Enhancing medication compliance for people with serious mental illness.
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Acute Disease↗
Biomedical subjects
J A Cramer
Publications and source records attributed to J A Cramer.
Development of the Quality of Life in Epilepsy Inventory for Adolescents: the QOLIE-AD-48.
PURPOSE: We report the development of an instrument to assess health-related quality of life (HRQOL) in adolescents with epilepsy. METHODS: A sample of 197 English-speaking adolescents (aged 11-17 years) with epilepsy completed a test questionnaire of 88 items. Also included were mastery and self-esteem scales to assess external validity. A parent simultaneously completed an 11-item questionnaire to evaluate the child's HRQOL. Both adolescent and parent questionnaires were repeated in 2-4 weeks. Demographic information and information pertaining to seizures were collected at baseline along with assessment of systemic and neurologic toxicity. RESULTS: The QOLIE-AD-48 contains 48 items in eight subscales: epilepsy impact (12 items), memory/concentration (10), attitudes toward epilepsy (four), physical functioning (five), stigma (six), social support (four), school behavior (four), health perceptions (three), and a total summary score, with higher scores indicating better HRQOL. Internal construct validity was demonstrated in a single-factor solution for the eight dimensions. All correlations were statistically significant at p < 0.05 level. Internal consistency reliability estimated by Cronbach's alpha coefficient was 0.74 for the summary score and ranged from a low of 0.52 (three-item Health Perceptions Scale) to 0.73-0.94 for the other individual scales. Good test-retest reliability was found for the overall measure (0.83). Summary score correlations with the two external validity scales, self-efficacy and self-esteem were 0.65 and 0.54, respectively. Statistically significant differences in summary scores indicating that HRQOL was increasingly better for adolescents as seizure severity decreases (no seizures = 77+/-13, low = 70+/-17, high = 63+/-17) were found among seizure-severity groups. CONCLUSIONS: These data describe the development of a robust instrument to evaluate HRQOL in adolescents with epilepsy. Empiric analyses provide strong evidence that the QOLIE-AD-48 is both a reliable and valid measure for adolescents with epilepsy.
Adolescent↗
New antiepileptic drugs: comparison of key clinical trials.
PURPOSE: Data accrued from clinical trials of five new antiepileptic drugs (AEDs) are compared for efficacy in reducing seizures and self-reported adverse events as a basis of selection among new AEDs. Drawbacks to use of these data also are demonstrated. METHODS: A review of double-blind, placebo-controlled clinical trials of a new AED or placebo added to a standard AED provided data on reduction of complex partial seizures (CPSs). Success is > or =50% fewer CPSs with a new AED or placebo; Overall Improvement is the success rate with drug minus the success rate with placebo. Adverse events were tabulated from product-labeling lists of COSTART items (incidence, > or =5%). The Summary Complaint score is the total number of reports of individual events for each AED. RESULTS: Efficacy data demonstrate differences in Overall Improvement rates among five new AEDs and placebos (p = 0.001). However, rates of response to placebo also differed significantly among trials (p = 0.01). Adverse events predominantly affect central nervous system, psychiatric, and general body systems. However, patients in the placebo control groups did not consistently report adverse effects. Summary Complaint scores differ among the five new AEDs, but variability in use of COSTART terms nullifies comparisons. CONCLUSIONS: Comparisons of data for five new AEDs provide information for selection among treatments when a second drug is needed to improve control of CPSs. However, significant differences among the control groups and other problems make comparisons between trials problematic. The final choice should be based on the need of the individual patient for superior seizure control versus minimal adverse effects.
Acetates↗
Quality of life assessment in clinical practice.
Health-related quality of life (HRQOL) includes aspects of physical, psychological, and social well-being issues for people with epilepsy. QOLIE questionnaires can be used to assess the effects of seizures and medications on cognitive function, memory, mood, physical health, and health perceptions. Monitoring HRQOL in epilepsy allows patients to express their concerns about a variety of issues affected by the diagnosis that often are not brought to the attention of the physician.
Humans↗
Complex partial and secondarily generalized seizure patients: cognitive functioning prior to treatment with antiepileptic medication. VA Epilepsy Cooperative Study 264 Group.
