Direct Oral Anticoagulants in Special Patient Populations.

Anticoagulants are a cornerstone of treatment in atrial fibrillation. Nowadays, direct oral anticoagulants (DOACs) are extensively used for this condition in developed countries. However, DOAC treatment may be inappropriate in certain patient populations, such as: patients with chronic kidney disease in whom DOAC concentrations may be dangerously elevated; frail elderly patients with an increased risk of falls; patients with significant drug-drug interactions (DDI) affecting either DOAC concentration or effect; patients at the extremes of body mass in whom an "abnormal" volume of distribution may result in inappropriate drug concentrations; patients with recurrent stroke reflecting an unusually high thromboembolic tendency; and, lastly, patients who experience major hemorrhage on an anticoagulant and in whom continued anticoagulation is deemed necessary. Herein we provide a fictional case-based approach to review the recommendations for the use of DOACs in these special patient populations.

Optimism and Longevity Beyond Age 85.

BACKGROUND: Optimism is associated with health benefits and improved survival among adults older than 65 years. Whether or not optimism beyond age 85 continues to confer survival benefits is poorly documented. We examine the hypothesis that being optimistic at ages 85 and 90 is associated with improved survival. METHOD: The Jerusalem Longitudinal Study (1990-2020) assessed comorbidity, depression, cognition, social and functional status, and 5-year mortality among a representative community sample, born during 1920-1921, at age 85 (n = 1096) and age 90 (n = 533). Overall optimism (Op-Total) was measured using a validated 7-item score from the Scale of Subjective Wellbeing for Older Persons. The 4 questions concerning positive future expectations (Op-Future) and 3 questions concerning positive experiences (Op-Happy) were also analyzed separately. We determined unadjusted mortality hazards ratios and also adjusted for gender, financial difficulty, marital status, educational status, activities of daily living dependence, physical activity, diabetes mellitus, hypertension, ischemic heart disease, cognitive impairment, and depression. RESULTS: Between ages 85-90 and 90-95 years, 33.2% (364/1096) and 44.3% (236/533) people died, respectively. All mean optimism scores declined from age 85 to 90, with males significantly more optimistic than females throughout. All measures of optimism (Op-Total, Op-Future, and Op-Happy) at ages 85 and 90 were significantly associated with improved 5-year survival from age 85 to 90 and 90 to 95, respectively, in both unadjusted and adjusted models. Findings remained unchanged after separately excluding depressed subjects, cognitively impaired subjects, and subjects dying within 6 months from baseline. CONCLUSIONS: These finding support the hypothesis that being optimistic continues to confer a survival benefit irrespective of advancing age.

Preparedness for End of Life-a Survey of Jerusalem District Nursing Homes.

OBJECTIVES: To evaluate the quality of end-of-life (EOL) care in nursing homes. DESIGN: Survey and semistructured interviews. SETTING: Jerusalem district nursing homes. PARTICIPANTS: Staff members of 28 long-term care and skilled nursing facilities in the Jerusalem area in Israel of various ethnic, religious, and administrative affiliations (N = 207). MEASUREMENTS: Qualitative analysis of semistructured interviews and statistical analysis of questionnaires. RESULTS: Most staff members reported that EOL preferences were unknown for more than 90% of residents and that fewer than 10% had a healthcare proxy. Most staff members recalled conducting fewer than five EOL conversations over the past year with residents or family members and could recall fewer than five cases in which a resident was allowed to die in the nursing home. According to staff opinions the prevalence of tube feeding was estimated at greater than 10%, initiated because of aspiration, malnutrition, and understaffing, often against family's preferences. More than 25% of staff members believed that pain management was inadequate. Knowledge about management of chronic pain was poor in half of nurses and nearly one-third of physicians. Most staff would rather not receive the treatments they administered to residents. CONCLUSION: Nursing homes in Jerusalem lack competency for quality EOL care, and there are multiple psychological, training, and policy challenges to improvement.

Tadalafil and acetazolamide versus acetazolamide for the prevention of severe high-altitude illness.

We report an open-label study comparing tadalafil and acetazolamide (n = 24) versus acetazolamide (n = 27) for prevention of high-altitude illness (HAI) at Mt. Kilimanjaro. Tadalafil group had lower rates of severe HAI compared with controls (4% vs 26%, p = 0.03), mostly because of decreased high-altitude pulmonary edema rates (4% vs 22%, p = 0.06).

Cardiac structure and function and renal insufficiency in the oldest old.

