Estimating the impact of single pill combination therapy for hypertension: projections of patient outcomes in Italy.

INTRODUCTION: Hypertension affects almost a third of the Italian population and is a major risk factor for cardiovascular disease. Management of hypertension is often hindered by poor adherence to complex treatment regimens. This analysis aimed to estimate the 10-year clinical outcomes associated with single pill combination (SPC) therapies compared with other treatment pathways for the management of hypertension in Italy. METHODS: A microsimulation modeling approach was used to project health outcomes over a 10-year period for people with hypertension. Input data for four treatment pathways [current treatment practices (CTP), single drug with dosage titration then sequential addition of other agents (start low and go slow, SLGS), free choice combination with multiple pills (FCC) and SPC] were sourced from the Global Burden of Disease 2017 data set. The model simulated clinical outcomes for 1 000 000 individuals in each treatment pathway, including mortality, chronic kidney disease (CKD), stroke, ischemic heart disease (IHD) and disability-adjusted life years (DALYs). RESULTS: Through improved adherence, SPC was projected to improve clinical outcomes versus CTP, SLGS, and FCC. SPC was associated with reductions in mortality, incidence of clinical events, and DALYs versus CTP of 5.4%, 11.5%, and 5.7%, respectively. SLGS and FCC were associated with improvements in clinical outcomes versus CTP, but smaller improvements than those associated with SPC. CONCLUSIONS: Over 10 years, combination therapies (including SPC and FCC) were projected to reduce the burden of hypertension compared with conventional management approaches in Italy. Due to higher adherence, SPC was associated with the greatest overall benefits versus other regimens.

A drug utilization study of thiocolchicoside-containing medicinal products for systemic use in France and Italy: A cross-sectional electronic medical records database study.

PURPOSE: The risk minimization measures (RMM) for systemic use of thiocolchicoside (TCC) was implemented across Europe during 2014-2016. RMM included restriction of use in age <16 years, maximum dose and duration, chronic conditions, contraindication in pregnancy, lactation or in women of childbearing potential [WOCBP] without appropriate contraception. The current Drug Utilization Study was aimed to describe the prescribing practices of TCC in France and Italy. METHOD: The study analyzed data (demographic, prescription, diagnosis, and concomitant treatment) from electronic medical record databases. It compares drug utilization during pre-implementation (baseline: year 2013) and post-implementation (years 1, 2, and 3) of RMM. This study included panels of general practitioners (FGP) and rheumatologists (FRH) in France and Italy (IGP). RESULTS: TCC was largely prescribed as adjuvant therapy in both pre-implementation (FGP: 93.5%, FRH: 88.8%, IGP: 86.6%) and post-implementation (FGP: 92.3%, FRH: 89.5%, IGP: 89.0%) periods. Prescribing patterns were different in France and Italy, with FGP and FRH mainly prescribing oral formulation (>95% and >80%, respectively), while IGP prescribing intramuscular formulation (>70%). Prescriptions to patients aged ≥16 years were >99% in all panels during both periods. An improvement was observed in compliance with treatment duration for oral formulation in the FGP panel post-implementation versus pre-implementation (66.2% vs. 46.7%; p < 0.001). There was no change in prescription rate post RMM implementation in pregnant (FGP: 0.5%, IGP: 4.7%) and in WOCBP without appropriate contraception (FGP: 89.3%, IGP: 93.4%). CONCLUSION: These results highlighted changes in prescribing practices of TCC after RMM implementation, which varied across panels and measures.

Projected impact of treatment intensification with statin, ezetimibe, and statin plus ezetimibe fixed-dose combination on MACE across six countries.

AIMS: The 2019 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) dyslipidaemia guidelines recommend achievement of low-density lipoprotein cholestrol (LDL-C) goals based on an individual's risk. We aimed to evaluate the impact of guideline adoption with statin, ezetimibe, and statin plus ezetimibe fixed-dose combination (FDC) on LDL-C goal achievement and incidence of major adverse cardiovascular events (MACE) across six countries. METHODS AND RESULTS: A simulation model with a five-year horizon (2020-2024) was developed based on Institute for Health Metrics and Evaluation Global Burden of Disease Study database with a business-as-usual (BAU) scenario representing status quo, intervention scenario-1 representing treatment with statin and ezetimibe as separate agents, and intervention scenario-2 representing treatment with statin or statin plus ezetimibe FDC. MACE was defined as the composite of myocardial infarction, ischaemic stroke, and cardiovascular death. The mean population LDL-C was reduced from 4.25 mmol/L in the BAU scenario, to 3.65 mmol/L and 3.59 mmol/L in intervention scenarios-1 and -2, respectively. Compared with BAU, intervention scenarios-1 and-2 resulted in relative reduction of MACE by 5.4% and 6.4% representing ∼3.7 and 4.4 million MACE averted, respectively, across six countries over 5 years. The absolute benefit in terms of MACE averted was highest for China, whereas France had highest relative reduction in MACE with both intervention scenarios compared with BAU. CONCLUSION: The 2019 ESC/EAS guideline-based treatment intensification with strategies based on statin, ezetimibe, and statin plus ezetimibe FDC is estimated to result in a substantial population-level benefit in terms of MACE averted compared with BAU.

