Rhonda L. Bohn

Noncompliance with antihypertensive medications: the impact of depressive symptoms and psychosocial factors.

OBJECTIVE: Addressing the epidemic of poor compliance with antihypertensive medications will require identifying factors associated with poor adherence, including modifiable psychosocial and behavioral characteristics of patients.DESIGN: Cross-sectional study, comparing measured utilization of antihypertensive prescriptions with patients’ responses to a structured interview.STUDY POPULATION: Four hundred ninety-six treated hypertensive patients drawn from a large HMO and a VA medical center.DATA COLLECTION: We developed a survey instrument to assess patients’ psychosocial and behavioral characteristics, including health beliefs, knowledge, and social support regarding blood pressure medications, satisfaction with health care, depression symptom severity, alcohol consumption, tobacco use, and internal versus external locus of control. Other information collected included demographic and clinical characteristics and features of antihypertensive medication regimens. All prescriptions filled for antihypertensive medications were used to calculate actual adherence to prescribed regimens in a 365-day study period.MAIN OUTCOME OF INTEREST: Adjusted odds ratios (ORs) of antihypertensive compliance, based on ordinal logistic regression models.RESULTS: After adjusting for the potential confounding effects of demographic, clinical, and other psychosocial variables, we found that depression was significantly associated with noncompliance (adjusted OR per each point increase on a 14-point scale, 0.93; 95% confidence interval [95% CI], 0.87 to 0.99); in unadjusted analyses, the relationship did not reach statistical significance. There was also a trend toward improved compliance for patients perceiving that their health is controlled by external factors (adjusted OR per point increase, 1.14; 95% CI, 0.99 to 1.33). There was no association between compliance and knowledge of hypertension, health beliefs and behaviors, social supports, or satisfaction with care.CONCLUSIONS: Depressive symptoms may be an under-recognized but modifiable risk factor for poor compliance with antihypertensive medications. Surprisingly, patient knowledge of hypertension, health beliefs, satisfaction with care, and other psychosocial variables did not appear to consistently affect adherence to prescribed regimens.

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 (> or =80%) were calculated. In a logistic regression model, good compliance (> 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.

Compliance with antihypertensive therapy among elderly Medicaid enrollees: the roles of age, gender, and race.

OBJECTIVES This study measured compliance and related demographic factors in a retrospective cohort of 4068 elderly outpatients newly starting antihypertensive therapy from 1982 through 1988. METHODS Logistic regression modeling of data from the New Jersey Medicaid program was used. RESULTS These patients filled antihypertensive prescriptions covering an average of only 179 days in the 365-day follow-up period (49%) Good compliance (> or = 80%) was associated with advanced age (odds ratio [OR] = 2.12, for patients 85 or older) and White race (OR = 0.55 for Blacks). There was no relationship between compliance and gender. CONCLUSIONS Despite the efficacy of antihypertensive therapy in preventing cardiovascular morbidity, such high rates of noncompliance may contribute to suboptimal patient outcomes.

Zolpidem use and hip fractures in older people.

OBJECTIVES: The widespread use of sedative‐hypnotics in older populations makes it imperative to identify hazardous regimens that should be avoided and safer regimens that may be used preferentially by older people. Although benzodiazepines have been shown to increase fall and fracture risk, zolpidem, a nonbenzodiazepine hypnotic, has been advocated as a safer alternative.

Anticonvulsant Medications and the Risk of Suicide, Attempted Suicide, or Violent Death

