Bruno Mazzei

Global DNA methylation in old subjects is correlated with frailty

Epigenetic variations have been widely described to occur during the aging process. To verify if these modifications are correlated with the inter-individual phenotypic variability of elderly people, we searched for a correlation between global DNA methylation levels and frailty. We found that the global DNA methylation levels were correlated to the frailty status in middle/advanced-aged subjects but not with age. A 7-year follow-up study also revealed that a worsening in the frailty status was associated to a significant decrease in the global DNA methylation levels. These results suggest that the relaxation of the epigenetic control in aging is specifically associated with the functional decline rather than with the chronological age of individuals. Thus, the modifications of DNA methylation, representing a drawbridge between the genetic and the environmental factors affecting the age-related decay of the organism, may play an important role in determining physiological changes over old age.

Prognostic significance of the short physical performance battery in older patients discharged from acute care hospitals.

We investigated the prognostic role of the Short Physical Performance Battery (SPPB) in elderly patients discharged from the acute care hospital. Our series consisted of 506 patients aged 70 years or more enrolled in a multicenter collaborative observational study. We considered three main outcomes: 1-year survival after discharge, functional decline, and hospitalization during follow-up. Independent predictors/correlates of the outcomes were investigated by Cox regression or logistic regression analysis when appropriate. The diagnostic accuracy of SPPB in relation to study outcomes was investigated by receiver operating characteristic (ROC) curve. SPPB score was associated with reduced mortality (hazard ratio [HR]=0.86, 95% confidence interval [CI] 0.78-0.95). When the analysis was adjusted for functional status at discharge, such an association was still near significant only for SPPB values >8 (HR=0.51; 95% CI 0.30-1.05). An SPPB score<5 could identify patients who died during follow-up with fair sensitivity (0.66), specificity (0.62), and area under the ROC curve (0.66). SPPB also qualified as independent correlate of functional decline (odds ratio [OR]=0.82; 95% CI 0.70-0.96), but not of rehospitalization or combined end-point death or rehospitalization. An SPPB score <5 could identify patients experiencing functional decline during follow-up with lower sensitivity (0.60), but higher specificity (0.69), and area under the ROC curve (0.69) with respect to mortality. In conclusion, SPPB can be considered a valid instrument to identify patients at major risk of functional decline and death after discharge from acute care hospital. However, it could more efficiently target patients at risk of functional decline than those at risk of death.

Targeting inflammation to slow or delay functional decline: where are we?

The role of inflammation in the pathophysiology of chronic age-related diseases is increasingly recognized, and inflammation could represent the common pathway linking diseases and disability. Thus, targeting inflammation could represent a useful strategy at preventing or delaying functional decline. In this paper we review recent evidence suggesting that selected drugs, such as statins, fibrates, angiotensin converting enzyme-inhibitors and angiotensin receptor blockers, and physical exercise may be able to contrast functional decline by blunting inflammation. Results from randomized trials investigating the effects of physical activity programs on inflammation and functional decline is still limited, and further investigations are warranted.

A cross-section analysis of FT3 age-related changes in a group of old and oldest-old subjects, including centenarians' relatives, shows that a down-regulated thyroid function has a familial component and is related to longevity.

Background: several studies suggest that a decreased thyroid activity might be favourable in oldest-old subjects and that subclinical thyroid hyperfunction may be detrimental. Objectives: to verify whether declining levels of circulating thyroid hormones may contribute to longevity. Design: cross-sectional observational study. Setting: all subjects were born in Calabria (southern Italy) and their ancestry in the region was ascertained up to the grandparents. Subjects: six hundred and four home-dwelling subjects (301 females, 303 males), divided into three groups: 278 individuals 60–85 years old; 179 children or nieces/nephews of centenarians who are 60–85 years old; 147 individuals older than 85 years. Methods: thyroid function parameters were measured in the frame of a comprehensive geriatric assessment. Results: FT3 and FT4 levels were negatively associated with age. Lower levels of FT3, FT4 and TSH were found in centenarians’ children and nieces/nephews with respect to age-matched controls. Indeed, being a relative of centenarians qualified as an independent correlate of thyroid parameters. Conclusions: age-related subtle thyroid hypofunction (either due to a familial component or due to a reset of the thyroid function occurring between the sixth and the eighth decade of life) appears to be related to longevity.

