Potential drug-drug and drug-disease interactions in well-functioning community-dwelling older adults.

WHAT IS KNOWN AND OBJECTIVE: There are few studies examining both drug-drug and drug-disease interactions in older adults. Therefore, the objective of this study was to describe the prevalence of potential drug-drug and drug-disease interactions and associated factors in community-dwelling older adults. METHODS: This cross-sectional study included 3055 adults aged 70-79 without mobility limitations at their baseline visit in the Health Aging and Body Composition Study conducted in the communities of Pittsburgh PA and Memphis TN, USA. The outcome factors were potential drug-drug and drug-disease interactions as per the application of explicit criteria drawn from a number of sources to self-reported prescription and non-prescription medication use. RESULTS: Over one-third of participants had at least one type of interaction. Approximately one quarter (25·1%) had evidence of had one or more drug-drug interactions. Nearly 10·7% of the participants had a drug-drug interaction that involved a non-prescription medication. % The most common drug-drug interaction was non-steroidal anti-inflammatory drugs (NSAIDs) affecting antihypertensives. Additionally, 16·0% had a potential drug-disease interaction with 3·7% participants having one involving non-prescription medications. The most common drug-disease interaction was aspirin/NSAID use in those with history of peptic ulcer disease without gastroprotection. Over one-third (34·0%) had at least one type of drug interaction. Each prescription medication increased the odds of having at least one type of drug interaction by 35-40% [drug-drug interaction adjusted odds ratio (AOR) = 1·35, 95% confidence interval (CI) = 1·27-1·42; drug-disease interaction AOR = 1·30; CI = 1·21-1·40; and both AOR = 1·45; CI = 1·34-1·57]. A prior hospitalization increased the odds of having at least one type of drug interaction by 49-84% compared with those not hospitalized (drug-drug interaction AOR = 1·49, 95% CI = 1·11-2·01; drug-disease interaction AOR = 1·69, CI = 1·15-2·49; and both AOR = 1·84, CI = 1·20-2·84). WHAT IS NEW AND CONCLUSION: Drug interactions are common among community-dwelling older adults and are associated with the number of medications and hospitalization in the previous year. Longitudinal studies are needed to evaluate the impact of drug interactions on health-related outcomes.

Glycemia and cognitive function in older adults using glucose-lowering drugs.

OBJECTIVES: In experimental studies, both high and low levels of plasma glucose are associated with cognitive impairment. In populations, less is known about the relationship between glycemia and cognitive function, especially in persons using glucose-lowering drugs. DESIGN: A cross-sectional study of 378 high-functioning black and white men and women aged 70 to 79 participating in the Health, Aging, and Body Composition Study (Health ABC) who used glucose-lowering medications. Glycemic measures included fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c). Cognitive function was assessed using the Modified Mini-Mental State Examination (3MS) and the Digit Symbol Substitution Test (DSS) at the same examination visit in which the glycemic measures were determined. SETTING: Memphis, Tennessee and Pittsburgh, Pennsylvania. RESULTS: We observed an "inverted-U" relationship (p =.0025 for 3MS, p=.0277 for DSS) between FPG (range 47 - 366 mg/dl) and performance on these two tests. The fasting plasma glucose levels associated with the highest score on the 3MS was 180 mg/dl and 135 mg/dl for the DSS. There was a monotonic inverse relationship between HbA1c and performance on 3MS and DSS without evidence of a threshold effect. CONCLUSION: Our findings suggest that older adults who are treated for diabetes may experience a small degree of cognitive impairment within the recommended fasting glucose levels, yet measures of long-term glycemic control support tight glycemic control. Given the high prevalence of diabetes and the common use of glucose-lowering drugs in older adults, further studies are needed to elucidate these relationships.

Effects of patient age and physician training on choice and dose of benzodiazepine hypnotic drugs.

We conducted a cross-sectional review of all prescriptions (N = 554) for triazolam and flurazepam hydrochloride written by nonpsychiatrists to outpatients at a university affiliated Veterans Administration hospital. We sought to determine whether triazolam, an agent with a short half-life, was used preferentially in older patients (age greater than or equal to 70 years). We also wanted to determine whether dosages of triazolam or flurazepam were lowered in elderly patients. Our findings showed that prescriber level of training was a much stronger determinant of drug choice than patient age. Attending physicians prescribed flurazepam twice as often as interns. Lower dosages of both agents were prescribed more frequently to older patients. Our data suggest that some physicians choose a benzodiazepine hypnotic out of habit rather than application of pharmacologic principles, but reduce doses appropriately when prescribing to elderly patients.

