Performance of the Multidimensional Geriatric Assessment and Multidimensional Prognostic Index in predicting negative outcomes in older adults with cancer.

The Multidimensional Geriatric Assessment (MGA) is currently used for assessing geriatric oncological patients, but a new prognostic index - the Multidimensional Prognostic Index (MPI) - has a demonstrated prognostic value in cancer patients too. The present work was designed to compare the MPI and MGA as predictors of 12-month mortality. 160 patients ≥70 years old with locally-advanced or metastatic solid cancers consecutively joining our Geriatric Oncology Program were administered a Comprehensive Geriatric Assessment to calculate their MGA and MPI scores. SETTINGS: Geriatric Clinic, Geriatric Surgery Clinic, Medical Oncology Unit, Padova Hospital, Italy. Using Cohen's Kappa coefficient, there was a poor concordance between the MPI and MGA. Severe MPI being associated with a higher mortality risk than Frail in the MGA. The ROC curves indicated that the MPI had a greater discriminatory power for 12-month mortality than the MGA. In our population of elderly cancer patients, the MPI performed better than the MGA in predicting mortality. Further evidence from larger prospective trials is needed to establish whether other geriatric scales, such as the GDS and CIRS-SI, could enhance the value of prognostic indexes applied to elderly cancer patients.

From adaptive licensing to adaptive pathways: delivering a flexible life-span approach to bring new drugs to patients.

The concept of adaptive licensing (AL) has met with considerable interest. Yet some remain skeptical about its feasibility. Others argue that the focus and name of AL should be broadened. Against this background of ongoing debate, we examine the environmental changes that will likely make adaptive pathways the preferred approach in the future. The key drivers include: growing patient demand for timely access to promising therapies, emerging science leading to fragmentation of treatment populations, rising payer influence on product accessibility, and pressure on pharma/investors to ensure sustainability of drug development. We also discuss a number of environmental changes that will enable an adaptive paradigm. A life-span approach to bringing innovation to patients is expected to help address the perceived access vs. evidence trade-off, help de-risk drug development, and lead to better outcomes for patients.

Drug utilization, safety, and effectiveness of exenatide, sitagliptin, and vildagliptin for type 2 diabetes in the real world: data from the Italian AIFA Anti-diabetics Monitoring Registry.

BACKGROUND AND AIMS: In Italy, the reimbursed use of incretin mimetics and incretin enhancers was subject to enrollment of patients into a web-based system recording the general demographic and clinical data of patients. We report the utilization data of glucagon-like peptide 1 (GLP1) receptor agonists and dipeptidylpeptidase-4 (DPP4) inhibitors in clinical practice as recorded by the Italian Medicines Agency (AIFA) Monitoring Registry. METHODS AND RESULTS: From February 2008 to August 2010, 75,283 patients with type 2 diabetes were entered into the registry and treated with exenatide, sitagliptin, or vildagliptin. The treatment was administered to patients in a wide range of ages (≥75 years, n = 6125 cases), body mass index (BMI) (≥35 kg/m(2), n = 22,015), and metabolic control (HbA(1c) ≥ 11% ((96 mmol/mol), n = 3151). Overall, 1116 suspected adverse drug reactions were registered, including 12 cases of acute pancreatitis (six on exenatide). Hypoglycemic episodes mainly occurred in combination with sulfonylureas. Treatment discontinuation for the three drugs (logistic regression analysis) was negatively associated with the male gender and positively with baseline HbA1c, diabetes duration, and, limitedly to DPP-4 inhibitors, with BMI. Treatment discontinuation (including loss to follow-up, accounting for 21-26%) was frequent. Discontinuation for treatment failure occurred in 7.7% of cases (exenatide), 3.8% (sitagliptin), and 4.1% (vildagliptin), respectively, corresponding to 27-40% of all discontinuations, after excluding lost to follow-up. HbA1c decreased on average by 0.9-1.0% (9 mmol/mol). Body weight decreased by 3.5% with exenatide and by 1.0-1.5% with DPP-4 inhibitors. CONCLUSIONS: In the real world of Italian diabetes centers, prescriptions of incretins have been made in many cases outside the regulatory limits. Nevertheless, when appropriately utilized, incretins may grant results at least in line with pivotal trials.

