The Italian Observational Study on Severe Osteoporosis (ISSO): 24-month results on incidence of fractures and adherence to treatment.

OBJECTIVES: To estimate the proportion of patients with very severe osteoporosis (those covered by the reimbursement criteria of the Italian National Health Service) experiencing new vertebral and non-vertebral fragility fractures in the first 24 months of a new anti-osteoporosis treatment. METHODS: Prospective observational study in men and post-menopausal women (aged > 21 years) initiating anti-osteoporosis treatment for very severe osteoporosis. Eligibility was based on teriparatide (TPD) reimbursement criteria in Italy: incident of vertebral or hip fracture during anti-resorptive treatment (minimum 1 year), or at least three prevalent severe vertebral fractures, or two prevalent severe vertebral fractures and a historical proximal hip fracture. Incidence of new clinical vertebral and non-vertebral fractures was documented by original x-rays and/or radiological reports, and a post-hoc analysis compared data from the TPD monotherapy population versus the total treated group. RESULTS: Overall, 767 patients (mean age 72.8 years, 90.7% women) were enrolled in the study, of whom 628, 538, 419 and 424 attended visits at 6, 12, 18 and 24 months, respectively. The most commonly prescribed therapy was TPD (single-agent; 64.5%), then bisphosphonates and other anti-resorptives (33.3%). A combination of different oral treatments was given to 22.5% of the patients. Overall treatment adherence at 24 months was 65.7%. In a post-hoc analysis, the overall incidence of new clinical vertebral and non-vertebral fractures in the total treated population was, respectively, 4.7% and 2.3% in the first 6 months; 1.8% and 1.6% in the 6-12 month period; 2.9% and 1.4% in the 12-18 month period; and 2.2% and 1.0% in the 18-24 month period. CONCLUSIONS: In patients with very severe osteoporosis, the risk of new vertebral and non-vertebral fractures declined after the first 6 months and remained low throughout the study.

Prevalence of cardiovascular pathologies in elderly population living in an industrialized area, compared to a control population residing in a rural area.

The development of cardiovascular pathologies is potentially connected to the surrounding environment, partly due to purely environmental factors, like exposition to pollutions, or anthropological ones, like the type of manual or stressing working activities. The relevant literature has already widely discussed the correlation between the acute and chronic exposition to atmospheric pollutants of different types and the pathogenetic events, such as the atherogenesis, thrombosis, and hypertension, The present study intends to verify this idea on a larger population exposed to different geographical conditions, comparing an agricultural village (Pachino-Siracusa) with an industrialized area (Augusta-Siracusa), both having identical sanitary services of basic importance. On the basis of the specific rates of hospitalizations, we compared the prevalence of cardiovasular pathologies in the resident populations. These studies confirmed the negative influence of the risk factors deriving from the environmental pollutions even on the cardiovascular aging, displaying an increased rate of hospitalization for angina pectoris, myocardial infarction and cardiac arrhytmias in the industrialized population.

Studies on health in elderly observation centers (abbreviated from Italian: COSA): a multidimensional evaluation (MDE) of an elderly population frequenting a diurnal center in Catania.

The worldwide progressive aging of the population forces us to reconsider the strategies of evaluation the effects of the geriatric "tsunami" on the health politics. The present study on the COSA (abbreviated from the Italian name: "Centro Osservazione Salute Anziani") has the aim to investigate the effects of a new form called Specialistic Geriatric Assistance on the already existing geriatric services in our territory, like UVG (Unità Valutazione Geriatrica), ADI (Assistenza Domiciliare Integrata), MMG (Medici di Medicina Generale). The present preliminary studies were carried out a group of elderly people frequenting the elderly day center "Villa Angela" located in Catania. We enrolled 42 subjects, 29 females and 13 males, in the age-range of 65-89 years (mean=73.6 years). An evaluation protocol was used for the participants, having two parts. The first part was a general one performing an accurate anamnestic examination, while the second part evaluated the cognitive and affective spheres, and the levels of autonomy and autosufficiency. The data obtained show that that the elderly population of the daily center "Villa Angela" in Catania is affected by numerous pathologies and comorbidities, which all increase the total risk of disabilities. The subjects use a high number of medicines (sometimes more than 10), which is not always justified by the pathologies found in them. Considering the functional profiles of the patients, the sanitary services offered to them are appropriate, because almost all of the elderly people were autonomous and autosufficient, having still adequate physical performances. The higher cognitive performance seemed to be reduced in more than 50% of the patients, showing almost always a slight or moderate deterioration. The depressive state measured by the GDS seemed to reach the deflection of joy of life 54.8%, while the established depression was detected in 12%. These results emphasize the importance of the functional psychogeriatric screening, which is able to reveal an early diagnosis of depression in the geriatric ages. For this, and many other motifs, we believe that these preliminary examinations suggest to organize at least one COSA available to our elderly people.