Concurrent use of nonsteroidal anti-inflammatory drugs and oral anticoagulants places elderly persons at high risk for hemorrhagic peptic ulcer disease.

BACKGROUND: Although joint use of nonsteroidal anti-inflammatory drugs (NSAIDs) and oral anticoagulants may increase the risk of gastrointestinal tract hemorrhage in elderly persons, no epidemiologic studies have been performed to quantify this risk. METHODS: We performed a retrospective cohort study of Tennessee Medicaid enrollees aged 65 years or older from 1984 through 1986. A total of 103,954 individuals contributed 209,066 person-years of follow-up, including 2203 person-years of current oral anticoagulant use, to the study. RESULTS: Of the cohort members, 1371 had confirmed hospitalizations for peptic ulcer disease. Of these, 661 (48%) presented with frank hematemesis or melena and thus met the definition for hemorrhagic peptic ulcer disease. Among current users of oral anticoagulants, the adjusted incidence of hospitalization for peptic ulcer disease was 14.3 per 1000 person-years, and the adjusted incidence of hospitalization for hemorrhagic peptic ulcer disease was 10.2 per 1000 person-years. Compared with nonusers, current anticoagulant users were at increased risk for hospitalization for ulcer disease (relative risk, 2.2; 95% confidence interval, 1.6 to 3.1), primarily due to the increased risk of hospitalization for hemorrhagic ulcers (relative risk, 3.3; 95% confidence interval, 2.3 to 4.9). Compared with nonusers of either drug, the relative risk of hemorrhagic peptic ulcer disease among current users of both anticoagulants and NSAIDs was 12.7 (95% confidence interval, 6.3 to 25.7). However, the prevalence of NSAID use among anticoagulant users was 13.5%, the same as in those who were not using anticoagulants. CONCLUSIONS: The nearly 13-fold increase in the risk of developing hemorrhagic peptic ulcer disease in concurrent users of oral anticoagulants and NSAIDs suggests that NSAIDs should be prescribed with extreme caution in patients undergoing anticoagulation therapy.

Incidence and risk factors for serious hypoglycemia in older persons using insulin or sulfonylureas.

BACKGROUND: Our knowledge about the risk of hypoglycemia associated with diabetes treatment is derived from studies that often exclude frail, elderly persons. OBJECTIVE: To determine the incidence and risk factors for developing serious hypoglycemia among older persons using sulfonylureas or insulin. METHODS: We conducted a population-based, retrospective cohort study of 19932 Tennessee Medicaid enrollees, aged 65 years or older, who used insulin or sulfonylureas from 1985 through 1989. The main end point was serious hypoglycemia defined as a hospitalization, emergency department admission, or death associated with hypoglycemic symptoms and a concomitant blood glucose determination of less than 2.8 mmol/L (< 50 mg/dL). RESULTS: We identified 586 persons with a first episode of serious hypoglycemia during 33,048 person-years of insulin or sulfonylurea use. The crude rates (per 100 person-years) of serious hypoglycemia were 1.23 (95% confidence interval [CI], 1.08-1.38) in users of sulfonylureas and 2.76 (95% CI, 2.47-3.06) among insulin users. Recent hospital discharge was the strongest predictor of subsequent hypoglycemia in older persons with diabetes. The adjusted relative risk of serious hypoglycemia occurring in days 1 through 30 after hospital discharge was 4.5 (95% CI, 3.5-5.7) compared with the risk associated with a hypoglycemic event occurring 366 or more days after hospital discharge. Other independent risk factors included advanced age (relative risk, 1.8; 95% CI, 1.4-2.3), black race (relative risk, 2.0; 95% CI, 1.7-2.4), and use of 5 or more concomitant medications (relative risk, 1.3; 95% CI, 1.1-1.5). CONCLUSIONS: In this population, the incidence of serious hypoglycemia is approximately 2 per 100 person-years, suggesting that many older adults can be safely treated with hypoglycemic drugs. Frail, elderly persons--the oldest-old, those using multiple medications, and those who are frequently hospitalized--are at a higher risk for drug-associated hypoglycemia. Such individuals may benefit from intensive education about the symptoms of hypoglycemia and close monitoring for adverse events related to diabetes treatment.

