Geographical Variation in Medication Prescriptions: A Multiregional Drug-Utilization Study

Background: Studies have emphasized the importance of geographical factors and general practitioner (GP) characteristics in influencing drug prescriptions. Objectives: To: (i) ascertain the prevalence rate (PR) of use of drugs in six therapeutic categories used for chronic conditions; (ii) assess how geographical characteristics and GP characteristics may influence drug prescribing. Methods: This study is part of the EDU.RE.DRUG Project, a national collaborative project founded by Italian Medicine Agency (AIFA). Cross-sectional analyses were undertaken employing the pharmacy-claim databases of four local health units (LHUs) located in two Italian regions: Lombardy and Campania. Six drug categories were evaluated: proton-pump inhibitors; antibiotics; respiratory-system drugs; statins; agents acting on the renin 12angiotensin system; psychoanaleptic drugs. The PR was estimated according to drug categories at the LHU level. A linear multivariate regression analysis was undertaken to evaluate the association between the PR and geographical area, age and sex of GPs, number of patients, and percentage of patients aged >65 per GP. Results: LHUs in Campania showed a PR that was significantly higher than that in Lombardy. Antibiotics showed the highest PR in all the LHUs assessed, ranging from 32.5% in Lecco (Lombardy) to 59.7% in Naples-2 (Campania). Multivariate linear regression analysis confirmed the association of the PR with geographical area for all drug categories. Being located in Campania increased the possibility of receiving a drug prescription from the categories considered, with estimates more marked for antibiotics, proton-pump-inhibitors, and respiratory-system drugs. Conclusions: This study provides information about the PR of medications used for treating common and costly conditions in Italy and highlighted a significant geographical variation. These insights could help to develop area-specific strategies to optimize prescribing behavior

Impact of the COVID-19 Pandemic on the Therapeutic Continuity among Outpatients with Chronic Cardiovascular Therapies

The COVID-19 pandemic poses major challenges to healthcare systems. We aimed to investigate the impact of the pandemic on prescription and adherence patterns of chronic cardiovascular therapies (lipid-lowering [LL], oral antidiabetic drugs [AD], and antihypertensives [AH]) using administrative pharmaceutical databases. For each treatment, two cohorts of prevalent cases in 2019 and 2020 were compared. We evaluated the percentage change in dispensed packages and treatment adherence as a proportion of days covered (PDC). For all therapies, an increase was observed during March–April 2020 (LL: +4.52%; AD: +2.72%; AH: +1.09%), with a sharp decrease in May–June 2020 (LL: −8.40%; AD: −12.09%; AH: −10.54%) compared to 2019. The impact of the COVID-19 pandemic on chronic cardiovascular treatments appears negligible on adherence: 533,414 patients showed high adherence to LL (PDC ≥ 80%) in January–February 2020, and 2.29% became poorly adherent (PDC < 20%) in the following four-month period (vs. 1.98% in 2019). A similar increase was also observed for AH (1.25% with poor adherence in 2020 vs. 0.93% in 2019). For AD, the increase was restrained (1.55% with poor adherence in 2020 vs. 1.37% in 2019). The rush to supply drugs at the beginning of lockdown preserved the continuity of chronic cardiovascular therapies

Sex-differences in factors and outcomes associated with adherence to statin therapy in primary care: need for customisation strategies

Despite the invaluable efficacy of statins, adherence to therapy is extremely poor in clinical practice. Improvement interventions should be as personalized as possible, but it is necessary to know factors that most influence adherence, and sex seems to be a key determinant. Thus, we aimed at exploring potential areas of sex-differences in statin adherence in a real-world population. For this purpose, we assessed adherence (as proportion of days covered) on a wide cohort of new statin users aged >40 years, and we evaluated its association with several covariates through sex-stratified log-binomial regression models. In addition, to compare also the benefits of optimal statin adherence in primary prevention of cardiovascular disease between men and women, we implemented sex-stratified Cox proportional hazard models. Our study showed that women are more likely to stop or be less adherent to statin treatment than men. Moreover, we observed significant sex-differences on effect size of several factors associated with adherence that should be taken into consideration for the management of patients. Finally, we observed no significant difference between men and women regarding statin efficacy in terms of reduction of incident hospitalization for ischemic heart disease and/or non-haemorrhagic cerebrovascular disease. These results invoke the responsibility of physicians to a prompt and personalized intervention. Physicians should consider routine screening for non-adherence in their clinical practice, target patients at higher risk of non-adherence, and improved motivation and communication

A pragmatic controlled trial to improve the appropriate prescription of drugs in adult outpatients: Design and rationale of the EDU.RE.DRUG study