The assessment of vertebral fractures in elderly women with recent hip fractures: the BREAK Study.

UNLABELLED: This study aimed to evaluate the prevalence of vertebral fractures in elderly women with a recent hip fracture. The burden of vertebral fractures expressed by the Spinal Deformity Index (SDI) is more strictly associated with the trochanteric than the cervical localization of hip fracture and may influence short-term functional outcomes. INTRODUCTION: This study aimed to determine the prevalence and severity of vertebral fractures in elderly women with recent hip fracture and to assess whether the burden of vertebral fractures may be differently associated with trochanteric hip fractures with respect to cervical hip fractures. METHODS: We studied 689 Italian women aged 60 years or over with a recent low trauma hip fracture and for whom an adequate X-ray evaluation of spine was available. All radiographs were examined centrally for the presence of any vertebral deformities and radiological morphometry was performed. The SDI, which integrates both the number and the severity of fractures, was also calculated. RESULTS: Prevalent vertebral fractures were present in 55.7% of subjects and 95 women (13.7%) had at least one severe fracture. The women with trochanteric hip fracture showed higher SDI and higher prevalence of diabetes with respect to those with cervical hip fracture, p=0.017 and p=0.001, respectively. SDI, surgical menopause, family history of fragility fracture, and type2 diabetes mellitus were independently associated with the risk of trochanteric hip fracture. Moreover, a higher SDI was associated with a higher percentage of post-surgery complications (p=0.05) and slower recovery (p<0.05). CONCLUSIONS: Our study suggests that the burden of prevalent vertebral fractures is more strictly associated with the trochanteric than the cervical localisation of hip fracture and that elevated values of SDI negatively influence short term functional outcomes in women with hip fracture.

Effect of inhaled glucocorticoids and beta(2) agonists on vertebral fracture risk in COPD patients: the EOLO study.

Although inhaled glucocorticoids (GCs) and beta(2) agonists are being more frequently prescribed in the management of chronic obstructive pulmonary disease (COPD), their role in the impairment of bone status and in fracture risk remains controversial. This study aimed to evaluate whether the dose of inhaled GCs and beta(2) agonists may independently influence bone status and vertebral fracture risk in COPD patients aged 50 years or over. COPD severity, presence of vertebral fractures on lateral chest X-ray, and bone status by quantitative ultrasound (QUS) at the calcaneus were evaluated. The risk of vertebral fractures was significantly increased in patients taking the highest daily dose (>1,500 microg) of inhaled GCs (OR = 1.4, CI 1.04-1.89). The highest dose of inhaled GCs was significantly associated with low values of stiffness index (OR = 1.74, CI 1.03-2.94). Inhaled beta(2) agonists were not associated either with increased risk of vertebral fracture or with reduced values of stiffness. Moreover, the risk of fractures was markedly increased in patients with very severe or severe COPD (OR = 2.05, CI 1.28-3.28, and OR = 1.40, CI 1.06-1.82, respectively). In conclusion, in COPD patients high doses of inhaled GCs, but not beta(2) agonists, are associated with an increased risk of vertebral fractures and a reduction of QUS at the calcaneus.

Time to market and patient access to new oncology products in Italy: a multistep pathway from European context to regional health care providers.

AIM: The main purpose of this study was to identify each sequential phase followed by an oncology product, from European assessment until to patient access in each Italian region (IR). METHODS: A panel of oncology products approved by the European Medicines Agency (EMA) in the period 2006-2008 was considered. The explored sequential phases included the times to market for: the EMA; pharmaceutical companies; the Italian Medicines Agency (Agenzia Italiana del Farmaco, AIFA); and IRs as final providers of health care. The IR's time to market was also analyzed by a Cox regression model. RESULTS: The overall mean time required before patients access was 2.3 years. EMA accounted for the greater proportion of time (31.8%), followed by AIFA (28.2%). However, the duration for both pharmaceutical companies and IRs was associated with the highest variability. An oncology product authorized with a risk-sharing agreement showed an early access in the IRs. On the contrary, the introduction in IRs having a compulsory formulary was delayed. Both a high forecast of economic impact and a high oncology product price can also delay the patient access. CONCLUSION: The process before patient access to an oncology product is time and cost consuming. This study identifies the main predictors that affect the missing overlap between market and patient access in Italy.

