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BACKGROUND: Severe Covid-19 is associated with a cytokine storm leading to the hyper-expression of cytokines such as IFN-gamma, TNF-alpha, and IL-6, which may be responsible for most severe symptoms and signs of the disease. The immune response of the atopic patient is mostly Th2-oriented, associated with the expression of cytokines such as IL-4, IL-5, and IL-13, and atopic patients express fewer ACE-2 receptors than non-atopic individuals do. We assessed whether atopic status may protect from the most severe consequences of Covid-19. METHODS: Atopic status along with co-factors such as diabetes, hypertension, coronary heart disease, and thrombosis was investigated in severe Covid-19 patients admitted to different Italian hospitals. Patients were classified as having a mild, severe, or very severe disease based on the need of respiratory assistance; severity was plotted against the different co-factors and underwent multivariate analysis. RESULTS: 531 adults aged 25 - 100 years were studied; 57 (11.7%) were atopic. Atopic status showed a significant association with a milder disease irrespective of all other co-factors considered (p

Objective:To investigate, through a questionnaire, older adults’ demographic and socio-economic characteristics, knowledge, attitudes and practices in terms of food safety and healthy diet; and to develop dietary and hygiene indices able to represent participants’ nutritional and food safety behaviour, exploring their association with demographic and socio-economic factors.Design:One-year cross-sectional study.Setting:Gemelli Teaching Hospital (Rome, Italy).Participants:People aged ≥65 years, Italian speaking, accessing the Centre of Ageing Medicine.Results:Mean age of the sample was 74 (sd 7·7) years. Subjective perception of a safe diet was high: 64·2 % of respondents believed they have a balanced diet. Interviewees got informed about proper nutrition mainly from television, magazines, newspapers, Internet (29·9 %) and from health professionals (34·8 %) such as dietitians, whereas 15·4 % from general practitioners. Regarding food safety, 33·8 % of participants reported to consume expired food, even more than once per month; between 80 and 90 % of participants reported to follow food safety practices during preparation and cooking, even though 49·3 % defrosted food at room temperature. Calculated dietary and hygiene indices showed that the elderly participants were far from having optimal nutritional and food safety behaviours.Conclusions:These results suggest it is necessary to increase the awareness of older adults in the matter of healthy diet and food safety. Specific and targeted educational interventions for the elderly and their caregivers could improve the adoption of recommended food safety practices and safe nutritional behaviours among older adults.

Kaposi’s sarcoma (KS) is an angioproliferative tumor showing an increased frequency and aggressiveness in HIV-infected subjects (AIDS-KS), due to the combined effects of inflammatory cytokines (IC), angiogenic factors, and the HIV-1 Tat protein. While the introduction of effective combined antiretroviral regimens greatly improved AIDS-KS incidence and course, it continues to be an incurable disease and the development of new rational targeted therapies is warranted. We used the BKV/Tat transgenic mouse model to evaluate the effects of IC and anti-Tat antibodies (Abs) treatment on KS-like lesions arising in BKV/Tat mice. We demonstrated here that IC-treatment increases the severity and delays the regression of KS-like lesions. Further, anti-Tat Abs reduced KS-like lesion severity developing in IC-treated mice when anti-Tat Abs were administered at an early-stage of lesion development as compared to more advanced lesions. Early anti-Tat Abs treatment also accelerated KS-like lesion regression and reduced the rate of severe-grade lesions. This effect was more evident in the first weeks after Ab treatment, suggesting that a longer treatment with anti-Tat Abs might be even more effective, particularly if administered just after lesion development. Although preliminary, these results are encouraging, and the approach deserves further studies for the development of anti-Tat Ab-based therapies for AIDS-KS. Clinical studies specifically addressing the effect of anti-Tat antibodies in treating AIDS-KS are not yet available. Nevertheless, the effectiveness of anti-Tat antibodies in controlling HIV/AIDS progression, likely due to the neutralization of extracellular Tat activities, is suggested by several cross-sectional and longitudinal clinical studies, indicating that anti-Tat Ab treatment or Tat-based vaccines may be effective to treat AIDS-KS patients or prevent the tumor in individuals at risk.

On February 20, 2020, a man living in the north of Italy was admitted to the emergency room with an atypical pneumonia that later proved to be COVID-19. This was the trigger of one of the most serious clusters of COVID-19 in the world, outside of China. Despite aggressive restraint and inhibition efforts, COVID-19 continues to increase, and the total number of infected patients in Italy is growing daily. After 6 weeks, the total number of patients reached 128,948 cases (April 5, 2020), with the higher case-fatality rate (15,887 deaths) dominated by old and very old patients. This sudden health emergency severely challenged the Italian Health System, in particular acute care hospitals and intensive care units. In 1 hospital, geriatric observation units were created, the experience of which can be extremely useful for European countries, the United States, and all countries that in the coming days will face a similar situation.

Physical activity has been demonstrated to be effective in the prevention and treatment of different chronic conditions, including type 2 diabetes (T2D). In particular, several studies highlighted how the beneficial effects of physical activity may be related to the stability of the DNA molecule, such as longer telomeric ends. Here we analyze the effect of exercise training on telomere length, spontaneous and H2O2-induced DNA damage, as well as the apoptosis level in leukocytes from untrained or trained T2D patients vs. age-matched control subjects (CS) (57–66 years). Moreover, expression analysis of selected genes belonging to DNA repair systems, cell cycle control, antioxidant and defence systems was performed. Subjects that participated in a regular exercise program showed a longer telomere sequence than untrained counterparts. Moreover, ex vivo treatment of leukocytes with H2O2 highlighted that: (1) oxidative DNA damage induced similar telomere attrition in all groups; (2) in T2D subjects, physical activity seemed to prevent a significant increase of genomic oxidative DNA damage induced by chronic exposure to pro-oxidant stimulus, and (3) decreased the sensitivity of leukocytes to apoptosis. Finally, the gene expression analysis in T2D subjects suggested an adaptive response to prolonged exercise training that improved the response of specific genes.

Background The phase II multicenter, randomized, open label, therapeutic trial (ISS T-002, Clinicaltrials.gov NCT00751595) was aimed at evaluating the immunogenicity and the safety of the biologically active HIV-1 Tat protein administered at 7.5 or 30 μg, given 3 or 5 times monthly, and at exploring immunological and virological disease biomarkers. The study duration was 48 weeks, however, vaccinees were followed until the last enrolled subject reached the 48 weeks. Reported are final data up to 144 weeks of follow-up. The ISS T-002 trial was conducted in 11 clinical centers in Italy on 168 HIV positive subjects under Highly Active Antiretroviral Therapy (HAART), anti-Tat Antibody (Ab) negative at baseline, with plasma viremia

Background: Tat is a key HIV-1 virulence factor, which plays pivotal roles in virus gene expression, replication, transmission and disease progression. After release, extracellular Tat accumulates in tissues and exerts effects on both the virus and the immune system, promoting immune activation and virus spreading while disabling the host immune defense. In particular, Tat binds Env spikes on virus particles forming a virus entry complex, which favors infection of dendritic cells and efficient transmission to T cells via RGD-binding integrins. Tat also shields the CCR5-binding sites of Env rendering ineffective virus neutralization by anti-Env antibodies (Abs). This is reversed by the anti-Tat Abs present in natural infection or induced by vaccination.Findings: Here we present the results of a cohort study, showing that the presence of anti-Tat Abs in asymptomatic and treatment-naïve HIV-infected subjects is associated with containment of CD4+ T-cell loss and viral load and with a delay of disease progression. In fact, no subjects with high anti-Tat Ab titers initiated antiretroviral therapy during the three years of follow-up. In contrast, no significant effects were seen for anti-Env and anti-Gag Abs. The increase of anti-Env Ab titers was associated with a reduced risk of starting therapy only in the presence of anti-Tat Abs, suggesting an effect of combined anti-Tat and anti-Env Abs on the Tat/Env virus entry complex and on virus neutralization.Conclusions: Anti-Tat immunity may help delay HIV disease progression, thus, targeting Tat may offer a novel therapeutic intervention to postpone antiretroviral treatment or to increase its efficacy. © 2014 Bellino et al.; licensee BioMed Central Ltd

