Soy isoflavones, lactobacilli, vitamin D3 and calcium. Observational study in menopause

An observational study in clinical practice was carried out to draw an updated profile on the actual trend in menopause management and to detect the clinical activity of a new phytoestrogen. Each gynaecologist observed up to 10 consecutive menopause women, and collected the data concerning history, life style, past and actual treatments, HRT refusal/withdrawal, current therapy, symptoms, visits/exams in the previous 3 months, through the website www.estronet.net, by a confidential and protected individual access. The 181 gynaecologists collected a sample of 1398 menopause women of which 607 not treated, 327 on estrogens, and 464 on phytoestrogens. The most used phytoestrogen in the study (87.1%) contains genistin and daidzin (30+30 mg) + lactobacilli, Ca and vit. D3 (Estromineral, EM) and was administered to 392 women (aged 54.1 years, BMI 24.8) for 112.9 days (mean) up to 1 year. Menopause symptoms improved on EM independently from their baseline severity and the improvement increased with treatment duration: flushing improved up to 96.2% at 1 year; nocturnal sweating 100%, palpitations 63.6%, and vaginal dryness 56%. Tumour fear, absence of symptoms and fear of weight gain were the most frequent reasons for refusal/withdrawal of HRT. Women treated (HRT or phytoestrogens) were more controlled both before and during the treatment. In presence of concomitant clinical conditions, EM was preferred. Phytoestrogens plus lactobacilli and mineral supplement showed a satisfactory clinical activity and safety

[Cost-effectiveness analysis of delayed-release dimethyl-fumarate in the treatment of relapsing-remitting multiple sclerosis in Italy]

INTRODUCTION: Disease Modifying Therapies (DMTs) have significantly improved clinical conditions of Relapsing Remitting Multiple Sclerosis (RRMS) patients. However, several unmet needs are still relevant in RRMS. Recently, a new therapy, delayed-release dimethyl-fumarate (DMF; also known as gastro-resistant DMF), has been approved and reimbursed by the Italian Drug Agency (AIFA) for the treatment of RRMS.OBJECTIVE: To compare the cost-effectiveness of DMF vs. pharmacological alternatives indicated for the first-line treatment of RRMS in Italy.METHODS: The analysis was conducted from the perspective of the Italian National Healthcare Service (NHS) and outcomes and costs were evaluated over a 50-year time horizon (equivalent to a lifetime horizon). Both outcomes and costs were discounted at 3.5%. The Markov model estimates the clinical and economic consequences of treating RRMS patients with the following therapeutic options: DMF, interferon (IFN) beta-1a intramuscular (IM); IFN beta-1a subcutaneous (SC) at two different doses, 22 mcg and 44 mcg; IFN beta-1b SC; glatiramer acetate (GA) SC 20 mg; oral teriflunomide. Clinical efficacy data used in this analysis came from an elaboration of the mixed treatment comparison (MTC) already published. According to the Italian NHS perspective, only the following direct costs were considered: pharmacological treatment acquisition, treatment monitoring, relapse management, direct costs associated with disability, adverse event management. Administration costs were assumed equal to €0, because every treatment included in the economic analysis can be self-administered. One-way and probabilistic sensitivity analyses were developed and cost effectiveness acceptability curves generated.RESULTS: In the base-case analysis, DMF was more efficacious than alternatives, in terms of both survival (19.496 vs. 19.297-19.461 discounted LYs, respectively), and QALYs (6.548 vs. 5.172- 6.212 discounted QALYs, respectively). Per-patient lifetime costs with DMF amounted to € 276,500, similarly to the other options. DMF was the drug with the largest effect of disability cost reduction. DMF was dominant vs. IFN beta-1a 44 mcg and cost-effective vs. all other IFNs, GA and teriflunomide, with incremental cost-effectiveness ratio (ICERs) between € 11,272 and € 23,409. All ICER values were lower than the € 50,000 per QALY threshold. One-way sensitivity analysis showed that, for all tested scenarios, ICER of DMF vs. therapeutic alternatives remained favourable (≤ 50.000 €/QALY gained) and the results of probabilistic sensitivity analysis showed that the probability for DMF of being favourable (≤ 50.000 €/QALY gained) was between around 70% and 93%, thus ensuring robustness of the results.CONCLUSIONS: The results of this economic analysis show that, at the current price and the described assumptions, DMF represents a cost-effective option vs. other available first-line treatments indicated in RRMS in the perspective of the Italian NHS.[Article in Italian

