Can We Slow Down Biological Age Progression? Study Protocol for the proBNPage Reduction (PBAR) Randomized, Double-Blind, Placebo-Controlled Trial (Effects of 4 "Anti-Aging" Food Supplements in Healthy Older Adults).

Purpose: The availability of a simple and reliable marker of biological age might allow an acceleration of the research in the field of longevity extension. Previous studies suggest that this marker might be the N-terminal of B-type natriuretic peptide precursor (NT-proBNP), from which proBNPage, a biological age surrogate, can be calculated. Objectives of the study: 1) To fine-tune the method of proBNPage progression assessment and 2) To establish whether 4 "anti-aging" treatments, which provided promising results in previous studies, can modify proBNPage progression. Patients and Methods: This is a double-blind randomized placebo-controlled clinical trial on 120 adults aged 65-80 years, free of cardiovascular diseases. Participants will be randomized into 3 groups: A) Coenzyme Q10 100 mg bid + Selenium 100 mcg; B) Resveratrol 350 mg bid + TA-65 (Astragalus Membranaceus extract) 100U; C) Placebo-1 bid + Placebo-2. They will be followed for 2 years and checked 8 times, to assess both proBNPage progression and treatment safety. Secondary variables (handgrip strength, aerobic capacity at the step test and quality of life) will also be assessed. Primary outcome will be the demonstration of significant changes of proBNPage, compared to baseline, in the 3 groups at 6, 12, 18 and 24 months. Secondary outcome will be the demonstration of similar changes of secondary variables. Statistical analyses will be mainly performed by repeated measures ANOVA (both according to intention to treat and per protocol) and paired t tests. The study was approved by the Ethics Committee Area Vasta Emilia Centro, Emilia-Romagna Region, ID: 64/2022/Sper/AOUBo. Trial registration: ClinicalTrials.gov, NCT05500742. Conclusion: The use of proBNPage as a surrogate of biological age may prove an easy method to select anti-aging treatments worthy of further, more complex assessments.

The Prognostic Significance of Early Glycemic Profile in Acute Ischemic Stroke Depends on Stroke Subtype.

It is still unclear whether early glycemic profile after admission for acute ischemic stroke (IS) has the same prognostic significance in patients with lacunar and non-lacunar infarction. Data from 4011 IS patients admitted to a Stroke Unit (SU) were retrospectively analyzed. Lacunar IS was diagnosed by clinical criteria. A continuous indicator of early glycemic profile was calculated as the difference of fasting serum glucose (FSG) measured within 48 h after admission and random serum glucose (RSG) measured on admission. Logistic regression was used to estimate the association with a combined poor outcome defined as early neurological deterioration, severe stroke at SU discharge, or 1-month mortality. Among patients without hypoglycemia (RSG and FSG > 3.9 mmol/L), an increasing glycemic profile increased the likelihood of a poor outcome for non-lacunar (OR, 1.38, 95%CI, 1.24-1.52 in those without diabetes; 1.11, 95%CI, 1.05-1.18 in those with diabetes) but not for lacunar IS. Among patients without sustained or delayed hyperglycemia (FSG < 7.8 mmol/L), an increasing glycemic profile was unrelated to outcome for non-lacunar IS but decreased the likelihood of poor outcome for lacunar IS (OR, 0.63, 95%CI, 0.41-0.98). Early glycemic profile after acute IS has a different prognostic significance in non-lacunar and lacunar patients.

Probability of Cardioembolic vs. Atherothrombotic Pathogenesis of Cryptogenic Strokes in Older Patients.

Some clinical, laboratory, ECG, and echocardiographic parameters could provide useful indications to assess the probability of cardioembolism or atherothrombosis in cryptogenic strokes. We retrospectively examined 290 patients with ischemic stroke aged ≥60 years, divided into 3 groups: strokes originating from large artery atherothrombosis (n = 92), cardioembolic strokes caused by paroxysmal atrial fibrillation (n = 88) and cryptogenic strokes (n = 110). In addition to echocardiographic and routine clinical-laboratory variables, neutrophil:lymphocyte ratio, red blood cell distribution width, mean platelet volume, P wave and PR interval duration and biphasic inferior P waves, both on admission and after 7 to 10 days, were also considered. By multiple logistic regression, cardioembolic strokes were compared with large artery atherothrombosis strokes, and beta coefficients were rounded to produce a scoring system. Late PR interval ≥188 ms, left atrium ≥4 cm, left ventricular end-diastolic volume <65 ml, and posterior circulation syndrome were associated with paroxysmal atrial fibrillation (positive scores). In contrast, male gender, hypercholesterolemia, and initial platelet count ≥290 × 109/L were associated with atherothrombosis of large arteries (negative scores). The algebraic sum of these scores produced values indicative of cardioembolism if >0 (positive predictive value 89.1%), or of atherothrombosis, if ≤0 (positive predictive value 72.5%). The area under the receiver operating characteristic curve was 0.85. Among cryptogenic strokes, 41.5% had a score >0 (probable atrial fibrillation) and 58.5% had a score ≤0 (possible atherothrombosis). In conclusion, a scoring system based on electrocardiogram, laboratory, clinical and echocardiographic parameters can provide useful guidance for further investigations and secondary prevention in older patients with cryptogenic stroke.

