The Clinical Utility of a Precision Medicine Blood Test Incorporating Age, Sex, and Gene Expression for Evaluating Women with Stable Symptoms Suggestive of Obstructive Coronary Artery Disease: Analysis from the PRESET Registry.

Background: Evaluating women with symptoms suggestive of coronary artery disease (CAD) remains challenging. A blood-based precision medicine test yielding an age/sex/gene expression score (ASGES) has shown clinical validity in the diagnosis of obstructive CAD. We assessed the effect of the ASGES on the management of women with suspected obstructive CAD in a community-based registry. Materials and Methods: The prospective PRESET (A Registry to Evaluate Patterns of Care Associated with the Use of Corus® CAD in Real World Clinical Care Settings) Registry (NCT01677156) enrolled 566 patients presenting with symptoms suggestive of stable obstructive CAD from 21 United States primary care practices from 2012 to 2014. Demographics, clinical characteristics, and referrals to cardiology or further functional and/or anatomical cardiac studies after ASGES testing were collected for this subgroup analysis of women from the PRESET Registry. Patients were followed for 1-year post-ASGES testing. Results: This study cohort included 288 women with a median age 57 years. The median body mass index was 29.2, with hyperlipidemia and hypertension present in 48% and 43% of patients, respectively. Median ASGES was 8.5 (range 1-40), with 218 (76%) patients having low (≤15) ASGES. Clinicians referred 9% (20/218) low ASGES versus 44% (31/70) elevated ASGES women for further cardiac evaluation (odds ratio 0.14, p < 0.0001, adjusted for patient demographics and clinical covariates). Across the score range, higher ASGES were associated with a higher likelihood of posttest cardiac referral. At 1-year follow-up, low ASGES women experienced fewer major adverse cardiac events than elevated ASGES women (1.3% vs. 4.2% respectively, p = 0.16). Conclusions: Incorporation of ASGES into the diagnostic workup demonstrated clinical utility by helping clinicians identify women less likely to benefit from further cardiac evaluation

Agreement between drug treatment data and a discharge diagnosis of diabetes mellitus in the elderly.

The authors examined agreement between drug treatment data and a discharge diagnosis of diabetes, considered whether agreement was modified by demographic variables and measures of comorbidity, and evaluated construct validity through consideration of relations with subsequent mortality. The study sample comprised 81,700 residents of New Jersey aged 65-99 years who had prescription drug coverage either through Medicaid or that state\u27s Pharmacy Assistance for the Aged and Disabled program and had at least one hospitalization between July 1, 1989, and June 30, 1991. In this population, 16.4% filled a prescription for insulin or an oral hypoglycemic agent during the 120 days before admission, and 16.3% had a discharge diagnosis of diabetes. Overall agreement between these two indicators was modest (kappa = 0.67, 95% confidence interval 0.66-0.67) and was weaker in those aged 85 years and above (kappa = 0.58, 95% confidence interval 0.56-0.60), those in nursing homes (kappa = 0.42, 95% confidence interval 0.39-0.44), and those with a high level of comorbidity (modified Charlson index \u3e or =5; kappa = 0.59, 95% confidence interval 0.56-0.62). Presence of a diagnosis of diabetes was associated with an apparent 24% reduction in the risk of death during the study interval (p\u3c0.001), while prior treatment for diabetes had little relation to mortality (p = 0.15). These paradoxical associations with mortality and the lower agreement between discharge diagnoses and drug treatments associated with older age, nursing home residence, and comorbidity suggest limitations in the use of claims data to identify diabetes in the elderly

Aging, comorbidity, and reduced rates of drug treatment for diabetes mellitus.

