Efficacy, safety and acceptability of the new pen needle 34G × 3.5 mm: a crossover randomized non-inferiority trial; AGO 02 study.

OBJECTIVE: Insulin injection aspects, such as fear of injection and pain, directly affect glycemic control, patient adherence and quality of life. Use of thinner and shorter needles could increase acceptance of injections. The aim of the study is to evaluate the non-inferiority of the new 34G × 3.5 mm needle compared to a 32G × 4 mm in patients with diabetes treated with insulin. METHODS: This is an open, randomized, two-period crossover, non-inferiority trial. Every treatment period lasted 3 weeks. Patients with type 1 or type 2 diabetes, treated with multiple daily insulin injections, were randomly assigned to receive a 34G × 3.5 mm or a 32G × 4 mm pen needle. The primary endpoint was the non-inferiority of the 34G × 3.5 mm in comparison with the 32G × 4 mm pen needle in terms of percentage absolute change of blood fructosamine (% |ΔFru|), using a non-inferiority margin of 20%. RESULTS: Overall 77 patients were randomized and 73 completed the study. Patients characteristics were: 52% male, 80.5% affected by type 1 diabetes, mean age 52 years (±14.6), mean BMI 24.5 kg/m2 (±5.6), HbA1c 8% (±1.1) and baseline fructosamine level 350 µmol/l (±84). Mean fructosamine levels increased by 0.56 µmol/l with the 34G needle, while a reduction of 7.29 µmol/l was documented with the 32G needle. The difference between the two groups (7.84 µmol/l) was not statistically significant (p = .27). The % |ΔFru| between the two groups was 7.55% (95% CI 5.67-9.44), meeting the non-inferiority criterion. Glycemic variability, expressed as standard deviation of fasting blood glucose and post-prandial glucose, was not different between the two treatment groups (p = .63 and p = .77, respectively). CONCLUSIONS: The 34G × 3.5 mm needle was non-inferior to the 32G × 4 mm needle regarding fructosamine levels and glycemic variability supporting the suitability of the 34G × 3.5 mm needle for insulin injection in patients with diabetes. CLINICAL TRIAL REGISTRATION: NCT02690467.

Treatment with insulin is associated with worse outcome in patients with chronic heart failure and diabetes.

AIMS: Up to one-third of patients with diabetes mellitus and heart failure (HF) are treated with insulin. As insulin causes sodium retention and hypoglycaemia, its use might be associated with worse outcomes. METHODS AND RESULTS: We examined two datasets: 24 012 patients with HF from four large randomized trials and an administrative database of 4 million individuals, 103 857 of whom with HF. In the former, survival was examined using Cox proportional hazards models adjusted for baseline variables and separately for propensity scores. Fine-Gray competing risk regression models were used to assess the risk of hospitalization for HF. For the latter, a case-control nested within a population-based cohort study was conducted with propensity score. Prevalence of diabetes mellitus at study entry ranged from 25.5% to 29.5% across trials. Insulin alone or in combination with oral hypoglycaemic drugs was prescribed at randomization to 24.4% to 34.5% of the patients with diabetes. The rates of death from any cause and hospitalization for HF were higher in patients with vs. without diabetes, and highest of all in patients prescribed insulin [propensity score pooled hazard ratio for all-cause mortality 1.27 (1.16-1.38), for HF hospitalization 1.23 (1.13-1.33)]. In the administrative registry, insulin prescription was associated with a higher risk of all-cause death [odds ratio (OR) 2.02, 95% confidence interval (CI) 1.87-2.19] and rehospitalization for HF (OR 1.42, 95% CI 1.32-1.53). CONCLUSIONS: Whether insulin use is associated with poor outcomes in HF should be investigated further with controlled trials, as should the possibility that there may be safer alternative glucose-lowering treatments for patients with HF and type 2 diabetes mellitus.

Comparison of Clinical Outcomes and Adverse Events Associated With Glucose-Lowering Drugs in Patients With Type 2 Diabetes: A Meta-analysis.