Prognostic significance of diabetes and stress hyperglycemia in acute stroke patients.

BACKGROUND: Hyperglycemic non-diabetic stroke patients have a worse prognosis than both normoglycemic and diabetic patients. Aim of this study was to assess whether hyperglycemia is an aggravating factor or just an epiphenomenon of most severe strokes. METHODS: In this retrospective study, 1219 ischemic or hemorrhagic stroke patients (73.7 ± 13.1 years) were divided into 4 groups: 0 = non-hyperglycemic non-diabetic, 1 = hyperglycemic non-diabetic, 2 = non-hyperglycemic diabetic and 3 = hyperglycemic diabetic. Hyperglycemia was defined as fasting blood glucose ≥ 126 mg/dl (≥ 7 mmol/l) measured the morning after admission, while the diagnosis of diabetes was based on a history of diabetes mellitus or on a glycated hemoglobin ≥ 6.5% (≥ 48 mmol/mol), independently of blood glucose levels. All diabetic patients, except 3, had Type 2 diabetes. The 4 groups were compared according to clinical history, stroke severity indicators, acute phase markers and main short term stroke outcomes (modified Rankin scale ≥ 3, death, cerebral edema, hemorrhagic transformation of ischemic lesions, fever, oxygen administration, pneumonia, sepsis, urinary infection and heart failure). RESULTS: Group 1 patients had more severe strokes, with larger cerebral lesions and higher inflammatory markers, compared to the other groups. They also had a high prevalence of atrial fibrillation, prediabetes, previous stroke and previous arterial revascularizations. In this group, the highest frequencies of cerebral edema, hemorrhagic transformation, pneumonia and oxygen administration were obtained. The prevalence of dependency at discharge and in-hospital mortality were equally high in Group 1 and Group 3. However, in multivariate analyses including stroke severity, cerebral lesion diameter, leukocytes and C-reactive protein, Group 1 was only independently associated with hemorrhagic transformation (OR 2.01, 95% CI 0.99-4.07), while Group 3 was independently associated with mortality (OR 2.19, 95% CI 1.32-3.64) and disability (OR 1.70, 95% CI 1.01-2.88). CONCLUSIONS: Hyperglycemic non-diabetic stroke patients had a worse prognosis than non-hyperglycemic or diabetic patients, but this group was not independently associated with mortality or disability when size, severity and inflammatory component of the stroke were accounted for.

Association of early glycemic change with short-term mortality in lobar and non-lobar intracerebral hemorrhage.

The association between early glycemic change and short-term mortality in non-diabetic patients with acute intracerebral hemorrhage (ICH) is unclear. We retrospectively investigated non-diabetic patients with lobar (n = 262) and non-lobar ICH (n = 370). Each patient had a random serum glucose test on hospital admission and a fasting serum glucose test within the following 48 h. Hyperglycemia was defined as serum glucose ≥ 7.8 mmol/l. Four patterns were determined: no hyperglycemia (reference category), persistent hyperglycemia, delayed hyperglycemia, and decreasing hyperglycemia. Associations with 30-day mortality were estimated using Cox models adjusted for major features of ICH severity. Persistent hyperglycemia was associated with 30-day mortality in both lobar (HR 3.00; 95% CI 1.28-7.02) and non-lobar ICH (HR 4.95; 95% CI 2.20-11.09). In lobar ICH, 30-day mortality was also associated with delayed (HR 4.10; 95% CI 1.77-9.49) and decreasing hyperglycemia (HR 2.01, 95% CI 1.09-3.70). These findings were confirmed in Cox models using glycemic change (fasting minus random serum glucose) as a continuous variable. Our study shows that, in non-diabetic patients with ICH, early persistent hyperglycemia is an independent predictor of short-term mortality regardless of hematoma location. Moreover, in non-diabetic patients with lobar ICH, both a positive and a negative glycemic change are associated with short-term mortality.