Background Although combined antiretroviral therapy (cART) has saved millions of lives, it is incapable of full immune reconstitution and virus eradication. The transactivator of transcription (Tat) protein is a key human immunodeficiency virus (HIV) virulence factor required for virus replication and transmission. Tat is expressed and released extracellularly by infected cells also under cART and in this form induces immune dysregulation, and promotes virus reactivation, entry and spreading. Of note, anti-Tat antibodies are rare in natural infection and, when present, correlate with asymptomatic state and reduced disease progression. This suggested that induction of anti-Tat antibodies represents a pathogenesis-driven intervention to block progression and to intensify cART. Indeed Tat-based vaccination was safe, immunogenic and capable of immune restoration in an open-label, randomized phase II clinical trial conducted in 168 cART-treated volunteers in Italy. To assess whether B-clade Tat immunization would be effective also in patients with different genetic background and infecting virus, a phase II trial was conducted in South Africa. Methods The ISS T-003 was a 48-week randomised, double-blinded, placebo-controlled trial to evaluate immunogenicity (primary endpoint) and safety (secondary endpoint) of B-clade Tat (30 μg) given intradermally, three times at 4-week intervals, in 200 HIV-infected adults on effective cART (randomised 1:1) with CD4+ T-cell counts ≥200 cells/µL. Study outcomes also included cross-clade anti-Tat antibodies, neutralization, CD4+ T-cell counts and therapy compliance. Results Immunization was safe and well-tolerated and induced durable, high titers anti-Tat B-clade antibodies in 97 % vaccinees. Anti-Tat antibodies were cross-clade (all vaccinees tested) and neutralized Tat-mediated entry of oligomeric B-clade and C-clade envelope in dendritic cells (24 participants tested). Anti-Tat antibody titers correlated positively with neutralization. Tat vaccination increased CD4+ T-cell numbers (all participants tested), particularly when baseline levels were still low after years of therapy, and this had a positive correlation with HIV neutralization. Finally, in cART non-compliant patients (24 participants), vaccination contained viral load rebound and maintained CD4+ T-cell numbers over study entry levels as compared to placebo. Conclusions The data indicate that Tat vaccination can restore the immune system and induces cross-clade neutralizing anti-Tat antibodies in patients with different genetic backgrounds and infecting viruses, supporting the conduct of phase III studies in South Africa. Trial registration ClinicalTrials.gov NCT01513135, 01/23/2012 Electronic supplementary material The online version of this article (doi:10.1186/s12977-016-0261-1) contains supplementary material, which is available to authorized users.

Purpose: The effects of exercise training on neuromuscular function of arm and leg muscles in type 2 diabetic patients (T2D) was investigated. \ud \ud Methods: Eight T2D sedentary male patients (61.0 ± 2.3 years) and eight sedentary healthy age matched control subjects (H, 63.9 ± 3.8 years) underwent a 16-week supervised combined endurance and resistance exercise program. Before and after training, maximal isometric (MVIC), isokinetic (15, 30, 60, 120, 180, 240° s−1) torque and muscle endurance of the elbow flexors (EF) and knee extensors (KE) were assessed. Simultaneously, surface electromyographic signals from biceps brachii (BB) and vastus lateralis (VL) muscles were recorded and muscle fiber conduction velocity (MFCV) estimated. \ud \ud Results: Following training, maximal torque of the KE increased during MVIC and isokinetic contractions at 15 and 30° s−1 in the T2D (+19.1 ± 2.7% on average; p < 0.05) but not in the H group (+7 ± 0.9%; p > 0.05). MFCV recorded from the VL during MVIC and during isokinetic contractions at 15 and 30° s−1 increased (+11.2 ± 1.6% on average; p < 0.01), but in the diabetic group only. Muscular endurance was lower in T2D (20.1 ± 0.7 s) compared to H (26.9 ± 1.3 s), with an associated increase in the MFCV slope after training in the KE muscles only. \ud \ud Conclusion: The effect of a combined exercise training on muscle torque appears to be angular velocity-specific in diabetic individuals, with a more pronounced effect on KE muscles and at slow contraction velocities, along with an associated increase in the MFCV. MFCV appears to be a more sensitive marker than torque in detecting the early signs of neuromuscular function reconditioning.

Objective.Hyperglycemia leads to increased production of reactive oxygen species (ROS) in type 2 diabetes, which reduces cellular antioxidant defenses and induces DNA lesions. The aim of this study was to investigate the effects on redox homeostasis and DNA oxidative damage of exercise training in patients with type 2 diabetes compared with nondiabetic individuals.Methods and Results.12 sedentary type 2 diabetic males (62.1 ± 4.3 yrs) and 12 sedentary healthy males (61.7 ± 3.9 yrs) were exposed to 4-month moderate training, 3 times per week, to evaluate the effect on plasma biomarkers of oxidative stress malondialdehyde and antioxidant status (GSSG, GSH/GSSG, and ascorbic acid) as well as basal and H2O2-induced DNA damage trough alkaline comet assay in peripheral blood lymphocytes. After training, glutathione and ascorbic acid levels increased in both groups, but only in diabetics the malondialdehyde as well as the DNA damage decreased.Conclusion.Our study demonstrates for the first time that moderate exercise training is not only effective in improving the redox homeostasis, through an increase of the endogenous antioxidant defences in healthy as well as in diabetic patients, but also, specifically in diabetic patients, effective in lowering the susceptibility to oxidative DNA damage and the lipid peroxidation levels.

The major determinants of the poor prognosis of the patients with proximal-third gastric cancer (proximal gastric cancer or PGC) when compared with that of patients with more distally located gastric tumors (distal gastric cancer or DGC) rely both on the more advanced age and tumor stage at the moment of clinical presentation and on the higher postoperative mortality for PGC patients. We reviewed hospital records of 707 patients with gastric cancer (187 with PGC and 520 with DGC) observed during the period 1981 through 1996 at the same surgical unit. Demographic and pathological data, type of treatment, and hospital morbidity and mortality rates were recorded. Univariate and multivariate survival analysis was used to calculate the 5-year survival probabilities with respect to the following clinical and pathological variables: age, sex, gross appearance according to Borrmann classification, histological type according to Lauren, stage of the disease, tumor location, and type of treatment. PGC was associated with more advanced tumor stage ( P < 0.0001), older age ( P = 0.039), and higher necessity of extended surgery ( P < 0.0001) when compared with DGC. Hospital mortality was 9.6 and 5 per cent in PGC and DGC patients respectively ( P = 0.033). Overall 5-year survival was 17.7 and 36.4 per cent in PGC and DGC patients ( P < 0.0001): 35.9 versus 57.6% ( P = 0.0001) and 3.7 versus 7.6 per cent ( P = 0.03) after radical and palliative surgery respectively. At multivariate survival analysis proximal location was found to be independently associated ( P = 0.0007) with poor survival. The multivariate model shows the proximal location as an independent predictor of lesser favorable outcome in gastric cancer. The major determinants of the poor prognosis of PGC with respect to DGC rely both on the more advanced age and tumor stage at the moment of clinical presentation and on the higher postoperative morbidity for PGC patients.