CONTEXT In 2008, the US Food and Drug Administration mandated warning labeling for anticonvulsant medications regarding the increased risk of suicidal thoughts and behaviors. The decision was based on a meta-analysis not sufficiently large to investigate individual drugs. OBJECTIVE To evaluate the risk of suicidal acts and combined suicidal acts or violent death associated with individual anticonvulsants. DESIGN A cohort study of the risk of suicidal acts and combined suicidal acts or violent death in patients beginning use of anticonvulsant medications compared with patients initiating a reference anticonvulsant drug. SETTING AND PATIENTS Patients 15 years and older from the HealthCore Integrated Research Database (HIRD) who began taking an anticonvulsant between July 2001 and December 2006. MAIN OUTCOME MEASURES Cox proportional hazards models and propensity score-matched analyses were used to evaluate risk of attempted or completed suicide and combined suicidal acts or violent death, controlling for psychiatric comorbidities and other risk factors, among individual anticonvulsants compared with topiramate and secondarily carbamazepine. RESULTS The study identified 26 completed suicides, 801 attempted suicides, and 41 violent deaths in 297,620 new episodes of treatment with an anticonvulsant (overall median follow-up, 60 days). The incidence of the composite outcomes of completed suicides, attempted suicides, and violent deaths for anticonvulsants used in at least 100 treatment episodes ranged from 6.2 per 1000 person-years for primidone to 34.3 per 1000 person-years for oxcarbazepine. The risk of suicidal acts was increased for gabapentin (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.11-1.80), lamotrigine (HR, 1.84; 95% CI, 1.43-2.37), oxcarbazepine (HR, 2.07; 95% CI, 1.52-2.80), tiagabine (HR, 2.41; 95% CI, 1.65-3.52), and valproate (HR, 1.65; 95% CI, 1.25-2.19), compared with topiramate. The analyses including violent death produced similar results. Gabapentin users had increased risk in subgroups of younger and older patients, patients with mood disorders, and patients with epilepsy or seizure when compared with carbamazepine. CONCLUSION This exploratory analysis suggests that the use of gabapentin, lamotrigine, oxcarbazepine, and tiagabine, compared with the use of topiramate, may be associated with an increased risk of suicidal acts or violent deaths.

Delayed nephrologist referral and inadequate vascular access in patients with advanced chronic kidney failure

We sought to determine whether late referral to a nephrologist in patients with chronic renal failure influences the adequacy of vascular access for hemodialysis. We analyzed data describing all health care encounters for all Medicare and Medicaid patients with end-stage renal failure in New Jersey between January 1991 and June 1996. Patients were required to have been diagnosed with renal disease at least 1 year prior to onset of hemodialysis. In the resulting cohort of 2,398 incident hemodialysis patients, 35% had their first nephrologist consultation < or =90 days prior to initiation of dialysis. After controlling for demographic characteristics, socio-economic status and underlying renal disease, we found that patients who were referred to a nephrologist >90 days prior to onset of hemodialysis were 38% more likely to have undergone predialysis vascular access surgery than those who were referred to a nephrologist < or =90 days before dialysis [OR: 1.38; 95% CI (1.15; 1.64)]. Similarly, patients referred late were 42% more likely to require central venous access for hemodialysis compared to those seen by a nephrologist early [OR: 1.42; 95% CI (1.17; 1.71)]. Inadequate development of vascular access for renal replacement therapy in patients with late nephrologist referral unnecessarily contributes to the burden of disease experienced by this vulnerable patient population.

Nonoccupational Risk Factors for Carpal Tunnel Syndrome

AbstractOBJECTIVE: To examine the relation between selected nonoccupational risk factors and surgery for carpal tunnel syndrome. DESIGN: Case-control study using an administrative database. PARTICIPANTS: Enrollees of New Jersey Medicine or Medicaid programs during 1989 to 1991. MEASUREMENTS: The outcome of interest was open or endoscopic carpal tunnel release. We examined the relation between carpal tunnel release and diabetes mellitus, thyroid disease, inflammatory arthritis, hemodialysis, pregnancy, use of corticosteroids, and hormone replacement therapy. MAIN RESULTS: In multivariate models, inflammatory arthritis was strongly associated with carpal tunnel release (odds ratio [OR] 2.9; 95% confidence interval [CI] 2.2, 3.8). However, corticosteroid use also appeared to be associated with a greater likelihood of undergoing carpal tunnel release, even in the absence of inflammatory arthritis (OR 1.6; 95% CI 1.2, 2.1). Diabetes had a weak but significant association with carpal tunnel release (OR 1.4; 95% CI 1.2, 1.8), as did hypothyroidism (OR 1.7; 95% CI 1.1, 2.8), although patients with hyperthyroidism did not have any change in risk. Women who underwent carpal tunnel release were almost twice as likely to be users of estrogen replacement therapy as controls (OR 1.8; 95% CI 1.0, 3.2). CONCLUSIONS: Although inflammatory arthritis is the most important nonoccupational risk factor for carpal tunnel release, these data substantiate the increase in risk associated with diabetes and untreated hypothyroidism. Further investigation in detailed clinical studies will be necessary to confirm whether changes in corticosteroid use and hormone replacement therapy offer additional means of risk reduction for this common condition.

Validation of claims‐based diagnostic and procedure codes for cardiovascular and gastrointestinal serious adverse events in a commercially‐insured population

To validate administrative claims codes with medical chart review for myocardial infarction (MI), ischemic stroke, and severe upper gastrointestinal (UGI) bleed events in a large, commercially‐insured US population.