The association of proBNPage with manifestations of age-related cardiovascular, physical, and psychological impairment in community-dwelling older adults.

NT-proB-type natriuretic peptide (NT-proBNP) serum concentration can be transformed by simple formulas into proBNPage, a surrogate of biological age strongly associated with chronological age, all-cause mortality, and disease count. This cross-sectional study aimed to assess whether proBNPage is also associated with other manifestations of the aging process in comparison with other variables. The study included 1117 noninstitutionalized older adults (73.1 ± 5.6 years, 537 men). Baseline measurements of serum NT-proBNP, erythrocyte sedimentation rate, hemoglobin, lymphocytes, and creatinine, which have previously been shown to be highly associated with both age and all-cause mortality, were performed. These variables were compared between subjects with and without manifestations of cardiovascular impairment (myocardial infarction (MI), stroke, peripheral artery disease (PAD), arterial revascularizations (AR)), physical impairment (long step test duration (LSTD), walking problems, falls, deficit in one or more activities of daily living), and psychological impairment (poor self-rating of health (PSRH), anxiety/depression, Mini Mental State Examination (MMSE) score < 24). ProBNPage (years) was independently associated (OR, 95% CI) with MI (1.08, 1.07-1.10), stroke (1.02, 1.00-1.05), PAD (1.04, 1.01-1.06), AR (1.06, 1.04-1.08), LSTD (1.03, 1.02-1.04), walking problems (1.02, 1.01-1.03), and PSRH (1.02, 1.01-1.02). For 5 of these 7 associations, the relationship was stronger than that of chronological age. In addition, proBNPage was univariately associated with MMSE score < 24, anxiety/depression, and falls. None of the other variables provided comparable performances. Thus, in addition to the known associations with mortality and disease count, proBNPage is also associated with cardiovascular manifestations as well as noncardiovascular manifestations of the aging process.

N-terminal pro B-type natriuretic peptide (NT-proBNP): a possible surrogate of biological age in the elderly people.

NT-proB-type natriuretic peptide (NT-proBNP) increases with age and is associated with all-cause mortality. With this study, we assessed its possible utilization as a marker of biological age in comparison with other variables. The study included 1079 non-institutionalized elderly subjects (mean age 72.8 ± 5.5 years, 561 women). Baseline measurements were performed of serum NT-proBNP and of some laboratory variables previously utilized to estimate biological age (creatinine, albumin, C-reactive protein, cholesterol, blood glucose, leukocytes, lymphocytes, hemoglobin, mean cell volume). During 7 years of follow-up, 114 all-cause deaths occurred. The logarithm of NT-proBNP was the most age-related parameter (r = 0.35, P < 0.0001). Its relationship with mortality, according to Cox regression and ROC curve (AUC = 0.707, 95% CI 0.654-0.759), was stronger than that of all other variables, including age. In multivariate analysis, only NT-proBNP and age remained independently associated with mortality. The regression lines between age and NT-proBNP (pg/ml) allowed a separate estimation of biological age ("proBNPage") for men (= [log(NT-proBNP) + 1.2068]/0.0827) and for women (= [log(NT-proBNP) - 1.5258]/0.0478). The hazard ratio of all-cause mortality for the fifth quintile of proBNP age (≥ 85 years) compared with the first quintile (< 61 years) was 7.9 (95% CI 3.6-17.5). Similarly, the difference between pro-BNPage and chronological age was associated with a hazard ratio of 3.5 in the fifth quintile (95% CI 1.9-6.4) and was associated with disease count (P for trend = 0.0002). In conclusion, NT-proBNP was the best indicator of biological age, which can be estimated by simple formulas and might be used for prognostic purposes or as a surrogate end point in epidemiological and intervention studies.

Prognostic role of nutritional status in elderly patients hospitalized for COVID-19: a monocentric study.