Background. The number of hepatic resections for benign and malignant lesions has constantly increased over the past 20 years, as a consequence, surgical experience acquired over the past few years has decreased post-operative morbidity and mortality rates. Aims. Analysing the relation between potential preoperative risk factors and the occurrence of severe post-operative complications, an attempt is made to identify the variables determining surgical risk in elective hepatic surgery both in normal and cirrhotic liver. Patients and Methods. The hospital records of 254 patients who underwent elective liver surgical procedures for hepatic lesions in our department, between 1984 and 1999, were reviewed. The following variables were entered into univariate and multivariate analysis: age, sex, nature of liver lesion (benign or malignant), presence of cirrhosis or cholestasis, synchronous resection of other organs, disorders of blood coagulation, intraoperative blood requirement, the extent of surgical procedures and Pringle's manoeuvre. Results and Conclusions. The multivariate analysis of the 254 surgical operations on the liver indicates that the most powerful independent predictors favouring a serious adverse effect includes intro-operative blood transfusions, advanced age and cirrhosis. Scrupulous preoperative clinical evaluation and expert surgical skills minimize intro-operative bleeding and proved to be the most significant factors influencing morbidity and mortality rates.

Optimal care for frail elderly patients depends on comprehensive assessment. This is especially true in the complex setting of interdisciplinary home care programs. To facilitate comprehensive assessment, as well as to generate a useful, policy-relevant patient database, standardized, multidimensional, and validated instruments are very helpful.The aim of the present study was to demonstrate that the Minimum Data Set assessment instrument for Home Care (MDS-HC) can be used to detect functional and cognitive impairment as defined by analogous research instruments.This was a cross-sectional correlation study.We studied 95 patients admitted to home care services of the Health Care Agency of Bergamo (Italy).The MDS-HC form was completed for all patients by well-trained nurses, independently of and with nurses blinded to the results from the research rating scales. The Barthel Activities of Daily Living (ADL) Index, the Instrumental Activities of Daily Living of Lawton (IADL), and the Mini Mental State Examination (MMSE) were considered the gold standard.Agreement between the MDS-HC scales and the research rating scales was assessed with Pearson's correlation coefficient. This coefficient was 0.74 for MDS-ADL versus Barthel Index, 0.81 for MDS-IADL versus Lawton Index, and 0.81 for Cognitive Performance Scale versus MMSE, indicating an excellent agreement.The MDS-HC scales, when performed by trained nurses using recommended protocols, provide a valid measure of function and cognitive status in frail home care patients. These findings point out the overall validity of the functional and clinical data contained in the MDS-HC assessment. Use of the MDS-HC gives the unique opportunity of setting up a database, a prerequisite for all epidemiological evidence-based medicine studies.

The hospital records of 639 patients affected by primary gastric cancer who were consecutively admitted to our unit during the period 1981-1995 were reviewed. Overall 220 underwent total gastrectomy (38 palliative), 12 had resection of the gastric stump, 195 had distal subtotal gastrectomy (55 palliative), 78 had bypass procedures, 72 had explorative laparotomy, and 62 had no operation. Univariate and multivariate analyses were used to evaluate 5-year survival with respect to the main clinical, pathologic, and treatment variables after both curative and palliative treatments. Overall the 5-year survival after curative treatment (320 patients-operative mortality excluded) was 55.5%: 91.1% for stage IA, 71.5% IB, 62.4% II, 37.5% IIIA, 31.5% IIIB. Among patients who underwent palliative treatment 5-year survival was 13.1% after gastric resection (total or distal subtotal), 4.9% after the bypass procedures, 0 after explorative laparotomy, and 0 after no operation. Univariate and multivariate survival analyses showed that variables independently associated with poor survival were advanced stage, upper location and D1 lymphadenectomy after curative treatment, tumor spread to distant sites, and nonresectional surgery after palliative treatment. Multivariate analysis showed that even though survival with gastric cancer depends on predetermined factors, the type of surgery can have a significant effect on prognosis after both curative and palliative treatment.

OBJECTIVES To identify factors associated with mortality in patients with Alzheimer’s disease, and to evaluate whether these factors vary according to severity of cognitive impairment. METHODS Data were from the SAGE database which includes information on all residents admitted between 1992 and 1995 to all Medicare/ Medicaid certified nursing homes of five US states. We conducted a longitudinal follow up study (median 23 months) on 9264 patients aged 65 years and above with a diagnosis of Alzheimer’s disease. Patient data including demographic characteristics, dementia severity, comorbidity, and other clinical and treatment variables were collected with the Minimum Data Set. Information on death was derived through linkage to Medicare files. Baseline characteristics were used to predict survival in univariate and multivariate Cox proportional hazard models. RESULTS Overall mortality rate was 50%, with a first year rate of 25.7%. Increased age (risk ratio (RR) 1.83; 95% confidence interval (95% CI) 1.65–2.03, for patients 85+ years), male sex (RR 1.81; 95% CI 1.70–1.94), limitation in physical function (RR 1.45; 95% CI 1.27–1.66), a condition of malnutrition (RR 1.31; 95%CI 1.23–1.39), the presence of pressure ulcers (RR 1.24; 95% CI 1.13–1.36), a diagnosis of diabetes mellitus (RR 1.32; 95% CI 1.21–1.43), and of cardiovascular diseases (RR 1.22; 95% CI 1.14–1.30) were independent predictors of death, regardless of the severity of baseline dementia. Sensory problems (hearing and vision) and urinary incontinence were associated with increased mortality only among patients with less severe dementia. The presence of disruptive behaviour, aphasia, and a diagnosis of Parkinson’s disease were not related to survival. African-Americans and other minority groups were less likely to die relative to white people. CONCLUSIONS Age, sex, functional limitation, and malnutrition seem to be the strongest predictors of death for patients with Alzheimer’s disease in nursing homes. Altogether, severity of dementia has no influence on survival, yet the predictive role of certain variables depends on the degree of impairment. Minority groups have a reduced risk of death relative to white people.

Single-blind randomized clinical trial, with a follow-up of 24 weeks.To determine the effects of hyperthermia via localized microwave diathermy on pain and disability in comparison to subacromial corticosteroid injections in patients with rotator cuff tendinopathy.Hyperthermia improves symptoms and function in several painful musculoskeletal disorders. However, the effects of microwave diathermy in rotator cuff tendinopathy have not yet been established.Ninety-two patients with rotator cuff tendinopathy and pain lasting for at least 3 months were recruited from the outpatient clinic of the Department of Orthopaedics and Traumatology, University Hospital, Rome, Italy. Participants were randomly allocated to either local microwave diathermy or subacromial corticosteroids. The primary outcome measure was the short form of the Disabilities of the Arm, Shoulder and Hand Questionnaire (QuickDASH). Secondary outcome measures were the Constant-Murley shoulder outcome score and a visual analog scale for pain assessment.At the end of treatment and at follow-up, both treatment groups experienced improvements in all outcome measures relative to baseline values. Changes over time in QuickDASH, Constant-Murley, and visual analog scale scores were not different between treatment arms.In patients with rotator cuff tendinopathy, the effects of localized microwave diathermy on disability, shoulder function, and pain are equivalent to those elicited by subacromial corticosteroid injections.

This study examined the concurrent and construct validity of the OMNI-Cycle Rating of Perceived Exertion (RPE) Scale, using elderly men and women. Seventy-six participants performed a load-incremented cycle-ergometer exercise test. Concurrent validity was determined by correlating OMNI-RPE responses with oxygen uptake, relative peak oxygen uptake, pulmonary ventilation, heart rate, respiratory rate, and respiratory-exchange ratio during a load-incremented cycle-ergometer protocol. Construct validity was established by correlating RPE derived from the OMNI-Cycle Scale with RPE from the Borg (6–20) Scale. Multilevel, mixed linear-regression models indicated that OMNI-RPE distributed as a significant (p < .05) positive linear function (r = .81–.92) for all physiological measures. OMNI-RPE was positively (p < .01) and linearly related to Borg-RPE in elderly men (r = .97) and women (r = .96). This study demonstrates both concurrent and construct validity of the OMNI-Cycle RPE Scale. These findings support the use of this scaling metric with elderly men and women to estimate RPE during cycle-ergometer exercise.