Massive right atrial myxoma: an unusual presentation in an elderly patient.

Primary heart tumors are rare with an estimated incidence ranging 0.0017-0.19%. Myxoma is the most prevalent primary heart tumor. The right atrium is an unusual location, occurring only in the 15-20% of myxoma cases. We describe the case of a massive right atrial myxoma causing right ventricular inflow and tricuspid valve obstruction. The tumor was detected by echocardiography and confirmed by abdomen-thoracic tomography. It was resected along with a section of tricuspid septal leaflet, followed by primary repair. In 2-year follow-up the patient is asymptomatic.

Cytokine serum profile in a group of Sicilian nonagenarians.

The aim of our study was to evaluate the possibility of using multiplex analysis of the cytokine profile as a marker for successful aging by comparing cytokine plasmatic levels of a group of Sicilian nonagenarians with those of young controls. We analyzed a panel of 17 cytokines, comprehensive of haematopoietic factors T helper 1 (Th1), Th2, inflammation regulatory cytokines, and chemokines. The assay was carried out using the Luminex system. Interleukin (IL)-6 levels (p = 0.01) were increased in nonagenarians, whereas no modifications of other proinflammatory cytokines and chemokines were observed. Interferon-gamma (IFN-γ) and IL-2 levels are unmodified, suggesting a substantial maintenance of relevant T cell functions. In addition, a significant increase of IL-12 serum levels in nonagenarians versus young controls that might be related to the increase of natural killer (NK) cell functions characterizing aging processes was observed. The analysis of Th2 cytokines show an increase of IL-13 and a reduction of IL-4 levels mirroring the maintenance of some effector's mechanisms of the immunoresponse in advanced ages. Our results suggest that the multiplex analysis of cytokine levels might be useful in defining a successful aging profile.

Aging and environmental factors: an estimation of the health state of the elderly population residing in industrialized vs. rural areas.

The possibilities have already been discussed that the environment of the living beings may influence the aging process, by causing alterations of the homeostatic capacities to such an extent that definitive pathologies will come into being. Therefore, the aim of the present study was at estimating the effective impact of the environmental pollution on the health state of the subjects residing in highly industrialized areas. For this purpose, we compared 2 populations over the age of 56 years, one from the industrialized areas and the other of agricultural character. The health indicator we utilized was the rate of hospitalization calculated for the main geriatric pathologies. It has been observed that among the residents of highly polluted areas, the hospitalizations were more frequent for the screened pathologies. This finding could be an indicator of an interference of the environmental pollution with the physiological process of aging. One can also suspect that for the cardiovascular pathologies also the factor of physical fatigue being more prevalent in the rural population might play an important role in the high occurrence of this type of diseases. On the basis of these findings we intend to emphasize that the sanitary programs of a given territory should consider in the development and application of a sanitary service the intrinsic characteristics of the given area, when designing the possibly most adequate health care service.

The bone mass (BM) and chronic cardiac decompensation (CCD) in an elderly population.

This study intended to evaluate the existing correlation between the cardiac compensation and the bone mass, investigating the bone mineral density (BMD) in a population suffering from CCD or chronic heart disease (CHD). We enrolled 171 patients, all over the age of 70, being in the functional N.Y.H.A. Class II (Population A: 85 patients) and in Class III (Population B: 86 patients). All patients underwent an analysis of their cardiac functions using a Doppler echo-cardiographic method measuring the ventricular ejection fraction (VEF), as well as the BMD by means of a computerized bone mineralometric DEXA method, performed in vertebral and femoral measurement sites. Both populations proved to be osteopenic, displaying reduced values of BMD. Higher bone mineral losses were measured in the patients who had more severe cardiac insufficiency. The present data revealed a significant reduction of BMD in the N.Y.H.A. Class III patients, in correlation with the VEF (p<0.001), both in the lumbar vertebral area (p<0.01) and even more in the femoral sites (p<0.001), where a direct correlation exists between BMD and the VEF. On the basis of these findings one can suggest that the actual VEF level has an influence on the bone turnover, reducing the mineral content through various mechanisms of action.