Advanced age and its related comorbidity may affect both the patterns and goals of diabetes treatment. We examined the relationships of demographic variables and comorbidity with drug treatment for diabetes in the elderly. We studied both the 81,700 residents of New Jersey, aged 65-99 years, who were hospitalized between July 1, 1989 and June 30, 1991 and had prescription drug coverage either through Medicaid or the Pharmacy Assistance for the Aged and Disabled program, and a sample of 80,000 nonhospitalized elderly beneficiaries in these programs. Rates of utilization of insulin or oral hypoglycemic drugs in the 120 days before admission were substantially lower in those aged \u3e or = 85 or in nursing homes. Among patients with previously treated and diagnosed diabetes, the likelihood of treatment after discharge declined with older age (odds ratio [OR] for treatment in those aged \u3e or =85 relative to 65-74 years: 0.57; 95% confidence interval [CI]: 0.45-0.72), nursing home residence (OR: 0.30; CI: 0.22-0.41), and higher levels of comorbidity (OR for modified Charlson index \u3e or = 5 relative to 0: 0.43; CI: 0.27-0.67). In patients who had a discharge diagnosis of diabetes but no prior treatment, those in nursing homes and those with greater comorbidity also had lower rates of diabetes treatment after discharge. Although the prevalence of diabetes increases with age and the risks of many consequences of diabetes remain high, the rate of drug treatment for diabetes declines with older age and greater comorbidity, perhaps because of concern about side effects or reduced treatment benefits due to competing risks of death. Absence of data from randomized clinical trials of diabetes treatment in the elderly appears to have resulted in considerable physician ambivalence on the benefits and risks of glycemic control in older diabetics

Noncompliance with congestive heart failure therapy in the elderly.

BACKGROUND: Noncompliance with long-term medication regimens, such as those employed in the treatment of congestive heart failure (CHF), has been found to be approximately 50%. However, no evaluation has been performed on a population-based cohort of elderly patients beginning the use of digoxin and followed up longitudinally for an extended observation period. METHODS: To study patterns of medication compliance, we conducted a retrospective follow-up of 7247 outpatients aged 65 to 99 years newly prescribed digoxin between 1981 and 1991, with the use of the complete prescription claims file of the New Jersey Medicaid program. Noncompliance was measured in terms of the number of days during the 12-month period after an initial digoxin prescription in which no CHF medication was available to the patient. RESULTS: Patients started on a regimen of digoxin were without digoxin or any other common alternative CHF drug for an average of 111 of the 365 days of follow-up. Only 10% of the population filled enough prescriptions to have daily CHF medication available for the entire year of follow-up. Compliance rates were higher in patients over 85 years of age, women, those taking multiple medications, and those with hospital or nursing home stays before the initiation of therapy. CONCLUSIONS: A large proportion of patients who begin digoxin therapy end CHF therapy or consume substantially less medication than expected in the first year of therapy. Such high rates of cessation could represent an important impediment to effective CHF therapy

Initiation of antihypertensive treatment during nonsteroidal anti-inflammatory drug therapy.

OBJECTIVE--To determine whether there is an increased risk for the initiation of antihypertensive therapy in older persons prescribed nonaspirin, nonsteroidal anti-inflammatory drugs (NSAIDs). DESIGN--Case-control study. SETTING--New Jersey Medicaid program. PATIENTS--Medicaid enrollees aged 65 years and older. The 9411 case patients were newly started on an antihypertensive medication between November 1981 and February 1990. A similar number of controls were randomly selected among other enrollees. MAIN OUTCOME MEASURES--We used logistic regression to determine the odds ratio for the initiation of antihypertensive therapy in patients using NSAIDs relative to nonusers, after adjusting for age, sex, race, nursing home residence, number of prescriptions filled, intensity of physician utilization, and days hospitalized. RESULTS--The adjusted odds ratio for the initiation of antihypertensive therapy for recent NSAID users compared with nonusers was 1.66 (95% confidence interval, 1.54 to 1.80). The odds ratio increased with increasing daily NSAID dose: the adjusted odds ratio for users of low average daily doses relative to nonusers was 1.55 (95% CI, 1.38 to 1.74), that for medium-dose users was 1.64 (95% CI, 1.44 to 1.87), and that for high-dose users was 1.82 (95% CI, 1.62 to 2.05). CONCLUSIONS--Use of NSAIDs may increase the risk for initiation of antihypertensive therapy in older persons. Given the high prevalence of NSAID use by elderly persons, this association may have important public health implications for the management of hypertension in the older population

Antihypertensive drug therapy and the initiation of treatment for diabetes mellitus.