The purpose was to examine whether the translation of verbal descriptors from English to Italian affects the validity of the OMNI Scale of Perceived Exertion. 82 people for whom Italian was the primary language performed an orientation trial and a maximal graded exercise test on a cycle ergometer. Ratings of perceived exertion for the overall body and physiological responses were measured during each exercise stage. Significant correlations were found between perceptual responses of the Italian version of the OMNI Cycle Scale of Perceived Exertion and oxygen uptake, pulmonary ventilation, heart rate, respiratory rate, and respiratory exchange ratio responses to a maximal graded exercise test on a cycle ergometer. These findings indicate that the Italian version of the OMNI Scale of Perceived Exertion gives a valid estimate of effort during cycle ergometer exercise.

The influence of temperature on the myocardial inotropic response to norepinephrine was studied in rats of different ages. Right papillary muscles isolated from 3-, 12-, and 24-month-old rats were superfused at two temperatures (29 degrees C and 37 degrees C) with progressively larger doses of norepinephrine. At 29 degrees C, the contraction duration was longer and the inotropic effect of norepinephrine was significantly smaller in 24-month muscles than in 3- and 12-month preparations. In muscles superfused at 37 degrees C, these age-related differences in the contraction duration and in the response to norepinephrine disappeared. Analysis of variance and covariance showed that temperature, but not age, is responsible for the differences in the inotropic response to norepinephrine observed. These results show that experimental conditions, among which temperature may play a major role, deeply affect the responsiveness of cardiac preparations to beta-adrenergic agonists.

The effect of aging was tested on experimental ventricular arrhythmias in isolated heart preparations from normal Wistar rats (NWR), Wistar Kyoto rats (WKY), and spontaneously hypertensive rats (SHR). Delayed afterdepolarizations and triggered activity induced by high-calcium perfusion (16 mM) in isolated papillary muscles were more frequent in the 24-month-old than in 6-month-old NWR. Reperfusion-VA were more severe in 14-month-old SHR than in WKY. The authors have previously shown that: (1) reperfusion- and reoxygenation-induced VA, in the isolated Langendorff perfused heart, were significantly more severe and frequent in 24-month-old than in 6-month-old NWR; (2) no age-related difference in the incidence of programmed electrical stimulation (PES, train of stimuli + 1 or 2 extrastimuli)-induced VA was observed in isolated NWR hearts during control perfusion, after coronary artery ligation or during hypoxia; (3) on the contrary, the incidence of PES-induced VA was significantly higher in isolated hearts from 14-month-old SHR than from 3-month-old SHR, and 3-month-old and 14-month-old WKY. It was concluded that "physiological" aging is associated with a higher propensity to calcium-related VA, while "pathological" aging characterized by hypertension of long duration increases the incidence of PES-induced VA, probably caused by myocardial fibrosis, which could facilitate reentry.

Study Objectives. To evaluate whether hospitalization affects blood pressure control in hypertensive patients, and to identify factors associated with attainment of adequate blood pressure control and with aggressive pharmacologic treatment. Design. Retrospective study. Setting. Eighty-one hospitals throughout Italy. Patients. A total of 3304 patients (59% women, 41% men) with a diagnosis of hypertension and uncontrolled blood pressure values at hospital admission. Measurements and Main Results. Patients' blood pressures were surveyed during study periods from 1988–1997. Controlled blood pressure was defined according to the sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (systolic < 140 mm Hg, diastolic < 90 mm Hg). Aggressive pharmacologic treatment was defined as an increase in the number of antihypertensive drugs that the patient was receiving at hospital discharge compared with the number of drugs on admission. Adequate blood pressure control was achieved in only 767 (23.2%) patients, but the proportion increased in each subsequent survey. Age (odds ratio [OR] for 10-year increase 0.82, 95% confidence interval [CI] 0.76–0.88) and male sex (OR 0.79, 95% CI 0.65–0.94) were associated with reduced likelihood of achieving adequate blood pressure control. In contrast, coronary heart disease (OR 1.38, 95% CI 1.14–1.66), year of survey (1995 vs 1988: OR 1.47, 95% CI 1.19–1.82; 1997 vs 1988: OR 1.27, 95% CI 1.02–1.42), length of hospital stay (medium vs lower tertile OR 1.20, 95% CI 0.96–1.49; higher vs lower tertile OR 1.42, 95% CI 1.13–1.77), and increase in number of antihypertensive drugs prescribed (OR 1.21, 95% CI 1.02–1.42 for one drug increase) were associated with improved blood pressure control. In 1753 (53.1%) patients, the number of antihypertensive drugs increased during their hospital stay. Younger age, fewer drugs on admission, lower comorbidity index, diagnosis of chronic heart failure, lengthy hospital stay, and increasing baseline values of systolic and diastolic blood pressure were associated with aggressive pharmacologic treatment. Conclusion. Adequate blood pressure control was achieved in only 25% of patients with hypertension despite a trend toward improvement in recent years. Advanced age was one of the main factors associated with less aggressive pharmacologic treatment and with inadequate blood pressure control.

Objective Urinary incontinence is a common problem among older persons living in different community settings. The multifactorial origin of urinary incontinence has been largely addressed, and many previous studies have identified several reversible factors associated with incontinence. The aim of this study was to estimate the risk of urinary incontinence associated with the use of oxidative or nonoxidative benzodiazepines. Methods We analyzed data from a large collaborative observational study group, the Italian Silver Network Home Care project, which collected data on patients admitted to home care programs (N = 4583). A total of 22 home health agencies participated in the project, which evaluated the implementation of the Minimum Data Set for Home Care instrument. The main outcomes measure was the prevalence of urinary incontinence and the association with benzodiazepine use. Results A total of 1475 individuals (21% of patients aged 60-74 years and 38% aged ≥75 years) reported urinary incontinence. Users of benzodiazepines had an increased risk of urinary incontinence of nearly 45% (odds ratio [OR], 1.44; 95% confidence interval [CI], 1.12-1.83). The risk seemed to be of greater magnitude for exposure to oxidative agents (adjusted OR, 1.47; 95% CI, 1.09-1.99) than to nonoxidative benzodiazepines (adjusted OR, 1.35; 95% CI, 0.93-1.96). Among the oxidative benzodiazepines, the effect mainly resulted from agents with a long elimination half-life (adjusted OR, 1.75; 95% CI, 1.13–2.72). Conclusions The metabolic pathway of the benzodiazepines is a good predictor of urinary incontinence. In frail elderly patients, oxidative benzodiazepines are potentially more harmful than nonoxidative agents. Among oxidative benzodiazepines, the best ones seem to be those with a short elimination half-life. Clinical Pharmacology & Therapeutics (2002) 72, 729–734; doi: 10.1067/mcp.2002.129318

Hypothesis Immediate enteral feeding following major abdominal surgery reduces postoperative complications and mortality when compared with parenteral nutrition. Design A prospective multicenter randomized trial. Setting A university hospital department of digestive surgery. Patients and Interventions Two hundred forty-one malnourished patients undergoing major elective abdominal surgery were randomly assigned to receive, after surgery, either enteral (enteral nutrition group: 119 patients) or parenteral nutrition (total parenteral nutrition group: 122 patients). The patients were monitored for postoperative complications and mortality. Results The rate of major postoperative complications was similar in the enteral and parenteral groups (enteral nutrition group: 37.8%; total parenteral nutrition group: 39.3%; P was not significant), as were the overall postoperative mortality rates (5.9% and 2.5%, respectively; P was not significant). Conclusion The present study failed to demonstrate that enteral feeding following major abdominal surgery reduces postoperative complications and mortality when compared with parenteral nutrition.