IMPORTANCE: Numerous glucose-lowering drugs are used to treat type 2 diabetes. OBJECTIVE: To estimate the relative efficacy and safety associated with glucose-lowering drugs including insulin. DATA SOURCES: Cochrane Library Central Register of Controlled Trials, MEDLINE, and EMBASE databases through March 21, 2016. STUDY SELECTION: Randomized clinical trials of 24 weeks' or longer duration. DATA EXTRACTION AND SYNTHESIS: Random-effects network meta-analysis. MAIN OUTCOMES AND MEASURES: The primary outcome was cardiovascular mortality. Secondary outcomes included all-cause mortality, serious adverse events, myocardial infarction, stroke, hemoglobin A1c (HbA1C) level, treatment failure (rescue treatment or lack of efficacy), hypoglycemia, and body weight. RESULTS: A total of 301 clinical trials (1,417,367 patient-months) were included; 177 trials (56,598 patients) of drugs given as monotherapy; 109 trials (53,030 patients) of drugs added to metformin (dual therapy); and 29 trials (10,598 patients) of drugs added to metformin and sulfonylurea (triple therapy). There were no significant differences in associations between any drug class as monotherapy, dual therapy, or triple therapy with odds of cardiovascular or all-cause mortality. Compared with metformin, sulfonylurea (standardized mean difference [SMD], 0.18 [95% CI, 0.01 to 0.34]), thiazolidinedione (SMD, 0.16 [95% CI, 0.00 to 0.31]), DPP-4 inhibitor (SMD, 0.33 [95% CI, 0.13 to 0.52]), and α-glucosidase inhibitor (SMD, 0.35 [95% CI, 0.12 to 0.58]) monotherapy were associated with higher HbA1C levels. Sulfonylurea (odds ratio [OR], 3.13 [95% CI, 2.39 to 4.12]; risk difference [RD], 10% [95% CI, 7% to 13%]) and basal insulin (OR, 17.9 [95% CI, 1.97 to 162]; RD, 10% [95% CI, 0.08% to 20%]) were associated with greatest odds of hypoglycemia. When added to metformin, drugs were associated with similar HbA1C levels, while SGLT-2 inhibitors offered the lowest odds of hypoglycemia (OR, 0.12 [95% CI, 0.08 to 0.18]; RD, -22% [-27% to -18%]). When added to metformin and sulfonylurea, GLP-1 receptor agonists were associated with the lowest odds of hypoglycemia (OR, 0.60 [95% CI, 0.39 to 0.94]; RD, -10% [95% CI, -18% to -2%]). CONCLUSIONS AND RELEVANCE: Among adults with type 2 diabetes, there were no significant differences in the associations between any of 9 available classes of glucose-lowering drugs (alone or in combination) and the risk of cardiovascular or all-cause mortality. Metformin was associated with lower or no significant difference in HbA1C levels compared with any other drug classes. All drugs were estimated to be effective when added to metformin. These findings are consistent with American Diabetes Association recommendations for using metformin monotherapy as initial treatment for patients with type 2 diabetes and selection of additional therapies based on patient-specific considerations.

The Drug Derived Complexity Index (DDCI) Predicts Mortality, Unplanned Hospitalization and Hospital Readmissions at the Population Level.

OBJECTIVE: to develop and validate the Drug Derived Complexity Index (DDCI), a predictive model derived from drug prescriptions able to stratify the general population according to the risk of death, unplanned hospital admission, and readmission, and to compare the new predictive index with the Charlson Comorbidity Index (CCI). DESIGN: Population-based cohort study, using a record-linkage analysis of prescription databases, hospital discharge records, and the civil registry. The predictive model was developed based on prescription patterns indicative of chronic diseases, using a random sample of 50% of the population. Multivariate Cox proportional hazards regression was used to assess weights of different prescription patterns and drug classes. The predictive properties of the DDCI were confirmed in the validation cohort, represented by the other half of the population. The performance of DDCI was compared to the CCI in terms of calibration, discrimination and reclassification. SETTING: 6 local health authorities with 2.0 million citizens aged 40 years or above. RESULTS: One year and overall mortality rates, unplanned hospitalization rates and hospital readmission rates progressively increased with increasing DDCI score. In the overall population, the model including age, gender and DDCI showed a high performance. DDCI predicted 1-year mortality, overall mortality and unplanned hospitalization with an accuracy of 0.851, 0.835, and 0.584, respectively. If compared to CCI, DDCI showed discrimination and reclassification properties very similar to the CCI, and improved prediction when used in combination with the CCI. CONCLUSIONS AND RELEVANCE: DDCI is a reliable prognostic index, able to stratify the entire population into homogeneous risk groups. DDCI can represent an useful tool for risk-adjustment, policy planning, and the identification of patients needing a focused approach in everyday practice.

Association of Drug Effects on Serum Parathyroid Hormone, Phosphorus, and Calcium Levels With Mortality in CKD: A Meta-analysis.