BACKGROUND: Symptomatic severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection incidence is higher in the elderly patients. Pre-existing geriatric conditions such as comorbidity and frailty seem related to worse hospital outcomes. AIMS: To assess the role of nutritional status as an independent prognostic factor for in-hospital death in elderly patients. METHODS: Consecutive elderly patients (age > 65 years) hospitalized for novel coronavirus disease (COVID-19) were enrolled. Demographics, laboratory and comorbidity data were collected. Nutritional status was evaluated using the Geriatric Nutritional Risk Index (GNRI). Uni- and multivariate Cox regression analyses to evaluate predictors for in-hospital death were performed. RESULTS: One hundred and nine hospitalized elderly patients (54 male) were consecutively enrolled. At univariate analysis, age (HR 1.045 [CI 1.008-1.082]), cognitive impairment (HR 1.949 [CI 1.045-3.364]), C-reactive protein (HR 1.004 [CI 1.011-1.078]), lactate dehydrogenases (HR 1.003 [CI 1.001-1.004]) and GNRI moderate-severe risk category (HR 8.571 [CI 1.096-67.031]) were risk factors for in-hospital death, while albumin (HR 0.809 [CI 0.822-0.964]), PaO2/FiO2 ratio (HR 0.996 [CI 0.993-0.999]) and body mass index (HR 0.875 [CI 0.782-0.979]) were protective factors. Kaplan-Meier survival curves showed a significative higher survival in patients without GNRI moderate or severe risk category (p = 0.0013). At multivariate analysis, PaO2/FiO2 ratio (HR 0.993 [CI 0.987-0.999], p = 0.046) and GNRI moderate-severe risk category (HR 9.285 [1.183-72.879], p = 0.034) were independently associated with in-hospital death. CONCLUSION: Nutritional status assessed by GNRI is a significative predictor of survival in elderly patients hospitalized for COVID-19. The association between GNRI and PaO2/FiO2 ratio is a good prognostic model these patients.

Medico-legal assessment of personal damage in older people: report from a multidisciplinary consensus conference.

Ageing of the global population represents a challenge for national healthcare systems and healthcare professionals, including medico-legal experts, who assess personal damage in an increasing number of older people. Personal damage evaluation in older people is complex, and the scarcity of evidence is hindering the development of formal guidelines on the subject. The main objectives of the first multidisciplinary Consensus Conference on Medico-Legal Assessment of Personal Damage in Older People were to increase knowledge on the subject and establish standard procedures in this field. The conference, organized according to the guidelines issued by the Italian National Institute of Health (ISS), was held in Bologna (Italy) on June 8, 2019 with the support of national scientific societies, professional organizations, and stakeholders. The Scientific Technical Committee prepared 16 questions on 4 thematic areas: (1) differences in injury outcomes in older people compared to younger people and their relevance in personal damage assessment; (2) pre-existing status reconstruction and evaluation; (3) medico-legal examination procedures; (4) multidimensional assessment and scales. The Scientific Secretariat reviewed relevant literature and documents, rated their quality, and summarized evidence. During conference plenary public sessions, 4 pairs of experts reported on each thematic area. After the last session, a multidisciplinary Jury Panel (15 members) drafted the consensus statements. The present report describes Conference methods and results, including a summary of evidence supporting each statement, and areas requiring further investigation. The methodological recommendations issued during the Conference may be useful in several contexts of damage assessment, or to other medico-legal evaluation fields.

Association of prestroke glycemic status with stroke mortality.

OBJECTIVE: The role of diabetes as a predictor of mortality after stroke remains uncertain, and there are very few data for pre-diabetes. This study investigated the association of pre-diabetes and diabetes with 30-day and 1-year mortality after ischemic stroke (IS) and primary intracerebral hemorrhage (ICH). RESEARCH DESIGN AND METHODS: Between 2006 and 2013, 2076 patients with IS and 586 patients with ICH (median age 79) were admitted to hospital within 24 hours after stroke onset and were treated in a stroke unit, where they underwent measurement of glycated hemoglobin (HbA1c). Diabetes was retrospectively defined based on medical history, diagnosis during hospital stay or HbA1c ≥6.5% (48 mmol/mol). Pre-diabetes was defined as HbA1c of 5.7%-6.4% (39-47 mmol/mol). Stroke severity was measured using the National Institutes of Health Stroke Scale (NIHSS). HRs were used to test the association of pre-diabetes and diabetes with 30-day and 1-year mortality after stroke onset. RESULTS: Among patients with IS, 830 had pre-diabetes and 632 had diabetes; 280 died within 30 days and the other 77 within 1 year. Among patients with ICH, 106 had pre-diabetes and 56 had diabetes; 150 died within 30 days and the other 92 within 1 year. In both stroke subtypes, pre-diabetes and diabetes were associated with higher 30-day mortality. In IS, however, the association was limited to patients with prestroke disability and very severe stroke. At NIHSS 25, HR was 1.58 (95% CI 1.07 to 2.35) for pre-diabetes and 1.67 (95% CI 1.14 to 2.46) for diabetes compared with normoglycemia. In ICH, the association was limited to women for pre-diabetes (HR 1.93, 95% CI 1.15 to 3.24) and to men for diabetes (HR 1.78, 95% CI 1.02 to 3.12). Prestroke glycemic status was unrelated to 1-year mortality. CONCLUSIONS: Both pre-diabetes and diabetes predict short-term mortality after acute stroke, but the association varies depending on both prestroke and stroke-related characteristics. These findings may explain the heterogeneous results obtained by previous studies.