The clinical and rehabilitative complexity in dementia with Lewy bodies (DLB): experience on a random sample of elderly patients dwelling in an RSA ("Residenza Sanitaria Assistita") of Catania.

This study was aimed at evaluating the occurrence of DLB in a population sample recovered in assisted sanitary residence (RSA=from the Italian name of "Residenza Sanitaria Assistita") in the Province of Catania. We considered 126 patients from a randomized population recovered in RSA of Viagrande (Catania) in the period from 1st March, 2005 and 31st March, 2007. Those who proved to be demented according to the DSM-III diagnostic protocols, and having a mini mental state examination (MMSE)-score <24 were divided in 2 groups: Group A, all the demented people without the DLB; and Group B, the DLB patients, according to the diagnostic criteria of McKeith. All patients underwent at admission, after 1 month, and at emission the following psychometric and functional tests: MMSE, geriatric depression scale (GDS) [Yesavage J.A., Brink T.L., Rose T.L., Adey M., 1983. The development and validation of geriatric depression screening scale: a preliminary report. J. Psych. Res. 17, 37], Barthel index (BI), activities of daily living (ADL) and instrumental ADL (IADL). Particular attention was dedicated to the presence of delirium during the last 15 days before the admission and during the recovery, the mortality and the prevalence of other complaints. The observed data confirm the prevalence of fragility of DLB patients in 20% of them, a fluctuation of the cognitive capacities, a better recovery of the affectivity, a reduced functional autonomy and autosufficiency. In addition, the DLB patients display a major presence of prevalent delirium, compared to the total population of demented patients, while in this last population only incidental delirium episodes occurred during the recovery period (31.6% vs. 16.6%; p<0.001). In the DLB population decubital lesions occurred more frequently, and were of more severe staging, compared to the controls (45% vs. 27%; p<0.001). Also, the mortality of the DLB patients was higher (about 30% vs. 17% in 12 months). These data confirm the particularity and higher complexity of the DLB patients recovered in the RSA.

Different characteristics of chronic heart failure (CHF) in elderly diabetics and non-diabetics.

Higher plasma concentrations of the N-terminal fragment of brain natriuretic peptide (NT-pro-BNP) and the tumor necrosis factor-alpha (TNF-alpha) have been observed in patients affected by chronic heart failure (CHF). Recent clinical studies have tried to correlate the plasma levels of these biomarkers with severity of the disease. To evaluate the role of NT-pro-BNP, TNF-alpha and C-reactive protein (CRP) in a population of geriatric patients affected by CHF, and to assess their different plasma levels in diabetics and in normoglycemic patients, we enrolled 57 patients affected by CHF: 29 patients were diabetic and 28 were normoglycemic. Clinical and echocardiographic examinations were performed in all patients, in order to evaluate the NYHA-class and the left ventricular ejection fraction (EF). All of them had been stabilized with medical therapy from at least 3 weeks. Plasma NT-pro-BNP, TNF-alpha and CRP levels were measured in each recruited patient. In the whole population we observed a linear correlation between NT-pro-BNP levels, EF and NYHA-class (p<0.05) but there was no significant correlation between TNF-alpha or CRP and the clinical or echocardiographic data (p=0.588 and p=0.9, respectively). Finally we evaluated, if there were significant differences in the biomarker concentrations between diabetics and normoglycemics. Both the clinical and the echocardiographic parameters of systolic dysfunction were comparable in these two groups. We observed a significant difference in CRP levels between the two groups (3.76+/-2.85 in diabetics vs. 1.42+/-2.35 in normoglycemics; p<0.001). The NT-pro-BNP levels were also higher in diabetics than in normoglycemic patients (12867.8+/-18042.0 vs. 6400.89+/-5655.0; p=0.07). Plasma TNF-alpha levels (23.03+/-11.52 vs. 23.31+/-12.0; p=0.93) and left ventricular EF (35.65+/-4.03 vs. 35.18+/-3.55; p=0.63) were similar in the two groups. In agreement with recent studies, we confirm a linear correlation between NT-pro-BNP, EF and the severity of disease in CHF patients. We also observed a greater cytokine activation in diabetics than in normoglycemic patients, demonstrating probably that in this group a greater inflammatory reaction is present.