HIV-1-infected patients develop a generalized vasculopathy that is clinically most evident as Kaposi's sarcoma (KS), a multifocally appearing endothelial cell-derived tumor. Fibroblast growth factor 2 (FGF-2) is a potent autocrine and paracrine mitogen of endothelial cells and has been implicated in the cell proliferation and angiogenesis observed in KS. Here we determined by ELISA the FGF-2 serum concentrations in different clinical groups of HIV-1-infected patients. AIDS-KS patients (n = 53) and HIV-1-infected patients without KS (n = 39) revealed significantly increased FGF-2 serum concentrations (median, 4.5 and 4.6 pg/ml, respectively), as compared with the healthy control group (n = 22; median, 2.2 pg/ml; p < 0.01). FGF-2 concentrations were highest in untreated HIV-1-infected patients (median, 8.6 pg/ml) and were significantly decreased in patients undergoing antiretroviral therapy (AZT-median, 4.5 pg/ml; HAART-median, 2.5 pg/ml; p < 0.01). In addition, FGF-2 serum concentrations above 5.2 pg/ml were associated with a statistically significant higher risk of death in HIV-1-infected patients. Multivariate analysis showed that this effect is independent of CD4 levels, localization of KS (cutaneous or visceral), AIDS-defining opportunistic diseases, and therapy. Circulating FGF-2 may contribute to AIDS-associated vasculopathy and may be a sensitive and easily accessible surrogate marker to determine the survival time of HIV-1-infected patients and the efficacy of antiretroviral therapy.

Objective: To evaluate whether the excess mortality in men with AD can be explained by a gender difference in the predictors of mortality. Methods: The authors studied 2,838 men and 6,385 women over 65 years of age with AD admitted, between 1992 and 1995, to 1 of nearly 1,500 nursing homes in five U.S. states (Kansas, Maine, Mississippi, New York, and South Dakota). Resident level data including sociodemographic characteristics, dementia severity, measures of physical disability, comorbidity, and other clinical variables were collected with the Minimum Data Set. Information on death was derived through linkage to Medicare enrollment files; the median follow-up was 23 months. Baseline characteristics were used to predict age at time of death in Cox proportional hazard models. Results: Men with AD had an increased risk of mortality relative to women, adjusted for differences in the distribution of age and race. The most important predictors of death in men were those related to the disease itself. These were the severity of dementia and the occurrence of episodes of delirium. Instead, death among women was associated with measures of disability, namely, impairment in performing the activities of daily living, presence of pressure sores, malnutrition, and comorbidity. Conclusion: These data suggest that the underlying mechanisms for AD may be different in men and women. Future studies of survival and progression of AD need to examine men and women separately.

OBJECTIVES: To quantify the impact of legislation on nursing home residents, psychotropic drug use, and the occurrence of falls in the US compared with five countries with no such regulation. DESIGN: A retrospective cross-sectional study SETTING: Nursing homes in five US states and selected nursing homes in Denmark, Iceland, Italy, Japan, and Sweden PARTICIPANTS: Residents in nursing homes in five US states and the aforementioned countries during 1993-1996 MAIN OUTCOME MEASURES: Using data collected using the Minimum Data Set, logistic regression provided estimates of the legislative effects on the use of antipsychotics and antianxiety/hypnotics while simultaneously adjusting for potential confounders. The occurrence of falls was evaluated similarly. RESULTS: Prevalence of antipsychotic and/or antianxiety/ hypnotic use varied substantially across countries. After adjustment for differences in age, gender, presence of psychiatric/neurologic conditions, and physical and cognitive functioning, residents in Denmark, Italy, and Sweden were at least twice as likely to receive these drugs (Denmark Odds Ratio (OR)=2.32; 95% Confidence Intervals (CI), 2.15-2.51; Italy OR = 2.05; 95% CI, 1.78-2.34; Sweden OR=2.50; 95% CI, 2.16-2.90); in Iceland, the risk was increased to greater than 6 times (OR=6.54; 95% CI, 5.75-7.44) that of the US. Residents were less likely to fall in Italy, Iceland, and Japan compared with the US, despite more extensive use of psychotropic medication, whereas residents in Sweden and Denmark were more likely to fall. CONCLUSIONS: Policy has had an impact on the prescribing of psychotropic medication in US nursing homes compared with other countries, but it is unclear if this is translated into better outcomes for residents.

BACKGROUND Early diagnosis of dementia is critical, but there is usually a time lag between onset of symptoms and referral for neuropsychological testing and dementia diagnosis. We aimed to identify factors correlated with this delayed referral. METHODS We studied 140 patients with cognitive deterioration referred to the Memory Clinic of the Catholic University (Rome) between 1995 and 1996. Alzheimer's disease or multi-infarct dementia was diagnosed according to National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria and Hachinski ischemic score. Global cognitive and neuropsychological functions were assessed with the Mini-Mental State Exam (MMSE) and the Mental Deterioration Battery. The performance on the Activities of Daily Living was used to measure physical function. The time between onset of signs of cognitive deterioration and referral for diagnosis (time to diagnosis: TTD) was estimated through a semistructured interview of the caregiver. Independent correlates of TTD were identified after adjustment for potential confounders and stratifying patients based on level of physical function. RESULTS Of 127 eligible patients, 63% had Alzheimer's disease, 26% multi-infarct dementia, and 11% had dementia of other types. Mean age was 73.9 +/- 8.2 years, and 59% of patients were females. The mean TTD was 13.8 +/- 10.8 months and did not differ by gender, household composition, or type of dementia. For patients with normal physical function, increased age (beta = .50), female sex (beta = .51), and low MMSE score (beta = .36) were associated with longer TTD. Among patients with physical impairment, only MMSE score showed an association with TTD, but it was of opposite direction (beta = -.31). These associations were consistent by type of dementia. CONCLUSIONS Age, gender, and degree of cognitive impairment are important correlates of the time between onset of signs/symptoms and referral for dementia diagnosis. These factors are independent of the type of dementia but are influenced by the level of physical function.

We performed this case control study to evaluate the risk of hypoglycemia associated with the use of antihypertensive drugs in older hospitalized diabetic patients treated with sulfonylureas and/or insulin. All diabetic patients admitted during 4 months in 1988, month in 1991, 4 months in 1993 and 4 months in 1995 (n = 3477, mean age 71.4 +/- 0.2 years, 1542 males and 1935 females) were enrolled in the study. During the four annual surveys 86 patients (mean age 71.1 +/- 1.4 years, 33 males and 53 females) presented hypoglycemia during hospital stay. The patients who presented hypoglycemia were less frequently users of sulfonylureas and more frequently users of a combination of insulin and sulfonylureas. Use of antihypertensive drugs was similar in the two groups studied, and among potentially interacting drugs considered in the analysis, sulfonamides were more frequently used in patients who experienced hypoglycemia. Moreover, patients with hypoglycemia used a higher number of drugs, had a longer length of stay and had a greater prevalence of hypoglycemia as admission problem. Finally, although not significant, liver and renal diseases were more frequent among patients with hypoglycemia. In the multivariate analysis, contemporary use of insulin and sulfonylureas, liver disease and length of stay were significantly associated with hypoglycemia, while none of the antihypertensive drugs showed a significant association with the occurrence of hypoglycemia during hospital stay. Our results indicate that antihypertensive drugs do not increase the risk of hypoglycemia in elderly diabetic patients.