Antihypertensive Drug Therapy and the Initiation of Treatment for Diabetes Mellitus

Although several antihypertensive medications have been associated with impaired glucose tolerance [1], thiazide diuretics have received the most attention in this regard. Since the introduction of chlorothiazide in 1957, several cases have been reported in which thiazide diuretics were associated with glucose intolerance [2-5]. In addition, many clinical studies have provided information on the effects of thiazide diuretics on glucose homeostasis. The Veterans Administration Cooperative Study Group on Antihypertensive Agents [6] found that hydrochlorothiazide increased the average fasting plasma glucose level by approximately 0.3 mmol/L after 10 weeks of treatment. In the Systolic Hypertension in the Elderly Program study [7], the treatment group showed an increase of 0.4 mmol/L in mean serum glucose levels over the baseline level after 1 year of thiazide diuretic therapy, whereas the placebo group showed an increase of 0.1 mmol/L. In the study conducted by the European Working Party on Hypertension in the Elderly [8], the thiazide treatment group showed an increase of 0.5 mmol/L in the fasting serum glucose level after 2 years, whereas the placebo group showed a decrease of 0.2 mmol/L (P < 0.001). In a randomized, crossover study of 50 patients, Pollare and coworkers [9] found that, when compared with placebo, hydrochlorothiazide reduced insulin-stimulated glucose uptake in patients with essential hypertension after 18 weeks of treatment. In contrast, patients treated with captopril showed improved carbohydrate metabolism, including an increase in insulin-stimulated glucose uptake, when compared with placebo recipients. Previous efforts to quantify the clinical risk for development of hyperglycemia requiring treatment in patients taking various antihypertensive regimens have been limited by the relative infrequency of this event and the limited range of antihypertensive agents used in large clinical trials [10]. For the same reasons, the risks of different agents have not been adequately compared. To address these issues, we conducted a casecontrol study of 11 855 New Jersey Medicaid enrollees newly started on hypoglycemic therapy. Methods Sources of Data The study sample was drawn from the state of New Jerseys Medicaid program for the years 1981 to 1990. Enrollment in the program was ascertained through the Medicaid eligibility file, which identifies all program participants, their dates of coverage, and demographic characteristics including age, gender, and race. Data on medication use were taken from the Medicaid pharmacy claims file, which contains information on all prescriptions filled by Medicaid recipients, including the National Drug Code and the date dispensed. Medications of interest were identified using the National Drug Code specific for each agent. Hospitalization data for all Medicaid recipients were also ascertained. Medicaid recipients who were eligible to receive Medicare benefits (crossover enrollees) were identified to acquire full information on utilization of hospital services. Medicaid covers payment for medications for these Medicare recipients, which enabled us to ascertain all prescription information for this group. Case Patients Case patients were Medicaid enrollees 35 to 99 years of age who filled a first prescription for a hypoglycemic agent between 1981 and 1990. All oral hypoglycemic medications and insulin preparations were included. The date of the first prescription for a hypoglycemic medication was defined as the index date. To ensure that study patients were active users of the Medicaid system, each case patient was required to be continuously eligible in the program for at least 120 days before the index date and to have filled a prescription for at least one drug of any kind during this period. No claims for a hypoglycemic agent could be made before the index date. Drug claims were searched back to 1981 to ensure that case patients and controls had not previously filled a prescription for a hypoglycemic agent. Of the 35 202 patients who filled a first prescription for a hypoglycemic agent during the defined study period, 443 had deficient eligibility records, and 4753 did not meet the specified age criteria. The additional requirement that case patients be continuously enrolled in Medicaid during the 120 days before the index date eliminated 9292 persons. Another 8859 patients were excluded from the case group because they had not filled a prescription for any other drug during the 120 days preceding the index date. The final case group included 11 855 patients. Controls We identified controls by selecting a random sample of Medicaid enrollees who met the same criteria for eligibility and use of the health care system as did case patients but who had not filled a prescription for a hypoglycemic agent on or before a randomly assigned index date. One control was randomly selected for each case. Definitions of Antihypertensive Drug Use To characterize current exposure to antihypertensive agents, all prescriptions filled during the 120 days before the index date were reviewed for both case patients and controls. Medications of principal interest included thiazide diuretics; angiotensin-converting enzyme inhibitors; centrally acting antiadrenergic agents; peripherally acting antiadrenergic agents; -blockers; calcium-channel blockers; and vasodilators. Categorization of patients taking multiple-agent regimens representing more than one category of antihypertensive agent was based on whether the regimen did or did not contain a thiazide diuretic. Drug-exposure