Urinary Incontinence in the Elderly and in the Oldest Old: Correlation with Frailty and Mortality

Urinary incontinence (UI) is very common in the elderly and has personal and social implications. Many authors have pointed out the necessity to analyze UI in correlation with the overall quality of aging, to better understand this syndrome and define measures for its prevention and treatment. In the present study, we addressed this problem by analyzing the UI correlation with frailty, which has emerged in the last decade as the geriatric syndrome correlated with individual homeostatic capacity and then as the basis of the age-related physical decline. In addition, the monitoring of our sample for a long period allowed us to estimate the prognostic significance of UI by analyzing the correlation between UI and mortality. The analysis was performed in a large sample that included numerous ultra-nonagenarians, a population segment that is still poorly known for UI and other geriatric parameters. We found a strict correlation between UI and frailty, suggesting that UI is correlated to the homeostatic and physiological decline leading to frailty. In addition, we found that UI is an independent mortality risk factor in ultra-nonagenarians, suggesting that the neurological sensitivity needed to be continent is lost very soon when the frailty associated physiological decline begins. On the whole, our study suggests that UI is a marker of frailty and that UI patients should be monitored and, in case, treated in a timely manner to avoid, or to limit, the effects of frailty such as malnutrition, falls, and the consequent accumulation of disabilities.

To grow old in southern Italy: A comprehensive description of the old and oldest old in Calabria

Background: The unprecedented growth of the elderly population is posing important social and medical problems as management of this population is highly demanding in terms of assistance and care. Consequently, many studies are focusing on the elderly subjects in order to better understand their needs by identifying various environmental, social, psychological, and genetic factors determining the quality of ageing. Objectives: Our aim was to carry out a survey of the elderly Calabrian population in order to highlight the social and medical conditions of this continuously growing population group. Methods: We have been monitoring the elderly population of Calabria for more than 10 years. For the present study, we collected data regarding 853 subjects by using two specific questionnaires, one for the subjects older than 90 years (400 subjects) and one for the subjects aged between 65 and 85 years (453 subjects). Results: The survey allowed us to carry out an extensive description of the ageing Calabrian population regarding the sociodemographic characteristics, living conditions, cognitive functioning, level of independence in activities of daily living, former and current diseases and health disorders. We could notice that males were in a better condition than females. In fact, male subjects turned out to have better physical performance and lower comorbidity, although their life expectancy is lower. Ultranonagenarians had a lower incidence of serious diseases (such as diabetes, osteoporosis and gastric ulcer), but a higher incidence of non-fatal chronic, debilitating conditions (cataract and bronchitis among others). Conclusion: The data we collected and analyzed offer a portrait of elderly Calabrian subjects, on who they are, how they feel, which social and psychological resources they have, and what their health status is. Analysis of the data highlighted that they are characterized by a lower physical performance in comparison to other European populations. Finally, the data presented here may also serve as a valuable source of information to characterize the ageing Calabrian population and improve the care of these subjects.