BACKGROUND: Serum parathyroid hormone (PTH), phosphorus, and calcium levels are surrogate outcomes that are central to the evaluation of drug treatments in chronic kidney disease (CKD). This systematic review evaluates the evidence for the correlation between drug effects on biochemical (PTH, phosphorus, and calcium) and all-cause and cardiovascular mortality end points in adults with CKD. STUDY DESIGN: Systematic review and meta-analysis. SETTING & POPULATION: Adults with CKD. SELECTION CRITERIA FOR STUDIES: Randomized trials reporting drug effects on biochemical and mortality end points. INTERVENTION: Drug interventions with effects on serum PTH, phosphorus, and calcium levels, including vitamin D compounds, phosphate binders, cinacalcet, bisphosphonates, and calcitonin. OUTCOMES: Correlation between drug effects on biochemical and all-cause and cardiovascular mortality. RESULTS: 28 studies (6,999 participants) reported both biochemical and mortality outcomes and were eligible for analysis. Associations between drug effects on surrogate biochemical end points and corresponding effects on mortality were weak and imprecise. All correlation coefficients were less than 0.70, and 95% credible intervals were generally wide and overlapped with zero, consistent with the possibility of no association. The exception was an inverse correlation between drug effects on serum PTH levels and all-cause mortality, which was nominally significant (-0.64; 95% credible interval, -0.85 to -0.15), but the strength of this association was very imprecise. Risk of bias within available trials was generally high, further reducing confidence in the summary correlations. Findings were robust to adjustment for age, baseline serum PTH level, allocation concealment, CKD stage, and drug class. LIMITATIONS: Low power in analyses and combining evidence from many different drug comparisons with incomplete data across studies. CONCLUSIONS: Drug effects on serum PTH, phosphorus, and calcium levels are weakly and imprecisely correlated with all-cause and cardiovascular death in the setting of CKD. Risks of mortality (patient-level outcome) cannot be inferred from treatment-induced changes in biochemical outcomes in people with CKD. Similarly, existing data do not exclude a mortality benefit with treatment. Trials need to address patient-centered outcomes to evaluate drug effectiveness in this setting.

The long-term effects of stillbirth on women with and without gestational diabetes: a population-based cohort study.

AIMS/HYPOTHESIS: The aim of this study was to estimate the incidence of type 2 diabetes (primary objective) and hospitalisation for cardiovascular events (secondary objective) in women with previous gestational diabetes mellitus (GDM) and in those with normal glucose tolerance (NGT) in pregnancy, and to evaluate the role of stillbirth in differentiating the risks. METHODS: This was a population-based cohort study using administrative data and involving 12 local health authorities. Women with GDM (n = 3,851) during the index period from 2002 to 2010 were propensity matched with women with NGT (n = 11,553). Information was collected on type 2 diabetes development and hospitalisation for cardiovascular events. RESULTS: During a median follow-up of 5.4 years, the incidence rate per 1,000 person-years of type 2 diabetes was 2.1 (95% CI 1.8, 2.5) in women without GDM and 54.0 (95% CI 50.2, 58.0) among women with GDM and pregnancy at term (incidence rate ratio [IRR] 26.9; 95% CI 22.1, 32.7 compared with NGT and pregnancy at term). A history of stillbirth increased the risk of type 2 diabetes development by about twofold, irrespective of GDM status. No significant interaction between stillbirth and GDM on type 2 diabetes risk was found. GDM was associated with a significantly higher risk of cardiovascular events compared with NGT (IRR 2.4; 95% CI 1.5, 3.8). CONCLUSIONS/INTERPRETATION: Pregnancy complicated by GDM and ending in stillbirth represents an important contributory factor in determining type 2 diabetes development. Women with GDM are at a high risk of future cardiovascular events. Women with pregnancy complicated by GDM and stillbirth deserve careful follow-up.

Patient satisfaction with in-centre haemodialysis care: an international survey.

