The association between frailty and incident cardiovascular disease events in community-dwelling healthy older adults.

Study objective: This study examined the association between frailty and incident cardiovascular disease (CVD) events, major adverse cardiovascular events (MACE), and CVD-related mortality. Design: Longitudinal cohort study. Setting: The ASPirin in Reducing Events in the Elderly (ASPREE) clinical trial in Australia and the United States. Participants: 19,114 community-dwelling older adults (median age 74.0 years; 56.4 % females). Interventions: Pre-frailty and frailty were assessed using a modified Fried phenotype and a deficit accumulation Frailty Index (FI) at baseline. Main outcome measures: CVD was defined as a composite of CVD death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization for heart failure; MACE included all except heart failure. Cox proportional hazards regression was used to analyze the association between frailty and CVD outcomes over a median follow-up of 4.7 years. Results: Baseline pre-frail and frail groups had a higher risk of incident CVD events (Hazard Ratio (HR): 1.31; 95 % Confidence Interval (CI): 1.14-1.50 for pre-frail and HR: 1.63; 95 % CI: 1.15-2.32 for frail) and MACE (pre-frail HR: 1.26; 95 % CI: 1.08-1.47 and frail HR: 1.51; 95 % CI: 1.00-2.29) than non-frail participants according to Fried phenotype after adjusting for traditional CVD risk factors. Effect sizes were similar or larger when frailty was assessed with FI; similar results for men and women. Conclusion: Frailty increases the likelihood of developing CVD, including MACE, in community-dwelling older men and women without prior CVD events. Screening for frailty using Fried or FI method could help identify community-dwelling older adults without prior CVD events who are more likely to develop CVD, including MACE, and may facilitate targeted preventive measures to reduce their risk.

The Association between Frailty and Dementia-Free and Physical Disability-Free Survival in Community-Dwelling Older Adults.

INTRODUCTION: Frailty is a common geriatric syndrome that adversely impacts health outcomes. This study examined correlates of physical frailty in healthy community-dwelling older adults and studied the effect of frailty on disability-free survival (DFS), defined as survival free of independence-limiting physical disability or dementia. METHODS: This is a post hoc analysis of 19,114 community-dwelling older adults (median age: 74.0 years, interquartile range or IQR: 6.1 years) from Australia and the USA enrolled in the "ASPirin in Reducing Events in the Elderly (ASPREE)" clinical trial. Frailty was assessed using a modified Fried phenotype and a deficit accumulation frailty index (FI) utilizing a ratio score derived from 66 items. Multinomial logistic regression was used to examine the correlates of frailty and Cox regression to analyze the association between frailty and DFS (and its components). RESULTS: At study enrollment, 39.0% were prefrail, and 2.2% of participants were frail, according to Fried phenotype. Older age, higher waist circumference, lower education, ethnoracial origin, current smoking, depression, and polypharmacy were associated with prefrailty and frailty according to Fried phenotype and FI. Fried phenotype defined prefrailty and frailty predicted reduced DFS (prefrail: HR: 1.67; 95% CI: 1.50-1.86 and frail: HR: 2.80; 95% CI: 2.27-3.46), affecting each component of DFS including dementia, physical disability, and mortality. Effect sizes were larger, according to FI. CONCLUSION: Our study showed that prefrailty is common in community-dwelling older adults initially free of cardiovascular disease, dementia, or independence-limiting physical disability. Prefrailty and frailty significantly reduced disability-free survival. Addressing modifiable correlates, like depression and polypharmacy, might reduce the adverse impact of frailty on dementia-free and physical disability-free survival.

The association between polypharmacy, frailty and disability-free survival in community-dwelling healthy older individuals.