This investigation of cognitive functioning in patients with symptomatic localization-related (partial) epilepsy prior to administration of antiepileptic medication is part of a nationwide prospective, double-blind study of drug efficacy and longitudinal changes in cognition associated with seizure disorders. Recently-diagnosed patients with complex partial or secondarily generalized tonic clonic seizures, equated for age, education and IQ, were compared with normal controls on a battery of neuropsychological tests: verbal and figural memory measures (Rey auditory verbal learning test, Rey Osterrieth complex figure), and a brief behavioral toxicity battery comprising measures of motor function, concentration and mental flexibility (Lafayette grooved pegboard, controlled word association test, Stroop, paced auditory serial addition test [PASAT]). Control subjects perform significantly better than both groups of seizure patients on several measures of motor speed/integration and memory, specifically the pegboard and the RAVLT learning (3-5) and recall trials. Secondarily generalized seizure patients show greatest impairment. They perform significantly worse than patients with complex partial seizures and control subjects on the controlled word association test and the most demanding Stroop color word trial, both measures of concentration and mental flexibility. These findings document deficits in memory as well as concentration and motor function in complex partial and in secondarily generalized seizure patients prior to treatment with antiepileptic medication.
Adult↗
Development and cross-cultural translations of a 31-item quality of life in epilepsy inventory.
PURPOSE: We report the development of a questionnaire to assess health-related quality-of-life (HRQOL) in people with epilepsy and the process of cross-cultural translations of the questionnaire. METHODS: A sample of 304 adults with epilepsy from 25 seizure clinics in the United States was used to derive an abbreviated questionnaire focusing on epilepsy-related issues from a longer, 89-item instrument (QOLIE-89). A rigorous forward-backward-forward system was used for cross-cultural translation. RESULTS: A 31-item questionnaire (QOLIE-31, version 1.0) resulted, comprising seven subscales covering general and epilepsy-specific domains. Subscale and total scores can be calculated. The subscales were grouped into two factors: Emotional/Psychological Effects (seizure worry, overall QOL, emotional well-being, energy/fatigue subscales) and Medical/Social Effects (medication effects, work-driving-social limits, cognitive function subscales). Cross-cultural translations were made from U.S.-English into Danish, Dutch, German, Canadian French, French, Italian, Spanish, Swedish, and U.K. English Versions 1.1. CONCLUSIONS: Our results support the reliability and validity of the QOLIE-31 (U.S.-English version 1.0) as a measure of HRQOLIE. Cross-cultural translations into nine other languages make it feasible to use the QOLIE-31 (version 1.1) in multinational clinical trials after validation in each population or concurrent with the clinical trial.
Adolescent↗
Commission on Outcome Measurement in Epilepsy, 1994-1997: final report.
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Anticonvulsants↗
Review of new antiepileptic drugs (AEDs)
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Anticonvulsants↗
Compliance with medication regimens for mental and physical disorders.
OBJECTIVE: The authors reviewed research on medication compliance in psychiatric treatment and compared compliance rates with compliance rates in treatment of physical disorders. METHODS: MEDLINE was used to locate reports in the literature on medication compliance in psychiatric treatment for the years 1975 through 1996. These reports and studies cited in the reports were reviewed to determine the methods used to assess compliance and the compliance rates reported. Ten reports describing assessment methods and including medication compliance rates for antidepressant medication and 24 reports for antipsychotic medication were selected. They were compared with 12 reports that used microelectronic monitoring to assess medication compliance of patients with a range of nonpsychiatric disorders. RESULTS: Studies of psychiatric patients used various methods of estimating medication compliance, including interviews with patients, clinicians' judgment, and pill counts, but overall showed low rates of compliance. Patients receiving antipsychotics took an average of 58 percent of the recommended amount of the medications, with a range from 24 to 90 percent. Patients receiving antidepressants took 65 percent of the recommended amount, with a range from 40 to 90 percent. The mean compliance rate for patients with physical disorders was 76 percent, with a range from 60 to 92 percent, although the microelectronic monitoring showed frequent omission of doses and discontinuation of medication. CONCLUSIONS: Compliance with medication regimens among patients with psychiatric disorders may be lower than among patients with physical disorders. However, the difference may be largely attributable to the methods used for estimating compliance. The findings suggest the need for new and improved methods for monitoring compliance and increasing patients' compliance with pharmacotherapy.
Antidepressive Agents↗
Enhancing patient compliance in the elderly. Role of packaging aids and monitoring.
Inadequate compliance with medications is a significant contributor to the costs of medical care in every therapeutic area. No matter how severe the consequence, there is no assurance that all patients will take their medications as prescribed. Elderly patients are a particular concern because of their common deficits in physical dexterity, cognitive skills and memory, and the number of medications that they are typically prescribed. To overcome problems of compliance in the elderly, healthcare providers are advised to prescribe a simple dosage regimen for all medications to be taken (preferably 1 or 2 doses daily), to help the patient select cues that assist them in remembering to take doses (time of day, meal-time, or other daily rituals), to provide devices to simplify remembering doses (medication boxes), and to regularly monitor compliance. A variety of compliance aids are available to help patients organise their medications (e.g. plastic boxes) or remember dose times (alarms). Medication packaged in standard pharmacy bottles should be identified with special labels, or dose charts can be provided to check the daily schedule. Single-unit doses, widely used in hospitals, may be cumbersome for elderly patients who have difficulty opening the foil-backed wrappers. Medication boxes with compartments that are filled weekly by the patient, family member or a home healthcare provider are useful organisers that simplify the patient's responsibilities for self-administration. Microelectronic devices can provide feedback that shows patients whether they have been taking doses as scheduled. Some systems are also designed to notify patients within a day if doses were omitted. No system is optimal for all patients, but elderly patients deserve a comprehensive assessment of their needs to enhance medication compliance.