The role of diastolic blood pressure when treating isolated systolic hypertension.

OBJECTIVE: To assess the role of treated diastolic blood pressure (DBP) level in stroke, coronary heart disease (CHD), and cardiovascular disease (CVD) in patients with isolated systolic hypertension (ISH). DESIGN: An analysis of the 4736 participants in the Systolic Hypertension in the Elderly Program (SHEP) was undertaken. The SHEP was a randomized multicenter double-blind outpatient clinical trial of the impact of treating ISH in men and women aged 60 years and older. MAIN OUTCOME MEASURES: Cox proportional hazards regression analysis, with DBP and systolic blood pressure (SBP) as time-dependent covariables. RESULTS: After adjustment for the baseline risk factors of race (black vs other), sex, use of antihypertensive medication before the study, a composite variable (diabetes, previous heart attack, or stroke), age, and smoking history (ever vs never) and adjustment for the SBP as a time-dependent variable, we found, for the active treatment group only, that a decrease of 5 mm Hg in DBP increased the risk for stroke (relative risk, [RR], 1.14; 95% confidence interval [CI], 1.05-1.22), for CHD (RR, 1.08; 95% CI, 1.00-1.16), and for CVD (RR, 1.11; 95% CI, 1.05-1.16). CONCLUSIONS: Some patients with ISH may be treated to a level that uncovers subclinical disease, and some may be overtreated. Further studies need to determine whether excessively low DBP can be prevented by more careful titration of antihypertensive therapy while maintaining SBP control. It is reassuring that patients receiving treatment for ISH never perform worse than patients receiving placebo in terms of CVD events.

Diuretic-based treatment and cardiovascular events in patients with mild renal dysfunction enrolled in the systolic hypertension in the elderly program.

BACKGROUND: It is expected that the treatment of hypertension in patients with renal disease decreases the risk of cardiovascular events, but the evidence in these patients is lacking. OBJECTIVE: To assess the effect of diuretic-based treatment on cardiovascular events in patients with isolated systolic hypertension and renal dysfunction. METHODS: A total of 4336 persons aged 60 years and older with systolic blood pressures of 160 mm Hg and higher and diastolic blood pressures of less than 90 mm Hg were randomly assigned to receive either placebo or chlorthalidone (12.5-25.0 mg/d), with the addition of atenolol (25-50 mg/d) or reserpine (0.05-0.10 mg/d) if needed, and observed for 5 years. The risk of first-occurring cardiovascular events, including stroke, transient ischemic attack, myocardial infarction, heart failure, coronary artery bypass surgery, angioplasty, aneurysm, endarterectomy, sudden death, or rapid death, was stratified according to baseline serum creatinine levels (35.4-84.0, 84.1-101.6, 101.7-119.3, and 119.4-212.2 micromol/L [0.4-0.9, 1.0-1.1, 1.2-1.3, and 1.4-2.4 mg/dL]). RESULTS: Systolic blood pressure reduction was not affected by baseline serum creatinine levels. Active treatment did not affect the risk of serum creatinine levels becoming elevated during follow-up. The risk of hypokalemia with active treatment decreased significantly with increasing baseline serum creatinine levels. In the 4 baseline serum creatinine groups, the relative risk (95% confidence interval) of cardiovascular events developing with active treatment was 0.73 (0.54-0.97), 0.63 (0.49-0.82), 0.62 (0.44-0.87), and 0.59 (0.38-0.91). The results were similar for the outcomes of stroke or coronary artery events and in analyses stratified by sex or age. CONCLUSION: Diuretic-based treatment of patients with isolated systolic hypertension prevents the development of cardiovascular events in older persons with mild renal dysfunction.

Type 2 diabetes in older well-functioning people: who is undiagnosed? Data from the Health, Aging, and Body Composition study.