OBJECTIVES: Polypharmacy and frailty are two common geriatric conditions. In community-dwelling healthy older adults, we examined whether polypharmacy is associated with frailty and affects disability-free survival (DFS), assessed as a composite of death, dementia, or persistent physical disability. METHODS: We included 19,114 participants (median age 74.0 years, IQR: 6.1 years) from ASPirin in Reducing Events in the Elderly (ASPREE) clinical trial. Frailty was assessed by a modified Fried phenotype and a deficit accumulation Frailty Index (FI). Polypharmacy was defined as concomitant use of five or more prescription medications. Multinomial logistic regression was used to examine the cross-sectional association between polypharmacy and frailty at base line, and Cox regression to determine the effect of polypharmacy and frailty on DFS over five years. RESULTS: Individuals with polypharmacy (vs. <5 medications) were 55% more likely to be pre-frail (Relative Risk Ratio or RRR: 1.55; 95%Confidence Interval or CI:1.44, 1.68) and three times more likely to be frail (RRR: 3.34; 95%CI:2.64, 4.22) according to Fried phenotype. Frailty alone was associated with double risk of the composite outcome (Hazard ratio or HR: 2.16; 95%CI: 1.56, 2.99), but frail individuals using polypharmacy had a four-fold risk (HR: 4.24; 95%CI: 3.28, 5.47). Effect sizes were larger when frailty was assessed using the FI. CONCLUSION: Polypharmacy was significantly associated with pre-frailty and frailty at baseline. Polypharmacy-exposed frailty increased the risk of reducing disability-free survival among older adults. Addressing polypharmacy in older people could ameliorate the impact of frailty on individuals' functional status, cognition and survival.

Validation of a Deficit-Accumulation Frailty Index in the ASPirin in Reducing Events in the Elderly Study and Its Predictive Capacity for Disability-Free Survival.

Frailty is a state of heightened vulnerability and susceptibility to physiologic stressors that increases with age. It has shown increasing utility in predicting a range of adverse health outcomes. Here, we characterize a 67-item deficit-accumulation frailty index (FI) in 19 110 community-dwelling individuals in the ASPirin in Reducing Events in the Elderly clinical trial. Participants aged 65-98 years were recruited from the United States and Australia and were without diagnosed dementia and cardiovascular disease, and major physical disability. The median FI score was .10 (interquartile range: .07-.14) at baseline, and the prevalence of frailty (FI > .21) increased from 8.1% to 17.4% after 6 years. FI was positively associated with age, and women had significantly higher scores than men at all ages. The FI was negatively correlated with gait speed (r = -.31) and grip strength (r = -.46), and strongly associated with a modified Fried's frailty phenotype (p < .0001, for all comparisons). Frailty was associated with the primary composite outcome capturing independent life lived free of major disability and dementia, and increased the rate of persistent physical disability (hazard ratio: 21.3, 95% confidence interval: 15.6-28.9). It added significantly to the predictive capacity of these outcomes above age, sex, and ethnicity alone. The FI is thus a useful biomarker of aging even among relatively healthy older individuals and provides important information about an individual's vulnerability to and risk of disease.

The Effect of Low-Dose Aspirin on Frailty Phenotype and Frailty Index in Community-Dwelling Older Adults in the ASPirin in Reducing Events in the Elderly Study.

BACKGROUND: Frailty is associated with chronic inflammation, which may be modified by aspirin. The purpose of this study was to determine whether low-dose aspirin reduces incident frailty in healthy older adult participants of the ASPirin in Reducing Events in the Elderly (ASPREE) trial. METHODS: In the United States and Australia, 19 114 community-dwelling individuals aged ≥70 and older (U.S. minorities ≥65 years) and free of overt cardiovascular disease, persistent physical disability, and dementia were enrolled in ASPREE, a double-blind, placebo-controlled trial of 100-mg daily aspirin versus placebo. Frailty, a prespecified study end point, was defined according to a modified Fried frailty definition (Fried frailty) and the frailty index based on the deficit accumulation model (frailty index). Competing risk Cox proportional hazard models were used to compare time to incident frailty by aspirin versus placebo. Sensitivity analysis was conducted to include frailty data with and without imputation of missing data. RESULTS: Over a median 4.7 years, 2 252 participants developed incident Fried frailty, and 4 451 had incident frailty according to the frailty index. Compared with placebo, aspirin treatment did not alter the risk of incident frailty (Fried frailty hazard ratio [HR]: 1.04, 95% confidence interval [CI] 0.96-1.13; frailty index HR: 1.03, 95% CI 0.97-1.09). The proportion of individuals classified as frail, and the trajectory in continuous frailty scores over time, were not different between the aspirin and placebo treatment groups. The results were consistent across a series of subgroups. CONCLUSIONS: Low-dose aspirin use in healthy older adults when initiated in older ages does not reduce risk of incident frailty or the trajectory of frailty.