Changes of the quality-of-life under the treatment of severe senile osteoporosis with teriparatide.

Despite being treated with antiresorptive drugs, the severe osteoporosis (SO) is being considered as a condition in which patients are still subject to one or more vertebral or femoral fractures, or non-vertebral or non-femoral fractures, i.e., of other parts of the body such as the wrist, shoulder, tibia, ribs or hip. These patients are defined as non-responders (NRs) to the antiresorptive therapy, and recent research has shown that they represent 10-25% of all SO patients. During the last almost 3 years a new drug has become available in Italy, called teriparatide (rh-PTH-1-34), produced in Escherichia coli using the recombinant-DNA technique. It shows remarkable trophic and anabolic actions on the bones, and proved to be very useful for treating the osteoporosis in general. This study describes our experience in using teriparatide for the treatment of SO in a sample of 141 elderly women of mean age 73.4+/-5.8 years, with a mean number of fractures of 3.0+/-0.85, with a spine deformity index (SDI) of 5.92+/-1.27 and a mean vertebral T-Score (L1-L4) of -3.15+/-0.39, and a mean femoral T-Score of -2.50+/-0.28. All these patients had been treated with antiresorptive drugs for at least 1 year: specifically 70 of them with Alendronate, 42 of them with Risedronate and 29 of them with Raloxifene. For 18 months, all these patients were injected subcutaneously with 20 microg of teriparatide, with the daily addition of 1 g of calcium and 880 IU of vitamin D. The study was continued for 24 months, at the end of which the patients continued to take only calcium and vitamin D. The patients underwent a CBM-DEXA control of vertebral column and femur every 6 months, and they were also administered a Quality-of-Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO). The QUALEFFO (41 items) questionnaire to evaluate the changes in the quality-of-life (QoL) and the consumption of non-steroidal anti-inflammatory drugs (NSAIDs) was also recorded. The results showed that teriparatide protected 96.5% against new fractures (only five new fractures occurred), bone mineral density (BMD) increased approximately by 12% in the vertebral column and by 11% in the femur, consumption of NSAIDs was reduced at the early stage approximately 80%, the QoL improved considerably and remained so during the 18 months of teriparatide treatment, with only a slight decrease during the 6 subsequent months.

Use of specific serotonin reuptake inhibitors (SSRIs) (Sertraline or Citalopram) in the treatment of depression reduces the cardiovascular risk in the elderly: evidence from a Sicilian population >80 years recovered in the assisted sanitary residences (RSA).

The correlation between depression and cardiovascular pathologies was studied in geriatric age. As a matter of fact, the high comorbidity of depression with the sudden cardiac deaths or other cardiovascular events requires a careful evaluation of these causalities. A total of 110 patients were analyzed, recovered in assisted sanitary residence (from the widely used Italian name: "residenza sanitaria assistita" abbreviated as RSA) during the last 12 months. All patients were above the age of 80 years at the admission (mean age was 83.2+/-2.8 years), and all of them have had a diagnosis of depression according to the DSM IV. All patients were treated with the antidepressive specific serotonin reuptake inhibitor (SSRI) (Citalopram, 20-40mg/day, or Sertraline 50-100mg/day). The patients were divided on the basis of their therapeutic response in two groups: Group A (responders) and Group B (non-responders). After 4, 6 and 12 months of treatment, we observed a reduction of the cardiovascular events (-75%, -83% and -60%, respectively). These findings confirm the existence of a correlation between the level of affectivity and the cardiac functions.

Management and treatment of decubital ulcers of an elderly population in the assisted sanitary residence of Futura-Viagrande (Catania, Sicily, Italy).