OBJECTIVE: To assess, in an older population, the prevalence of diagnosed and undiagnosed diabetes, the number needed to screen (NNTS) to identify one individual with undiagnosed diabetes, and factors associated with undiagnosed diabetes. RESEARCH DESIGN AND METHODS: Socioeconomic and health-related factors were assessed at the baseline examination of the Health, Aging, and Body Composition (Health ABC) Study, a cohort of 3,075 well-functioning people aged 70-79 years living in Memphis, Tennessee and Pittsburgh, Pennsylvania (42% blacks and 48% men). Diabetes was defined according to the 1985 World Health Organization criteria (fasting glucose > or =7.8 mmol/l or 2-h glucose > or =11.1 mmol/l) and the 1997 American Diabetes Association criteria (fasting glucose > or =7.0 mmol/l). RESULTS: The prevalence of diagnosed and undiagnosed diabetes was 15.6 and 8.0%, respectively, among all participants (NNTS 10.6), 13.9 and 9.1% among white men (NNTS 9.5), 7.8 and 7.4% among white women (NNTS 12.4), 22.7 and 9.1% among black men (NNTS 8.5), and 21.6 and 6.2% among black women (NNTS 12.6). In multivariate analyses, compared with individuals without diabetes, individuals with undiagnosed diabetes were more likely to be men and were more likely to have a history of hypertension, higher BMI, and larger waist circumference. NNTS was lowest in men (9.1), individuals with hypertension (8.7), individuals in the highest BMI quartile (6.9), and individuals in the largest waist circumference quartile (6.8). CONCLUSIONS: In approximately one-third of all older people with diabetes, the condition remains undiagnosed. Screening for diabetes may be more efficient among men and individuals with hypertension, high BMI, and large waist circumference.

Bleeding risk, physical functioning and non-use of anticoagulation among patients with stroke and atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is common among people with stroke. Anticoagulation medications can be used to manage the deleterious impact of AF after stroke, however, may not be prescribed due to concerns about post-stroke falls and decreased functioning. Thus, the purpose of this study was to identify, among people with stroke and AF, predictors of anticoagulation prescription at hospital discharge. METHODS: This is a secondary analysis of a retrospective cohort study of data retrieved via medical records, including National Institutes of Health Stroke Scale score, Functional Independence Measure (FIM) motor score (motor or physical function), ambulation on second day of hospitalization, Morse Falls Scale (fall risk) and HAS-BLED score (Hypertension; Abnormal renal and liver function; Stroke; Bleeding; Labile INRs; Elderly >65; and Drugs or alcohol). Data analyses included bivariate comparisons between people with and without anticoagulation at discharge. Logistic-regression modeling was used to assess predictors of discharge anticoagulation. RESULTS: There were 334 subjects included in the analyses, whose average age was 75 years old. Anticoagulation was prescribed at discharge for 235 (70%) of patients. In the adjusted regression analyses, only the FIM motor score (adjusted OR = 1.015, 95% CI 1.001-1.028) and the HAS-BLED score (adjusted OR = 0.36, 95% CI 0.22-0.58) were significantly associated with anticoagulation prescription at discharge. CONCLUSION: It appears that in this sample, post-stroke anticoagulation decisions appear to be made based on clinical factors associated with bleed risk and motor deficits or physical functioning. However, opportunities may exist for improving clinician documentation of specific reasoning for non-anticoagulation prescription.

Diagnosis and treatment of outpatient insomnia by psychiatric and nonpsychiatric physicians.

Insomnia is commonly encountered in general medical practice, but little is known about how primary care physicians manage this problem. We reviewed medical records describing 536 patient encounters in which either triazolam (Halcion) or flurazepam (Dalmane) was prescribed for outpatient use. Only 12% of the progress notes written by internists or surgeons contained even a remote reference to sleep, whereas 74% of psychiatrist's notes contained at least some sleep symptom documentation. In a multivariate analysis including the number of medical and psychiatric diagnoses, patient age, and physician gender, only the prescriber department was independently associated with the presence of symptom documentation. We also found that 30% of the prescriptions written by internists or surgeons were for inappropriately large quantities of these drugs (180 or more doses) compared with 6% of the prescriptions written by psychiatrists. We conclude that the evaluation of insomnia by nonpsychiatrists is often incomplete and that hypnotic drugs may be inappropriately prescribed by these physicians. Further efforts are needed to improve the management of insomnia by primary care physicians in the outpatient setting.

