Giampiero Mazzaglia

Adherence to Antihypertensive Medications and Cardiovascular Morbidity Among Newly Diagnosed Hypertensive Patients

Background— Nonadherence to antihypertensive treatment is a common problem in cardiovascular prevention and may influence prognosis. We explored predictors of adherence to antihypertensive treatment and the association of adherence with acute cardiovascular events. Methods and Results— Using data obtained from 400 Italian primary care physicians providing information to the Health Search/Thales Database, we selected 18 806 newly diagnosed hypertensive patients ≥35 years of age during the years 2000 to 2001. Subjects included were newly treated for hypertension and initially free of cardiovascular diseases. Patient adherence was subdivided a priori into 3 categories—high (proportion of days covered, ≥80%), intermediate (proportion of days covered, 40% to 79%), and low (proportion of days covered, ≤40%)—and compared with the long-term occurrence of acute cardiovascular events through the use of multivariable models adjusted for demographic factors, comorbidities, and concomitant drug use. At baseline (ie, 6 months after index diagnosis), 8.1%, 40.5%, and 51.4% of patients were classified as having high, intermediate, and low adherence levels, respectively. Multiple drug treatment (odds ratio, 1.62; 95% CI, 1.43 to 1.83), dyslipidemia (odds ratio, 1.52; 95% CI, 1.24 to 1.87), diabetes mellitus (odds ratio, 1.40; 95% CI, 1.15 to 1.71), obesity (odds ratio, 1.50; 95% CI, 1.26 to 1.78), and antihypertensive combination therapy (odds ratio, 1.29; 95% CI, 1.15 to 1.45) were significantly (P<0.001) associated with high adherence to antihypertensive treatment. Compared with their low-adherence counterparts, only high adherers reported a significantly decreased risk of acute cardiovascular events (hazard ratio, 0.62; 95% CI, 0.40 to 0.96; P=0.032). Conclusions— The long-term reduction of acute cardiovascular events associated with high adherence to antihypertensive treatment underscores its importance in assessments of the beneficial effects of evidence-based therapies in the population. An effort focused on early antihypertensive treatment initiation and adherence is likely to provide major benefits.

Combining electronic healthcare databases in Europe to allow for large-scale drug safety monitoring: the EU-ADR Project

In this proof‐of‐concept paper we describe the framework, process, and preliminary results of combining data from European electronic healthcare record (EHR) databases for large‐scale monitoring of drug safety.

Patterns of persistence with antihypertensive medications in newly diagnosed hypertensive patients in Italy: a retrospective cohort study in primary care.

Objective To describe patterns of persistence and related primary care costs associated with first antihypertensive treatment. Design and setting Retrospective cohort study during 2000–2001, using information from 320 Italian general practitioners. Participants We studied 13 303 patients with newly diagnosed hypertension, who received a first single antihypertensive prescription within 3 months after diagnosis. Main outcome measures Persistence with first-line single treatment, categorized as follows: continuers: patients continuing the first-line medication for at least 1 year; combiners: patients receiving an additional antihypertensive drug and continuing the initial medication; switchers: patients changing from the first-line to another class of antihypertensive drug and discontinuing the initial treatment; discontinuers: patients stopping the first-line treatment without having another prescription until the end of the follow-up. Primary care costs were expressed as the cost of hypertension management per person-year of follow-up. Results In the study cohort, 19.8% were continuers, 22.1% were combiners, 15.4% were switchers, and 42.6% were discontinuers. Continuation was greatest with angiotensin II type 1 receptor blocking agents (25.2%), calcium channel blockers (23.9%) and angiotensin-converting enzyme inhibitors (23.3%). Severe hypertension [hazards ratio 1.30; 95% confidence interval (CI) 1.18 to 1.43] and severe health status (hazards ratio 1.22; 95% CI 1.15 to 1.30) increased the risk of discontinuation. The likelihood of needing an additional antihypertensive drug was associated with mild-to-severe baseline blood pressure, diabetes (hazards ratio 1.20; 95% CI 1.06 to 1.36), and familial history of cardiovascular disease (hazards ratio 1.24; 95% CI 1.10 to 1.39). Discontinuers accounted for 22.4% of the total primary care cost. Initial treatment with angiotensin II type 1 receptor blocking agents and β-blockers resulted in incremental primary care costs of &U20AC;145.2 and &U20AC;144.2, respectively, compared with diuretics. Combiners and switchers increased the primary care cost by &U20AC;140.1 and &U20AC;11.7, compared with continuers. Conclusion Persistence with first-line single antihypertensive drugs is extremely low during the first year of treatment. Potential cost saving should be possible by reducing the high frequency of discontinuation. Diuretics represent the least expensive therapeutic option, although further investigations in the long-term are needed to analyse the effects of persistence on therapeutic effectiveness and related costs.

