The antidepressant clomipramine induces programmed cell death in Leishmania amazonensis through a mitochondrial pathway

Parasitology Research - Despite many efforts, the currently available treatments for leishmaniasis are not fully effective. To discover new medications, drug repurposing arises as a promising...     

Characteristics of Nondisabled Older Patients Developing New Disability Associated with Medical Illnesses and Hospitalization

OBJECTIVE: To identify demographic, clinical, and biological characteristics of older nondisabled patients who develop new disability in basic activities of daily living (BADL) during medical illnesses requiring hospitalization. DESIGN: Longitudinal observational study. SETTING: Geriatric and Internal Medicine acute care units. PARTICIPANTS: Data are from 1,686 patients aged 65 and older who independent in BADL 2 weeks before hospital admission, enrolled in the 1998 survey of the Italian Group of Pharmacoepidemiology in the Elderly Study. MEASUREMENTS: Study outcome was new BADL disability at time of hospital discharge. Sociodemographic, functional status, and clinical characteristics were collected at hospital admission; acute and chronic conditions were classified according to the International Classification of Disease, ninth revision; fasting blood samples were obtained and processed with standard methods. RESULTS: At the time of hospital discharge 113 patients (6.7%) presented new BADL disability. Functional decline was strongly related to patients' age and preadmission instrumental activities of daily living status. In a multivariate analysis, older age, nursing home residency, low body mass index, elevated erythrocyte sedimentation rate, acute stroke, high level of comorbidity expressed as Cumulative Illness Rating Scale score, polypharmacotherapy, cognitive decline, and history of fall in the previous year were independent and significant predictors of BADL disability. CONCLUSION: Several factors might contribute to loss of physical independence in hospitalized older persons. Preexisting conditions associated with the frailty syndrome, including physical and cognitive function, comorbidity, body composition, and inflammatory markers, characterize patients at high risk of functional decline.     

White blood cell count is associated with some features of metabolic syndrome in a very old population

BACKGROUND AND AIMS: Although the association between white blood cell (WBC) counts and the risk of cardiovascular disease has been repeatedly described, its biological mechanism is still unclear. A significant correlation has been demonstrated in adults between WBC counts and some risk factors for coronary heart disease (CHD), including insulin resistance. The aims of this study were: 1) to investigate the association between WBC count and some risk factors for atherosclerosis in a sample of octo-nonagenarians; and 2) to test the hypothesis of an association between WBC count and "metabolic syndrome", a clinical condition mediated by insulin resistance. METHODS AND RESULTS: The study involved 160 free-living healthy octo-nonagenarians participating in the Val Vibrata Aging Project, whose WBC count, and anthropometric and metabolic parameters were measured using standardised methods. WBC count correlated positively with the logarithm of triglyceride, apoprotein B and glucose levels, and negatively with high-density lipoprotein cholesterol: the subjects with low high-density lipoprotein and high triglyceride levels had higher WBC count than normal subjects. The WBC count were significantly higher in the subjects with four or more of six features of metabolic syndrome than in those with three or less. CONCLUSIONS: The results of this study support the existence of a significant association between WBC count and some of the typical features of metabolic syndrome in very old subjects.     

The value of serum albumin and high-density lipoprotein cholesterol in defining mortality risk in older persons with low serum cholesterol