OBJECTIVES: To evaluate patient experiences of specific aspects of haemodialysis care across several countries. DESIGN: Cross-sectional survey using the Choices for Healthy Outcomes in Caring for End-Stage Renal Disease (CHOICE) questionnaire. SETTING: Haemodialysis clinics within a single provider in Europe and South America. PARTICIPANTS: 2748 adults treated in haemodialysis. PRIMARY AND SECONDARY OUTCOMES: The primary outcome was patient satisfaction with overall care. Secondary outcomes included patient experiences of individual aspects of dialysis care. RESULTS: 2145 (78.1%) adults responded to the questionnaire. Fewer than half (46.5% (95% CI 44.5% to 48.6%)) rated their overall care as excellent. Global perceptions of care were uninfluenced by most respondent characteristics except age and depressive symptoms; older respondents were less critical of their care (adjusted OR for excellent rating 1.44 (1.01 to 2.04)) and those with depressive symptoms were less satisfied (0.56 (0.44 to 0.71)). Aspects of care that respondents most frequently ranked as excellent were staff attention to dialysis vascular access (54% (52% to 56%)); caring of nurses (53% (51% to 55%)); staff responsiveness to pain or discomfort (51% (49% to 53%)); caring, helpfulness and sensitivity of dialysis staff (50% (48% to 52%)); and ease of reaching dialysis staff by telephone (48% (46% to 50%)). The aspects of care least frequently ranked as excellent were information provided when choosing a dialysis modality (23% (21% to 25%)), ease of seeing a social worker (28% (24% to 32%)), information provided about dialysis (34% (32% to 36%)), accuracy of information from nephrologist (eg, about prognosis or likelihood of a kidney transplant; 37% (35% to 39%)) and accuracy of nephrologists' instructions (39% (36% to 41%)). CONCLUSIONS: Haemodialysis patients are least satisfied with the complex aspects of care. Patients' expectations for accurate information, prognosis, the likelihood of kidney transplantation and their options when choosing dialysis treatment need to be considered when planning healthcare research and practices.

Effect of pioglitazone versus metformin on cardiovascular risk markers in type 2 diabetes.

INTRODUCTION: Besides its critical role in metabolic homeostasis, peroxisome proliferator-activated receptor (PPAR)-γ modulates several cellular responses involved in atherothrombosis. This multicenter, double-blind, randomized study investigated the effects of two oral hypoglycemic agents on markers of inflammation, platelet activation, thrombogenesis, and oxidative stress in patients with type 2 diabetes. METHODS AND RESULTS: The primary objective of this study was to evaluate the effect on C-reactive protein (CRP) after a 16-week treatment period with either pioglitazone or metformin. Additionally, markers of vascular inflammatory response, platelet activation, thrombogenesis, oxidative stress, glucose, and lipid metabolism, as well as liver function, were measured. In total, 50 patients completed the study. Pioglitazone-treated patients were found to have statistically significantly larger decreases in mean CRP levels (-0.4 mg/dL) compared to those treated with metformin (-0.2 mg/dL) (P=0.04), as well as greater reductions in levels of mean fasting plasma glucose (-27 vs. -9 mg/dL; P=0.01), serum insulin (-2 vs. -1.9 mU/L; P=0.014), homeostatic model assessment (HOMA) (-1.2 vs. -0.9; P=0.015), and E-selectin (-12.4 vs. +3.4 µg/mL; P=0.01). Mean glycated hemoglobin (HbA1c) levels decreased in both treatment groups from baseline to week 16 (-0.4% in the pioglitazone group, -0.2% in the metformin group; P=0.36). Pioglitazone treatment was also found to be associated with a statistically significant increase in total cholesterol levels (+10 mg/dL in the pioglitazone arm, -3 mg/dL in the metformin arm; P=0.05) and a decrease in liver enzyme levels. CONCLUSIONS: The favorable changes in markers of systemic and vascular inflammatory response with pioglitazone suggest that it may positively influence the atherothrombotic process in type 2 diabetes.

Association of aspirin use with major bleeding in patients with and without diabetes.