Effectiveness of risk minimization measures for valproate: a drug utilization study based on implementation of a risk minimization programme in Europe, analysis of data from the UK.

OBJECTIVE: Since 2014, valproate has not been recommended for use in girls and women of childbearing potential unless other treatments are ineffective or not tolerated. Risk minimization measures (RMMs) of valproate were implemented to reduce the potential risks of developmental disorders among pregnant women. A drug utilization study was carried out to assess the effectiveness of RMMs. METHODS: This was a multinational, non-interventional cohort study. For the UK, existing data from the Clinical Practice Research Datalink database were used. The primary study endpoint was a change in the proportion of valproate initiations preceded by other medications relevant for valproate indications before and after implementation of RMMs. RESULTS: The proportion of valproate initiations preceded by medications related to valproate indications increased after RMM implementation in incident female users in the UK from 66.4% to 72.4%. The proportion of incident prescriptions for epilepsy and bipolar disorder with prior medication related to valproate indications increased, from 36.2% to 44.1% and 72.9% to 77.8%, respectively. The incidence rate of valproate-exposed pregnancies decreased from 16.9 to 10.9 per 1000 person-years in the pre- and post-implementation periods, respectively. CONCLUSIONS: Results from this study indicated some improvement in physician prescribing and a potential reduction in valproate-exposed pregnancies in the UK. Given only modest improvement has been achieved, additional RMMs were implemented in 2018.

Projecting the long-term benefits of single pill combination therapy for patients with hypertension in five countries.

OBJECTIVE: To project the 10-year clinical outcomes associated with single pill combination (SPC) therapies compared with multi-pill regimens for the management of hypertension in five countries (Italy, Russia, China, South Korea and Mexico). METHODS: A microsimulation model was designed to project health outcomes between 2020 and 2030 for populations with hypertension managed according to four different treatment pathways: current treatment practices (CTP), single drug with dosage titration then sequential addition of other agents (start low and go slow, SLGS), free choice combination with multiple pills (FCC) and combination therapy in the form of a single pill (SPC). Model inputs were derived from the Global Burden of Disease 2017 dataset. Simulated outcomes of mortality, chronic kidney disease (CKD), stroke, ischemic heart disease (IHD), and disability-adjusted life years (DALYs) were estimated for 1,000,000 patients on each treatment pathway. RESULTS: SPC therapy was projected to improve clinical outcomes over SLGS, FCC and CTP in all countries. SPC reduced mortality by 5.4% in Italy, 4.9% in Russia, 4.5% in China, 2.3% in South Korea and 3.6% in Mexico versus CTP and showed greater reductions in mortality than SLGS and FCC. The projected incidence of clinical events was reduced by 11.5% in Italy, 9.2% in Russia, 8.4% in China, 4.9% in South Korea and 6.7% in Mexico for SPC versus CTP. CONCLUSIONS: Ten-year projections indicated that combination therapies (FCC and SPC) are likely to reduce the burden of hypertension compared with conventional management approaches, with SPC showing the greatest overall benefits due to improved adherence.

Cost-effectiveness of the COPD Patient Management European Trial home-based disease management program.

Purpose: Efficient management of COPD represents an international challenge. Effective management strategies within the means of limited health care budgets are urgently required. This analysis aimed to evaluate the cost-effectiveness of a home-based disease management (DM) intervention vs usual management (UM) in patients from the COPD Patient Management European Trial (COMET). Methods: Cost-effectiveness was evaluated in 319 intention-to-treat patients over 12 months in COMET. The analysis captured unplanned all-cause hospitalization days, mortality, and quality-adjusted life expectancy. Costs were evaluated from a National Health Service perspective for France, Germany, and Spain, and in a pooled analysis, and were expressed in 2015 Euros (EUR). Quality of life was assessed using the 15D health-related quality-of-life instrument and mapped to utility scores. Results: Home-based DM was associated with improved mortality and quality-adjusted life expectancy. DM and UM were associated with equivalent direct costs (DM reduced costs by EUR -37 per patient per year) in the pooled analysis. DM was associated with lower costs in France (EUR -806 per patient per year) and Spain (EUR -51 per patient per year), but higher costs in Germany (EUR 391 per patient per year). Evaluation of cost per death avoided and cost per quality-adjusted life year (QALY) gained showed that DM was dominant (more QALYs and cost saving) in France and Spain, and cost-effective in Germany vs UM. Nonparametric bootstrapping analysis, assuming a willingness-to-pay threshold of EUR 20,000 per QALY gained, indicated that the probability of home-based DM being cost-effective vs UM was 87.7% in France, 81.5% in Spain, and 75.9% in Germany. Conclusion: Home-based DM improved clinical outcomes at equivalent cost vs UM in France and Spain, and in the pooled analysis. DM was cost-effective in Germany with an incremental cost-effectiveness ratio of EUR 2,541 per QALY gained. The COMET home-based DM intervention could represent an attractive alternative to UM for European health care payers.