Epidemiology of gout and hyperuricaemia in Italy during the years 2005–2009: a nationwide population-based study

Objective To assess the epidemiology of gout and hyperuricaemia in the Italian general population during the years 2005–2009. Methods Using the Italian primary care database (Health Search/CSD Longitudinal Patient Database), the prevalence, incidence and recurrence rates of gout and/or hyperuricaemia (serum urate level >360 mmol/l (6 mg/dl)) in outpatients aged ≥18 years during the years 2005–2009 were estimated. Rates together with 95% CI were measured overall and stratified by age, gender and calendar year. The characteristics of patients with newly diagnosed gout and hyperuricaemia were investigated and compared with the general population. Results The prevalence of gout increased from 6.7 per 1000 inhabitants in 2005 to 9.1 per 1000 inhabitants in 2009. It increased with advancing age and was fourfold higher in men. A similar trend was observed for asymptomatic hyperuricaemia (85.4 per 1000 inhabitants in 2005 vs 119.3 per 1000 inhabitants in 2009). The incidence of gout remained stable during the observation years (0.93 per 1000 person years in 2005 vs 0.95 in 2009). Recurrent episode rate was 19.1% during the first year following the first gout attack and 31.6% during the following 5 years. Advanced age, increased levels of uric acid, nephrolithiasis and concomitant use of ciclosporin were the main predictors of recurrence of gout attacks. Conclusion The prevalence of gout and hyperuricaemia increased in Italy from 2005 to 2009. A high recurrence rate for gout attack was observed during the first year following the first episode. Early management of hyperuricaemia in patients at higher risk of recurrent gout attack should be considered in primary care.

Food deprivation increases brain nitric oxide synthase and depresses brain serotonin levels in rats

We studied nitric oxide (NO) synthase activity and serotonin content in the diencephalon of 24 hr food deprived rats. NO synthase activity was significantly increased whereas serotonin levels together with those of tryptophan and 5-hydroxyindoleacetic acid (5-HIAA) were reduced in food deprived rats when compared to control rats. NG-Nitro-L-arginine (L-NO Arg), an inhibitor of NO synthase, was used as a tool to study the role of NO in food deprivation. Twenty-four hr food deprived male Sprague-Dawley rats were intraperitoneally (i.p.) administered L-NO Arg (12.5, 25 and 50 mg/kg) before food presentation. Control rats received a NaCl (0.9%) solution. Food consumption was monitored 1 and 2 hr after food presentation. L-NO Arg administration produced a dose-dependent reduction in food intake. Pretreatment with metergoline (2 mg/kg) but not with ritanserin (1 mg/kg) antagonized the anorectic effect of L-NO Arg. Moreover, in the diencephalon L-NO Arg significantly reduced NO synthase activity whereas it increased serotonin levels. Our data indicate that NO might have a physiological role in the regulation of food intake and suggest that brain NO may modulate the central serotoninergic system.

Detection and Awareness of Moderate to Advanced CKD by Primary Care Practitioners: A Cross-sectional Study From Italy

BACKGROUND Chronic kidney disease (CKD) is a strong independent predictor of cardiovascular disease. Although general practitioners (GPs) represent the first line for identification of these high-risk patients, their diagnostic approach to CKD is ill defined. STUDY DESIGN Cross-sectional evaluation of database of Italian GPs. SETTING & PARTICIPANTS Representative sample of adult Italian population regularly followed up by GPs in 2003. OUTCOMES Frequency of serum creatinine testing, prevalence of CKD (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m(2)), awareness of CKD assessed from use of diagnostic codes (Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM]) for CKD, and referral to nephrologists. RESULTS Of 451,548 individuals in the entire practice population, only 77,630 (17.2%) underwent serum creatinine testing. Female sex (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.06 to 1.12), advanced age (OR, 2.70; 95% CI, 2.63 to 2.78), diabetes (OR, 1.31; 95% CI, 1.20 to 1.42), hypertension (OR, 1.10; 95% CI, 1.02 to 1.19), autoimmune diseases (OR, 1.42; 95% CI, 1.11 to 1.82), and recurrent urinary tract infections (OR, 1.63; 95% CI, 1.10 to 2.42) were all associated with serum creatinine testing. Conversely, use of either nonsteroidal anti-inflammatory drugs (OR, 1.03; 95% CI, 0.89 to 1.21) or aminoglycosides or contrast media (OR, 0.78; 95% CI, 0.54 to 1.14) was not associated with serum creatinine testing. In the subgroup with serum creatinine data, the age-adjusted prevalence of CKD was 9.33% (11.93% in women, 6.49% in men). However, in patients with eGFR less than 60 mL/min/1.73 m(2), serum creatinine values were apparently normal (<1.2 mg/dL in women, <1.4 mg/dL in men) in 54%, and GPs used ICD-9-CM codes for CKD in only 15.2%. Referral to nephrologists ranged from 4.9% for patients with eGFR of 59 to 30 mL/min/1.73 m(2) to 55.7% for those with eGFR less than 30 mL/min/1.73 m(2). LIMITATIONS The prevalence of decreased kidney function may be overestimated because of the more frequent serum creatinine testing in sicker individuals and lack of creatinine calibration. CONCLUSIONS In primary care, CKD stages 3 to 5 are frequent, but its awareness is scarce because of limited rates of serum creatinine testing and difficulty recognizing decreased eGFR in the absence of increased serum creatinine testing.