BACKGROUND: People over the age of 85 years have a high incidence of cardiovascular disease and chronic kidney disease. HYPOTHESIS: There is an association between renal function and cardiac structure and function in subjects 85 years of age. METHODS: Subjects born in the years 1920 and 1921 were recruited from the Jerusalem Longitudinal Cohort Study. Echocardiography was performed at the subject's home with assessment of cardiac structure and function. Glomerular filtration rate (GFR) was assessed by the Cockroft-Gault formula, with abnormal GFR defined as ≤60 mL/min/1.73 m(2). RESULTS: There were 310 subjects who were enrolled. When GFR was examined as a continuous variable, linear regression showed a small although statistically significant relationship between GFR and left atrial volume (r = 0.15, P < 0.014), left ventricular mass index (r = 0.12, P < 0.04), and ejection fraction (r = 0.19, P < 0.03) but not with indices of diastolic function (r = 0.02, P < 0.72). However, using the accepted clinical cutoff of 60 mL/min/1.73 m(2), there were no significant differences between subjects with normal and abnormal GFR in indices of cardiac structure. Ejection fraction (57.0 ± 10.4% vs 54.4 ± 10.3%; P = 0.08) and indices of diastolic function (E/e' 12.4 ± 5.0 vs 12.3 ± 4.6; P = 0.89) were not significantly different between the 2 groups. CONCLUSIONS: A weak and clinically insignificant association was found between GFR as a continuous variable and indices of cardiac function. However, using the clinically accepted cutoff, no association between abnormal GFR and cardiac structure or function was observed.

Changing profile of health and function from age 70 to 85 years.

BACKGROUND: Old age has traditionally been considered to begin at age 65. The improving health and functional status observed among older people may necessitate reevaluation of this cut-off point. OBJECTIVE: To present the changing prevalence of common geriatric syndromes, functional parameters, common disease status and health care utilization, at ages 70, 78 and 85, in order to help address the question of when does contemporary aging actually begin. METHODS: Medical, psychosocial, cognitive, and functional status, and health service utilization at age 70, 78 and 85 were assessed through the Jerusalem Longitudinal Cohort Study (1990-2010), which prospectively followed a representative sample (born 1920-1921), of 1,861 people, all of whom underwent home-based comprehensive assessment. RESULTS: At age 70, the cohort had good health, low comorbidity, preserved cognition, mobility and independence in basic and instrumental activities of daily activities (ADL). Rising comorbidity, declining cognitive status, increasing depression, and difficulty in ADLs were seen at 78. By age 85, compared to age 70, comorbidity had tripled, depression, hearing and visual impairment, falls, dizziness and mobility problems had doubled; 23% of subjects had cognitive impairment, 42.5% suffered urinary incontinence, and dependence in basic and instrumental ADLs was common (37.8 and 51.7%, respectively). Home care was 4.5, 10.1, and 24.6%, and hospitalization in the previous year occurred among 12.3, 18.8 and 27.8% at ages 70, 78 and 85, respectively. CONCLUSIONS: At age 70, the overall health profile was favorable, prevalence of geriatric syndromes was low, cognitive and functional status was preserved, and health service utilization was low. The progressive deterioration seen at ages 78 and more profoundly so at age 85, suggest that a cut-off point beyond age 70 years may serve to better define entry into old age.

Going outdoors daily predicts long-term functional and health benefits among ambulatory older people.

OBJECTIVE: This article examines the association between frequency of going out of the house and health and functional status among older people. METHOD: A randomly chosen cohort of ambulatory participants born in 1920 or 1921 from the Jerusalem Longitudinal Study underwent assessments for health, functional, and psychosocial variables at ages 70 and 77. Twelve-year mortality data were collected. RESULTS: Women went out daily less than did men. Participants going out daily at age 70 reported significantly fewer new complaints at age 77 of musculoskeletal pain, sleep problems, urinary incontinence, and decline in activities of daily living (ADLs). Logistic regression analysis indicated that not going out daily at age 70 was predictive of subsequent dependence in ADL, poor self-rated health, and urinary incontinence at age 77. DISCUSSION: Going out daily is beneficial among independent older people, correlating with reduced functional decline and improved health measures.

Holocaust survivors in old age: the Jerusalem Longitudinal Study.