Incidence of and risk factors for hospital-acquired diarrhea in three tertiary care public hospitals in Bangladesh.

During April 2007-April 2010, surveillance physicians in adult and pediatric medicine wards of three tertiary public hospitals in Bangladesh identified patients who developed hospital-acquired diarrhea. We calculated incidence of hospital-acquired diarrhea. To identify risk factors, we compared these patients to randomly selected patients from the same wards who were admitted > 72 hours without having diarrhea. The incidence of hospital-acquired diarrhea was 4.8 cases per 1,000 patient-days. Children < 1 year of age were more likely to develop hospital-acquired diarrhea than older children. The risk of developing hospital-acquired diarrhea increased for each additional day of hospitalization beyond 72 hours, whereas exposure to antibiotics within 72 hours of admission decreased the risk. There were three deaths among case-patients; all were infants. Patients, particularly young children, are at risk for hospital-acquired diarrhea and associated deaths in Bangladeshi hospitals. Further research to identify the responsible organisms and transmission routes could inform prevention strategies.

Epidemiological and molecular analyses of a non-seasonal outbreak of acute icteric hepatitis E in Bangladesh.

Acute hepatitis due to hepatitis E virus (HEV) is endemic in Bangladesh, but its epidemiological characteristics and virological features remain obscure. An outbreak of acute icteric hepatitis E occurred in Rajshahi, Bangladesh during 2010 when 200 patients with visible jaundice visited physicians within a period of 1 month (January-February). Clinical and epidemiological data were collected from these patients using questionnaires. Nucleic acids were isolated from 15 patients who were selected at random to ascertain their HEV genotypes. Near-complete nucleotide sequences of the HEV genome were detected in two patients and partial ORF2 regions in the other 13 patients. All patients tested positive for IgM antibodies to HEV but negative for other hepatitis viruses. Most patients were icteric and complained of vomiting, fever, itching, and abdominal pain. All 15 HEV sequences formed a single cluster within genotype 1a. Two of the 7,186-nt HEV sequences were 99.8% identical. This is the first study to report the clinical, epidemiological, and molecular characterization of an outbreak of acute hepatitis E in Bangladesh.

Hospital-based surveillance for Japanese encephalitis at four sites in Bangladesh, 2003-2005.

We investigated the epidemiology and etiology of encephalitis at four tertiary hospitals in Bangladesh during 2003-2005. Patients who met a clinical case definition for acute encephalitis and had cerebrospinal fluid (CSF) pleocytosis were eligible for enrollment; a standardized sampling pattern was used to enroll eligible patients. Recent Japanese encephalitis virus (JEV) infection was defined by presence of IgM antibodies against JEV in CSF or serum. Twenty (4%) of 492 cases had laboratory evidence of recent JEV infection; two died. All JE cases occurred during May-December, and cases were identified among all age groups. All cases resided in rural areas. Fifteen patients were re-assessed 4-6 weeks after hospitalization; 5 (33%) patients had physical disabilities and 7 (47%) reported cognitive difficulties. Infection with JEV is clearly an etiology of encephalitis in Bangladesh. Population-based studies to quantify burden of disease could assess options for targeted immunization programs.