Introduction: Pharmacological intervention is an important component of patient care. However, drugs are often inappropriately used. It is necessary for countries to implement strategies to improve the rational use of drugs, including independent information for healthcare professionals and the public, which must be supported by well-trained staff. The primary objectives of the EDU.RE.DRUG (Effectiveness of informative and/or educational interventions aimed at improving the appropriate use of drugs designed for general practitioners and their patients) study are the retrospective evaluation of rates of appropriate prescribing indicators (APIs) and the assessment of the effectiveness of informative and/or educational interventions addressed to general practitioners (GPs) and their patients, aimed at improving prescribing quality and promoting proper drug use. Methods and analysis: This is a prospective, multicentre, open-label, parallel-arm, controlled, pragmatic trial directed to GPs and their patients in two Italian regions (Campania and Lombardy). The study data are retrieved from administrative databases (Demographic, Pharmacy-refill, and Hospitalization databases) containing healthcare information of all beneficiaries of the National Health Service in the Local Health Units (LHUs) involved. According to LHU, the GPs/patients will be assigned to one of the following four intervention arms: (1) intervention on GPs and patients; (2) intervention on GPs; (3) intervention on patients; and (4) no intervention (control). The intervention designed for GPs consists of reports regarding the status of their patients according to the APIs determined at baseline and in two on-line Continuous Medical Education (CME) courses. The intervention designed for patients consists in flyers and posters distributed in GPs ambulatories and community pharmacies, focusing on correct drug use. A set of indicators (such as potential drug–drug interactions, unnecessary duplicate prescriptions, and inappropriate prescriptions in the elderly), adapted to the Italian setting, has been defined to determine inappropriate prescription at baseline and after the intervention phase. The primary outcome was a composite API. Ethics and dissemination: The study was approved by the Ethics Committee of the University of Milan on 7th June 2017 (code 15/17). The investigators will communicate trial results to stakeholders, collaborators, and participants via appropriate presentations and publications. Registration details: NCT04030468. EudraCT number 2017-002622-2

Twelve Variants Polygenic Score for Low-Density Lipoprotein Cholesterol Distribution in a Large Cohort of Patients With Clinically Diagnosed Familial Hypercholesterolemia With or Without Causative Mutations

BACKGROUND: A significant proportion of individuals clinically diagnosed with familial hypercholesterolemia (FH), but without any disease-causing mutation, are likely to have polygenic hypercholesterolemia. We evaluated the distribution of a polygenic risk score, consisting of 12 low-density lipoprotein cholesterol (LDL-C)- raising variants (polygenic LDL-C risk score), in subjects with a clinical diagnosis of FH. METHODS AND RESULTS: Within the Lipid Transport Disorders Italian Genetic Network (LIPIGEN) study, 875 patients who were FH-mutation positive (women, 54.75%; mean age, 42.47±15.00 years) and 644 patients who were FH-mutation negative (women, 54.21%; mean age, 49.73±13.54 years) were evaluated. Patients who were FH-mutation negative had lower mean levels of pretreatment LDL-C than patients who were FH-mutation positive (217.14±55.49 versus 270.52±68.59 mg/dL, P<0.0001). The mean value (±SD) of the polygenic LDL-C risk score was 1.00 (±0.18) in patients who were FH-mutation negative and 0.94 (±0.20) in patients who were FH-mutation positive (P<0.0001). In the receiver operating characteristic analysis, the area under the curve for recognizing subjects characterized by polygenic hypercholesterolemia was 0.59 (95% CI, 0.56–0.62), with sensitivity and specificity being 78% and 36%, respectively, at 0.905 as a cutoff value. Higher mean polygenic LDL-C risk score levels were observed among patients who were FH-mutation negative having pretreatment LDL-C levels in the range of 150 to 350 mg/dL (150–249 mg/dL: 1.01 versus 0.91, P<0.0001; 250–349 mg/dL: 1.02 versus 0.95, P=0.0001). A positive correlation between polygenic LDL-C risk score and pretreatment LDL-C levels was observed among patients with FH independently of the presence of causative mutations. CONCLUSIONS: This analysis confirms the role of polymorphisms in modulating LDL-C levels, even in patients with genetically confirmed FH. More data are needed to support the use of the polygenic score in routine clinical practice

Lipoprotein(a) Genotype Influences the Clinical Diagnosis of Familial Hypercholesterolemia