Age-specific rate of undiagnosed diabetes and prediabetes in acute stroke.

AIMS: We investigated age-specific rates of undiagnosed diabetes and prediabetes among patients with acute stroke. METHODS: We used data from 2223 patients with acute stroke consecutively admitted to an Italian Stroke Unit (SU) between 2010 and 2015. Information from medical records and glycated hemoglobin (HbA1c) measured on admission was retrospectively used to screen for diabetes and prediabetes defined according to standard criteria. RESULTS: Overall rate of diabetes undiagnosed at admission and diabetes still undiagnosed at SU discharge were 9.7% and 6.7% but age-specific prevalence peaked up to 12.0% and 9.0% after age 80. At admission, the proportion of all undiagnosed diabetes on total diabetes cases was one out of every two cases before age 60 and three out of every four cases after age 80. In these same age intervals, one out of every three diabetes cases was still undiagnosed at SU discharge. Regardless of age, about three out of ten patients with acute stroke had prediabetes. Less than 2% of these patients had a prediabetes diagnosis before or after SU admission. CONCLUSIONS: In patients with acute stroke, diabetes is substantially underdiagnosed before age 60 and after age 80. Prediabetes is highly prevalent but mostly undiagnosed at all ages.

Predictors of cognitive impairment assessed by Mini Mental State Examination in community-dwelling older adults: relevance of the step test.

BACKGROUND: Several predictors of cognitive impairment assessed by Mini Mental State Examination (MMSE) have previously been identified. However, which predictors are the most relevant and what is their effect on MMSE categories remains unclear. METHODS: Cross-sectional and longitudinal study using data from 1116 older adults (72.6 ±â€¯5.6 years, 579 female), 350 of whom were followed for 7 years. At baseline, the following variables were collected: personal data, marital status, occupation, anthropometric measures, risk factors, previous cardiovascular events, self-rated health and physical activity during the last week. Furthermore, routine laboratory tests, abdominal echography and a step test (with measurement of the time needed to ascend and descend two steps 20 times) were performed. The associations of these variables with cross-sectional cognitive deficit (MMSE < 24) and longitudinal cognitive decline (decrease of MMSE score over 7 years of follow-up) were investigated using logistic regression models. RESULTS: Cross-sectional cognitive deficit was independently associated with school education ≤ 5 years, prolonged step test duration, having been blue collar or housewife (P ≤ 0.0001 for all) and, with lower significance, with advanced age, previous stroke and poor recent physical activity (P < 0.05). Longitudinal cognitive decline was mainly associated with step test duration (P = 0.0001) and diastolic blood pressure (P = 0.0002). The MMSE categories mostly associated with step test duration were orientation, attention, calculation and language, while memory appeared to be poorly or not affected. CONCLUSIONS: In our cohort of older adults, step test duration was the most relevant predictor of cognitive impairment.

Risk of Exclusion From Stroke Rehabilitation in the Oldest Old.