OBJECTIVES: To investigate the relationship between low cholesterol and mortality in older persons to identify, using information collected at a single point in time, subgroups of persons with low and high mortality risk. DESIGN: Prospective cohort study with a median follow-up period of 4.9 years. SETTINGS: East Boston, Massachusetts; New Haven, Connecticut; and Iowa and Washington counties, Iowa. PARTICIPANTS: Four thousand one hundred twenty-eight participants (64% women) age 70 and older at baseline (mean 78.7 years, range 70-103); 393 (9.5%) had low cholesterol, defined as < or =160 mg/dl. MEASUREMENTS: All-cause mortality and mortality not related to coronary heart disease and ischemic stroke. RESULTS: During the follow-up period there were 1,117 deaths. After adjustment for age and gender, persons with low cholesterol had significantly higher mortality than those with normal and high cholesterol. Among subjects with low cholesterol, those with albumin> 38 g/L had a significant risk reduction compared with those with albumin < or =38 g/L (relative risk (RR) = 0.57; 95% confidence interval (CI) = 0.41-0.79). Within the higher albumin group, high-density lipoprotein cholesterol (HDL-C) level further identified two subgroups of subjects with different risks; participants with HDL-C <47 mg/dl had a 32% risk reduction (RR = 0.68; 95% CI = 0.47-0.99) and those with HDL-C > or =47 mg/dl had a 62% risk reduction (RR = 0.38; 95% CI = 0.20-0.68), compared with the reference category; those with albumin < or =38 g/L and HDL-C <47 mg/dl. CONCLUSIONS: Older persons with low cholesterol constitute a heterogeneous group with regard to health characteristics and mortality risk. Serum albumin and HDL-C can be routinely used in older patients with low cholesterol to distinguish three subgroups with different prognoses: (1) high risk (low albumin), (2) intermediate risk (high albumin and low HDL-C), and (3) low risk (high albumin and high HDL-C).     

The ratio of older women to men: historical perspectives and cross-national comparisons

In nearly all populations throughout the world there are substantially more older women than men. Although there are many biological explanations for why women have greater longevity than men, the higher proportion of women in the older population appears to be a phenomenon of the twentieth century. Using contemporary data on population size and life expectancy in a large number of countries and historical life table data from a diverse subset of countries, cross-national contrasts and historical trends in the female to male ratio are explored. In the 1990's, only 4 countries had fewer women than men in the age group 75 years and older. The number of women per 100 men aged 75+ in the remainder of the world's countries ranged from 100 to 355. In general, countries with a lower overall life expectancy had a lower number of women per 100 men aged 75+, while countries with higher overall life expectancy had a higher female to male ratio in this age group. A hundred years ago there were nearly equal numbers of women and men aged 75+ in many countries. In all countries studied, the female to male ratio increased as the century progressed. Historical life table data were used to calculate the probability of surviving through 5 stages of life: ages 0 to 5, 5 to 15, 15 to 40, 40 to 65, and 65 to 85. Although the probability of survival through all age intervals increased dramatically during the century, the current disparity in the size of the older populations of men and women can be explained primarily by the divergence in male and female probabilities of survival for the two older age intervals as the century progressed. Thus, with higher life expectancy, whether it be comparing countries or over time within a country, the proportion of the older population that is female is greater. Changes in survival probability in middle and late life, rather than childhood and young adulthood, have been responsible for the increased number of women compared to men in the older population.     

Diabetes mellitus, glycemic control, and incident depressive symptoms among 70- to 79-year-old persons: the health, aging, and body composition study

BACKGROUND: Cross-sectional studies find an elevated prevalence of depression among subjects with diabetes mellitus (DM). The causal mechanisms and temporal sequence of this association have not been clearly delineated. This study investigated the prospective relationship between DM and depressive symptoms. METHODS: The Health, Aging, and Body Composition Study was a cohort study conducted in the metropolitan areas of Memphis, Tenn, and Pittsburgh, Pa. The analysis included 2522 community-dwelling subjects, aged 70 to 79 years, without baseline depressive symptoms. Incident depressed mood was defined as use of antidepressants at follow-up visits or presence of depressive symptoms (score >or=10 on the 10-item Center for Epidemiological Studies Depression scale). Presence of incident depressed mood at 2 consecutive annual clinic visits defined the incidence of recurrent depressed mood. Diabetes mellitus status, glycosylated hemoglobin (HbA1c) level, and DM-related comorbidities were assessed at baseline. Diabetes mellitus status was further characterized as absent, controlled (HbA1c level <7%), or uncontrolled (HbA1c level >or=7%). Discrete time survival analysis was used to estimate depressive events risk. RESULTS: During a mean follow-up of 5.9 years, participants with DM had a higher age-, sex-, race-, and site-adjusted incidence of depressed mood (23.5% vs 19.0%) (P = .02) and recurrent depressed mood (8.8% vs 4.3%) (P<.001) than those without DM. Diabetes mellitus was associated with a 30% increased risk of incident depressed mood (odds ratio [OR], 1.31; 95% confidence interval [CI], 1.07-1.61), which was attenuated after adjustment for DM-related comorbidities (OR, 1.20; CI, 0.97-1.48). A stronger relationship was observed between DM and recurrent depressed mood (OR, 1.91; CI, 1.32-2.76), particularly among participants with poor glycemic control. CONCLUSION: Among well-functioning older adults, DM is associated with increased risk of depressive symptoms.     

