Association between periodontal disease and non-fatal ischemic stroke: a case-control study.

OBJECTIVE: This study aimed to investigate the association between clinical and radiological markers of periodontal disease and ischemic stroke and to assess the potential influence of inflammatory response on the observed associations. METHODS: A prospective case-control study including a series of 48 cases with a minor ischemic stroke and 47 controls was conducted at the University Hospital of Dijon. Vascular risk factors, clinical dental examination (plaque index, gingival index, percentage of pockets >5 mm, percentage of bleeding on probing (BOP) sites), dental panoramic (bone loss) and biological parameters (CRP, total cholesterol, HDL, LDL, fasting glucose) were collected. Conditional regression analyses were performed to identify factors associated with ischemic stroke. RESULTS: The prevalence of hypertension, high CRP and glucose levels and overall odontological variables was higher in stroke patients. In multivariable analyses, hypertension (OR = 12.56; 95% CI = 2.29-69.96, p = 0.004), CRP levels >5 mg/L (OR = 18.54; 95% CI = 2.01-171.17, p = 0.010), BOP (OR = 1.049; 95% CI = 1.012-1.88, p = 0.009) and bone loss >20% (OR = 1.053; 95% CI = 1.017-1.091, p = 0.004) were associated with ischemic stroke. Among stroke patients, there was a non-significant trend towards higher CRP levels in patients with bone loss >20% compared with those with bone loss <20% (8.1 ± 1.27 mg/L vs 3.12 ± 3.14 mg/L, p = 0.25), whereas other biological parameters were very similar between the two groups. CONCLUSION: This case-control study demonstrates that periodontal disease, especially markers such as BOP and bone loss, is independently associated with ischemic stroke.

Determinants and consequences of renal function variations with aldosterone blocker therapy in heart failure patients after myocardial infarction: insights from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study.

BACKGROUND: We evaluated the effect of the selective mineralocorticoid receptor antagonist eplerenone on renal function and the interaction between changes in renal function and subsequent cardiovascular outcomes in patients with heart failure and left ventricular systolic dysfunction after an acute myocardial infarction in the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS). METHODS AND RESULTS: Serial changes in estimated glomerular filtration rate (eGFR) were available in 5792 patients during a 24-month follow-up. Patients assigned to eplerenone had a decline in eGFR with an adjusted mean difference of -1.4±0.3 mL · min(-1) · 1.73 m(-2) compared with placebo (P<0.0001), an effect that appeared within the first month (-1.3±0.4 mL · min(-1) · 1.73 m(-2)) and persisted throughout the study. Overall, 914 patients experienced a decline in eGFR >20% in the first month, 16.9% and 14.7% in the eplerenone and placebo groups, respectively (odds ratio, 1.15; 95% confidence interval, 1.02-1.30; P=0.017). In multivariate analyses, determinants of this early decline in eGFR were female sex, age ≥65 years, smoking, left ventricular ejection fraction <35%, and use of eplerenone and loop diuretic. An early decline in eGFR by >20% was associated with worse cardiovascular outcomes independently of baseline eGFR and of the use of eplerenone, which retained its prognostic benefits even under these circumstances. CONCLUSIONS: In patients with heart failure after acute myocardial infarction and receiving standard medical care, an early decline in eGFR is not uncommon and is associated with poor long-term outcome. Eplerenone induced a moderately more frequent early decline in eGFR, which did not affect its clinical benefit on cardiovascular outcomes.

Hypo- and hyperglycemia predict outcome in patients with left ventricular dysfunction after acute myocardial infarction: data from EPHESUS.

BACKGROUND: Hyperglycemia predicts death in cardiovascular disease, but intensive glucose-lowering strategies increase mortality rates in diabetes. The present analysis investigated the prognostic value of postadmission blood glucose (BG) concentration on clinical outcomes in high-risk patients with heart failure after acute myocardial infarction. METHODS AND RESULTS: A total of 6,496 patients from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) were categorized into 4 groups by plasma glucose concentration: ≤4.5 mmol/L (hypoglycemia), 4.5-5.5 mmol/L (normoglycemia), 5.5-8.3 mmol/L (elevated glucose level), and >8.3 mmol/L (severe hyperglycemia). We evaluated the time to all-cause death (primary end point) and time to cardiovascular death or hospitalization (secondary end point). Hypo- and severe hyperglycemia were prevalent in 509 (8%) and 1,588 (24%) patients, respectively. There was a U-shaped relationship between BG level and incidence of all-cause death (11.8% in patients with normoglycemia vs 15.1% and 19.9% in those with hypo- and severe hyperglycemia; P < .001). The incidence of the secondary end point was increased only in hyperglycemic patients (36% vs 23% in normoglycemic patients; P < .001). In multivariate Cox regression analysis, hypoglycemia (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.06-1.81; P = .002) and severe hyperglycemia (HR 1.52, CI 1.27-1.83; P < .0001) proved to be strong predictors of all-cause death. There was no significant interaction between eplerenone treatment and blood glucose levels regarding clinical outcomes. CONCLUSIONS: In heart failure after acute myocardial infarction, both hypo- and hyperglycemia at the postacute phase identify patients with increased risk of death during long-term follow-up.

[Sarcoïdosis and anti-TNF: a paradoxical class effect? Analysis of the French Pharmacovigilance system database and literature review]. / Sarcoïdose et anti-TNF : un effet paradoxal de classe? Analyse des cas de la base française de Pharmacovigilance et revue de la littérature.

