[Innovative medicinal products: the new criteria of the Italian Medicines Agency.] / Farmaci innovativi: i nuovi criteri dell'Agenzia Italiana del Farmaco.

The Italian Medicines Agency (AIFA), which has the dual function of a regulatory and a reimbursement authority, has recently established new criteria to define innovative medicinal products. Indeed, the decision making process to grant the innovative status is based on the evaluation of the unmet medical need, the added therapeutic value compared to existing therapeutic options and the overall quality of clinical evidence, which is assessed based on the GRADE system. Following this evaluation, if a medicinal product is granted the status of "full innovativeness" for a specific therapeutic indication, its manufacturer can access dedicated yearly funds amounting to 500 million Euros each, depending on the type of medicine (one fund for oncology, the other for all other innovative medicinal products). Alternatively, the product can be granted the status of "conditional innovativeness" which allows immediate access to all Regional formularies, with no additional re-assessments at the local level. The third possible outcome is that no innovativeness is recognized. Starting from January 2018, a full report explaining the rationale for the Agency Committee's decision is made publicly available on the AIFA's website.

Effects of hyperpolypharmacy and potentially inappropriate medications (PIMs) on functional decline in older patients discharged from acute care hospitals.

AIM: To comparatively investigate the effects of hyperpolypharmacy and potentially inappropriate medications (PIMs) on functional decline in older patients after hospital discharge. METHODS: Our series consisted of 733 patients aged ≥65 consecutively enrolled in a multicenter observational longitudinal study. PIMs were defined on the basis of updated versions of Beers and STOPP criteria. The occurrence of functional decline was defined as the loss of independency in at least 1 basic activity of daily living (BADL) from discharge through 3-month follow-up visit. RESULTS: After adjusting for several potential confounders, hyperpolypharmacy (OR = 2.20; 95%CI = 1.11-4.37) and Beers violations (OR = 1.99; 95%CI = 1.17-3.49) were significantly associated with functional decline, while STOPP (OR = 1.10; 95%CI = 0.64-1.88) and combined Beers + STOPP violations (OR = 1.72; 95%CI = 0.97-3.05) were not. In logistic regression models simultaneously including both hyperpolypharmacy and PIMs, hyperpolypharmacy was always associated with functional decline (OR = 1.98; 95%CI = 1.0-3.97 in the model including Beers violations; OR = 2.19; 95%CI = 1.11-4.35 in the model including STOPP violations; OR = 2.04; 95%CI = 1.02-4.06 in the model including combined Beers and STOPP violations). Beers violations (OR = 1.89; 95%CI = 1.09-3.28) also remained significantly associated with the outcome in this latter analysis, but not STOPP or combined Beers and STOPP violations. CONCLUSIONS: Hyperpolypharmacy, and to a lesser extent Beers violations predict functional decline in older patients discharged from acute care hospitals, whilst STOPP criteria are no longer associated with the outcome after adjusting for potential confounders. Hyperpolypharmacy is associated with functional decline independent of PIMs.

Advanced Age and Medication Prescription: More Years, Less Medications? A Nationwide Report From the Italian Medicines Agency.

BACKGROUND: In older adults co-occurrence of multiple diseases often leads to use of multiple medications (polypharmacy). The aim of the present study is to describe how prescription of medications varies across age groups, with specific focus on the oldest old. METHODS: We performed a cross-sectional study using 2013 data from the OsMed Health-DB database (mean number of medicines and defined daily doses prescribed in 15,931,642 individuals). There were 3,378,725 individuals age 65 years or older (21.2% of the study sample). RESULTS: The mean number of prescribed medications progressively rose from 1.9 in the age group <65 years to 7.4 in the age group 80-84 years and then declined, with a more marked reduction in the age group 95 years or older with a mean number of 2.8 medications. A similar pattern was observed for the mean number of defined daily doses. Among participants age ≥65 years, proton pump inhibitors were the most commonly prescribed medication (40.9% of individuals ≥65 years), followed by platelet aggregation inhibitors (32.8%) and hydroxy-methylglutaryl-coenzyme A reductase inhibitors (26.1%). A decline in prescription was observed among individuals age 90 years or older, but this reduction was less consistent for medications used to treat acute conditions (ie, antibiotics and glucocorticoids) rather than preventive medicines commonly used to treat chronic diseases (ie, antihypertensive medications and hydroxy-methylglutaryl-coenzyme A reductase inhibitors). CONCLUSIONS: The burden of medication treatment progressively increases till age 85 and substantially declines after age of 90 years. Patterns of medication prescription widely vary across age groups.