Association between anemia and physical disability in older patients: role of comorbidity

BACKGROUND AND AIMS: In older persons, anemia is a common medical disorder and is often associated with comorbidity and poor health outcomes. We evaluated the relationship between anemia and physical disability in a sample of older hospitalized patients, taking into account the role of comorbidity. METHODS: Cross-sectional analysis of the baseline data of the Italian Group of Pharmacoepidemiology in the Elderly Study. Patients aged 65 years or older (n=10,903), admitted to participating centers in the 1993-1998 survey period, were included. Anemia was defined according to the World Health Organization (WHO) criteria; physical disability was defined as need for assistance in performing at least one Activity of Daily Living (ADL) in the week before admission. Comorbidity was ascertained using the Charlson Index. RESULTS: Prevalence of anemia was 41.1%. In the unadjusted analysis, anemia was associated with increased likelihood of disability, in both women (Odds Ratio [OR]: 1.54; 95% Confidence Interval [CI]: 1.38-1.71) and men (OR 1.70; CI 1.52-1.90). After inclusion of demographics and life-style factors in multivariate analysis, the strength of association was only modestly attenuated, whereas nutritional factors and disease-related variables resulted in a greater reduction of the strength of association. In analyses stratified by comorbidity severity, the association between anemia and disability was statistically significant only in patients with the lowest comorbidity levels (p for anemia Charlson Index interaction term <0.05, in both women and men). CONCLUSIONS: Among hospitalized subjects, anemia is associated with ADL disability. The disablement process associated with anemia may be partially explained by nutritional and disease-related factors. However, anemia appears to have an independent effect, particularly in subjects with low comorbidity.     

Moderate Alcohol Intake and Risk of Functional Decline: The Health, Aging, and Body Composition Study

OBJECTIVES: To investigate the prospective relationship between alcohol consumption and incident mobility limitation. DESIGN: Cohort study. SETTING: The Health Aging and Body Composition study, conducted in Memphis, Tennessee, and Pittsburgh, Pennsylvania. PARTICIPANTS: Three thousand sixty‐one adults aged 70 to 79 without mobility disability at baseline. MEASUREMENTS: Incidence of mobility limitation, defined as self‐report at two consecutive semiannual interviews of any difficulty walking one‐quarter of a mile or climbing stairs, and incidence of mobility disability, defined as severe difficulty or inability to perform these tasks at two consecutive reports. Alcohol intake, lifestyle‐related variables, diseases, and health status indicators were assessed at baseline. RESULTS: During a follow‐up time of 6.5 years, participants consuming moderate levels of alcohol had the lowest incidence of mobility limitation (total: 6.4 per 100 person‐years (person‐years); men: 6.4 per 100 person‐years; women: 7.3 per 100 person‐years) and mobility disability (total: 2.7 per 100 person‐years; men: 2.5 per 100 person‐years; women: 2.9 per 100 person‐years). Adjusting for demographic characteristics, moderate alcohol intake was associated with lower risk of mobility limitation (hazard ratio (HR)=0.70, 95% confidence interval (CI)=0.55–0.89) and mobility disability (HR=0.66, 95% CI=0.45–0.95) than never or occasional consumption. Additional adjustment for lifestyle‐related variables substantially reduced the strength of the associations (HR=0.85, 95% CI=0.66–1.08 and HR=0.81, 95% CI=0.56–1.18, respectively). Adjustment for diseases and health status indicators did not affect the strength of the associations, suggesting that lifestyle is most important in confounding this relationship. CONCLUSION: Lifestyle‐related characteristics mainly accounted for the association between moderate alcohol intake and lower risk of functional decline over time. These findings do not support a direct causal effect of alcohol intake on physical function.     