Background Evidence suggests that LPA risk genotypes are a possible contributor to the clinical diagnosis of familial hypercholesterolemia (FH). This study aimed at determining the prevalence of LPA risk variants in adult individuals with FH enrolled in the Italian LIPIGEN (Lipid Transport Disorders Italian Genetic Network) study, with (FH/M+) or without (FH/M-) a causative genetic variant. Methods and Results An lp(a) [lipoprotein(a)] genetic score was calculated by summing the number risk-increasing alleles inherited at rs3798220 and rs10455872 variants. Overall, in the 4.6% of 1695 patients with clinically diagnosed FH, the phenotype was not explained by a monogenic or polygenic cause but by genotype associated with high lp(a) levels. Among 765 subjects with FH/M- and 930 subjects with FH/M+, 133 (17.4%) and 95 (10.2%) were characterized by 1 copy of either rs10455872 or rs3798220 or 2 copies of either rs10455872 or rs3798220 (lp(a) score ≥1). Subjects with FH/M- also had lower mean levels of pretreatment low-density lipoprotein cholesterol than individuals with FH/M+ (t test for difference in means between FH/M- and FH/M+ groups <0.0001); however, subjects with FH/M- and lp(a) score ≥1 had higher mean (SD) pretreatment low-density lipoprotein cholesterol levels (223.47 [50.40] mg/dL) compared with subjects with FH/M- and lp(a) score=0 (219.38 [54.54] mg/dL for), although not statistically significant. The adjustment of low-density lipoprotein cholesterol levels based on lp(a) concentration reduced from 68% to 42% the proportion of subjects with low-density lipoprotein cholesterol level ≥190 mg/dL (or from 68% to 50%, considering a more conservative formula). Conclusions Our study supports the importance of measuring lp(a) to perform the diagnosis of FH appropriately and to exclude that the observed phenotype is driven by elevated levels of lp(a) before performing the genetic test for FH

Erythrocytes nuclear abnormalities and leukocyte profile of the immune system of Adélie penguins (Pygoscelis adeliae) breeding at Edmonson Point, Ross Sea, Antarctica

Antarctic seabirds well adapted to extreme environments often deal during their life cycle with sub-optimal conditions and occasionally with severe environmental stress. Climate changes, pollution, habitat loss, increasing human presence can all significantly affect organism's health status from molecular to individual up to population level. In the present study, erythrocyte nuclear abnormalities (ENAs) and white blood cells (WBCs) differential were investigated in 19 adults of Adelie penguin (Pygoscelisadeliae) breeding at Edmonson Point, Antarctic Specially Protected Area (ASPA n. 165) in the Ross Sea. Micronuclei (MN) accounted for 10.50% of observed abnormalities in penguin erythrocytes while kidney-shaped nucleus (KSN) was the most abundant (20.88%). Heterophils (HE) were the most common WBC (36.93%) in agreement with the generic avian leukocytes profile while eosinophils (EO) were the lowest (7.45%). A low number of lymphocytes were detected resulting in a higher heterophils to lymphocytes ratio. ENAs and H:L ratio are confirmed as reliable indexes of penguin's health status since they reflect their individual adaptation during breeding season. These baseline data will be useful for future studies as indicators of penguin's health status mainly as response to environmental changes

The Italian Museo Nazionale dell’Antartide

These abstract proceedings were produced based on the program for the POLAR2018 SCAR/IASC Open Science Conference, updated until 25 May 2018

Evaluation of the performance of Dutch Lipid Clinic Network score in an Italian FH population: The LIPIGEN study

Background and aims: Familial hypercholesterolemia (FH) is an inherited disorder characterized by high levels of blood cholesterol from birth and premature coronary heart disease. Thus, the identification of FH patients is crucial to prevent or delay the onset of cardiovascular events, and the availability of a tool helping with the diagnosis in the setting of general medicine is essential to improve FH patient identification.Methods: This study evaluated the performance of the Dutch Lipid Clinic Network (DLCN) score in FH patients enrolled in the LIPIGEN study, an Italian integrated network aimed at improving the identification of patients with genetic dyslipidaemias, including FH.Results: The DLCN score was applied on a sample of 1377 adults (mean age 42.9 +/- 14.2 years) with genetic diagnosis of FH, resulting in 28.5% of the sample classified as probable FH and 37.9% as classified definite FH. Among these subjects, 43.4% had at least one missing data out of 8, and about 10.0% had 4 missing data or more. When analyzed based on the type of missing data, a higher percentage of subjects with at least 1 missing data in the clinical history or physical examination was classified as possible FH (DLCN score 3-5). We also found that using real or estimated pre-treatment LDL-C levels may significantly modify the DLCN score.Conclusions: Although the DLCN score is a useful tool for physicians in the diagnosis of FH, it may be limited by the complexity to retrieve all the essential information, suggesting a crucial role of the clinical judgement in the identification of FH subjects