A multicenter survey on profile of care for hip fracture: predictors of mortality and disability.

UNLABELLED: Because delay in time to surgery beyond 24-48 h has been observed in many studies to be associated with adverse outcomes, a survey in nine centers in Italy was undertaken to examine the impact of time to surgery on mortality and disability at 6 months after hospitalization. INTRODUCTION: Delays in surgery for hip fracture have been reported to be associated with negative outcomes. However, most studies are based on retrospective analysis of hospital discharge data, which cannot determine functional status or general health status of patients prior to the fracture. METHODS: Using a prospective cohort design, data were collected on 3,707 patients aged >50 years during hospitalization for hip fracture and in a 6-month postdischarge follow-up. Baseline information included age, gender, living arrangement, prefracture walking ability, walking aid, ASA grade, type and reason of fracture, time to surgery, type of surgery, date and destination at discharge, and osteoporosis treatment. Follow-up data included living arrangement, walking ability, and mortality. RESULTS: Six-month mortality was positively associated with increasing age, comorbidity, prefracture functional disability, and having surgery more than 48 h after admission. Higher levels of functional status at 6 months were independently associated with surgery occurring within 24 h of the fracture and with osteoporosis therapy at discharge. Walking disability was associated with older age, comorbidity, disability before fracture, and time to surgery after 24 h. CONCLUSIONS: Delay in surgery is a major cause of mortality and disability at 6 months, and interventions to modify this pattern of care are urgently needed.

Osteoporosis risk in patients with chronic obstructive pulmonary disease: the EOLO study.

Chronic obstructive pulmonary disease (COPD) appears to be associated with osteoporosis. The aim of the study was to evaluate the prevalence of osteoporosis risk (OP risk) in a sample of patients with COPD. In 3030 patients (1768 men and 1262 women) aged >50 yr, we evaluated COPD severity with spirometry and OP risk by using a quantitative ultrasound device. We analyzed several risk factors for osteoporosis, such as age, gender, body mass index (BMI), fracture history, smoking status, glucocorticoid (GC) treatment in univariate and in multinomial logistic regressions. The risk of osteoporosis was higher in women and in older participants, among those with more severe COPD, treated with GC. In multivariate analysis, we found interactions between fracture history and smoking and between age and gender. Significant associations were found with BMI and GC treatment, whereas only a tendency, not statistically significant, was found for very severe COPD being associated to high risk of osteoporosis. In COPD patients the risk of osteoporosis is high, in particular at severe stages of the disease, but seems to be due to traditional risk factors, such as older age, female gender, low BMI, history of smoking and fractures, GC treatment.

Vertebral fractures in patients with chronic obstructive pulmonary disease: the EOLO Study.

SUMMARY: This study aimed to evaluate the prevalence of vertebral fractures to investigate the determinants of vertebral fracture risk in patients with COPD. The risk of vertebral fractures is strictly related to the severity of the disease. The use of glucocorticoids and the presence of low values of quantitative ultrasound (QUS) may represent additional risk factors. INTRODUCTION: Chronic obstructive pulmonary disease (COPD) appears to be associated with osteoporosis. Our study aimed to evaluate the prevalence of vertebral fractures and to investigate the main determinants of vertebral fracture risk in patients with COPD. METHODS: In 3,030 ambulatory COPD patients (1,778 men and 1,262 women) aged 50 years or over, we evaluated: COPD severity, presence of vertebral fractures on lateral chest X-ray and bone status by using a quantitative ultrasound device. RESULTS: In men there was a strong association between COPD severity and fractures (p < 0.001), conversely in women the association between COPD severity and fractures was at limit (p = 0.049). In men, but not in women, glucocorticoid treatment was significantly associated with vertebral fractures. The patients with high or moderate risk of osteoporosis presented an increased risk of vertebral fracture (OR 2.71; 95% CI 2.04-3.60 and OR 1.54; 95% CI 1.26-1.88, respectively). Logistic regression analysis showed that COPD severity and glucocorticoid treatment, both inhaled and oral, were associated with increased risk of vertebral fractures. CONCLUSION: In COPD patients the risk of vertebral fractures is strictly related to the severity of the disease. The use of glucocorticoids and reduced QUS at calcaneous may represent additional risk factors.

Metal contents in tench otoliths: relationships to the aquatic environment.