categories were mutually exclusive so that patients were either characterized as exposed to a single category of antihypertensive therapy or placed in one of the multiple-category groups, but not both. Three time windows of exposure before the index date were created: 1 to 45 days, 1 to 90 days, and 91 to 120 days. A patient was considered to be currently exposed to an agent if he or she filled a prescription for a medication of interest in the 45 days before the index date. This was the exposure window of primary interest. In addition, we examined records of patients who filled a prescription for a medication of interest 1 to 90 days before the index date and 91 to 120 days before the index date to study people with evidence of a more prolonged duration of exposure. Covariates Because other medications can also directly and indirectly affect glucose metabolism, we measured exposure to potassium supplements, potassium-sparing diuretics, oral glucocorticoids, estrogen-containing compounds, and niacin. In addition, exposure status for these agents was characterized according to the previously defined exposure windows. Other covariates included demographic variables (age, gender, race, residence in a nursing home) the number of days hospitalized, and the number of prescriptions filled in the 120-day period before the index date. Statistical Analysis Differences in categorical variables between case patients and controls were assessed with chi-square tests. Relative risks for new use of a hypoglycemic agent within each exposure category were estimated from odds ratios calculated by unconditional logistic regression [11] using the SAS CATMOD program [12]. For these analyses, the reference category was the absence of exposure to any antihypertensive medication. Models were constructed with patients characterized according to the study definitions of duration of exposure (current exposure or exposure of more prolonged duration). Covariates in the models included age, gender, race, nursing home residency, number of days in the hospital, number of drug claims, glucocorticoid exposure, potassium supplementation, estrogen exposure, and niacin exposure. Because of temporal trends in the pattern of antihypertensive drug prescribing [13], the study sample was stratified according to index date (pre-1985 or 1985 to 1990), and models were constructed for each subsample. Confidence intervals (CIs) for the estimated odds ratios and significance tests for differences between individual odds ratios were calculated using the estimated standard errors. To control for potential surveillance bias (that is, the possibility that patients receiving antihypertensive agents may have had closer medical supervision and may have had more laboratory tests than patients not receiving antihypertensive therapy) and to make the case and control groups more comparable, we did a separate analysis of the 8005 current users of antihypertensive medications (4794 case patients and 3211 controls). In these models, current exposure to thiazide diuretics was the reference exposure. This model also included the same potential confounding variables mentioned above. Results We found no consistent trend when examining the relation between age and the likelihood of starting a hypoglycemic medication (Table 1) in the age range studied. Patients 55 to 74 years of age were more likely to be started on a hypoglycemic agent than patients 35 to 54 years of age, although no significant difference was found between patients 75 years of age or older and patients 35 to 54 years of age. No significant differences in gender distribution were observed between case patients and controls. Blacks and other non-whites were more likely to be started on hypoglycemic therapy than whites. Patients in nursing homes were less likely to start hypoglycemic therapy than noninstitutionalized patients. Patients who had a greater number of hospital days or who filled more prescriptions were more likely to be started on a hypoglycemic medication. No relation was found between index date (pre-1985 or 1985 to 1990) and the likelihood of being started on hypoglycemic therapy. Table 1. Characteristics of the Study Sample and Their Relation to Starting a Hypoglycemic Medication The relative risk for the initiation of hypoglycemic therapy was significantly increased among patients who were current users

The economic impact of factor VIII inhibitors in patients with haemophilia.

Summary.  The impact on the cost of care for haemophilia patients with inhibitors is not well defined. To quantify the effect on health care expenditures associated with inhibitors to factor VIII (FVIII) or FIX, we conducted a retrospective cohort study examining product use and outcomes in adult and paediatric haemophilia patients with and without inhibitors. Twelve patients with inhibitors to FVIII or FIX (cases) identified in the haemophilia surveillance system (HSS) at two centres were matched on age, severity of haemophilia, and treatment centre to haemophilia patients without inhibitors. Patients with HIV or significant liver disease were excluded from the study. All eligible non‐inhibitor control patients were selected for inclusion in the study, resulting in a total of 28 controls. We then tracked product usage and hospitalizations from programme entry until 1998 or loss to follow‐up, producing a total database of 184 person‐years of experience. A descriptive matched analysis was conducted to examine annual differences in the cost of product used and hospitalizations. We found that the median cost for factor products among haemophilia patients with inhibitors was