CONTEXT: The benefit of aspirin for the primary prevention of cardiovascular events is relatively small for individuals with and without diabetes. This benefit could easily be offset by the risk of hemorrhage. OBJECTIVE: To determine the incidence of major gastrointestinal and intracranial bleeding episodes in individuals with and without diabetes taking aspirin. DESIGN, SETTING, AND PARTICIPANTS: A population-based cohort study, using administrative data from 4.1 million citizens in 12 local health authorities in Puglia, Italy. Individuals with new prescriptions for low-dose aspirin (≤300 mg) were identified during the index period from January 1, 2003, to December 31, 2008, and were propensity-matched on a 1-to-1 basis with individuals who did not take aspirin during this period. MAIN OUTCOME MEASURES: Hospitalizations for major gastrointestinal bleeding or cerebral hemorrhage occurring after the initiation of antiplatelet therapy. RESULTS: There were 186,425 individuals being treated with low-dose aspirin and 186,425 matched controls without aspirin use. During a median follow-up of 5.7 years, the overall incidence rate of hemorrhagic events was 5.58 (95% CI, 5.39-5.77) per 1000 person-years for aspirin users and 3.60 (95% CI, 3.48-3.72) per 1000 person-years for those without aspirin use (incidence rate ratio [IRR], 1.55; 95% CI, 1.48-1.63). The use of aspirin was associated with a greater risk of major bleeding in most of the subgroups investigated but not in individuals with diabetes (IRR, 1.09; 95% CI, 0.97-1.22). Irrespective of aspirin use, diabetes was independently associated with an increased risk of major bleeding episodes (IRR, 1.36; 95% CI, 1.28-1.44). CONCLUSIONS: In a population-based cohort, aspirin use was significantly associated with an increased risk of major gastrointestinal or cerebral bleeding episodes. Patients with diabetes had a high rate of bleeding that was not independently associated with aspirin use.

Sexual dysfunction in women with ESRD requiring hemodialysis.

BACKGROUND AND OBJECTIVES: The few existing studies of sexual dysfunction in women on hemodialysis are limited by small sample size. This large, cross-sectional study evaluated the prevalence and correlates of female sexual dysfunction in advanced kidney disease. DESIGN, SETTING, PARTICIPANTS, METHODS: A total of 1472 women with ESRD undergoing hemodialysis were recruited to a multinational, cross-sectional study conducted within a collaborative dialysis network in Europe and South America. Sexual dysfunction was identified by the Female Sexual Function Index. Correlates of self-reported sexual dysfunction were identified by regression analyses. RESULTS: Of the 1472 women, 659 completed questionnaires (45%). More than half (362 of 659 [55%]) lived with a partner, and 232 of 659 (35%) reported being sexually active. Of these 659 respondents, 555 (84%) reported sexual dysfunction. Women with a partner (282 of 362 [78%]) were less likely to report sexual dysfunction than those without a partner (273 of 297 [92%]) (P<0.001). Sexual dysfunction was independently associated with age, depressive symptoms, less education, menopause, diabetes, and diuretic therapy. Nearly all women who were not wait-listed for a kidney transplant and were living without a partner (249 of 260 [96%]) reported sexual dysfunction. More than half (128 of 232 [55%]) of sexually active women reported sexual dysfunction, associated with age, depressive symptoms, menopause, low serum albumin, and diuretic therapy. CONCLUSIONS: This descriptive study suggests most women on hemodialysis experience sexual problems. Additional research on the relevance of sexual dysfunction to symptom burden and quality of life in these women is needed.

Prevalence and correlates of erectile dysfunction in men on chronic haemodialysis: a multinational cross-sectional study.

BACKGROUND: Factors associated with erectile dysfunction in men on haemodialysis are incompletely identified due to suboptimal existing studies. We determined the prevalence and correlates of erectile dysfunction and identified combinations of clinical characteristics associated with a higher risk of erectile dysfunction using recursive partitioning and amalgamation (REPCAM) analysis. METHODS: We conducted a multinational cross-sectional study in men on haemodialysis within a collaborative network. Erectile dysfunction and depressive symptoms were evaluated using the erectile function domain of the International Index of Erectile Function questionnaire and the Center for Epidemiological Studies-Depression Scale, respectively. RESULTS: Nine hundred and forty-six (59%) of 1611 eligible men provided complete data for erectile dysfunction. Eighty-three per cent reported erectile dysfunction and 47% reported severe erectile dysfunction. Four per cent of those with erectile dysfunction were receiving pharmacological treatment. Depressive symptoms were the strongest correlate of erectile dysfunction [adjusted odds ratio 2.41 (95% confidence interval (CI) 1.57-3.71)]. Erectile dysfunction was also associated with age (1.06, 1.05-1.08), being unemployed (1.80, 1.17-2.79) or receiving a pension (2.05, 1.14-3.69) and interdialytic weight gain (1.9-2.87 kg, 1.92 [CI 1.19-3.09]; >2.87 kg, 1.57 [CI 1.00-2.45]). Married men had a lower risk of erectile dysfunction (0.49, 0.31-0.76). The prevalence of erectile dysfunction was highest (94%) in unmarried and unemployed or retired men who have depressive symptoms. CONCLUSIONS: Most men on haemodialysis experience erectile dysfunction and are untreated. Given the prevalence of this condition and the relative lack of efficacy data for pharmacological agents, we suggest that large trials of pharmacological and non-pharmacological interventions for erectile dysfunction and depression are needed.