TRANSCULTURALIZATION RECOMMENDATIONS FOR DEVELOPING LATIN AMERICAN CLINICAL PRACTICE ALGORITHMS IN ENDOCRINOLOGY--PROCEEDINGS OF THE 2015 PAN-AMERICAN WORKSHOP BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY.

The American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE) convened their first Workshop for recommendations to optimize Clinical Practice Algorithm (CPA) development for Latin America (LA) in diabetes (focusing on glycemic control), obesity (focusing on weight loss), thyroid (focusing on thyroid nodule diagnostics), and bone (focusing on postmenopausal osteoporosis) on February 28, 2015, in San Jose, Costa Rica. A standardized methodology is presented incorporating various transculturalization factors: resource availability (including imaging equipment and approved pharmaceuticals), health care professional and patient preferences, lifestyle variables, socio-economic parameters, web-based global accessibility, electronic implementation, and need for validation protocols. A standardized CPA template with node-specific recommendations to assist the local transculturalization process is provided. Participants unanimously agreed on the following five overarching principles for LA: (1) there is only one level of optimal endocrine care, (2) hemoglobin A1C should be utilized at every level of diabetes care, (3) nutrition education and increased pharmaceutical options are necessary to optimize the obesity care model, (4) quality neck ultrasound must be part of an optimal thyroid nodule care model, and (5) more scientific evidence is needed on osteoporosis prevalence and cost to justify intervention by governmental health care authorities. This 2015 AACE/ACE Workshop marks the beginning of a structured activity that assists local experts in creating culturally sensitive, evidence-based, and easy-to-implement tools for optimizing endocrine care on a global scale.

Public health impact of human papillomavirus vaccination on prevention of cervical cancer in France.

OBJECTIVE: To evaluate the cervical cancer (CC) reduction at individual and population level following different prevention strategies (age-specific vaccination and/or screening) in France. METHODS: A lifetime Markov model was constructed with 11 health states covering the progression from human papillomavirus (HPV) infection to the development of precancerous lesions, CC and death. A screening module took into account the effects of detection and early treatment. Cohorts of girls were entered into the model at age 11 years; the model was run for 95 years using one-year cycles. RESULTS: Vaccination combined with screening substantially reduced the incidence of precancerous lesions and CC compared with screening alone. Vaccination was beneficial regardless of age at vaccination, but the greatest benefit was obtained with an early vaccination. The clinical results were the best for vaccination at 11-13 years when lifetime horizon was considered, and for vaccination at 15-17 years for shorter observation period. CONCLUSION: The model results indicate that HPV vaccination offers additional protection against CC when combined with screening. The optimum starting age for vaccination varies depending on the observation period duration.

Air pollution and doctors' house calls for respiratory diseases in the Greater Paris area (2000-3).

This study describes the short-term relationships between the daily levels of PM10, PM2.5, NO2 and the number of doctors' house calls for asthma, upper respiratory diseases (URD) and lower respiratory diseases (LRD) in Greater Paris for the years 2000-3. Doctors' house calls are a relevant health indicator for the study of short-term health effects of air pollution. Indeed, it is potentially more sensitive than indicators such as general hospital admissions due to the severity of diseases motivating the call. In this study, time-series analysis was used. The daily numbers of doctor's house calls were adjusted for time trends, seasonal factors, day of the week, influenza, weather and pollen. Up to 15 days of lag between exposure and health effects was considered using distributed lag models. A total of about 1,760,000 doctors' house calls for all causes occurred during the study period, among which 8027 were for asthma, 52,928 for LRD and 74,845 for URD. No significant increase in risk was found between air pollution and doctors' house calls for asthma. No significant association was found between NO2 and doctors' house calls. An increase of 10 microg/m3 in the mean levels of PM10 and PM2.5 encountered during the 3 previous days was associated with an increase of 3% (0.8% and 5.3%) and 5.9% (2.9% and 9.0%) in the number of doctor's house calls for URD and LRD, respectively. Considering up to 15 days between exposure and health outcomes, effects persist until 4 days after exposure and then decrease progressively. No morbidity displacement was observed. This study shows a significant heath effect of ambient particles (PM2.5 and PM10). When compared to the RRs obtained for mortality or hospital admissions in the same area, the values of the RRs obtained in this study confirm the higher sensibility of doctor's house calls for respiratory diseases as a health indicator.

Meningitis due to Capnocytophaga canimorsus: contribution of 16S RNA ribosomal sequencing for species identification.

We report a case of Capnocytophaga canimorsus meningitis, which is distinguishable from previous reports by the use of 16S rRNA sequencing for species identification. Our case report highlights the interest of molecular new tools for bacteriological diagnosis of human infections.