OBJECTIVE: To investigate whether oldest-old age (≥85y) is an independent predictor of exclusion from stroke rehabilitation. DESIGN: Retrospective cohort study. SETTING: Stroke unit (SU) of a tertiary hospital. PARTICIPANTS: Elderly patients (N=1055; aged 65-74y, n=230; aged 75-84y, n=432; aged ≥85y, n=393) who, between 2009 and 2012, were admitted to the SU with acute stroke and evaluated by a multiprofessional team for access to rehabilitation. The study excluded patients for whom rehabilitation was unnecessary or inappropriate. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Access to an early mobilization (EM) protocol during SU stay and subsequent access to postacute rehabilitation after SU discharge. Analyses were adjusted for prestroke and stroke-related characteristics. RESULTS: 32.2% of patients were excluded from EM. Multivariable-adjusted odds ratios (ORs) of EM exclusion were 1.30 (95% confidence interval [CI], .76-2.21) for ages 75 to 84 years and 2.07 (95% CI, 1.19-3.59) for ages ≥85 years compared with ages 65 to 74 years. Of 656 patients admitted to EM and who, at SU discharge, had not yet fully recovered their prestroke functional status, 18.4% were excluded from postacute rehabilitation. For patients able to walk unassisted at SU discharge, the probability of exclusion did not change across age groups. For patients unable to walk unassisted at SU discharge, ORs of exclusion from postacute rehabilitation were 3.74 (95% CI, 1.26-11.13) for ages 75 to 84 years and 9.15 (95% CI, 3.05-27.46) for ages ≥85 years compared with ages 65 to 74 years. CONCLUSIONS: Oldest-old age is an independent predictor of exclusion from stroke rehabilitation.

Inverse Association Between Neck Pain and All-Cause Mortality in Community-Dwelling Older Adults.

Objective: In a previous study, we found an apparent protective effect of neck pain on all-cause mortality in subjects older than age 85 years. The present longitudinal investigation was performed to verify this unexpected finding in a larger sample and to establish its significance. Design: Population follow-up study. Setting: Three towns of Northern Italy. Subjects: We examined 5,253 community-dwelling residents age 65-102 years (55% female). Methods: Through a postal questionnaire, baseline information was obtained concerning cardiovascular risk factors, self-rated health, physical activity, cardiovascular events, medical therapy, and presence of pain in the main joints. Seven-year all-cause mortality was the end point. Results: During follow-up, 1,250 people died. After adjustment for age, sex, anti-inflammatory drugs, physical activity, and main risk factors, neck pain was inversely associated with mortality (hazard ratio = 0.74, 95% confidence interval = 0.64-0.86, P < 0.001). This association was present, with high significance, in each of the eight following subgroups: men, women, age 65-74 years, age 75-84 years, age ≥85 years and residents of each of the three towns. The subjects without neck pain (N = 3,158) were older, more often men, less often hypercholesterolemic, less physically active, and had more frequently had a stroke than the subjects with neck pain (N = 2,095). There were no differences in the causes of death between subjects with or without neck pain. Conclusion: This study has confirmed the existence of an independent inverse association between neck pain and mortality in the elderly, suggesting that reduced sensitivity to neck pain may be a new marker of frailty.

Accuracy of Lung Ultrasound in Patients with Acute Dyspnea: The Influence of Age, Multimorbidity and Cognitive and Motor Impairment.

Discriminating between causes of dyspnea may be difficult, particularly in the elderly. The aim of this retrospective study of 83 inpatients with acute dyspnea was to assess the influence of age, multimorbidity and cognitive or motor impairment on the diagnostic accuracy of lung ultrasound (LUS) in discriminating acute heart failure (AHF) from noncardiogenic dyspnea (NCD). Univariate analysis indicates that LUS misdiagnosis was associated with the following parameters: history of stroke (p = 0.037), lower activity of daily living (p = 0.039), higher modified-Rankin scale (mRS) (p = 0.027) and need of two operators to complete LUS because of reduced patient compliance (p = 0.030). Regression analysis identified only history of stroke (p = 0.048) as an independent predictor of LUS misdiagnosis. This study supports LUS usefulness to differentiate AHF from NCD. Our data suggest that diagnostic accuracy of LUS is affected by history of stroke as a proxy for severe motor impairment but not by age, cognitive impairment and multimorbidity.

Physical Activity and Other Determinants of Survival in the Oldest Adults.