Randomized trials have shown that angiotensin-converting enzyme (ACE) inhibitors reduce mortality and morbidity, and improve symptoms and exercise tolerance in selected patients with congestive heart failure (CHF). There is, however, no evidence on the effectiveness of ACE inhibitors in the typical, very old and frail patients with CHF.To compare the effects of ACE inhibitors and digoxin on 1-year mortality, morbidity, and physical function among patients aged 85 years.We conducted a retrospective cohort study using the SAGE database, a long-term care database linking patient information with drug utilization data. Among 64637 patients with CHF admitted to all nursing homes in 5 states between 1992 and 1995, we identified 19492 patients taking either an ACE inhibitor (n = 4911) or digoxin (n = 14890). Record of date of death was derived from Medicare enrollment files, and we used the part A Medicare files to identify hospital admissions and discharge diagnoses. As a measure of physical function, we used a scale for activities of daily living performance. The effect of ACE inhibitors was estimated using Cox proportional hazards models with digoxin users as the reference group.The overall mortality rate among ACE inhibitor recipients was more than 10% less than that of digoxin users (relative rate, 0.89; 95% confidence interval, 0.83-0.95). Mortality was equally reduced regardless of concomitant cardiovascular conditions and baseline physical function. Treatment with ACE inhibitors was associated with a tendency toward reduced hospital admissions that was more evident among patients with greater functional impairment. The adjusted relative rate for hospitalization for any reason was 0.96 (95% confidence interval, 0.91-1.01). The rate of functional decline was greatly reduced among ACE inhibitor recipients (relative rate, 0.74; 95% confidence interval, 0.69-0.80), and this effect was consistent and independent of background comorbidity and baseline physical function.These data suggest that survival and functional benefits of ACE inhibitor therapy extend to patients with CHF 85 years and older, and mostly women, both systematically underrepresented in randomized trials. Alternatively, digoxin has a detrimental effect in this population.

Increasing prevalence, use of health services, and number of deaths have made congestive heart failure (CHF) a new epidemic in the United States. Yet there are no adequate data to guide treatment of the more typical and complex cases of patients who are very old and frail.Using the SAGE database, we studied the cases of 86,094 patients with CHF admitted to any of the 1492 long-term care facilities of 5 states from 1992 through 1996. We described their clinical and functional characteristics and their pharmacologic treatment to verify agreement with widely approved guidelines. We evaluated age- and sex-related differences, and we determined predictors of receiving an angiotensin-converting enzyme (ACE) inhibitor by developing a multiple logistic regression model.The mean age of the population was 84.9 +/- 8 years. Eighty percent of the patients 85 years of age or older were women. More than two thirds of patients underwent frequent hospitalizations related to CHF in the year preceding admission to a long-term care facility. Coronary heart disease and hypertension were the most common causes. Half of the patients received digoxin and 45% a diuretic, regardless of background cardiovascular comorbidities. Only 25% of patients had a prescription for ACE inhibitors. The presence of cardiovascular comorbidity, already being a recipient of a large number of medications, a previous hospitalization for CHF, and admission to the facility in recent years were associated with an increased likelihood of receiving an ACE inhibitor. The presence of severe physical limitation was inversely related to use of ACE inhibitors, as were a series of organizational factors related to the facilities.Patients in long-term care who have CHF little resemble to those enrolled in randomized trials. This circumstance may explain, at least in part, the divergence from pharmacologic management consensus guidelines. Yet the prescription of ACE inhibitors varies significantly across facilities and depends on organizational characteristics.

Tumour necrosis factor-alpha (TNF) has been regarded as a potential mediator of cancer cachexia. Assessment of TNF circulating levels in cancer patients and their correlation with weight loss has led to controversial results.We measured TNF circulating levels in 28 patients with gastrointestinal cancer and 29 controls with benign gastrointestinal diseases at different times (08.00 h, 14.00 h, 20.00 h) before operation.TNF activity was not detected in any of controls at any times. In cancer patients, TNF circulating levels were detectable in 18 cases (64.3%) and appeared to be discontinuous. TNF levels above the limit of detection were present in 15 patients (53.6%) at 08.00 h, in 14 (50%) at 014.00 h and in nine (32.1%) at 20.00 h. Mean TNF levels were 14.3 +/- 4 pg mL(-1) at 08.00 h, 16.7 +/- 4.6 pg mL(-1) at 14.00 h (P = 0.05) and 18.5 +/- 10.2 pg mL(-1) at 20.00 h (P0.05 vs. 08.00 h and 14.00 h). According to Spearman's analysis, the sum of TNF concentrations at the three times significantly correlated with the severity of weight loss (Spearman's correlation coefficient = - 0.420; P = 0.026). TNF concentrations were consistently and significantly higher in patients with severe weight loss than in those with moderate or light weight loss at 08.00 h (26.3 +/- 8.3, 8.9 +/- 4.2, 3.8 +/- 2.1, respectively; P = 0.04 at one-way ANOVA). TNF levels were higher in anorectic than in nonanorectic patients at any hour, but the differences were not statistically significant.The present study demonstrates that TNF is intermittently or discontinuously detectable in patients with gastrointestinal cancer and that its levels correlate with the severity of weight loss.

Benzodiazepine use is a well-identified risk factor for falls and the resulting femur fractures in elderly adults. Benzodiazepines not requiring hepatic biotransformation may be safer than agents undergoing oxidation because oxidative activity has been shown to decline with age. The association between the use of either oxidative or nonoxidative benzodiazepines and the risk of femur fracture among elderly adults living in nursing homes was studied. A nested case-control study was conducted using the Systematic Assessment of Geriatric drug use via Epidemiology (SAGE) database; the records of 9,752 patients hospitalized for incident femur fracture during the period 1992 to 1996 were extracted, matching by age, gender, state, and index date to the records of 38,564 control patients. Conditional logistic regression models were conducted to estimate the odds ratios (ORs) for femur fracture with adjustment for potential confounders. The adjusted OR for the overall use of benzodiazepines was 1.10 (95% confidence interval [CI], 0.98-1.20); the risk seemed of only slightly greater magnitude for exposure to nonoxidative agents (1.18; 95% CI, 1.03-1.36) than to oxidative benzodiazepines (1.08; 95% CI, 0.95-1.23). Among the latter, the effect was mainly accounted for by the use of agents with a long elimination half-life. A dose relationship was observed exclusively among users of long half-life oxidative benzodiazepines. The risk associated with the use of nonoxidative benzodiazepines showed no relationship to the age of the patients. In contrast, patients aged 85 years or older receiving oxidative benzodiazepines at high dosages or as needed had a two- to three-fold increased risk of femur fracture than did patients in the younger age group. Among older individuals, the use of benzodiazepines slightly increased the risk of femur fracture, mainly irrespective of the metabolic fate of the drug. Our results suggest that the use of nonoxidative benzodiazepines does not carry a lower risk for femur fracture than does the use of oxidative benzodiazepines. However, the latter agents may be associated with a somewhat higher risk of side effects among the oldest old, especially at higher dosages.

Patterns of drug use among the elderly vary greatly depending on level of cognitive function, yet no systematic evaluation of drug use by type of dementia has been performed. We compared patterns of drug use among patients with Alzheimer's disease (AD) and vascular dementia (VaD) to examine their relation to cognitive impairment. We used a population-based data set with over 350,000 residents admitted between 1992 and 1995 to all Medicare-Medicaid-certified nursing homes in five states. After excluding patients with a history of mental disorders or retardation, we identified 23,073 patients age 65 years and over with a diagnosis of AD and 76,087 with VaD. We examined over 350 resident data items (demographic, diagnostic, clinical, treatment) collected with the federally mandated Minimum Data Set, drug data (brand name, dosage, route and frequency of administration for all drugs), and Medicare hospital claims. Cognitive status was measured with a 7-point cognitive performance scale. Estimates of drug use were adjusted for age, gender, race, and prevalence of respective disease. Patients with AD were younger and had more severe cognitive impairment than those with VaD. The latter had more comorbid clinical conditions (3.1 +/- 1.9 vs 2.3 +/- 1.7 for patients with AD) and received a greater number of total drugs (6.1 +/- 4.6 vs 5.3 +/- 4.3). Overall use of cardiovascular, anti-Parkinson, pulmonary, antineoplastic, and nutritional agents was less frequent among patients with AD than those with VaD. Results were consistent across different levels of cognitive impairment. Thus, patients with AD have fewer associated diseases and appear to be less intensively medically treated.