Appropriateness of clinical and organizational criteria for intra-articular injection therapies in osteoarthritis. A Delphi method consensus initiative among experts in Italy

OBJECTIVE: The aim of the study was to identify the main aspects involved in patient selection, the choice of therapeutic agents and the safety profile, as well as the medico-legal and organizational aspects of intra-articular injection therapies for osteoarthritis.METHODS: A committee of 10 experts from Italian universities, public hospitals, territorial services, research institutes and patient associations was set up. Fifty-two clinicians from a large number of Italian medical centers specialized in intra-articular injection therapy took part in a Delphi process aimed at obtaining consensus statements among the participants.RESULTS: Large consensus was obtained for statements grouped under the following main themes: treatment indications; drug/medical device choice; treatment efficacy; and appropriate setting.CONCLUSIONS: The consensus statements developed by a large number of experts may be used as a practical reference tool to help physicians treat osteoarthritis patients by means of intra-articular injection therapies

[Tecfidera® (delayed-release dimethylfumarate) in the treatment of relapsing-remitting multiple sclerosis]

The present health technology assessment (HTA) evaluates the clinical and economic profile of delayed-release dimethylfumarate (DMF, also known as gastro-resistant DMF) in the treatment of relapsing-remitting multiple sclerosis (RRMS) in Italy. Chapter 1 briefly introduces the condition (multiple sclerosis and, more specifically, the relapsing-remitting form) and provides an overall description of the main therapeutic options for physicians, in terms of clinical evidence, regulatory status in Europe and approval status and reimbursement (refunding) criteria in Italy. In the next sections (Chapters 2-5), key-topics regarding RRMS are analysed: epidemiology, clinical burden, quality of life/social impact and the economic implications for healthcare services, patients and society. In Chapter 6, the clinical evidence supporting the use of DMF in RRMS is summarized. Data from phase III randomized clinical trials (DEFINE, CONFIRM), plus the pooled post-hoc analysis of the two studies, were evaluated to assess the level of clinical benefit provided by DMF. Finally, in Chapter 7, a review of the health economic evidence assessing DMF is performed, with a specific focus on Italy. Overall, the methodological quality of registration studies, together with the robustness and consistency of the study results, support the conclusion that DMF is an effective and safe treatment for RRMS. The economic assessment of DMF in Italy, based on cost-effectiveness and budget impact analyses (adopting clinical input data from a mixed treatment comparison and economic input data relative to the Italian healthcare setting), confirm that DMF is a cost-effective and economically sustainable treatment for the Italian National Healthcare Service. These findings are in line with the results of most international publications and the assessments from well-recognized HTA agencies (e.g. NICE/SMC). In summary, both the clinical and economic evidence analyzed in this HTA substantiate DMF as an important therapeutic option for the treatment of RRMS

Improvement in the management of chronic obstructive pulmonary disease following a clinical educational program: results from a prospective cohort study in the Sicilian general practice setting

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder of the lungs associated with progressive disability. Although general practitioners (GPs) should play an important role in the COPD management, critical issues have been documented in the primary care setting. The aim of this study was to evaluate the effectiveness of an educational program for the improvement of the COPD management in a Sicilian general practice setting. The effectiveness of the program, was evaluated by comparing 15 quality-of-care indicators developed from data extracted by 33 GPs, at baseline vs. 12 and 24 months, and compared with data from a national primary care database (HSD). Moreover, data on COPD-related and all-cause hospitalizations over time of COPD patients, was measured. Overall, 1,465 patients (3.2%) had a registered diagnosis of COPD at baseline vs. 1,395 (3.0%) and 1,388 (3.0%) over time (vs. 3.0% in HSD). COPD patients with one spirometry registered increased from 59.7% at baseline to 73.0% after two years (vs. 64.8% in HSD). Instead, some quality of care indicators where not modified such as proportion of COPD patients treated with ICS in monotherapy that was almost stable during the study period: 9.6% (baseline) vs. 9.9% (after 2 years), vs. 7.7% in HSD. COPD-related and all-cause hospitalizations of patients affected by COPD decreased during the two observation years (from 6.9% vs. 4.0%; from 23.0% vs. 18.9, respectively). Our study showed that educational program involving specialists, clinical pharmacologists and GPs based on training events and clinical audit may contribute to partly improve both diagnostic and therapeutic management of COPD in primary care setting, despite this effect may vary across GPs and indicators of COPD quality of care