Adherence to Selective Serotonin and Serotonin-Norepinephrine Reuptake Inhibitor Prescriptions Affects Overall Medication Adherence in Older Persons: Evidence From the Italian Nationwide OsMed Health-DB Database.

OBJECTIVE: This study aimed to evaluate prevalence of prescription of and adherence to selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) and whether adherence to these classes of drugs affects overall medication adherence in older persons. METHODS: In a cross-sectional analysis of administrative data comprehensive of all prescribed drugs reimbursed by the Italian national health care system, new prescriptions of SSRIs and SNRIs to persons aged 65 years or older were analyzed (n = 380,400 in 2011; 395,806 in 2012; 409,741 in 2013, from a total sample of 3,762,299 persons aged 65 years or older) as well as prescriptions of antihypertensives, statins, other psychiatric drugs, antidiabetics, antiplatelets, anticoagulants, drugs for chronic obstructive pulmonary disease, and antiosteoporotics. Adherence was estimated by calculating the proportion of days covered by drugs dispensed during a period of 365 days. Adherence was defined as a proportion of days covered of more than 80%. RESULTS: Prevalence of SSRI and SNRI prescriptions varied from 11.4% in 2011 to 12.1% in 2013. Adherence to SSRI and SNRI prescriptions ranged from 31.2% in persons aged ≥ 95 years in 2011 to 41.8% in persons aged 75-84 years in 2013. Persons adherent to SSRI and SNRI prescriptions were more likely to be adherent to the other medications, after adjustment for age, gender, and number of drugs prescribed. The highest association was found for adherence to psychiatric drugs (OR = 1.9; 95% CI, 1.8-2.0). CONCLUSIONS: Adherence to SSRI and SNRI prescriptions is poor in older persons. However, people adherent to these classes of antidepressants are more likely to be adherent to the other medications they are prescribed. Studies are needed to evaluate the reasons for and the potential benefits of increasing adherence to antidepressants on overall adherence.

INSULIN-LIKE GROWTH FACTOR-1 AND ANEMIA IN OLDER SUBJECTS: THE INCHIANTI STUDY.

OBJECTIVE: Recent studies indicate a role for the age-related decline of anabolic hormones, especially testosterone, in the onset of "anemia of aging." Some of testosterone's erythropoietic activities are mediated by insulin-like growth factor (IGF)-1, which also seems to have independent erythropoietic effects. However, the associations among IGF-1, anemia, and hemoglobin (Hb) have not been adequately investigated in older populations. METHODS: We used data from a representative sample of 953 subjects ≥65 years who participated in the InCHIANTI (Invecchiare in Chianti) Study and were not on growth hormone (GH) or erythropoietin therapy and were not diagnosed with hematologic malignancies or other cancers. Anemia was defined according to the World Health Organization (WHO) criteria by Hb level ≤13 g/dL in males and ≤12 g/dL in females. Backward multiple regression analyses including age, IGF binding protein (IGFBP)-3, testosterone, comorbidities, inflammatory markers, and anemia-related measures were used to address the relationship between IGF-1 and Hb and between IGF-1 and anemia in both sexes. RESULTS: We found that 46/410 (11.2%) males and 71/543 (13.0%) females were defined as anemic. After adjustment for age, anemic males (100 ± 54 vs. 130 ± 56, P<.001) and females (89.1 ± 48 vs. 110 ± 52, P = .001) exhibited lower IGF-1 levels than their nonanemic counterparts. IGF-1 levels were independently and negatively associated with anemia in males (ß ± SE = -0.0005 ± 0.0002, P = .04) but not in females (ß ± SE = -0.0002 ± 0.0002, P = .40). In both males (ß ± SE = 0.002 ± 0.001, P = .03) and females (ß ± SE = 0.002 ± 0.0009, P = .03), IGF-1 levels were independently and positively associated with Hb levels. CONCLUSION: In older males but not in females, IGF-1 levels are negatively associated with anemia. IGF-1 levels are independent and positive determinants of Hb concentration in both sexes.