Sensitive, specific, and rapid detection of Leishmania donovani DNA by loop-mediated isothermal amplification.

We have applied a loop-mediated isothermal amplification (LAMP) technique to detect Leishmania donovani DNA. The LAMP technique detected 1 fg of L. donovani DNA, which was 10-fold more sensitive than a conventional polymerase chain reaction (PCR). All nested PCR-positive blood samples from visceral leishmaniasis patients were positive with the LAMP technique, and DNA samples from L. infantum, L. major, L. mexicana, L. tropica, L. braziliensis, Plasmodium falciparum, and healthy humans were negative with the LAMP technique. The advantages of the LAMP method are its shorter reaction time, a lack of requirement of sophisticated equipment, and visual judgment of positivity based on the turbidity of reaction mixture. Our LAMP technique can be a better alternative to a conventional PCR, especially under field conditions.

Etiologies of bacterial meningitis in Bangladesh: results from a hospital-based study.

We conducted a study at four hospitals from June 2003 to July 2005 to investigate the etiologies of bacterial meningitis in Bangladesh. A total of 2,609 patients met the clinical case definition, and 766 had cerebrospinal fluid tested by at least one of the following methods: latex agglutination, 16S rRNA gene sequencing, or real-time polymerase chain reaction for Neisseria meningitidis A and C, Streptococcus pneumoniae, and Haemophilus influenzae type b (Hib); culture results were noted from patient records. In total, 189 patients (24%) of those tested, representing all age groups, were diagnosed with bacterial meningitis; 136 (18%) had meningococcal, 23 (3%) had pneumococcal, and 25 (3%) had Hib infection. Twenty percent of patients with Hib meningitis (5/25) were > 15 years old. Case-fatality ratios were 10% for N. meningitidis, 22% for S. pneumoniae, and 24% for Hib. Bacterial meningitis from vaccine-preventable pathogens causes significant morbidity and mortality in Bangladesh in adults and children.

Enzyme-linked immunosorbent assay to detect urinary antibody against recombinant rKRP42 antigen made from Leishmania donovani for the diagnosis of visceral leishmaniasis.

We recently reported the production of the recombinant kinesin-related protein of Leishmania donovani with a molecular weight of 42 kd (rKRP42) and the value of the antigen in serum-based ELISA for the diagnosis of visceral leishmaniasis (VL). In this study, the rKRP42 antigen was validated with ELISA using urine samples (rKRP42 urine ELISA). The urine-based ELISA showed 94% sensitivity (108 positives among 115 VL samples) and 99.6% specificity (239 negatives among 240 non-VL samples). The sensitivity and specificity are almost similar to our previous results by ELISA with acetone-treated L. donovani promastigote antigen and direct agglutination test, both methods being done by use of urine samples. A comparison of the rKRP42 urine ELISA with the commercially available urinary antigen detection kit (KAtex) using 108 VL samples showed much higher sensitivity of the ELISA (96.3%) than KAtex (55.6%). The use of the rKRP42 antigen with urine samples will facilitate epidemiologic studies.

Direct agglutination test with urine samples for the diagnosis of visceral leishmaniasis.

A new direct agglutination test (DAT) for use with urine samples for the diagnosis of visceral leishmaniasis (VL) has been developed and compared with the conventional DAT with serum samples and our previously reported enzyme-linked immunosorbent assay (ELISA) with urine samples (urine ELISA). The new DAT, in which anti-human IgG was used as enhancing antibody, was tested with urine samples from 75 VL patients and 225 non-VL patients and healthy people. The sensitivity of the new DAT (90.7%), was almost the same as that of the conventional DAT (91.0%) and the urine ELISA (93.3%). The specificity of the new DAT (96.4%) was nearly identical with that of the urine ELISA (97.3%). A urine-based DAT has several advantages over the conventional DAT: sample collection is non-invasive and it can process larger numbers of samples with smaller amounts of antigen.