Predictive Validity of Measures of Comorbidity in Older Community Dwellers: The Insufficienza Cardiaca negli Anziani Residenti a Dicomano Study

OBJECTIVES: To compare the ability of five measures of comorbidity to predict mortality and incident disability in basic activities of daily living (BADLs) in unselected older persons.

Electronic healthcare databases for active drug safety surveillance: is there enough leverage?

To provide estimates of the number and types of drugs that can be monitored for safety surveillance using electronic healthcare databases.

Chronic disease prevalence from Italian administrative databases in the VALORE project: A validation through comparison of population estimates with general practice databases and national survey

BackgroundAdministrative databases are widely available and have been extensively used to provide estimates of chronic disease prevalence for the purpose of surveillance of both geographical and temporal trends. There are, however, other sources of data available, such as medical records from primary care and national surveys. In this paper we compare disease prevalence estimates obtained from these three different data sources.MethodsData from general practitioners (GP) and administrative transactions for health services were collected from five Italian regions (Veneto, Emilia Romagna, Tuscany, Marche and Sicily) belonging to all the three macroareas of the country (North, Center, South). Crude prevalence estimates were calculated by data source and region for diabetes, ischaemic heart disease, heart failure and chronic obstructive pulmonary disease (COPD). For diabetes and COPD, prevalence estimates were also obtained from a national health survey. When necessary, estimates were adjusted for completeness of data ascertainment.ResultsCrude prevalence estimates of diabetes in administrative databases (range: from 4.8% to 7.1%) were lower than corresponding GP (6.2%-8.5%) and survey-based estimates (5.1%-7.5%). Geographical trends were similar in the three sources and estimates based on treatment were the same, while estimates adjusted for completeness of ascertainment (6.1%-8.8%) were slightly higher. For ischaemic heart disease administrative and GP data sources were fairly consistent, with prevalence ranging from 3.7% to 4.7% and from 3.3% to 4.9%, respectively. In the case of heart failure administrative estimates were consistently higher than GPs’ estimates in all five regions, the highest difference being 1.4% vs 1.1%. For COPD the estimates from administrative data, ranging from 3.1% to 5.2%, fell into the confidence interval of the Survey estimates in four regions, but failed to detect the higher prevalence in the most Southern region (4.0% in administrative data vs 6.8% in survey data). The prevalence estimates for COPD from GP data were consistently higher than the corresponding estimates from the other two sources.ConclusionThis study supports the use of data from Italian administrative databases to estimate geographic differences in population prevalence of ischaemic heart disease, treated diabetes, diabetes mellitus and heart failure. The algorithm for COPD used in this study requires further refinement.

Using electronic health care records for drug safety signal detection: a comparative evaluation of statistical methods.

Background:Drug safety monitoring relies primarily on spontaneous reporting, but electronic health care record databases offer a possible alternative for the detection of adverse drug reactions (ADRs). Objectives:To evaluate the relative performance of different statistical methods for detecting drug-adverse event associations in electronic health care record data representing potential ADRs. Research Design:Data from 7 databases across 3 countries in Europe comprising over 20 million subjects were used to compute the relative risk estimates for drug-event pairs using 10 different methods, including those developed for spontaneous reporting systems, cohort methods such as the longitudinal gamma poisson shrinker, and case-based methods such as case-control. The newly developed method “longitudinal evaluation of observational profiles of adverse events related to drugs” (LEOPARD) was used to remove associations likely caused by protopathic bias. Data from the different databases were combined by pooling of data, and by meta-analysis for random effects. A reference standard of known ADRs and negative controls was created to evaluate the performance of the method. Measures:The area under the curve of the receiver operator characteristic curve was calculated for each method, both with and without LEOPARD filtering. Results:The highest area under the curve (0.83) was achieved by the combination of either longitudinal gamma poisson shrinker or case-control with LEOPARD filtering, but the performance between methods differed little. LEOPARD increased the overall performance, but flagged several known ADRs as caused by protopathic bias. Conclusions:Combinations of methods demonstrate good performance in distinguishing known ADRs from negative controls, and we assume that these could also be used to detect new drug safety signals.