Decubital lesions indicate the gravity of the pathologies of the elderly patients, representing a serious cause of disability and of mortality. The present study was aimed at evaluating the decubital lesions during 1 year of treatment in an assisted sanitary residence (abbreviated as RSA from the Italian name), through observations of the assistential and therapeutical outcomes, aimed at improving the quality of life of the recovered elderly patients. We had 131 patients involved from a total of 308 recovered patients in the RSA. Their mean age was 83.4+/-1.3 years (74 women and 57 men). All cases were treated, considering the actual clinical stages, according to the advanced protocols on the basis of the guidelines of the National Pressure Ulcer Advisory Panel (NPUAP). All patients were evaluated by using the Braden-scale at the start and after 30 days for having a risk for the development of decubital ulcers and also for monitoring the modifications during the therapy, while the improvements were evaluated only clinically, establishing the reduction of the stage of the lesions. A precise analysis of the data revealed a higher prevalence of decubital lesions at the entrance to the RSA, particularly the advanced Grades III and IV (84 patients, 27% of all recovered subjects), compared to those with lower gravity Grades I and II (47 cases, 15% of all recovered subjects). Complete healing was observed only in a few cases (18.0%), mainly in the lower grades. Applying the therapeutic methods and protocols of NPUAP, most of the ulcers displayed an improving tendency. We had only a few mortal cases due to the ulcers (3 deaths of 131 patients), nevertheless, numerous death cases for other causes occurred among the patients, having advanced grades of ulcers (12%). Our data confirm the statement that the decubital ulcers represent the marker of severity of the polypathological state of the fragile elderly patients.

Quality of life in osteoporotic women with inadequate clinical response to antiresorptive drugs: results from the ICARO study.

BACKGROUND AND AIMS: Osteoporotic fractures are a major public health problem notably affecting quality of life. The observational, multicenter study ICARO was designed to evaluate inadequate clinical response to antiresorptive drugs. The aim of the present study was to evaluate the impact of the clinical response to treatment on the health-related quality of life in women with postmenopausal osteoporosis. METHODS: 880 osteoporotic women (mean age 68.0+/-8 years; range 53-79) in treatment with antiresorptive drugs for at least one year were analyzed. All subjects had at least 50% compliance to treatment (i.e., patients took >50% of prescribed doses). The "inadequate clinical response" (ICR), as opposed to "adequate clinical response" (ACR), was defined as the Xrays revealing evident new vertebral or non-vertebral fragility fractures at least 6 months after initiation of antiresorptive therapy. The QUALEFFO- 41 questionnaire was used to evaluate changes in quality of life prospectively. RESULTS: 220 subjects (25%) had an ICR. Non-responders had a higher incidence of multiple vertebral fractures compared with responders. The quality of life data in the study subjects showed a significantly increased score (indicative of lower quality of life) in the total mean score (37.89+/-16.7 vs 45.84+/-18.2, p<0.01), as well as in all the domains/subdomains examined in the QUALEFFO-41 questionnaire in ICR, when compared with ACR. CONCLUSIONS: Inadequate clinical response in subjects on antiresorptive drugs is associated with increased severity of the disease and with a significant reduction in the quality of life.

The use of bisphosphonates in palliative treatment of bone metastases in a terminally ill, oncological elderly population.

According to the guidelines of WHO [WHO, 1999. Cancer Pain and Palliative Care Program. Cancer Pain Release, vol. 13], the term terminally ill patient refers to oncological patients whose life expectancy is lower than 90 days, and the index of their physical state (defined as the Karnofsky Index) is below 50. The terminally ill oncological patients are treatable with the palliative cures, representing a treatment system aimed at improving the quality of life (QOL) of both the patient and the family members, decreasing the physical and psychical sufferance of the patient. The present study followed 35 terminally ill oncological patients with bone metastases, at their homes, for the University of Catania. These patients had previously been followed by the Local Sanitary Unit (ASL 3) of Catania, and established a life expectancy not longer than 3 months. Independently from the basic neoplastic disease resulting in the bone metastases, all the patients were treated with sodium clodronate (SC) intravenously, 300 mg every second day, in order to decrease the bone pains. The visual analogue scale (VAS) for pain relief, the autonomy (IADL) and autosufficiency (ADL, Barthel Index) were evaluated after 1, 3, and 6 months of treatment. The results indicate an overall significant improvement both in the pain symptoms and the QOL. Also the compromised autonomy and autosufficiency of this population seemed to be improved, at least as compared to the predicted and expected results at the start of this trial, and also compared to the relevant literature. One can conclude that the i.v. application of 300 mg of SC every other day produced a significant pain reduction and improved the QOL, and helped in maintaining the actual autonomy and autosufficiency. On this basis we suggest the use of this compound in the given type of terminally ill patients.