Aged↗
Consequences of intermittent treatment for hypertension: the case for medication compliance and persistence.
OBJECTIVE: To review patient compliance with once-daily antihypertensive medications and the impact of partial compliance on healthcare outcomes. DATA SOURCES: A MEDLINE search of the literature using the terms "patient compliance," "antihypertensive medications," and "hypertension" for the period 1976-1996 was conducted. In addition, papers cited in reference lists of source articles were reviewed. STUDY SELECTION: Articles were selected if they described patterns of compliance, including rates for differing dosing regimens. Articles discussing once-daily dosing were selected only if they included information on the methodology for compliance assessment. Thirteen reports met these criteria. DATA SYNTHESIS: Patterns of compliance vary, with only a partial relationship to dosing regimens. Overall compliance was 76% for once-daily antihypertensive medications, with a wide range found (53% to 85%). These data were comparable to the mean 75% compliance found for other medical disorders. CONCLUSIONS: Persistence with treatment is necessary for reduction of long-term consequences of hypertension. Enhancing compliance with antihypertensive medications could thus have a profound impact on health outcomes. Once-daily dosing should be coupled with selection of a drug with long duration of action to overcome problems of missed doses. Widespread adoption of simple compliance enhancement methods could lead to decreased morbidity and mortality from cardiovascular disease and stroke.
Antihypertensive Agents↗
Alternate endpoints for seizure measurement.
The type of seizure measurement selected should be tailored to the needs of the clinical trial. These needs change as the development of the investigational agent moves along. Protocol designers who look toward nontraditional outcome measures might acquire valuable data that could be used to differentiate their drug from other new treatments. Most importantly, as clinical trials evolve into effectiveness studies, clinicians are provided with useful data on which to base selection of a drug of first choice to treat each type of seizure disorder.
Anticonvulsants↗
The effect of food on the pharmacokinetics of multiple-dose terbinafine in young and elderly healthy subjects.
Pharmacokinetic (PK) parameters for terbinafine were assessed in 15 elderly and 15 young healthy subjects randomized to receive 250 mg Lamisil once daily for 15 d in a two-period, two-treatment, two-sequence, crossover (fed versus fasted) design within age groups. On each treatment day except days 8 and 15, subjects took Lamisil with food at 8:00 a.m. On days 8 and 15, subjects took the drug under either fed or fasting conditions according to treatment sequence, and 24 h PK profiles were obtained. Two analyses of the pharmacokinetic data were undertaken. In a noncompartmental analysis, AUC0-24h, Cmax, C0h, and tmax were computed for each subject on each of days 8 and 15, and the influences of food condition and age on these variables were assessed by analysis of variance. AUC0-24h and C0h were found to be larger (p < 0.5) among elderly subjects than young subjects on day 15, and tmax was prolonged (p < 0.05) under the fed condition on day 15. Similar trends on day 8, as well as generally higher exposures under the fed condition on both days, were not statistically significant. A three-compartment model fitted to the complete sequence of 33 terbinafine concentrations measured over 29 d for each subject separately permitted a within-subject assessment of the food effect that confirmed prolonged absorption and increased bioavailability (p < 0.05) under the fed condition. Across-subject comparisons of oral clearances estimated with the model also confirmed the increased exposures (lower clearances) among the elderly (p < 0.05). The drug was well tolerated in both age groups. In particular, greater drug exposure in the elderly did not result in greater toxicity, as indicated by the safety evaluations in the study.
Adolescent↗
A tandem solid phase extraction, reversed-phase HPLC method for determining SDZ WAG 994 in dog, monkey and rat blood.