OBJECTIVES: To examine the hypothesis that Holocaust exposure during young adulthood negatively affects physical aging, causing greater morbidity, faster deterioration in health parameters, and shorter survival. DESIGN: A longitudinal cohort study of the natural history of an age-homogenous representative sample born in 1920/21 and living in Jerusalem. SETTING: Community-based home assessments. PARTICIPANTS: Four hundred fifty-eight subjects of European origin aged 70 at baseline and 77 at follow-up. MEASUREMENTS: Comprehensive assessment of physical, functional, and psychosocial domains; biographical history of concentration camp internment (Camp), exposure to Nazi occupation during World War II (Exposure), or lack thereof (Controls); and 7-year mortality data from the National Death Registry. RESULTS: Holocaust survivors of the Camp (n=93) and Exposure (n=129) groups were more likely than Controls (n=236) to be male and less educated and have less social support (P=.01), less physical activity (P=.03), greater difficulty in basic activities of daily living (P=.009), poorer self-rated health (P=.04), and greater usage of psychiatric medication (P=.008). No other differences in health parameters or physical illnesses were found. Holocaust survivors had similar rates of deterioration in health and illness parameters over the follow-up period, and 7-year mortality rates were identical. Proportional hazard models showed that being an elderly Holocaust survivor was not predictive of greater 7-year mortality. CONCLUSION: Fifty years after their Holocaust trauma, survivors still displayed significant psychosocial and functional impairment, although no evidence was found to support the hypothesis that the delayed effects of the trauma of the Holocaust negatively influence physical health, health trajectories, or mortality.

Evolution of medication use in Jerusalem elders: Results from the Jerusalem Longitudinal Study.

BACKGROUND: While overall rates of medication use have been increasing over time, less is known about how medication use changes within individuals as they age. OBJECTIVE: The aim of this study was to evaluate changes in medication use and predictors of medication accrual among community-dwelling elders followed for a 7-year period, from age 70 +/- 1 years to age 77 +/- 1 years. METHODS: The study was a community-based, longitudinal, cohort study. The study group consisted of 280 patients from the Jerusalem Longitudinal Study, a population-based sample of Jerusalem residents born in 1920-1 who underwent extensive evaluation in 1990-1 and again in 1997-8. The main outcome measure of the study was the change in the total number of medications taken between baseline and follow-up. Medication use was assessed by home interviews. RESULTS: Half of the sample were men. Medication use more than doubled over the 7-year study period, from a mean of 2.0 to 5.3 medications per patient (p < 0.001), and 57 patients (20%) increased their total drug use by six or more medications. Vitamins, minerals and cardiovascular medications were the most commonly prescribed medications at follow-up, and accounted for approximately half of the total increase in medication use. On multivariable logistic regression analyses, decline in self-rated health was the strongest predictor of above-median increases in medication use (odds ratio [OR] 3.2; 95% CI 1.8, 6.2). The only nonclinical predictor of above-median increases in medication use was good social engagement at baseline (OR 1.8; 95% CI 1.1, 3.1). CONCLUSION: Medication use in Jerusalem elders grew rapidly over the 1990s, more than doubling in volume over a 7-year period. While health status was the factor most strongly predictive of the degree of change, the magnitude of increase for elders as a whole suggests major changes in prescribing practices over this interval.

Low alanine aminotransferase activity in older people is associated with greater long-term mortality.

OBJECTIVES: To find possible association between liver enzymes and mortality in older people. DESIGN: A prospective cohort study. SETTING: Jerusalem. PARTICIPANTS: A systematically selected representative sample of 455 70-year-old ambulatory individuals was prospectively followed for 12 years. MEASUREMENTS: An extensive social and medical profile was developed at age 70 using a detailed interview and physical and ancillary examination. Information on mortality was obtained annually. Differences in survival between subjects stratified according to liver enzyme levels were assessed using the Kaplan-Meier method. Multivariable survival analyses using a Cox proportional hazards model were performed to determine the association between liver enzyme levels at age 70 and mortality over 12 years. RESULTS: Median alanine aminotransferase (ALT) activity of the study population was 11.00 U/L for women and 13.00 U/L for men. Twelve-year survival rates for women with ALT below and above the median levels were similar (78%). For men, these rates were 54% and 65%, respectively (P < .001). Proportional hazards models demonstrated that this greater mortality risk was independent of numerous common risk factors for mortality (hazard ratio (HR) = 1.5, 95% confidence interval (CI) = 1.08-2.19). Adding an interaction between sex and low ALT to the model demonstrated a higher risk of mortality for men with low ALT levels (HR = 2.42, 95% CI = 1.15-5.08). No such risk was demonstrated for the other liver enzymes. CONCLUSION: ALT activity represents a strong and independent surrogate marker for mortality in community-dwelling elderly men.

The impact of visual impairment on health, function and mortality.