Failure to limit quantities of benzodiazepine hypnotic drugs for outpatients: placing the elderly at risk.

PURPOSE: The long-term use of benzodiazepine hypnotics by the elderly is associated with serious side effects, and prescriptions of large quantities of these agents allow such use. Therefore, we determined the quantities of these agents prescribed to outpatients in our Veterans Administration teaching hospital, and the relationship of patient age to total number of doses prescribed per prescription. PATIENTS AND METHODS: Pharmacy and patient records related to 655 consecutive prescriptions for triazolam (Halcion) and flurazepam (Dalmane) were reviewed. Only 266 (41%) of the prescriptions were for 30 or fewer doses, while 178 (27%) were written for 180 or more doses. RESULTS: Thirty-six percent of prescriptions for patients aged 65 years or older were for 180 or more doses, compared with 24% for those aged 45 to 64 years old, and 16% of the prescriptions for patients less than 45 years old (p less than 0.0001). In a multivariate analysis controlling for six other factors related to the total number of doses prescribed, patients aged 65 years or older were still more likely to receive a prescription for 180 or more doses (relative risk 1.9, 95% confidence interval 1.3, 2.8). CONCLUSION: We conclude that inappropriately large quantities of benzodiazepine hypnotics were commonly prescribed, and that patients aged 65 years or older were at greatest risk for receiving such prescriptions.

Serum uric acid, diuretic treatment and risk of cardiovascular events in the Systolic Hypertension in the Elderly Program (SHEP).

OBJECTIVE: To assess longitudinally the association of serum uric acid and its change due to diuretic treatment with cardiovascular events in hypertensive patients. DESIGN: Cohort study in a randomized trial. SETTING: Cohort of hypertensive patients. PARTICIPANTS: A total of 4327 men and women, aged > or = 60 years, with isolated systolic hypertension, randomized to placebo or chlorthalidone, with the addition of atenolol or reserpine if needed, were observed for 5 years. MAIN OUTCOME MEASURES: Major cardiovascular events, coronary events, stroke and all-cause mortality. RESULTS: Cardiovascular event rates for quartiles of baseline serum uric acid were: I, 32.7 per 1000 person-years; II, 34.5 per 1000 person-years; III, 38.1 per 1000 person-years; and IV, 41.4 per 1000 person-years (P for trend = 0.02). The adjusted hazard ratio (HR), of cardiovascular events for the highest quartile of serum uric acid versus the lowest quartile was 1.32 (95% CI, 1.03-1.69). The benefit of active treatment was not affected by baseline serum uric acid. After randomization, an increase of serum uric acid < 0.06 mmol/l (median change) in the active treatment group was associated with a HR of 0.58 (0.37-0.92) for coronary events compared with those with a serum uric acid increase > or = 0.06 mmol/l. This difference was not explained by blood pressure effects. Those with a serum uric acid increase > or = 0.06 mmol/l in the active treatment group had a similar risk of coronary events as the placebo group. CONCLUSIONS: Serum uric acid independently predicts cardiovascular events in older persons with isolated systolic hypertension. Monitoring serum uric acid change during diuretic treatment may help to identify patients who will most benefit from treatment.

Prevalence and clinical implications of American Diabetes Association-defined diabetes and other categories of glucose dysregulation in older adults: the health, aging and body composition study.