ESTIMATING GLOMERULAR FILTRATION RATE MIGHT HELP TO AVOID HYPOGLYCEMIA

antinuclear antibody, antiglomerular basement membrane antibody, serum electrophoresis, hepatitis B and C, and human immunodeficiency virus serology. His prostate-specific antigen was 20.5mg/L; CA19-9 was not raised. He had a positive c-antineutrophil cytoplasmic antibody (ANCA) with positive proteinase 3 antibody at 24 Au/mL (range 0–10). A skin biopsy was not done. The following tests revealed no evidence of malignancy: bronchoscopy and biopsy, pleural fluid and urine cytology, upper and lower gastrointestinal endoscopy, cystoscopy, and prostate biopsy. Computerized tomography (CT) of the thorax and abdomen showed a focal, low soft-tissue-density mass within the liver consistent with metastasis; bowel gas obscured the pancreas, and the prostate was enlarged (Figure 1). He was started on prednisolone and methotrexate (stopped once results of the CTscan were available), and his purpura disappeared, and inflammatory markers returned to normal. A liver biopsy was planned, but the patient died suddenly after a respiratory arrest. Postmortem examination revealed pulmonary embolism secondary to a deep vein thrombosis. A moderately differentiated adenocarcinoma of the pancreas was found, with liver and peritoneal metastases. Paraneoplastic vasculitis associated with solid tumors is rare. In a review, only 36 of more than 200 patients who had simultaneous cancer and vasculitis had a solid tumor, the majority had hematological malignancy. Bronchogenic carcinoma is the cancer most frequently associated with vasculitis. ANCA is usually negative in secondary vasculitis. There are few reports of ANCA-associated paraneoplastic vasculitis. Only two previous reported cases of pancreatic carcinoma and vasculitis could be found, and both were associated with Wegener’s granulomatosis. Diagnosis of vasculitis in this patient was based on the clinical picture, with involvement of skin and possibly kidney (hematuria) and lung (hemoptysis). The history of epistaxis and retinal vein occlusions raises the possibility of Wegener’s granulomatosis with positive c-ANCA. The role of the patient’s medications, including antibiotics, in the vasculitis is unlikely, because drug-induced vasculitis is usually ANCA negative. This patient had pancreatic carcinoma, which is also associated with Trousseau’s syndrome. The development of recurrent superficial thrombophlebitis characterizes this syndrome. Thrombi may occur in the arterial or the venous system. Patients typically have thromboembolic phenomena that are manageable with heparin-based anticoagulation, but these conditions are unresponsive to warfarin. This syndrome is most commonly associated with solid tumors of the adenocarcinoma type. Pancreatic tumors, especially those of the body or tail, seem to be associated with the highest risk of this syndrome. This patient had thrombophlebitis and a pulmonary embolism some months before admission, for which he was on warfarin. He also had a history of retinal vein occlusions. He was taking low-molecular-weight heparin during his admission, which should have been more effective than warfarin and a suitable alternative to unfractionated heparin. No case report has been found of paraneoplastic vasculitis caused by pancreatic carcinoma and Trousseau’s syndrome in the same patient. In summary, a patient with a solid neoplasm, c-ANCA positive paraneoplastic vasculitis, and Trousseau’s syndrome is presented. Because malignancy is associated with ANCA-positive vasculitis, it should be considered as part of the differential diagnosis in patients presenting with vasculitis. Diagnosis is important, because immunosuppressive regimens have the theoretical risk of provoking malignancy or its dissemination.

Seasonal hypertension: A clue to explain the high prevalence of unrecognized hypertension in the elderly? Gruppo Italiano di Farmacovigilanza nell’Anziano (GIFA)

Background and aims: Blood pressure is known to be influenced by the season, particularly in the elderly. The association between cold weather and unrecognized hypertension has not been previously studied. The present study aimed at assessing whether recognition of hypertension in the elderly follows a seasonal pattern. Methods: All patients over 64 with either first-listed or secondary diagnosis of hypertension at discharge (N=4487) out of 24585 consecutively admitted to 69 wards of Geriatrics or Internal Medicine during ten bi-monthly observation periods (May–June and September-October) were enrolled. The main outcome of the study was the prevalence of unrecognized hypertension, defined as no mention of hypertension and/or antihypertensive drugs in clinical histories collected on admission, and a first-listed or secondary discharge diagnosis of hypertension. Results: We found a total of 928 patients with unrecognized hypertension. Being admitted in the September–October period was independently associated with the outcome unrecognized hypertension (OR 1.25, 95% CI 1.08–1.46), as were smoking addiction (OR 1.57, 95% CI 1.23–2.0) and allocation to a medical ward (OR 1.21, 95% CI 1.04–1.41). Negative correlates of the outcome were multiple pathologies (OR 0.85, 95% CI 0.73–0.99), discharge diagnosis of coronary artery disease (OR 0.77, 95% CI 0.64–0.92) or diabetes mellitus (OR 0.81, 95% CI 0.67–0.97). Conclusions: Hypertension in the elderly may at least partly follow a seasonal pattern, and this finding may be relevant for screening and therapeutic decisions.