BACKGROUND AND AIMS: Our aim was to determine the impact of visual impairment on self-rated health, function and mortality amongst a community-dwelling elderly cohort. METHODS: The study design was prospective and longitudinal, subjects being taken from an age-homogeneous, community-dwelling cohort comprising 452 subjects aged 70 in 1990 and 839 subjects aged 77 in 1998. Comprehensive data were collected by structured interviews and medical examinations carried out during home visits. Data included each subject's demographic and socio-economic profile, medical history, physical findings, functional status and self-rated health status. Visual acuity was measured using a Snellen chart and visual impairment was defined as best-eye corrected visual acuity of 20/40 or worse on Snellen chart testing. RESULTS: Measured and self-reported visual impairment correlated closely, and were significantly more prevalent amongst subjects with low education and poor financial status. Visually impaired subjects showed significantly greater dependence in ADL and IADL, poor self-rated health, less ability to rely on friends, increased loneliness and, in men aged 77, increased visits to the emergency room and hospital admissions. Visual impairment at age 70 significantly predicted poor self-rated health (p=0.029, OR 2.36, 95% CI 1.09-5.10), dependence in ADL (p=0.007, OR 2.91, 95% CI 1.34-6.33), general tiredness (p=0.037, OR 2.40, 95% CI 1.06-5.44), and mortality, with a two-and-a-half-fold increase in risk of death at seven years (p=0.0017,OR 2.84, 95% CI 1.48-5.46). CONCLUSIONS: Visual impairment in the elderly increases the risk of social, functional and medical decline.

Strategies to enhance longevity and independent function: the Jerusalem Longitudinal Study.

PURPOSE: To analyze the impact of medical and social factors on survival and function from age 70 to 82 and point to possible genetic basis for differences. MATERIALS AND METHODS: Longitudinal, cohort study of a representative sample of Jerusalem residents, born 1920-1921. At age 70, 463 subjects underwent a thorough interview eliciting social determinants as well as a medical history and examination and laboratory investigation. At age 77,265 of the survivors, 71%, were re-examined. In 2002, all death certificates in Israel were reviewed. End points were performance of basic and advanced tasks with ease at age 77 and survival to age 82 or life span in subjects who had succumbed. The independent influence of each factor was tested using logistic regression. RESULTS: 89.6% of women were alive after 6 years and 77.4% after 12. Survival for men was 79.9% and 59.8%, respectively. Social factors predominated in the correlation with longer life: financial security, p=.0004; volunteer activity, p=.0002; regular exercise, p=.0002; positive self-assessed health, p<.0001; and activities of daily living (ADL) independence, p<.0001. Less striking but significant correlation for longevity was noted for avoiding naps, p=.04 and instrumental activities of daily living (IADL) independence, p=.048. Medical conditions associated with increased mortality included diabetes, p<.0001; coronary artery disease, p=.0002; impaired vision, p=.0007; and renal insufficiency, p=.008. Anemia and disturbed sleep did not independently correlate with mortality while the association with hypertension did not reach statistical significance, p=.056. In a regression to determine the independent impact of medical and social factors on mortality, unimpaired renal function, good vision, avoiding afternoon naps, volunteer or compensated work, physical activity and IADL independence all correlated with improved survival. Moreover, good vision, volunteer work or work for pay and physical activity were independently associated with continued ADL independence after 7 years. CONCLUSIONS: These findings highlight the ability of social, economic and functional factors to modify genetic influence on survival and function. Increased physical and social activity is an important tool to lengthen the span of robust function. The role of heredity in determining function and mortality may be expressed through diverse pathways.

Candidate genes associated with ageing and life expectancy in the Jerusalem longitudinal study.

In an exploratory study, 11 common polymorphisms were examined for contributing to longevity including: apolipoprotein E (apoE), methylenetetrahydrofolate reductase (MTHFR), cathepsin D (CAD), superoxide dismutase 2 (SOD2), angiotensinogen (AGT) and insulin-like growth factor 2 (IGF2), Leiden factor 7, p53 oncogene, dopamine D4 receptor (DRD4) and the serotonin transporter (SERT). Genotype and allele frequencies of these genes were compared in 224 older (75 years) Jewish Jerusalem residents of Ashkenazi ethnicity to a group of 441 younger subjects (22 years). Nominally significant results provide suggestive evidence in the Ashkenazi group that apoE, MHTFR, SOD2, IGF2 ApaI, and factor VII are risk factors for a single outcome, survival to 75. Overall, the more genetically homogenous Ashkenazi ethnic group showed evidence for association in five genes examined suggesting that future studies in this population would gainfully focus on this ethnic group.