Using data on history of diabetes, fasting glucose (FG) and the oral glucose tolerance test (OGTT), the authors contrasted cardiovascular disease (CVD) risk factors (body mass index, blood pressure, lipids and glycated hemoglobin) in 3052 African-American and White adults aged 70-79 in mutually exclusive categories of diagnosed diabetes, undiagnosed diabetes defined by the American Diabetes Association (ADA), isolated post-challenge hyperglycemia (IPH; FG < 126 mg/dL and 2 h post-OGTT > or = 200 mg/dL), impaired fasting glucose (IFG; FG > or = 110 but < 126 mg/dL), and individuals who were non-diabetic by both ADA and World Health Organization (WHO) criteria (FG < 126 mg/dL and 2 h post-challenge glucose < 200 mg/dL). The prevalence of diagnosed diabetes, undiagnosed ADA diabetes and IPH were 15.2, 3.8 and 4.7%, respectively, with more diagnosed and undiagnosed ADA diabetes in African-Americans than Whites. Compared to mean glycated hemoglobin (HbA(1c)) among ADA/WHO non-diabetic individuals (6.0%), HbA(1c) was substantially higher in the diagnosed diabetes and undiagnosed ADA diabetes groups (8.0% and 7.7%), but not in the IPH group (6.3%). The diagnosed and undiagnosed ADA diabetic groups had worse CVD risk factor profiles than the ADA/WHO non-diabetic group. IPH subjects had elevated levels of some CVD risk factors, but differences were more modest than those for the diabetic groups. Among people with IPH, those who also had IFG had worse CVD profiles than those with IPH alone. Although the OGTT may identify additional adults with more CVD risk factors than normals, these differences appear to be clustered among those who also have IFG.

Individual sulfonylureas and serious hypoglycemia in older people.

OBJECTIVE: To compare the risk of serious hypoglycemia associated with the use of individual sulfonylureas in older people. DESIGN: A retrospective cohort study. SETTING: The Tennessee Medicaid Program. PATIENTS: A total of 13,963 Medicaid enrollees, aged 65 years or older, who were prescribed one of six sulfonylureas from 1985 to 1989. MAIN OUTCOME MEASURE: Hospitalization, emergency room admission, or death associated with neuroglycopenic or autonomic symptoms, myocardial infarction, stroke, or injury, with a concomitant blood glucose determination of less than 2.8 mmol/L (50 mg/dL). RESULTS: We identified 255 persons with a first episode of serious hypoglycemia during 20,715 person-years of sulfonylurea use. The crude rate (per 1000 person-years) of serious hypoglycemia was highest in glyburide users, 16.6 (95% confidence interval [CI], 13.2 to 19.9 and lowest among users of tolbutamide, 3.5 (95% CI, 1.2 to 5.9). Users of tolbutamide, tolazamide, and glipizide had lower risks of serious hypoglycemia than users of chlorpropamide, whereas the risk of serious hypoglycemia among glyburide users did not differ from that of chlorpropamide users. Among second generation sulfonylureas, the adjusted relative risk of severe hypoglycemia among glyburide users, compared with glipizide users, was 1.9 (95% CI, 1.2 to 2.9). An increased risk of serious hypoglycemia associated with use of glyburide compared with glipizide occurred in all strata, including those defined by gender, race, nursing home residence, dose, and duration of use. CONCLUSIONS: Significant differences in risk of serious hypoglycemia were observed among users of individual agents. This may be explained by duration, timing, or potency of hypoglycemic action. These data confirm previous findings that chlorpropamide use is associated with high risk of hypoglycemia and indicate that among second generation sulfonylureas, glipizide is less associated with hypoglycemia than is glyburide. More information comparing the effectiveness of glycemic control among individual sulfonylureas is needed to assist prescribers in selecting a specific agent for use in clinical practice.

Prevalence of undiagnosed non-insulin-dependent diabetes mellitus and impaired glucose tolerance in a cohort of older persons with hypertension.

OBJECTIVE: To determine the prevalence of undiagnosed non-insulin-dependent diabetes mellitus (NIDDM) and impaired glucose tolerance (IGT) in a cohort of older persons with hypertension. To examine the usefulness of screening for NIDDM in this study population. DESIGN: Cross-sectional study. SETTING: University of Tennessee, Memphis and the General Clinical Research Center (GCRC). PATIENTS: Ninety-five participants in the Trial of Nonpharmacologic Interventions in the Elderly (TONE) study who agreed to participate in an ancillary study. MEASUREMENTS: A standard oral glucose tolerance test (OGTT) with insulin and C-peptide levels was performed before the beginning of the TONE intervention. RESULTS: In this cohort, 43 participants (45.3%) had normal glucose tolerance (NGT), 41 (43.2%) had IGT, and 11 (11.6%) had undiagnosed NIDDM. The positive predictive value for NIDDM of a fasting glucose > or = 115 mg/dL in our participants was 57%. Hyperinsulinemia occurred in only one participant, a subject in the IGT group. CONCLUSIONS: Our data demonstrate that undiagnosed NIDDM is common in our cohort of older persons who are being treated for essential hypertension and that impaired glucose tolerance may be more common than in the general population of the same age. Further, our data show that the vast majority of this older, obese, hypertensive cohort did not have fasting hyperinsulinemia. We also infer that a fasting glucose alone has a low positive predictive value for screening of NIDDM in our older cohort. As the prevalence of NIDDM and impaired glucose tolerance in older hypertensive patients in the general population is unknown, we believe that further investigation is needed to characterize the relationship of hypertension, glycemic status, and hyperinsulinemia in the general population.

