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Biomedical subjects

J A Cramer

Publications and source records attributed to J A Cramer.

At least 19 recordsLinked to original sources
PubMed2006

Patient satisfaction with an injection device for multiple sclerosis treatment.

OBJECTIVES: To develop a measure of treatment satisfaction assessing attributes specific to injected interferon-beta-1a (IFN-beta-1a) for multiple sclerosis (MS), and to test pain and instrument sensitivity to change among patients changing injection devices. MATERIALS AND METHODS: The MS Treatment Concerns Questionnaire (MSTCQ) was developed and tested with pain assessments before and 3 months after patients changed devices from Rebiject to Rebiject II. RESULTS: The MSTCQ was organized with two domains: Injection System Satisfaction and Side Effects (three subscales: Injection Site Reactions, Global Satisfaction, and Flu-Like Symptoms). Significant improvements (P = 0.002 to P < 0.001) occurred with the new injection device in all MSTCQ subscales (except Flu-Like Symptoms), and all pain measures (P < 0.0001). Clinically meaningful improvement was demonstrated in all scales, except Flu-Like Symptoms, by effect sizes (0.23-0.59). CONCLUSIONS: These statistically significant and clinically meaningful improvements in MSTCQ and pain measures show the value of technologically advanced devices in domains of concern to patients.

Adjuvants, Immunologic↗
PubMed2004

Compliance with inhaled insulin treatment using the AERx iDMS Insulin Diabetes Management System.

OBJECTIVE: The AERx Insulin Diabetes Management System [AERx iDMS, jointly developed by Novo Nordisk (Bagsvaerd, Denmark) and Aradigm Corp. (Hayward, CA)] provides insulin by pulmonary administration. This investigation was designed as a pilot trial to demonstrate the ability of patients to use the electronic device to deliver mealtime inhaled insulin doses and explore the impact on compliance. METHODS: AERx iDMS was evaluated in a substudy of a 12-week, multicenter open trial by adult patients with type 2 diabetes previously on any insulin regimen. The device was used for dosing fast-acting human insulin immediately before main meals, in combination with bedtime NPH insulin. The AERx iDMS device recorded the date and time of each insulin inhalation, insulin units used, and inhalation technique during aerosol delivery. Compliance was defined as the percentage of prescribed doses taken during the treatment period, dose timing, and the efficiency of dosing technique. RESULTS: Insulin dosing for 49 patients (age 59.1 +/- 7.7 years) using AERx iDMS was monitored for 78.9 +/- 10 days (range, 41-94 days) with 226 +/- 35 doses (range, 122-272 doses). Patients inhaled on average 2.9 +/- 0.3 doses of insulin daily, taking an average of 11.8 +/- 5.6 units per dose. Compliance with the prescribed regimen was 94.3 +/- 9.1% (range, 45-100%). Overall, 4.2 +/- 9.5% of prescribed doses were omitted. Hemoglobin A1c decreased 0.77 +/- 0.96% from baseline to the end of the study. Inhalation technique was excellent, with 97% of patients experiencing fewer than five inadequate doses. CONCLUSIONS: Excellent compliance with AERx iDMS dosing, timing, and inhalation technique showed that the device was well accepted by patients. The electronic monitoring feature could be used as an educational tool to help patients and clinicians manage insulin dosing.

Administration, Inhalation↗
PubMed2001

Naltrexone in the treatment of alcohol dependence.

BACKGROUND: Although naltrexone, an opiate-receptor antagonist, has been approved by the Food and Drug Administration for the treatment of alcohol dependence, its efficacy is uncertain. METHODS: We conducted a multicenter, double-blind, placebo-controlled evaluation of naltrexone as an adjunct to standardized psychosocial treatment. We randomly assigned 627 veterans (almost all men) with chronic, severe alcohol dependence to 12 months of naltrexone (50 mg once daily), 3 months of naltrexone followed by 9 months of placebo, or 12 months of placebo. All patients were offered individual counseling and programs to improve their compliance with study medication and were encouraged to attend Alcoholics Anonymous meetings. RESULTS: There were 209 patients in each group; all had been sober for at least five days before randomization. At 13 weeks, we found no significant difference in the number of days to relapse between patients in the two naltrexone groups (mean, 72.3 days) and the placebo group (mean, 62.4 days; 95 percent confidence interval for the difference between groups, -3.0 to 22.8). At 52 weeks, there were no significant differences among the three groups in the percentage of days on which drinking occurred and the number of drinks per drinking day. CONCLUSIONS: Our findings do not support the use of naltrexone for the treatment of men with chronic, severe alcohol dependence.