OBJECTIVE: To quantify the risk for the occurrence of hyperglycemia requiring initiation of therapy among patients taking various antihypertensive regimens. DESIGN: Case-control study. SETTING: New Jersey Medicaid program. PATIENTS: The study included New Jersey Medicaid enrollees 35 years of age or older. The 11,855 case patients were newly started on a hypoglycemic agent (oral agent or insulin) between 1981 and 1990. The 11,855 controls were selected randomly from among other Medicaid enrollees. MEASUREMENTS AND MAIN RESULTS: The frequency of initiation of hypoglycemic therapy was increased for users of virtually all antihypertensive agents relative to nonusers after adjustment for age, gender, race, nursing home residency, number of days hospitalized, total number of prescriptions, and selected medication exposures. The estimated relative risk for initiation of hypoglycemic therapy was 1.40 for patients receiving thiazide diuretics (95% CI, 1.26 to 1.58) and ranged from 1.56 to 1.77 for patients receiving other antihypertensive medications, depending on the medication category. A higher risk was associated with multiple-agent regimens, whether they excluded a thiazide diuretic (odds ratio, 1.76; CI, 1.49 to 2.07) or included one (odds ratio, 1.93; CI, 1.75 to 2.13). When the analysis was restricted to users of antihypertensive agents (n = 8005), the risk associated with other single-agent antihypertensive regimens was not significantly different from that associated with thiazide diuretics. However, patients receiving multiple-agent regimens continued to be at increased risk for hyperglycemia requiring hypoglycemic therapy relative to those who used thiazide diuretic therapy alone. CONCLUSION: The association between antihypertensive therapy and the initiation of treatment for diabetes mellitus is more closely related to the intensity of therapy than to the individual agent used. Our data do not support the hypothesis that thiazide diuretics are more strongly associated with the initiation of hypoglycemic therapy than are other antihypertensive agents

Reduction of bacteriuria and pyuria after ingestion of cranberry juice.

OBJECTIVE--To determine the effect of regular intake of cranberry juice beverage on bacteriuria and pyuria in elderly women. DESIGN--Randomized, double-blind, placebo-controlled trial. SUBJECTS--Volunteer sample of 153 elderly women (mean age, 78.5 years). INTERVENTION--Subjects were randomly assigned to consume 300 mL per day of a commercially available standard cranberry beverage or a specially prepared synthetic placebo drink that was indistinguishable in taste, appearance, and vitamin C content but lacked cranberry content. OUTCOME MEASURES--A baseline urine sample and six clean-voided study urine samples were collected at approximately 1-month intervals and tested quantitatively for bacteriuria and the presence of white blood cells. RESULTS--Subjects randomized to the cranberry beverage had odds of bacteriuria (defined as organisms numbering \u3e or = 10(5)/mL) with pyuria that were only 42% of the odds in the control group (P = .004). Their odds of remaining bacteriuric-pyuric, given that they were bacteriuric-pyuric in the previous month, were only 27% of the odds in the control group (P = .006). CONCLUSIONS--These findings suggest that use of a cranberry beverage reduces the frequency of bacteriuria with pyuria in older women. Prevalent beliefs about the effects of cranberry juice on the urinary tract may have microbiologic justification

The effects of initial drug choice and comorbidity on antihypertensive therapy compliance: results from a population-based study in the elderly.

Approximately half of all elderly patients have elevated blood pressure, and proper treatment of this disorder leads to decreased cardiovascular morbidity in patients 65 and older. This study examined the effect of initial drug choice and comorbidity on medication compliance. We conducted a retrospective follow-up of 8643 outpatients aged 65 to 99 with newly prescribed antihypertensive therapy (AHT) from 1982 to 1988 in the New Jersey Medicaid and Medicare programs. Compliance was measured in terms of the number of days in which AHT was available to the patient during the 12 months following the initiation of therapy. Odds ratios (OR) and 95% confidence intervals (CI) for the outcome of good compliance (\u3e or =80%) were calculated. In a logistic regression model, good compliance (\u3e or =80%) was significantly associated with use of newer agents such as angiotensin converting enzyme inhibitors (OR 1.9, 95% CI 1.6 to 2.2) and calcium channel blockers (OR 1.7, 95% CI 1.5 to 2.1) as compared to thiazides, the presence of comorbid cardiac disease (OR 1.2, 95% CI 1.1 to 1.2), and multiple physician visits (OR 2.2, 95% CI 1.8 to 2.5). Good compliance was inversely associated with use of multiple pharmacies (OR 0.4, 95% CI 0.4 to 0.5) and number of medications prescribed overall (OR 0.8, 95% CI 0.7 to 0.9). Drug choice, comorbidity, and health services utilization were significantly associated with AHT compliance and represent important considerations in the management of high blood pressure. Noncompliance may be an important cause of treatment failure in elderly hypertensives