The burden of nephrotoxic drug prescriptions in patients with chronic kidney disease: A Retrospective population-based study in Southern Italy

Background: The use of nephrotoxic drugs can further worsening renal function in chronic kidney disease (CKD) patients. It is therefore imperative to explore prescribing practices that can negatively affect CKD patients. Aim: To analyze the use of nephrotoxic drugs in CKD patients in a general population of Southern Italy during the years 2006-2011. Methods: The general practice "Arianna" database contains data from 158,510 persons, registered with 123 general practitioners (GPs) of Caserta. CKD patients were identified searching: CKD-related ICD-9 CM codes among causes of hospitalization; CKD-relevant procedures undergone in hospital (e.g. dialysis); drug prescriptions issued for a CKD-related indication. A list of nephrotoxic drugs was compiled and validated by pharmacologists and nephrologists. The summary of product characteristics was used to classify drugs as 'contraindicated' or 'to be used with caution' in renal diseases. Frequency of nephrotoxic drug use, overall, by drug class and single compounds, by GPs within one year prior or after first CKD diagnosis and within one year after dialysis entry was calculated. Results: Overall, 1,989 CKD patients and 112 dialysed patients were identified. Among CKD patients, 49.8% and 45.2% received at least one prescription for a contraindicated nephrotoxic drug within one year prior or after first CKD diagnosis, respectively. In detail, 1,119 CKD patients (56.3%) had at least one nonsteroidal anti-inflammatory drugs (NSAIDs) prescription between CKD diagnosis and end of follow-up. A large proportion of CKD patients (35.6%) were treated with NSAIDs for periods exceeding 90 days. Contraindicated nephrotoxic drugs were used commonly in CKD, with nimesulide (16.6%) and diclofenac (11.0%) being most frequently used. Conclusions: Contraindicated nephrotoxic drugs were highly prescribed in CKD patients from a general population of Southern Italy. CKD diagnosis did not seem to reduce significantly the prescription of nephrotoxic drugs, which may increase the risk of preventable renal function deterioration

How Much Are Biosimilars Used in Clinical Practice? A Retrospective Italian Population-Based Study of Erythropoiesis-Stimulating Agents in the Years 2009-2013

Purpose To explore the prescription patterns of erythropoiesis-stimulating agents (ESAs) in four large Italian geographic areas, where different health policy interventions to promote biosimilar use in routine care are undertaken. Methods A retrospective drug utilization study was conducted during the years 2009-2013. The data sources were the administrative databases of the Tuscany region and of the Caserta, Palermo, and Treviso Local Health Units (LHUs). The characteristics, prevalence, and switching patterns of different ESAs (biosimilars and reference products), stratified by indication for use, were calculated over time and across centers. Results Overall, 49,491 patients were treated with ESAs during the years 2009-2013 in the four centers. Of these, 41,286 patients (83.4 %) were naive users. The prevalence of ESA use increased from 2.9 to 3.4 per 1000 inhabitants in the years 2009-2011 but decreased thereafter (3.0 per 1000 in 2013). Moreover, the proportion of biosimilar users increased overall from 1.8 % in 2010 to 33.6 % in 2013, with larger increase in Treviso (from 0.0 to 45.0 %) and Tuscany (from 0.7 to 37.6 %) than in Caserta (from 7.5 to 22.9 %) and Palermo (from 0.0 to 27.7 %). Switching between different ESAs during the first year of therapy was frequent (17.0 %), much more toward reference products than toward biosimilars. Conclusion Overall, the prevalence of ESA use decreased slightly, while use of biosimilar ESAs, especially in naive patients, increased significantly but to different extents in these four large Italian geographic areas. Switching between different ESAs during the first year of treatment was very frequent, which may affect pharmacovigilance monitoring. New strategies are necessary to further improve market penetration of low-cost medicines, such as biosimilars, and also to harmonize effective health policy interventions that aim to reduce pharmaceutical expenses and optimize patient benefit across all regions