Alcoholics Anonymous↗
PubMed2001

Review of treatment options for refractory epilepsy: new medications and vagal nerve stimulation.

PURPOSE: the choices available for patients whose partial seizures are poorly controlled include seven new antiepileptic drugs (AEDs) or vagal nerve stimulation (VNS) as add-on therapy. Comparisons are needed to help physicians and patients select among the options for treatment. METHODS: we compared efficacy and adverse events of new treatments from controlled clinical trials of patients with uncontrolled partial seizures. Response rates (> or =50% decrease in partial seizures) at doses recommended in product labeling for adjunct therapy were tabulated for overall success (placebo response rate subtracted from AED response rate). Adverse events listed in product labeling were tabulated as complaint rates (placebo events subtracted from AED events). VNS trials used low dose stimulation as a pseudo-placebo. RESULTS: overall success rates fell into two general groups with ranges of 12-20% for gabapentin (GBP), lamotrigine (LTG), tiagabine (TGB), zonisamide and 27-29% for levetiracetam, oxcarbazepine, and topiramate (TPM). Summary Complaint Scores also fell into two general groups with ranges of -27 to -82 for GBP, levetiracetam, TGB, zonisamide and -113 to -205 for LTG, oxcarbazepine and TPM. VNS scores were in the lower or higher success and summary complaint categories depending on whether scores from the pseudo-placebo group were subtracted from the high dose group. CONCLUSIONS: these data allow comparisons among AEDs and VNS using similar data from standard types of clinical trials.

Anticonvulsants↗
PubMed2001

A systematic review of the safety profile of levetiracetam: a new antiepileptic drug.

PURPOSE: This report provides detailed review of safety information on levetiracetam (LEV) (Keppra), a new antiepileptic drug. METHODS: The integrated summary of safety report submitted for regulatory review was examined to collate information about abnormal laboratory tests values and adverse event reports collected during the overall LEV development program. Analyses included 3347 patients exposed to LEV in clinical trials for epilepsy, cognition, and anxiety disorders. RESULTS: Safety data from all studies depict a similar pattern of adverse effects, predominantly somnolence, asthenia, and dizziness that occurred most frequently during the first month of LEV treatment. Changes in laboratory test values from placebo-controlled trials that were statistically significant remained in the normal range (red blood cells, hematocrit, hemoglobin, white blood cells, and neutrophils). Reports of the coding term 'infection' (common cold, upper respiratory infection) were not preceded by low neutrophil counts that might suggest impaired immunological status. Selection of adverse event coding terms probably contributed to the high rate of adverse effects termed 'infection.' Higher incidences of adverse effects, particularly behavioral effects, were found among epilepsy patients than in elderly patients with cognitive disorders or patients with anxiety disorders given lower doses. CONCLUSIONS: This review of patients evaluated during the clinical development program suggests that LEV was well tolerated and safe for patients with seizure, cognitive and anxiety disorders. Overall incidence of adverse effects in the LEV groups was little higher than reports from the placebo groups. Of course, this data was derived from clinical trials that are of relatively short duration, and provide data on only several thousand patients. Therefore, long-term side effects, and/or rare side effects cannot be ruled out on the basis of this analysis.

Anticonvulsants↗
PubMed2001

Development and validation of the Headache Needs Assessment (HANA) survey.

OBJECTIVE: To develop and validate a brief survey of migraine-related quality-of-life issues. The Headache Needs Assessment (HANA) questionnaire was designed to assess two dimensions of the chronic impact of migraine (frequency and bothersomeness). METHODS: Seven issues related to living with migraine were posed as ratings of frequency and bothersomeness. Validation studies were performed in a Web-based survey, a clinical trial responsiveness population, and a retest reliability population. Headache characteristics (eg, frequency, severity, and treatment), demographic information, and the Headache Disability Inventory were used for external validation. RESULTS: The HANA was completed in full by 994 adults in the Web survey, with a mean total score of 77.98 +/- 40.49 (range, 7 to 175). There were no floor or ceiling effects. The HANA met the standards for validity with internal consistency reliability (Cronbach alpha =.92, eigenvalue for the single factor = 4.8, and test-retest reliability = 0.77). External validity showed a high correlation between HANA and Headache Disability Inventory total scores (0.73, P<.0001), and high correlations with disease and treatment characteristics. CONCLUSIONS: These data demonstrate the psychometric properties of the HANA. The brief questionnaire may be a useful screening tool to evaluate the impact of migraine on individuals. The two-dimensional approach to patient-reported quality of life allows individuals to weight the impact of both frequency and bothersomeness of chronic migraines on multiple aspects of daily life.