The development and validation of a sensitive and specific HPLC method for SDZ WAG 994 (I) in dog, monkey and rat blood is described. Sample preparation entailed double solid phase extraction (SPE) of I and the internal standard from 0.5 ml of animal blood using a phenyl and propyl sulfonic acid cation exchange column, sequentially. Chromatographic separation was achieved on a YMC Basic C-8 narrowbore HPLC column and the eluates were detected by UV absorption at 266 nm. The method has a linear response up to at least 1800 ng/ml with a limit of quantification of 1 ng/ml across all species. Analysis of 'blinded' quality control dog and monkey blood samples over 3 or 4 days produced median precisions of 2.89 and 4.77%, and median reproducibilities of 4.86 and 10.9%, respectively. Curve fitting of variability estimates indicated that concentration independent error contributed 3-9% of the total method error for the tandem SPE procedure. Extracted endogenous material from blood matrices, several potential metabolites and cyclohexyladenosine were well resolved from the peaks of interest. The stability of I in dog blood stored at -20 degrees C is at least 6 months. The overall absolute and relative recovery of I using the tandem SPE procedure was 85.5 +/- 5.1% and 96.5 +/- 5.0%, respectively. The ruggedness of the method has been demonstrated by multiple analyses, from several toxicokinetic studies, performed by different analysts using comparable instrumentation.
Adenosine↗
Quality of life as an outcome measure for epilepsy clinical trials.
Assessment of health-related quality of life (HRQOL) has been developed to the point where well-validated instruments are being used in clinical trials. Data on the impact of new treatments can be used for formulary and regulatory decisions if the clinical trials are designed with appropriate instruments and sample sizes. However, more information is needed about the clinical significance of small differences in total or scale scores. Similarly, pharmacoeconomic studies should be prospective assessments that include evaluation of HRQOL as well as cost. In the future, these new aspects of outcome assessment are expected to be used as an adjunct to traditional seizure frequency and adverse effect reports in the selection of antiepileptic drugs.
Anticonvulsants↗
Ethical issues in the planning and conduct of clinical trials of anti-epileptic drugs.
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Anticonvulsants↗
Effect of valproate on cognitive functioning. Comparison with carbamazepine. The Department of Veterans Affairs Epilepsy Cooperative Study 264 Group.
OBJECTIVE: To assess the effects of carbamazepine vs valproate sodium on cognitive functioning in patients with epilepsy compared with normal control subjects. DESIGN: Patients with recently diagnosed, previously unmedicated seizures participated in a prospective randomized double-blind Department of Veterans Affairs multicenter study of the efficacy and toxicity of carbamazepine vs valproate. MAIN OUTCOME MEASURE: A behavioral toxicity battery was administered prior to treatment and again 6 and 12 months after the initiation of antiepileptic medication. RESULTS: There were no significant differences in the effect of carbamazepine vs valproate on motor speed and coordination, memory, or concentration and mental flexibility, and there was no significant decline in neuropsychological performance from pretreatment baseline levels for either drug. No significant differences in performance were found between patients with low (mean, 52.8 micrograms/mL) vs high (mean, 94.4 micrograms/mL) serum valproate levels within the therapeutic range. Patients treated with either carbamazepine or valproate did not show practice effects experienced by normal controls, a finding that may reflect a subtle compromise in cognitive functioning. CONCLUSION: The impact of carbamazepine and valproate monotherapy on cognitive functioning is similar: both drugs produce minimal negative effects compared with pretreatment baseline performance.
Adult↗
Pharmacokinetics and pharmacodynamics of multiple-dose terbinafine.
Data from clinical trials of terbinafine for the treatment of onychomycosis were analyzed with the following two objectives: 1) to identify demographic predictors of the duration and extent of systemic drug exposure; and 2) to explore whether increased systemic exposure or demographic predictors of increased exposure were associated with altered safety or efficacy. Demographic predictors of exposure were identified by a model-free, nonparametric approach applied to the sparse pharmacokinetic data from the onychomycosis studies. Those covariates were then incorporated into a multicompartmental nonlinear mixed effects model. Post hoc parameter estimates from the nonlinear mixed effects model provided individual measures of exposure. Safety scores were derived for adverse events that were frequently attributed to drug exposure and for liver function tests. Terbinafine was found to have an average terminal half-life (t1/2) of approximately 3 weeks. That terminal elimination phase contributed so little to the total exposure, however, that average concentrations accumulated only approximately two-fold at steady state with once daily dosing. Age and concomitant hypertension were predictors of higher plasma concentrations of terbinafine; smokers had lower levels than nonsmokers. Although some statistically significant associations between adverse events and systemic exposure were found, in all cases the actual frequency of the adverse events and systemic exposure were found, in all cases the actual frequency of the adverse events was low, and there were no trends in severity with respect to exposure. Above-normal levels of gamma-glutamyl transferase were associated with exposure, but there was no trend in severity with respect to exposure. No other liver function test abnormalities were associated with exposure, nor were there any significant associations between adverse events or liver function abnormalities and demographic subgroups that differed with respect to exposure. Among patients taking the active drug there were no significant associations between exposure levels and efficacy, nor were there differences in efficacy between demographic subgroups that differed with respect to exposure.
Adult↗