OBJECTIVES: To identify and characterize the observations of sarcoidosis occurring during anti-TNF blockade collected in the French Pharmacovigilance system database and reported in the literature. RESULTS: Seven cases were reported in the French Pharmacovigilance system database and 39 cases (37 original) have been reported internationally. Monoclonal antibodies (infliximab and adalimumab) and fusion protein (etanercept) are equally involved. Sarcoidosis have been confirmed histologically and occurred predominantly in the rheumatoid arthritis (22) and spondylarthropathy (16). CONCLUSION: The lack of protopathic bias suggests that these paradoxical sarcoidosis occurring during treatment with anti-TNF are a class-effect, as with psoriasis, uveitis, and IBD reported under similar conditions. Their pathogenesis remains unclear.

Reduced Diuretic Dose in Patients Treated With Eplerenone: Data From the EPHESUS Trial.

BACKGROUND: Loop diuretics are used for congestion relief, and dose adaptations are usually a consequence of the clinicians' clinical judgement about the congestive status of the patient. In EPHESUS (Eplerenone in Patients With Systolic Dysfunction After Myocardial Infarction), many patients required diuretics for congestion relief. We thus hypothesized that blinded allocation to eplerenone would lead clinicians to reduce loop diuretics, as a consequence of the improvement in patients' status. METHODS: Cox and mixed-effects models were used over a median follow-up of 1.3 years in 6632 patients. RESULTS: A total of 6632 patients were included; at baseline, 3352 (50.5%) did not have diuretics, 2195 (33.1%) had diuretic doses between 1 and 40 mg/day, and 1085 (16.4%) had diuretic doses >40 mg/day. Patients with higher furosemide equivalent doses had a worse clinical status. Both baseline and follow-up incremental loop diuretic doses were associated with worse prognosis. Eplerenone treatment was associated with lower prescribed loop diuretic doses throughout the follow-up; lower doses were observed at 90 days and decreased further at 180 days and beyond. Eplerenone treatment led to a mean furosemide equivalent dose reduction of -2.2 mg/day (-2.9 to -1.6) throughout the follow-up. Eplerenone was effective in reducing morbidity and mortality regardless of the baseline loop diuretic dose used: hazard ratio for the outcome of cardiovascular death or heart failure hospitalization was 0.83 ([95% CI, 0.75-0.92]; P for interaction, 0.54). CONCLUSIONS: Eplerenone treatment led to a loop diuretic dose reduction during follow-up without evidence of treatment effect modification by loop diuretics. These findings suggest that eplerenone reduces congestive signs and symptoms, which enables clinicians to reduce loop diuretic doses.

[The human and economic burden of cancer in France in 2014, based on the Sniiram national database]. / Poids humain et économique des cancers en France en 2014, les données du Sniiram.

INTRODUCTION: The national health insurance information system (Sniiram) can be used to estimate the national medical and economic burden of cancer. This study reports the annual rates, characteristics and expenditure of people reimbursed for cancer. METHODS: Among 57 million general health scheme beneficiaries (86% of the French population), people managed for cancer were identified using algorithms based on hospital diagnoses and full refund for long-term cancer. The reimbursed costs (euros) related to the cancer, paid off by the health insurance, were estimated. RESULTS: In 2014, 2.491 million people (4.4%) covered by the general health scheme had a cancer managed (men 1.1 million, 5.1%; women 1.3 million, 4.9%). The annual (2012-2014) average growth rate of patients was 0.8%. The spending related to the cancer was 13.5 billion: 5 billion for primary health care (drugs 2.3 billion), 7.5 billion for the hospital (drugs 1.3 billions) and 900 million for sick leave and invalidity pensions. Spending annual average growth rate (2012-2014) was 4% (drugs 2%). The rates of patients and the relative spending were 1.8% and 2.5 billion for the breast cancer (women), 1.5% and 1.0 billion for prostate cancer, 0.9% and 1.5 billion for the colon cancer, and 0.19% and 1.3 billion for lung cancer. DISCUSSION: Cancers establish one of the first groups of chronic diseases pathologies in terms of patients and spending. If the numbers of patients remain stables, the spending increases, mainly for medicines.

Prevalence and economic burden of cardiovascular diseases in France in 2013 according to the national health insurance scheme database.

BACKGROUND: Cardiovascular diseases (CVDs) constitute the second leading cause of death in France. The Système national d'information interrégimes de l'assurance maladie (SNIIRAM; national health insurance information system) can be used to estimate the national medical and economic burden of CVDs. OBJECTIVES: To describe the rates, characteristics and expenditure of people reimbursed for CVDs in 2013. METHODS: Among 57 million general health scheme beneficiaries (86% of the French population), people managed for CVDs were identified using algorithms based on hospital diagnoses either during the current year (acute phase) or over the previous 5 years (chronic phase) and long-term diseases. The reimbursed costs attributable to CVDs were estimated. RESULTS: A total of 3.5 million people (mean age, 71 years; 42% women) were reimbursed by the general health scheme for CVDs (standardized rate, 6.5%; coronary heart disease, 2.7%; arrhythmias/conduction disorders, 2.1%; stroke, 1.1%; heart failure, 1.1%). These frequencies increased with age and social deprivation, and were higher in Northern and Eastern France and Réunion Island. The total sum reimbursed by all schemes for CVDs was € 15.1 billion (50% for hospital care and 43% for outpatient care [including 15% for drugs and 12% for nurses/physiotherapists]); coronary heart disease accounted for € 4 billion, stroke for € 3.5 billion and heart failure for € 2.5 billion (i.e. 10% of the total expenditure reimbursed by all national health insurance schemes for all conditions). CONCLUSION: CVDs constitute the leading group in terms of numbers of patients reimbursed and total reimbursed expenditure, despite a probable underestimation of both numbers and expenditure.