Comorbidity affects the relationship between glycemic control and cardiovascular outcomes in diabetes: a cohort study.

BACKGROUND: Recent studies have shown mixed results regarding the effectiveness of intensive glucose-lowering therapy in reducing risk for cardiovascular events. OBJECTIVE: To determine whether attaining hemoglobin A(1c) (HbA(1c)) targets of 6.5% or less or 7.0% or less for glycemic control at baseline provides differential benefits for patients with high versus low-to-moderate levels of comorbidity. DESIGN: 5-year longitudinal observational study of patients with type 2 diabetes. Patients were categorized into high and low-to-moderate comorbidity subgroups by using the Total Illness Burden Index (TIBI), a validated patient-reported measure of comorbidity. SETTING: 101 diabetes outpatient clinics and 103 general practitioners' clinics in Italy. PATIENTS: 2613 (83%) of 3074 patients with type 2 diabetes, sampled randomly from diabetes outpatient clinic rosters and recruited consecutively from general practitioners' clinics, who completed the baseline questionnaire. MEASUREMENTS: TIBI score, total mortality, and incident cardiovascular events. Hazard ratios (HRs) were adjusted for age and sex. RESULTS: Attaining an HbA(1c) level of 6.5% or less at baseline was associated with lower 5-year incidence of cardiovascular events in the low-to-moderate comorbidity subgroup (adjusted HR, 0.60 [95% CI, 0.42 to 0.85]; P = 0.005) but not in the high comorbidity subgroup (adjusted HR, 0.92 [CI, 0.68 to 1.25]; P = 0.61; P for subgroup by HbA(1c) interaction = 0.048). Similarly, attaining a baseline HbA(1c) level of 7.0% predicted fewer cardiovascular events in the low-to-moderate comorbidity subgroup (adjusted HR, 0.61 (CI, 0.44 to 0.83; P = 0.001) but not in the high comorbidity subgroup (adjusted HR, 0.88 [CI, 0.66 to 1.17]; P = 0.38; P for subgroup by HbA(1c) interaction = 0.093). LIMITATIONS: The observational nature of the study does not allow causal inference. The length of the data collection period was limited. Information on clinical management was not available. CONCLUSION: Patients with the high levels of comorbidity common in type 2 diabetes may receive diminished cardiovascular benefit from intensive blood glucose control. Comorbidity should be considered when tailoring glucose-lowering therapy in patients with type 2 diabetes. PRIMARY FUNDING SOURCE: Pfizer of Italy.

Aspirin for primary prevention of cardiovascular events in people with diabetes: meta-analysis of randomised controlled trials.

OBJECTIVE: To evaluate the benefits and harms of low dose aspirin in people with diabetes and no cardiovascular disease. DESIGN: Meta-analysis of randomised controlled trials. DATA SOURCES: Medline (1966-November 2008), the Cochrane central register of controlled trials (Cochrane Library 2008;issue 4), and reference lists of retrieved articles. Review methods Randomised trials of aspirin compared with placebo or no aspirin in people with diabetes and no pre-existing cardiovascular disease were eligible for inclusion. Data on major cardiovascular events (death from cardiovascular causes, non-fatal myocardial infarction, non-fatal stroke, and all cause mortality) were extracted and pooled with a random effect model. Results are reported as relative risks with 95% confidence intervals. RESULTS: Of 157 studies in the literature searches, six were eligible (10 117 participants). When aspirin was compared with placebo there was no statistically significant reduction in the risk of major cardiovascular events (five studies, 9584 participants; relative risk 0.90, 95% confidence interval 0.81 to 1.00), cardiovascular mortality (four studies, n=8557, 0.94; 0.72 to 1.23), or all cause mortality (four studies, n=8557; 0.93, 0.82 to 1.05). Significant heterogeneity was found in the analysis for myocardial infarction (I(2)=62.2%; P=0.02) and stroke (I(2)=52.5%; P=0.08). Aspirin significantly reduced the risk of myocardial infarction in men (0.57, 0.34 to 0.94) but not in women (1.08, 0.71 to 1.65; P for interaction=0.056). Evidence relating to harms was inconsistent. CONCLUSIONS: A clear benefit of aspirin in the primary prevention of major cardiovascular events in people with diabetes remains unproved. Sex may be an important effect modifier. Toxicity is to be explored further.