Identifying older diabetic patients at risk of poor glycemic control

BackgroundOptimal glycemic control prevents the onset of diabetes complications. Identifying diabetic patients at risk of poor glycemic control could help promoting dedicated interventions. The purpose of this study was to identify predictors of poor short-term and long-term glycemic control in older diabetic in-patients.MethodsA total of 1354 older diabetic in-patients consecutively enrolled in a multicenter study formed the training population (retrospective arm); 264 patients consecutively admitted to a ward of general medicine formed the testing population (prospective arm). Glycated hemoglobin (HbA1c) was measured on admission and one year after the discharge in the testing population. Independent correlates of a discharge glycemia ≥ 140 mg/dl in the training population were assessed by logistic regression analysis and a clinical prediction rule was developed. The ability of the prediction rule and that of admission HbA1c to predict discharge glycemia ≥ 140 mg/dl and HbA1c > 7% one year after discharge was assessed in the testing population.ResultsSelected admission variables (diastolic arterial pressure < 80 mmHg, glycemia = 143–218 mg/dl, glycemia > 218 mg/dl, history of insulinic or combined hypoglycemic therapy, Charlsons index > 2) were combined to obtain a score predicting a discharge fasting glycemia ≥ 140 mg/dl in the training population. A modified score was obtained by adding 1 if admission HbA1c exceeded 7.8%. The modified score was the best predictor of both discharge glycemia ≥ 140 mg/dl (sensitivity = 79%, specificity = 63%) and 1 year HbA1c > 7% (sensitivity = 72%, specificity = 71%) in the testing population.ConclusionA simple clinical prediction rule might help identify older diabetic in-patients at risk of both short and long term poor glycemic control.

Pre-admission functional decline predicts functional improvement among older patients admitted to acute care hospital

Background Functional decline from preadmission to admission may represent an important predictor of functional trajectories during hospitalization among older patients. Therefore, we aimed at describing the impact of preadmission decline on functional trajectories among older hospitalized patients. Methods Our series consisted of 2,011 patients aged 65 years or more consecutively admitted to four acute care wards of Geriatric Medicine participating to a multicenter observational study. Enrolled patients underwent comprehensive geriatric assessment (CGA) by Inter-RAI Minimum Data Set. Main outcomes were functional decline or improvement from hospital admission to discharge based on Activities of Daily Living (ADL) scale. The main exposure variable was ADL decline during the preadmission period (ie, 3 days before the onset of acute illness), and its impact on functional trajectories during stay was investigated by Cox regression models after adjusting for potential confounders. Results After adjusting for potential confounders, preadmission functional decline was significantly associated with functional improvement during stay (hazard ratio [HR] = 6.65; 95% confidence interval [CI] = 5.01-8.84), but not with functional decline. Severe cognitive impairment (HR = 0.28, 95% CI = 0.13-0.60), visual impairment (HR = 0.60, 95% CI = 0.41-0.89), and weight loss (HR = 0.67, 95% CI = 0.47-0.94) were associated with functional improvement during stay. Hearing impairment (HR = 1.94, 95% CI = 1.17-3.23) and mild (HR = 2.54, 95% CI = 1.41-4.58) or severe cognitive impairment (HR = 2.72, 95% CI = 1.13-6.56) were associated with functional decline during stay. Conclusions Patients experiencing recent preadmission functional decline should be considered as those for which the geriatric approach may lead to the better functional result in the acute care setting. CGA allows to individuate risk factors to be addressed in the acute care setting.