Activities of Daily Living↗
PubMed2001

Quantitative assessment of seizure severity for clinical trials: a review of approaches to seizure components.

Quantitative assessment of seizure severity has been approached using a variety of systems. This review describes currently available methods and possible new approaches to seizure assessment for clinical trials. A review of the literature on methods of seizure assessments resulted in tabulation of the seizure rating scales known as VA, Chalfont-National Hospital, Liverpool, Hague, and the Occupational Hazard Scale. Seizures have been evaluated by simply counting all events, counting events by type, by clinician ratings, patient ratings, and combinations. Each of the scales has advantages and disadvantages. Most scales share core components: seizure frequency, seizure type, seizure duration, postictal events, postictal duration, automatisms, seizure clusters, known patterns, warnings, tongue biting, incontinence, injuries, and functional impairment. This review revealed a partial consensus about aspects of seizures that are important markers for severity. However, usefulness of the existing scales is limited by lack of data on responsiveness. New approaches are needed to assess changes in seizure severity as a result of an intervention in a clinical trial.

Clinical Trials as Topic↗
PubMed2001

Assessing the severity of seizures and epilepsy: which scales are valid?

A review of the literature on methods of seizure or epilepsy severity assessments resulted in tabulation of the seizure rating scales known as US Department of Veterans Affairs (VA), Chalfont-National Hospital, Liverpool, Hague, and others. Each of the scales reviewed has some advantages, but none of them appears to be adequate to assess seizure or epilepsy severity. Most of the scales use similar components of seizures to evaluate severity. However, the disadvantages of each scale outweigh its usefulness. New approaches are needed to assess seizure severity for individuals and for use as an outcome measure after intervention such as surgery or medication changes.

Diagnosis, Differential↗
PubMed2001

Use of the Medication Event Monitoring System to estimate medication compliance in patients with schizophrenia.

OBJECTIVE: To determine the feasibility of using the Medication Event Monitoring System (MEMS) to estimate medication compliance in patients with schizophrenia or schizoaffective disorder. SUBJECTS AND SETTING: Fourteen of 35 consecutive patients admitted to a psychiatric inpatient hospital with schizophrenia or schizoaffective disorder who met eligibility requirements and gave informed consent. INTERVENTION: After random assignment to either risperidone or typical antipsychotic treatment, medication upon discharge from hospital was dispensed in a bottle with a MEMS cap which recorded the number of bottle openings and the date and time of each opening. The first 6 patients were asked to return monthly for data downloading. The next 8 were asked to return weekly during the first month and every 2 weeks thereafter; they were also paid $5 for returning each bottle. OUTCOME MEASURES: MEMS data collected over a 6-month period and hospital readmission data. RESULTS: Patient medication compliance data were collected from 10 (71%) of 14 patients during the first month, from 7 (58%) of 12 (2 patients dropped out) during the second and from 5 (45%) of 11 (a third patient dropped out) during months 3-6. Mean compliance rates were 63% for the first month and ranged from 56% to 45% over the next 5. First-month compliance rates were significantly lower for those who were subsequently readmitted to hospital (n = 7) than for those who were not (p < 0.01). CONCLUSIONS: Electronic monitoring devices can be used to estimate compliance with medication regimens in patients with severe schizophrenic disorders, but there are methodological improvements that can be made to increase data recovery and compliance, and these are discussed.

Adult↗
PubMed2000

Comparison between the QOLIE-31 and derived QOLIE-10 in a clinical trial of levetiracetam.