OBJECTIVES: To determine the role of physical activity as a possible survival determinant in the oldest adults. DESIGN: Prospective, longitudinal, population-based cohort. SETTING: The Pianoro Study of community-dwelling older adults in three towns in northern Italy. PARTICIPANTS: Noninstitutionalized individuals aged 85 and older (n = 500; mean age 89.6 ± 3.1, 65% female). MEASUREMENTS: Participants provided information on marital status, educational level, previous work activity, cardiovascular risk factors, previous cardiovascular events, self-rated health, joint pain, and functional status. Physical activity was quantified using the Physical Activity Scale for the Elderly. Seven-year mortality was known for all subjects. RESULTS: During the 7 years of follow-up, 365 subjects died. According to Cox proportional hazards regression, the following factors were found to be independently associated with mortality: PASE score (hazard ratio (HR) = 0.987, 95% confidence interval (CI) = 0.981-0.993, P < .001), male sex (HR = 1.642, 95% CI = 1.411-2.068, P < .001), age in years (HR = 1.077, 95% CI = 1.040-1.116, P < .001), previous stroke (HR = 1.908, 95% CI = 1.362-2.673, P < .001), poor self care (HR = 1.662, 95% CI = 1.231-2.246, P < .001), neck pain (HR = 0.649, 95% CI = 0.497-0.849, P = .002), self rated health (HR = 0.991, 95% CI = 0.985-0.997, P = .002). CONCLUSION: In the oldest adults, accurate quantification of physical activity may provide important prognostic information. The predictive value of cardiovascular risk factors, except age, male sex, and prior stroke, was confirmed to be negligible. An unexpected inverse association between neck pain and mortality may require further investigation.

Integrated Use of Lung Ultrasound and Chest X-Ray in the Detection of Interstitial Lung Disease.

BACKGROUND: Current data have shown that lung ultrasound (LUS) may be useful in the detection of interstitial lung disease (ILD) by the evaluation of B-lines, the sonographic marker of pulmonary interstitial syndrome. Nevertheless, no prospective study has compared LUS to chest X-ray (CXR) for ILD assessment, and there is no general agreement on the specific echographic diagnostic criteria for defining ILD. OBJECTIVES: The aims of this study were (1) to compare the accuracy of LUS and CXR in the detection of ILD using high-resolution CT (HRCT) as the gold standard and (2) to compare the accuracy of different echographic diagnostic criteria for ILD diagnosis. METHODS: LUS was performed on 104 patients undergoing HRCT for suspected ILD. In 49 patients, a CXR scan performed within 3 months of HRCT was analyzed. ILD was defined as the presence of ≥5 B-lines in ≥3 chest areas. A total B-line score (TBLS) was also calculated, as in previous studies. The observers evaluating LUS and CXR were blinded to the HRCT results and clinical data. RESULTS: On HRCT, ILD was assessed in 50 patients. CXR was specific (91%; 95% CI 80-100) but not sensitive (48%; 95% CI 28-67). Conversely, LUS showed high sensitivity (92%; 95% CI 84-99) and low specificity (79%; 95% CI 69-90). Using a TBLS, sensitivity did not change, while specificity decreased. CONCLUSIONS: LUS could be a sensitive tool for ILD detection. CXR and LUS have different but complementary features, and their combined use could reduce the need for HRCT. The use of different diagnostic criteria for defining ILD does not affect sensitivity but influences specificity.

The Effect of Age on Characteristics and Mortality of Intracerebral Hemorrhage in the Oldest-Old.

BACKGROUND: Incidence of acute intracerebral hemorrhage (ICH) increases with age, but there is a lack of information about ICH characteristics in the oldest-old (age ≥85 years). In particular, there is a need for information about hematoma volume, which is included in most clinical scales for prediction of mortality in ICH patients. Many of these scales also assume that, independent of ICH characteristics, the oldest-old have a higher mortality than younger elderly patients (age 65-74 years). However, supporting evidence from cohort studies is limited. We investigated ICH characteristics of oldest-old subjects compared to young (<65 years), young-old (65-74 years) and old-old (75-84 years) subjects. We also investigated whether age is an independent mortality predictor in elderly (age ≥65 years) subjects with acute ICH. METHODS: We retrospectively collected clinical and neuroimaging data of 383 subjects (age 34-104 years) with acute supratentorial primary ICH who were admitted to an Italian Stroke Unit (SU) between October 2007 and December 2014. Measured ICH characteristics included hematoma location, volume and intraventricular extension of hemorrhage on admission CT scan; admission Glasgow Coma Scale ≤8 and hematoma expansion (HE) measured on follow-up CT-scans obtained after 24 h. General linear models and logistic models were used to investigate the association of age with ICH characteristics. These models were adjusted for pre-admission characteristics, hematoma location and time from symptom onset to admission CT scan. Limited to elderly subjects, Cox models were used to investigate the association of age with in-SU and 1-year mortality: the model for in-SU mortality adjusted for pre-admission and ICH admission characteristics and the model for 1-year mortality additionally adjusted for functional status and disposition at SU discharge. RESULTS: Independent of pre-admission characteristics, hematoma location and time from symptom onset to admission CT-scan, oldest-old subjects had the highest admission hematoma volume (p < 0.01). Age was unrelated to all other ICH characteristics including HE. In elderly patients, multivariable adjusted risk of in-SU and 1-year mortality did not vary across age categories. CONCLUSIONS: Oldest-old subjects with acute supratentorial ICH have higher admission hematoma volume than young and young-old subjects but do not differ for other ICH characteristics. When taking into account confounding from ICH characteristics, risk of in-SU and 1-year mortality in elderly subjects with acute supratentorial ICH does not differ across age categories. Our findings question use of age as an independent criterion for stratification of mortality risk in elderly subjects with acute ICH.