Infection by human herpesvirus 8 (HHV-8) is associated with the development of Kaposi’s sarcoma (KS). Since regression of KS can be achieved by treatment of the patients with alpha interferon (IFN-α), we analyzed the effects of IFN-α or anti-IFN-α antibodies (Ab) on HHV-8 latently infected primary effusion lymphoma-derived cell lines (BCBL-1 and BC-1) and on peripheral blood mononuclear cells (PBMC) from patients with all forms of KS and from at-risk subjects. IFN-α inhibited in a dose-dependent manner the amplification of HHV-8 DNA in BCBL-1 cells induced to lytic infection with tetradecanoyl phorbol acetate (TPA). This effect was associated with the inhibition of the expression of HHV-8 nut-1 and kaposin genes that are induced early and several hours, respectively, after TPA treatment. In addition, IFN-α inhibited virus production and/or release from BCBL-1 cells. Inhibition of nut-1 and kaposin genes by IFN-α was also observed in BC-1 cells induced with n -butyrate. Conversely, the addition of anti-IFN-α Ab to TPA-induced BCBL-1 cells resulted in a larger number of mature enveloped particles and in a more extensive cytopathic effect due to the neutralization of the endogenous IFN produced by these cells. IFN was also produced by cultured PBMC from HHV-8-infected individuals, and this was associated with a loss of viral DNA during culture. However, the addition of anti-IFN-α Ab or anti-type I IFN receptor Ab promoted the maintenance of HHV-8 DNA in these cells that was associated with the detection of the latency-associated kaposin RNA. Finally, the addition of IFN-α reduced the HHV-8 load in PBMC. Thus, IFN-α appears to have inhibitory effects on HHV-8 persistent infection of PBMC. These results suggest that, in addition to inhibiting the expression of angiogenic factors that are key to KS development, IFN-α may induce KS regression by reducing the HHV-8 load and/or inhibiting virus reactivation.

To investigate whether differences in the number and type of comorbid conditions may help explain the gender gap in mortality among patients with AD.The prevalence and incidence of AD are higher among women, who also have more severe cognitive impairment and accelerated decline. However, men have an exceedingly higher mortality.The authors conducted a retrospective cohort study on 5,831 men and 17,918 women with a diagnosis of AD. Data were from the Systematic Assessment of Geriatric drug use via Epidemiology (SAGE) database, which includes information on residents of 1,492 nursing homes in five US states (1992-1995). Men and women were compared with respect to demographic characteristics, dementia severity, psychiatric and behavioral symptoms, indicators of physical disability, and general health status. Also compared were age- and race-adjusted prevalence of all comorbid conditions at each level of cognitive impairment. In survival analyses, the risk of death and of hospitalization were determined by gender and level of cognitive impairment. Finally, gender-related differences in the intensity of pharmacologic treatment were examined.Women were older than men (83+/-7 versus 81+/-7 years) and were more likely to exhibit severe cognitive deterioration (27% versus 19% among men). Overall, there were no significant gender-related differences on several measures of physical disability (activities of daily living performance, gait and history of falls, incontinence, pressure sores), but significantly more women were underweight (45% versus 37% among men). However, the age- and race-adjusted 1-year mortality rate was 17% for women and 31% for men. The mortality rate of women at the highest degree of dementia severity was lower than the rate for men with minimal cognitive impairment. At any level of cognitive impairment, the prevalence of arrhythmia, chronic obstructive pulmonary disease, PD, and cancer was higher among men. Women were also less likely to be hospitalized, and they received fewer medications for each given disease.The survival advantage of women with AD relative to men may occur as a result of fewer comorbid clinical conditions associated with the diagnosis of dementia.

Home care programs for the treatment of frail elderly have been developed in many countries around the world. In the Silver Network project all services are provided in an integrated fashion by one "single entry" center, differently from the traditional fee-for-service or not integrated systems. The delivery of health and social services for frail elderly individuals are integrated and coordinated by a case manager who uses a "second generation" assessment instrument, the Minimum Data Set for Home Care (MDS-HC). We describe the principal clinical and functional characteristics of nearly 1300 patients admitted between 1997 and 1998 to such an integrated home care program in eleven Italian Health Agencies. The database, derived from the serial MDS-HC assessments of each patient, provides a unique opportunity to delineate the different criteria for eligibility for home care, and compare the selected populations of the participating Health Agencies.

We conducted a retrospective cohort study to examine whether patients with Alzheimer's disease (AD) or vascular dementia (VaD) differed in the number and type of associated comorbid conditions. In addition, we evaluated the impact of the severity of cognitive impairment on hospitalization and mortality of patients in each group. We studied 161,106 patients over age 65, with any degree of cognitive impairment, residing in any of 1,573 Medicare/Medicaid-certified nursing homes of 5 states of the USA between 1992 and 1995. Patients were assessed with the federally mandated Minimum Data Set (MDS). The MDS has been cross-linked to Medicare eligibility files and to the Medicare Provider Analysis and Review database. AD patients were younger, and more likely to be female and Caucasian than VaD patients. For comparable levels of cognitive impairment, AD patients appeared to have fewer comorbid conditions, including those that were not risk factors for VaD. In addition, patients with AD had decreased morbidity and mortality relative to patients with VaD. These findings support the hypothesis that AD patients are a healthier group of demented patients.

Because there is a lack of databases specific to long-term care, standardized assessments of nursing home residents are seen as a potential new resource for studying an important but neglected population. We describe the design and principal population characteristics of the first integrated database combining detailed clinical information and administrative claims data.We studied nearly 300,000 residents admitted between 1992 and 1994 to all Medicare/Medicaid certified nursing homes of five U.S. states (Kansas, Maine, Mississippi, New York, and South Dakota). The database crosslinks: (a) Resident Data: over 350 items (demographic, diagnostic, clinical, and treatments) collected with the Minimum Data Set; (b) Drug Data: brand name, dosage route, and frequency of administration for all drugs consumed by each resident; (c) Medicare Data: eligibility and inpatient hospital claims; (d) Facilities Data: structural and staffing information on nursing homes; and (e) Country Data: information on population, health professions and facility data, and economic parameters.Ninety-two percent of the residents were aged 65 years and older. Residents were predominantly white (85%) and female (72%). The average number of medical diagnoses was above three, and residents were receiving an average of six medications. Sixty-five percent of residents had at least one hospital claim following the initial assessment, most commonly related to cardiovascular diseases and metabolic disorders. Fifty-five percent of the facilities were for-profit and 33% were of small size. Quality indicators and staffing level varied significantly by state.The SAGE (Systematic Assessment of Geriatric drug use via Epidemiology) database provides a unique resource to study the relation between treatments received and outcomes experienced, particularly functional and health services outcomes, that have not been possible before in very old, frail people.