Management of erectile dysfunction in general practice.

INTRODUCTION: In recent years, the availability of effective oral pharmacological treatment for erectile dysfunction (ED) has revolutionized its management; however, it is still unclear how everyday clinical practice has changed in response to this evolving scenario. AIM: The aim of this study is to describe general practitioners' (GPs) beliefs and attitudes toward the management of ED. METHODS: Each GP was asked to recruit consecutive men aged >or=18 years and sexually active, with already known erectile problems or with newly diagnosed ED. MAIN OUTCOMES MEASURES: A written questionnaire was used to investigate GPs' sociodemographic characteristics and their beliefs toward the management of ED. RESULTS: Overall, 127 GPs (53.4%) returned the questionnaire and 124 enrolled patients for the study. Only 9.5% of the GPs reported routinely inquiring about ED of patients >40 years of age, whereas 45.7% did it only when the patient raised the problem. GPs' gender and age were associated with their beliefs about ED treatment and referral to specialist care. Overall, 932 patients were enrolled, of whom 38% had newly diagnosed ED. The problem came to light for initiative of patient in 80% of cases, and 84.8% of men were prescribed a treatment. Patients who on their own initiative discussed of their condition had an almost 3-fold increased probability to be treated than those whose GP began the discussion about ED (odds ratio [OR] = 2.6, confidence interval [CI] 95% 1.5-4.5). Patients followed by female physicians were significantly more likely to be referred to a specialist than those followed by male physicians (OR = 3.3, CI 95% 1.4-5.0). CONCLUSIONS: The management of ED has become an integral component of clinical practice in primary care. Nevertheless, barriers in addressing sexual issues still persist. Appropriate training is needed for a proactive approach to ED screening and management in men over 40s.

Glycated haemoglobin or mean blood glucose as indicators of metabolic control in Type 2 diabetes?

The aim of the study was to assess whether HbA(1c) levels reflected mean blood glucose (MBG) levels in Type 2 diabetes. Despite the good correlation between HbA(1c) and MBG, one-third of the patients had consistently higher HbA(1c) or lower HbA(1c) levels than that expected under the hypothesis that HbA(1c) is solely determined by MBG, suggesting the existence of different haemoglobin glycation phenotypes. The use of HbA(1c) alone for glycemic control monitoring in these patients could be insufficient to clearly trace their risk of complications.

Quality of diabetes care predicts the development of cardiovascular events: results of the QuED study.

BACKGROUND AND AIM: In the context of the QuED Study we assessed whether a quality of care summary score was able to predict the development of cardiovascular (CV) events in patients with type 2 diabetes. METHODS AND RESULTS: The score was calculated using process and intermediate outcome indicators (HbA1c), blood pressure, low-density lipoprotein cholesterol, microalbuminuria) and ranged from 0 to 40. Overall, 3235 patients were enrolled, of whom 492 developed a CV event after a median follow-up of 5 years. The incidence rate (per 1000 person-years) of CV events was 62.4 in patients with a score < or =10, 54.8 in those with a score between 15 and 20, and 39.8 in those with a score >20. In adjusted multilevel regression models, the risk to develop a CV event was 89% greater in patients with a score of < or =10 (rate ratio [RR]=1.89; 95% confidence interval [CI] 1.43-2.50) and 43% higher in those with a score between 10 and 20 (RR=1.43; 95% CI 1.14-1.79), as compared to those with a score >20. A difference between centers of 5 points in the mean quality score was associated with a difference of 16% in CV event risk (RR=0.84; 95% CI 0.72-0.98). CONCLUSION: Our study documented for the first time a close relationship between a score of quality of diabetes care and long-term outcomes.

Aspirin and Simvastatin Combination for Cardiovascular Events Prevention Trial in Diabetes (ACCEPT-D): design of a randomized study of the efficacy of low-dose aspirin in the prevention of cardiovascular events in subjects with diabetes mellitus treated with statins.

