings from SHIELD.

PURPOSE: This study assessed awareness of metabolic syndrome and evaluated health knowledge, attitudes and behaviours of respondents at risk. METHODS: Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes (SHIELD), a longitudinal US population-based survey initiated in 2004, included respondents, > or = 18 years of age, reporting a diagnosis of metabolic syndrome. Prevalence of metabolic syndrome was compared in SHIELD and National Health and Nutrition Examination Survey (NHANES) 1999-2002 survey. The proportion of SHIELD respondents who had heard of and/or understood metabolic syndrome was estimated. Respondents at high risk for metabolic syndrome were stratified into attitude-behaviour categories of 'Already Doing It', 'I Know I Should' and 'Don't Bother Me' and differences in attitudes and behaviours were evaluated with chi-square tests. RESULTS: Prevalence of reported metabolic syndrome was 0.6% in SHIELD screening questionnaire respondents (n = 211,097) vs. 25.9% in NHANES (n = 10,780). Less than 15% of SHIELD baseline questionnaire respondents (n = 22,001) had heard of or understood metabolic syndrome. Attitudes toward health status were more favourable in the 'Doing' group (27% reported fair/poor health) compared with those in the 'Should' (38%) and 'Don't' (54%) groups (p < 0.0001). The 'Don't' group was most likely to prefer medications to lifestyle change (13% vs. 2-4%) compared with 'Should' and 'Doing' groups (p < 0.0001). More 'Doing' respondents (79%) than 'Should' (59%) and 'Don't' (48%) respondents reported exercising regularly (p < 0.0001). CONCLUSIONS: The lack of knowledge about metabolic syndrome reported in SHIELD indicates limited penetration of this concept into public awareness. With behaviour categories, respondents who report healthy attitudes are more likely to embrace lifestyle changes, while respondents who do not care may be more difficult to treat.

Old yellow enzyme at 2 A resolution: overall structure, ligand binding, and comparison with related flavoproteins.

BACKGROUND: Old yellow enzyme (OYE) was the first flavoenzyme purified, but its function is still unknown. Nevertheless, the NADPH oxidase activity, the flavin mononucleotide environment and the ligand-binding properties of OYE have been extensively studied by biochemical and spectroscopic approaches. Full interpretation of these data requires structural information. RESULTS: The crystal structures of oxidized and reduced OYE at 2 A resolution reveal an alpha/beta-barrel topology clearly related to trimethylamine dehydrogenase. Complexes of OYE with p-hydroxybenzaldehyde, beta-estradiol, and an NADPH analog show all three binding at a common site, stacked on the flavin. The putative NADPH binding mode is novel as it involves primary recognition of the nicotinamide mononucleotide portion. CONCLUSIONS: This work shows that the striking spectral changes seen upon phenol binding are due to close physical association of the flavin and phenolate. It also identifies the structural class of OYE and suggests that if NADPH is its true substrate, then OYE has adopted NADPH dependence during evolution.