Hypertension is prevalent in the elderly, but an information gap remains regarding the old, frail, individuals with complex conditions living in long-term care.To analyze the patterns of antihypertensive drug therapy among elderly patients living in nursing homes to elucidate their conformity with consensus guidelines.We used a long-term care database that merged sociodemographic, functional, clinical, and treatment information on nearly 300000 patients admitted to the facilities of 5 US states between 1992 and 1994.Hypertension was diagnosed in 80206 patients (mean age, 82.7+/-7.8 years). The prevalence was higher among women and among blacks. About one fourth of patients had 6 or more comorbid conditions; 26%, 22%, and 29% had concomitant diagnoses of coronary heart disease, congestive heart failure, and cerebrovascular disease, respectively. Seventy percent of patients were treated pharmacologically. Calcium channel blockers were the most common agents (26%), followed by diuretics (25%), angiotensin-converting enzyme inhibitors (22%), and beta-blockers (8%). The relative use of these drugs changed according to the presence of other cardiovascular conditions. Adjusting for potential confounders, the relative odds of receiving antihypertensive therapy were significantly decreased for the oldest subjects (or =85 years old: odds ratio, 0.85; 95% confidence interval, 0.81-0.89) and those with marked impairment of physical (odds ratio, 0.77; 95% confidence interval, 0.73-0.81) and cognitive (odds ratio, 0.67; 95% confidence interval, 0.64-0.70) function.Among very old, frail hypertensive patients living in nursing homes, the pattern of treatment seems not to follow recommended guidelines; age, functional status, and comorbidity appear to be important determinants of treatment choice.

Background: using data from a cross-national data base we report the prevalence of urinary incontinence in nursing home residents, describe the main factors associated with bladder incontinence, and compare the usage of incontinence-related tests and care practices across countries. Results: urinary incontinence is highly prevalent (43-65%) in the seven countries studied. Dependency in ambulating, cognitive impairment and urinary tract infections are significantly associated with urinary incontinence in nursing home populations in most countries. Large cross-country differences are observed in the percentage of elderly undergoing incontinence-related testing and in the percentage of residents using appliances and programmes to treat or prevent incontinence. Conclusion: this study of different cultural approaches and strategies to evaluate and treat urinary incontinence may stimulate a public debate on the quality of care in nursing homes and promote the sharing of care practices designed to reduce urinary incontinence.

A series of 101 consecutive patients undergoing pancreatic resection for cancer was retrospectively analyzed to define factors that may affect the immediate postoperative outcome. Overall morbidity and mortality were 28.7% and 10.9%, respectively, although these figures were greatly reduced during the last years; the complication rate dropped from 55.6% (1981-1987) to 20.0% (1993-1995) and the mortality from 16.7% to 6.7%. At univariate statistical analysis the patient characteristics (sex, age, American Society of Anesthesiologists (ASA) class, nutritional status, jaundice), tumor characteristics (site, size, TNM stage, and grading), and type of surgery were found not to affect postoperative morbidity and mortality. In contrast, a significantly lower rate of compli- cations was observed in patients not undergoing gastric resection, in those who received 3 units or less of blood intraoperatively, and in subjects operated more recently (after 1990). At multivariate analysis the period when the operation was performed was the only independent variable that affected the immediate postoperative outcome. Among the examined factors, only the experience acquired over time regarding the intra- and perioperative treatment of these patients seems able to lower the rate of postoperative complications.

Cognitive impairment is associated with an increased mortality in older people. The prevalence and impact of comorbidity on functional status and mortality of demented patients has not been fully elucidated. Using a population-based data set, we describe the prevalence of cognitive impairment, functional status, principal comorbid conditions and 1-year survival for over 300,000 patients admitted to the nursing homes in five US states. Sixty-one percent of patients have some level of cognitive impairment, and this correlates with the degree of physical frailty. Severer cognitive impairment is associated with a higher mortality rate. Yet, patients with cognitive impairment appear to have fewer comorbid conditions and are less likely to receive medications and special treatments than residents with normal cognitive status. Additional studies are needed to understand whether demented patients may paradoxically be considered healthier or, instead, are only neglected.

OBJECTIVE: A prospective multicenter randomized trial was designed to evaluate the clinical efficacy of postoperative protein-sparing therapy. SUMMARY BACKGROUND DATA: The metabolic effect of postoperative protein-sparing therapy has been shown by several studies, but the clinical utility of this treatment has not been investigated by large prospective trials. METHODS: Six hundred seventy-eight patients undergoing major elective abdominal surgery were randomly assigned to receive either protein-sparing therapy after surgery (protein-sparing therapy group) or conventional therapy (control group). The patients were monitored for postoperative complications and mortality. RESULTS: The rate of major postoperative complications was similar in both groups (protein-sparing therapy group, 19.5%; control group, 20.9%; p=0.66) as were the overall postoperative mortality rates (4.7% and 3.5%, respectively; p=0.43). CONCLUSIONS: The present study indicates that routine protein-sparing therapy for patients normonourished or mildly malnourished undergoing major abdominal surgery is not clinically justified.

Laxatives are frequently taken especially by older persons, who have multiple diseases and are disabled. Major differences exist among countries in the type of laxatives taken, and knowledge of the intake patterns is important because of the potential adverse effects associated with particular ingredients. Laxatives and factors related to their use are described in a sample of 3257 patients admitted to 58 hospitals of the Gruppo Italiano di Farmacovigilanza nell'Anziano (GIFA) in 1991. The mean age was 68.2 years, median 73 years, more than 30% were ageor = 80 years, and 48.7% were men. The overall prevalence rates of laxative use during hospital stay and prior to admission were 11.5% and 11.3%, respectively. Increasing age was independently associated with laxative use after adjusting for gender, activities of daily living, cognitive function, number of active medical problems, medications taken, Italian region and length of stay. After excluding the prescriptions for hyperammoniemia, lactulose was the most frequently taken laxative (prevalence: 6.7% during hospital stay and 4.3% prior to hospital admission), followed by anthranoid laxatives such as senna, cascara, rhein and aloe (1.9% in-hospital and 3.3% pre-hospital). Other less frequently taken laxatives were picosulfate, phenolphthalein, lactitol, glycerol, bisacodyl and docusate. These patterns differ substantially from those reported by surveys conducted in other countries. Further studies are needed to assess the risks and benefits related to the intake of specific laxative ingredients.

BACKGROUND Doppler echocardiography has been proposed to detect left ventricular (LV) diastolic dysfunction in the elderly. However, the validity of this technique in differentiating the effects of pathology from those of normal aging has not been defined. METHODS Doppler indices of LV diastolic function were obtained in 85 patients (34 hypertensive, 29 with coronary artery disease, 22 with both conditions) and in 56 healthy volunteers. RESULTS A linear correlation with age was found for all parameters in controls, and for many parameters in patients. Also, in the presence of heart diseases, age exerted a powerful, independent effect on Doppler parameters. None of these differed between patients and controls in advanced age. CONCLUSION Due to the prevailing age-related variations in Doppler indices of diastolic performance occurring beyond the age of 65, Doppler echocardiography cannot be employed to diagnose LV diastolic dysfunction in the elderly.

Epstein-Barr virus (EBV) encodes genes that permit its persistence in human B lymphocytes and genes that ensure its replication in epithelial cells. Immune restraints on the virus are usually so effective that most EBV infections are limited to a minute fraction of B lymphocytes and of epithelial cells. As a result, most EBV infections are never symptomatic. Occasionally, the virus causes disease, often with the cooperation of the immune system or other less characterized cofactors. Infectious mononucleosis, a generally self-limited lymphoproliferative illness common in adolescents and young adults, is due to primary EBV infection and to the brisk cellular immune response it elicits. Lymphoproliferative disorders of EBV-infected B cells arise almost exclusively when cellular immunity is grossly compromised. EBV-positive Burkitt's lymphoma contain a translocated and deregulated c-myc oncogene and EBV-positive non-Hodgkin's lymphomas are characterized by the presence of Reed-Sternberg's and Hodgkin's cells, features that have not been directly linked to EBV. Many recent observations, however, including evidence that virus infection precedes malignant transformation and is often associated with a characteristic pattern of viral gene expression, provide continued interest in the relationship between the virus and these haematological malignancies.