Glycemic control of older adults with type 2 diabetes: findings from the Third National Health and Nutrition Examination Survey, 1988-1994.

BACKGROUND: Although nearly half of all people who have diabetes are aged 65 or older, glycemic control of older adults with diabetes has not been well described. METHODS: We conducted a cross-sectional study of 1,482 participants with self-reported type 2 diabetes in the Third National Health and Nutrition Examination Survey, 1988-1994 (NHANES III), a nationally representative sample of the US noninstitutionalized civilian population. Variables included in this analysis included age, sociodemographic factors, drug treatment, and level of glycemic control. RESULTS: The mean % (+/-SE) HbA1c was 7.78 +/- 0.21, 7.64 +/- 0.18, 7.71 +/- 0.14, and 7.27 +/- 0.14 in persons aged 20 to 54, 55 to 64, 65 to 74 and > or = 75 years, respectively. The mean mg/dL (+/-SE) fasting plasma glucose (FPG) was 175.9 +/- 7.6, 164.5 +/- 6.1, 183.3 +/- 5.3, and 158.5 +/- 5.5 in the four age groups and older, respectively. When controlling for race, gender, education, and duration of diabetes, age was not significantly associated with levels of HbA1c [P (trend) =0.17] or FPG [P (trend) =0.19]. Among NHANES III participants aged 65 or older, ADA guidelines for glycemic control (HbA1c < 7%) were achieved by 71%, 44%, and 27% of persons using no drug therapy, oral hypoglycemic agents, and insulin, respectively. CONCLUSIONS: Although many older adults with type 2 diabetes do not achieve targets for glucose control, there is no evidence to suggest that community-dwelling older adults with diabetes are treated less vigorously than younger persons with diabetes.

In vitro effects of acetaminophen and its analogues on human platelet aggregation and thromboxane B2 synthesis.

We examined the effect of acetaminophen and the structural analogues 2,6-dimethylacetaminophen, 3,5-dimethylacetaminophen, and N-acetyl-p-benzoquinone imine on human platelet aggregation, 14C-serotonin secretion, and thromboxane B2 synthesis. Preincubation with 1 mM acetaminophen for 2 min completely inhibited arachidonic acid- and collagen-stimulated platelet aggregation. Thromboxane B2 production and 14C-serotonin secretion by arachidonic acid-stimulated platelets also were completely inhibited. Preincubation of platelets with 1 mM 3,5-dimethylacetaminophen inhibited collagen and arachidonic acid-induced aggregation and arachidonic acid-stimulated thromboxane B2 synthesis, while treatment with 2,6-dimethylacetaminophen did not inhibit aggregation and blocked thromboxane B2 formation to a much lesser degree. Preincubation with 1 mM N-acetyl-p-benzoquinone imine inhibited arachidonic acid-induced aggregation and 14C-serotonin secretion but had no effect on arachidonic acid-induced thromboxane B2 formation and collagen-induced platelet aggregation.

Rational use of benzodiazepines in the elderly.