A monitoring of the quality of waters was attempted determining metal accumulation in target organs as otoliths of freshwater fish. Tenchs of age ranging between 2 and 10 years were sampled in three different canals receiving wastewater from industrial, agricultural and urban activities. Metal contents were determined in both lapilli and asterisci otoliths, using inductively coupled plasma-atomic emission spectroscopy (ICP-AES). Analytical data are reported for minor metals and for some trace metals. Al, Fe and Zn have contents depending on the environment where the fish has lived, while Na, K, Ca and Sr contents are insensitive to the different aquatic habitat. Considering the two types of otolith separately, lapilli display a different affinity for trace metals (Al, Fe and Zn), while in asterisci this affinity is matched only for zinc. The high affinity of zinc for both types of otoliths suggests using this metal for discriminating the fresh waters by checking its accumulation in otoliths, as well as correlating this accumulation with age of the fish: a negative power curve equation is proposed. Since highest concentrations are found in individuals of 2-3 yr., it is advisable to use this fish for such environmental studies.

Case study of groundwater pollution in a critical area of the Southern-Friuli exposed to agricultural and landfill pressures.

Groundwater of the Southern-Friuli displays high levels of agricultural pollutants, such as nitrates and triazinic herbicides not only in the surficial layers, but also in the deeper ones, below 150 m. Some wells of the district of Gonars was monitored. The examined waters, used for irrigation but also for drinkable use, are exposed to environmental risk due to both agricultural practices and presence of many waste disposal sites. Heavy metals, nitrates and triazinic herbicides were measured in samples taken at four wells in three periods having different rain conditions. We found that groundwater quality is affected mainly by agricultural practices: nitrates and triazines are present at levels very near as well as superior to the maximum concentration allowable by Italian law. These agricultural contaminants have similar levels at all sampled sites: no difference was detected between dry periods and rain ones. Heavy metal contents are negligible in all cases; this fact suggests that ion-exchange, sorbing and complexing properties of the soils hinder the way of the metal leachates towards underlying groundwater. Zinc constitutes an exception; it is found at levels near or superior to the maximum allowable concentration (CMA), and the highest contents are observed in rain periods; different sites display different zinc levels, suggesting that this metal could have various point sources. Nitrates fertilisers were found in all sites at similar levels, very near to CMA (50 mg/L). Triazines are specific herbicides for corn growing, highly diffused here: their use in recent years is forbidden by Italian law, but the presence in groundwater of parent triazines and metabolites is a persistent problem of this area. The Italian law indicates a CMA of 0.10 microgram/L for the sum of atrazine and desethylatrazine, but we found that desethylatrazine by itself exceeds largely CMA in all sites.

Prevalence rates of hearing impairment and comorbid conditions in older people: the Veneto Study.

OBJECTIVES: To investigate the prevalence rate of hearing impairment, assessed by both the Sanders' questionnaire and the speech audiometry test, and its association with health-related factors in the older population of the Veneto region of Italy. DESIGN: A cross-sectional survey. SETTING: A community-based population. PARTICIPANTS: 2398 noninstitutionalized individuals aged 65 years and older residing in the Veneto region of Italy. MEASUREMENTS: Prevalence rates of hearing impairment and odds ratios for its association with potential risk factors. MAIN RESULTS: The prevalence of self-reported hearing impairment at home was 8.1% in men and 7.4% in women, and in a social environment it was 11.1% and 9.3%, respectively. Women were less likely to report hearing difficulties in both environments, and increased risks were found for depression, age, and poor self-rated health. Participants with diabetes or cognitive impairment had increased odds only at home, in contrast to people with a low education level, who had increased odds only in a social environment. The prevalence assessed by speech audiometry was 19% in both sexes. Increased age, diabetes, and poor self-rated health were associated with impaired speech intelligibility, cognitive impairment was associated with 4-fold increased odds among past users of alcohol, and men with a low education level were about three times as likely as others to have hearing impairment. CONCLUSIONS: Speech audiometry testing detected a higher prevalence of hearing impairment than use of a self-reported questionnaire and was associated with poor self-rated health, history of diabetes, and cognitive impairment among past users of alcohol and among men with low levels of education. The association between hearing deficit and depressive symptomatology was confirmed only with self-reported hearing impairment.