Homocysteinemia and early outcome of acute ischemic stroke in elderly patients.

OBJECTIVES: Plasma total homocysteine (tHcy) is a risk factor for ischemic stroke (IS) but its relationship with IS outcome is uncertain. Moreover, previous studies underrepresented older IS patients, although risk of both hyperhomocysteinemia and IS increases with age. We investigated whether, in elderly patients with acute IS, tHcy measured on admission to the Stroke Unit (SU) is an independent predictor of SU discharge outcomes. MATERIALS AND METHODS: Data are for 644 consecutive patients aged 80.3 ± 8.7 years, admitted to an Italian SU with diagnosis of acute IS. Plasma tHcy was measured on SU admission. Investigated outcomes included mortality during SU stay and poor functional status (modified Rankin Scale score ≥3) at SU discharge for survivors. The association of plasma tHcy with the study outcomes was assessed using Odds Ratios (OR) and their corresponding 95% confidence intervals (95%CI) from logistic regression models adjusted for demographics, pre-stroke features, IS severity, and laboratory data on SU admission (serum C-reactive protein, serum albumin, and renal function). RESULTS: Median plasma tHcy was 16.7 µmol/L (interquartile range, 13.0-23.3 µmol/L). Outcome incidence was 5.3% for mortality and 49.7% for poor functional status. Plasma tHcy was unrelated to mortality in both univariate and multivariable-adjusted analyses. Conversely, plasma tHcy was associated with poor functional status of survivors in univariate analyses (P = 0.014). Multivariable-adjusted analyses showed that, compared to normal homocysteinemia (tHcy <16 µmol/L), risk of being discharged with poor functional status significantly increased for moderate (tHcy ≥30 mol/L) but not mild (16.0-29.9 µmol/L) hyperhomocysteinemia. CONCLUSIONS: In elderly patients with acute IS, high admission plasma tHcy is unrelated to mortality during SU stay but is an independent predictor of poor functional status at SU discharge in survivors. The association, however, is limited to patients with moderate hyperhomocysteinemia.

No Direct Survival Effect of Light to Moderate Alcohol Drinking in Community-Dwelling Older Adults.

OBJECTIVES: To assess the relationship between light to moderate alcohol consumption and mortality, particularly accounting for baseline health status and physical activity. DESIGN: Prospective, longitudinal, population-based study. SETTING: The Pianoro Study, which consisted of community-dwelling older adults in three towns in northern Italy. PARTICIPANTS: Noninstitutionalized individuals of both sexes aged 65 and older (N = 5,256; 2,318 abstainers, 2,309 light to moderate drinkers (≤2 alcoholic units/d)). MEASUREMENTS: Baseline information about demographic characteristics, lifestyle factors, physical activity (Physical Activity Scale for the Elderly (PASE)), perceived health status (visual analog scale (VAS)), dependency level, risk factors, and previous cardiovascular events was obtained using a structured questionnaire. Follow-up information was obtained 6 years later from 2,752 survivors, and mortality information was obtained from death certificates. RESULTS: Male sex, being physically active, and good health status were independently associated with light to moderate drinking (P < .001). An apparent protective effect of light to moderate drinking on mortality was evident in the unadjusted analysis and after adjusting for age, sex, risk factors, and cardiovascular events (adjusted hazard ratio (aHR) = 0.77, 95% confidence interval (CI) = 0.68-0.88, P < .001), but after also adjusting for PASE and VAS, the relationship was no longer significant (aHR = 0.92, 95% CI = 0.80-1.05, P = .19). Follow-up physical activity was associated with baseline alcohol consumption; baseline physical activity did not predict alcohol consumption during follow-up. CONCLUSION: After accounting for health status and physical activity, light to moderate alcohol drinking had no direct protective effect on mortality.