Potentially Inappropriate Medications and Functional Decline in Elderly Hospitalized Patients

OBJECTIVES: To verify whether the use of potentially inappropriate medications (PIMs) is associated with loss of independence in elderly in-patients by promoting adverse drug reactions (ADRs).
DESIGN: Prospective observational study.
PARTICIPANTS: Five hundred six patients aged 65 and older admitted to 11 acute care medical wards.
MEASUREMENTS: In-hospital loss of one or more activities of daily living (ADLs) and three or more ADLs. PIMs were identified according to diagnosis-independent Beers criteria and ascertained by study physicians based on daily review of medical and nurse records. The relationship between risk factors and outcomes was assessed using logistic regression.
RESULTS: Overall, 104 patients (20.6%) were taking at least one PIM at the time of admission (baseline users), and 49 (9.7%) were newly prescribed at least one PIM during their hospital stay. The loss of one or more ADLs occurred in 9.6% of baseline users, 16.3% of new users, and 8.5% of nonusers ( P =.21) and that of three or more ADLs in 7.7% of baseline users, 12.2% of new users, and 4.8% of nonusers ( P =.10). The lack of association was confirmed after correction for potential confounders, including ADRs. The occurrence of ADRs was strongly associated with both outcomes (odds ratio (OR)=7.80, 95% confidence interval (CI)=3.53–17.3 for the loss of ≥1 ADLs; OR=3.98, 95% CI=1.50–10.5 for the loss of ≥3 ADLs), but PIMs caused only six of 106 ADRs.
CONCLUSIONS: ADRs to any drugs more than the use of PIMs might be associated with functional decline in elderly hospitalized patients, but because the power of this study was too limited to definitively exclude a direct relationship between PIMs and functional decline, this merits further investigation.     

Elevated C-reactive protein levels and metabolic syndrome in the elderly: The role of central obesity data from the InChianti study

Metabolic syndrome (MS) and "low grade" systemic inflammation (LGSI) are very common findings in the older population. Although MS and LGSI have been associated in adults, it is not known what is the real contribution of MS, and its single components, to LGSI in older persons, due to the potential confounding effect of comorbidity and aging. We investigated the relationship between increased C-reactive protein (CRP) plasma levels, a marker of LGSI, and MS in 1044 older (> or =65 years) community dwelling Italian individuals enrolled the InChianti study. Metabolic syndrome was defined by the NCEP-ATP III-AHA/NHLBI criteria. High sensitivity CRP (hs.CRP) levels were measured by enzyme-linked immunosorbent assay, and defined as high when >3mg/L. The overall prevalence of MS was 31%. The prevalence of high hs.CRP was 54.5% in subjects with, and 41.3% in those without MS (p<0.001). MS was associated with high hs.CRP levels after adjustment for age, gender, and comorbidity (OR: 1.93, 95% CI: 1.46-2.55). Compared to subjects with MS and no LGSI, individuals with MS and LGSI were characterized by higher waist circumference, BMI, and HOMA score. Multivariate logistic regression analysis confirmed the association between waist circumference and high hs.CRP levels in subjects with MS (waist circumference III vs. I tertile OR: 2.60, 95% CI: 1.79-3.77) independent of age, gender, and important confounding variables including comorbidity. Additional analyses, conducted with and without dichotomization of hs.CRP levels, confirmed the central role of waist circumference in the LGSI phenomenon, independent of gender and diagnosis of MS. We conclude that in older individuals, MS is associated with LGSI, but the association is mainly supported by a strong independent correlation between waist circumference and high hs.CRP levels. In the absence of this specific MS component, it seems that the contribution of MS to LGSI would be modest at best.