BACKGROUND: Despite the high cardiovascular risk, evidence of efficacy of preventive strategies in individuals with diabetes is scant. In particular, recommendations on the use of aspirin in patients with diabetes mostly reflect an extrapolation from data deriving from other high risk populations. Furthermore, the putative additive effects of aspirin and statins in diabetes remain to be investigated. This aspect is of particular interest in the light of the existing debate regarding the need of multiple interventions to reduce total cardiovascular risk, which has also led to the proposal of a polypill. Aim of the study is to evaluate the efficacy of aspirin in the primary prevention of major cardiovascular events in diabetic patients candidate for treatment with statins. These preventive strategies will be evaluated on the top of the other strategies aimed at optimizing the care of diabetic patients in terms of metabolic control and control of the other cardiovascular risk factors. METHODS/DESIGN: The ACCEPT-D is an open-label trial assessing whether 100 mg/daily of aspirin prevent cardiovascular events in patients without clinically manifest vascular disease and treated with simvastatin (starting dose 20 mg/die). Eligible patients will be randomly assigned to receive aspirin + simvastatin or simvastatin alone. ELIGIBILITY CRITERIA: male and female individuals aged >=50 years with diagnosis of type 1 or type 2 diabetes, already on treatment with statins or candidate to start the treatment (LDL-cholesterol >=100 mg/dL persisting after 3 months of dietary advise). The primary combined end-point will include cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and hospital admission for cardiovascular causes (acute coronary syndrome, transient ischemic attack, not planned revascularization procedures, peripheral vascular disease). A total of 515 first events are needed to detect a reduction in the risk of major cardiovascular events of 25% (alpha = 0.05; 1-beta = 0.90). Overall, 5170 patients will be enrolled. The study will be conducted by diabetes specialists and general practitioners. DISCUSSION: The study will provide important information regarding the preventive role of aspirin in diabetes when used on the top of the other strategies aimed to control cardiovascular risk factors. TRIAL REGISTRATION: Current Controlled Trials ISRCTN48110081.

Identifying patients at risk for microalbuminuria via interaction of the components of the metabolic syndrome: a cross-sectional analytic study.

BACKGROUND AND OBJECTIVES: The objective of this study was to investigate correlates of risk for having microalbuminuria in individuals with one or more cardiovascular risk factors. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The study involved 1919 individuals who attended general practice settings, were aged 55 to 75 yr, and did not have a history of cardiovascular events or diabetes but had one or more cardiovascular risk factors. A tree-based regression technique and multivariate analysis were used to identify distinct, homogeneous subgroups of patients with different likelihood of having microalbuminuria; interaction between correlates of microalbuminuria and risk for microalbuminuria was also investigated. RESULTS: The prevalence of microalbuminuria was 5.9%. Patients who did not have hypertension and had postload glycemia < 140 mg/dl showed the lowest prevalence of microalbuminuria (1.9%) and represented the reference class. The likelihood of microalbuminuria was seven times higher in men with hypertension and homeostatic model assessment levels in the upper tertile and four times higher in women with the same characteristics. Individuals with hypertension and lower homeostatic model assessment levels and normotensive individuals with postload glycemia > or = 140 mg/dl had a more than three-fold increased likelihood of having microalbuminuria. Treatment with statins was associated with a 54% reduction in the likelihood of having microalbuminuria, whereas levels of triglycerides > 150 mg/dl and fibrinogen levels in the upper tertile were associated with a significantly higher risk for microalbuminuria. CONCLUSIONS: The likelihood of having microalbuminuria in a population-based study of elderly individuals is strongly related to the interaction between the components of the metabolic syndrome, particularly hypertension, insulin resistance, and impaired glucose tolerance.

AHA/ADA vs. ESC/EASD recommendations on aspirin as a primary prevention strategy in people with diabetes: how the same data generate divergent conclusions.

Recently, major scientific societies in Europe and USA have issued guidelines on diabetes and cardiovascular (CV) disease. The conclusions of the two panels of experts regarding the use of aspirin for the primary prevention of CV disease in individuals with diabetes are totally divergent. The US statement recommends the use of aspirin for primary prevention in all individuals aged > 40 or with additional risk factors. In contrast, in the European guidelines there is no mention of aspirin for the primary prevention of myocardial infarction or CV death, while it is recommended for the prevention of stroke. Both recommendations seem mainly based on extrapolations from data on other high-risk groups, rather than on a comprehensive review of pertinent data. Actually, a body of evidence suggests that the efficacy of aspirin in patients with diabetes is substantially lower than in individuals without diabetes. Nevertheless, existing knowledge is mainly derived from dated trials, including small numbers of patients, and hardly representing current strategies for the management of CV risk factors. The high level of uncertainty regarding the balance between benefits and risks of aspirin therapy have important implications for clinical practice, auditing activities, and the design and conduct of randomized clinical trials.