In the 40 years since the introduction of benzodiazepines into clinical practice, considerable controversy has surrounded their use. While there is little evidence to suggest widespread abuse or long term use in most age groups, benzodiazepines continue to be widely prescribed to older adults in both community and long term care settings. Several studies have described an increased sensitivity to the clinical effects and toxicity of benzodiazepines in older adults. However, it is unclear whether these observations are attributable to age-related changes in benzodiazepine pharmacokinetics or pharmacodynamics. Benzodiazepines are the safest and most effective agents available for the pharmacological management of symptoms of anxiety and insomnia. However, the acute administration of benzodiazepines is associated with impairments in cognition, memory, coordination and balance, and long term use, even at therapeutic dosages, has been associated with symptoms of withdrawal upon abrupt discontinuation. Therefore, it is essential that the practitioner develop a treatment plan when utilising these agents to treat older patients. This plan may also involved the implementation of psychotherapy or other nonpharmacological modalities in the management of anxiety or insomnia. Although we recommend initiating benzodiazepines using the lowest available dosage, older patients should be treated with enough drug to produce a therapeutic response. For most clinical situations of anxiety or insomnia, we recommend prescribing limited quantities (e.g. a 2-week supply with a return visit for re-evaluation of effectiveness and adverse effects) of a drug with a short elimination half-life. Persistent anxiety or insomnia in the elderly may require a medical and possibly psychiatric evaluation. If benzodiazepines are used continuously for 6 weeks or longer, we recommend a gradual taper over 2 to 12 weeks with frequent follow-up to evaluate for signs of withdrawal or the return of symptoms.

Epidemiology of adverse drug reactions in the elderly by drug class.

As the growth of the elderly population continues, the burden on the health care system and society will also increase. Since chronic diseases such as hypertension, coronary artery disease, arthritis, stroke, cancer and diabetes mellitus are more prevalent with age, the number of people with multiple chronic diseases will also increase. These patients are likely to be treated for some or all of their conditions with drug therapies. When used appropriately, drugs may be the single most important intervention in the care of an older patient, but when used inappropriately they no longer provide therapeutic benefit, and they may even endanger the health of an older patient by causing an adverse drug reaction (ADR). Factors believed to be responsible for increased adverse reactions in elderly patients are polypharmacy (including prescription and over-the-counter medications), increased drug-drug interaction, pharmacokinetic changes, pharmacodynamic changes, the pathology of aging and compliance. The exact role that age plays in ADRs is not clear. This is in part because few older patients are included in the large randomised trials, and so much of the information used to ascertain the age-associated risks of drugs comes from observational studies. Although the interactions of aging, concurrent comorbidities and polypharmacy are known, older patients do appear to be at increased risk. Improvements in the management of drug therapies of older patients can lead to improvements in their overall health, functioning and safety, as well as providing potential benefits to society by ameliorating some of the burden of their health care.

Medications and the older driver.

Table 4 provides a summary of the evidence that specific medications adversely affect the safety of the older driver. The preponderance of evidence suggests that benzodiazepines adversely affect the safety of the older driver, particularly for high doses and long half-life compounds. This conclusion is based upon the very consistent psychomotor function data showing pronounced dose-related impairment, the more limited epidemiologic data on crash involvement, epidemiologic data associating benzodiazepines with other types of injuries, and the fact that the reasons for most benzodiazepine use are not plausible confounders. This conclusion thus reinforces the need to prescribe benzodiazepines cautiously, including assessment of nonpharmacologic alternatives, use of the lowest possible dose for the shortest possible time, and avoidance of the very long half-life compounds. As more new nonbenzodiazepine anxiolytics and hypnotics become available, their effects on the safety of the elderly driver need to be determined. There is some evidence that cyclic antidepressants, currently the mainstay for treatment of depression in the elderly population, adversely affect driving safety; however, because of the paucity of experimental and epidemiologic data concerning the effects of depression per se on driving, further research is needed. Nevertheless, the existing data reinforce the need for careful prescribing of antidepressants, particularly avoidance of agents with high side-effect profiles (such as amitriptyline and imipramine) in the older driver. For hypoglycemics, although there is sufficient evidence of driving impairment to create a basis for concern, there are many unresolved questions. Currently, diabetic patients should be advised concerning the risk and management of hypoglycemia. For other sedating drugs, it always is prudent to advise patients concerning potential effects on driving. Unlike younger drivers, the typical older driver is a medication-taker. There now is a substantial body of evidence that commonly used medications can interfere with driving safety. Because many questions remain unanswered, there is a pressing need for further research that more fully elucidates how patient characteristics, disease, and drugs interact to affect driving safety; however, sufficient data are available to reinforce an underlying theme in geriatric medicine that is not yet fully implemented in practice: the need for caution in pharmacotherapy, with selection of a drug, dose, and regimen suitable for the unique characteristics of this population.