PURPOSE: to determine whether the QOLIE-10, an abbreviated quality of life questionnaire, provides results similar to the more detailed QOLIE-31 instrument when the ten items are derived from the QOLIE-31. METHODS: the QOLIE-31 was completed by 246 patients participating in UCB protocol N132 at baseline and after 18 weeks of treatment with levetiracetam (LEV 1000 or 3000 mg) or placebo added to standard therapy. QOLIE-10 components and total scores were calculated from the QOLIE-31 data. RESULTS: baseline QOLIE-10 components and total score correlated highly with corresponding QOLIE-31 scores, both at baseline and follow-up (range 0.70-0.95). Changes from baseline to follow-up were significantly different (ANCOVA) among treatment groups for both the QOLIE-10 and QOLIE-31 for the total score (P = 0.02, P = 0.009, respectively), seizure worry (P = 0.005, P = 0.0003) and cognitive functioning (P = 0.01, P = 0.01). One subscale (overall QOL) showed significant change with the QOLIE-31 (P = 0.04), but not with the QOLIE-10 (P = 0.07). Differences in QOLIE-10 scores were found between responders (> or = 50% partial onset seizure reduction) and non-responders for the total score (P = 0.0001) and two components (overall QOL P = 0.002, social function P = 0.0003). In the QOLIE-31, the total score and six subscale scores (all except medication effects) were significantly different. Both instruments were able to detect change over time. Responsiveness assessed by effect sizes (- 0.1 for non-responders, 0.4 for responders, 0.8 for seizure-free patients) and the Guyatt statistic (0.1, 0.6 and 1.0, respectively) was similar for both instruments. CONCLUSIONS: although the QOLIE-10 was designed as a screening tool, it can be scored and used in research. The total score did discern differences among treatments in a clinical trial. Nonetheless, questionnaires with multiple, multi-item subscales provide more detailed information than abbreviated forms. The QOLIE-31 is preferred where time and resources are available.

Adolescent↗
PubMed2000

Cue-dose training with monetary reinforcement: pilot study of an antiretroviral adherence intervention.

OBJECTIVE: To assess the feasibility and efficacy of two interventions for improving adherence to antiretroviral therapy regimens in HIV-infected subjects compared with a control intervention. DESIGN: Randomized, controlled, pilot study. SETTING: Department of Veterans Affairs HIV clinic and community-based HIV clinical trials site. PARTICIPANTS: Fifty-five HIV-infected subjects on stable antiretroviral therapy regimens. Subjects were predominantly male (89%) and African American (69%), and had histories of heroin or cocaine use (80%). INTERVENTIONS: Four weekly sessions of either nondirective inquiries about adherence (control group, C), cue-dose training, which consisted of the use of personalized cues for remembering particular dose times, and feedback about medication taking using Medication Event Monitoring System (MEMS) pill bottle caps, which record time of bottle opening (CD group), or cue-dose training combined with cash reinforcement for correctly timed bottle opening (CD+CR). MEASUREMENTS: Opening of the pill bottle within 2 hours before or after a predetermined time was measured by MEMS. RESULTS: Adherence to the medication as documented by MEMS was significantly enhanced during the 4-week training period in the CD+CR group, but not in the CD group, compared with the control group. Improvement was also seen in adherence to antiretroviral drugs that were not the object of training and reinforcement. Eight weeks after training and reinforcement were discontinued, adherence in the cash-reinforced group returned to near-baseline levels. CONCLUSIONS: Cue-dose training with cash reinforcement led to transient improvement in adherence to antiretroviral therapy in a population including mostly African Americans and subjects with histories of drug abuse. However, we were not able to detect any sustained improvement beyond the active training period, and questions concerning the timing and duration of such an intervention require further study. Randomized, controlled clinical studies with objective measures of adherence can be conducted in HIV-infected subjects and should be employed for further evaluation of this and other adherence interventions.

Anti-HIV Agents↗
PubMed2000

Quality of life in schizophrenia: a comparison of instruments. Department of Veterans Affairs Cooperative Study Group on Clozapine in Refractory Schizophrenia.

Health-related quality of life in schizophrenia can be assessed by direct patient response or by a rating based on a structured interview. This study compares both types of instruments using a series of five standards: (1) sensitivity to change over time, (2) sensitivity to treatment effect, (3) correlation with symptom severity, (4) correlation with global clinical ratings, and (5) correlation with other measures of health-related quality of life. Four hundred and twenty-three inpatients with schizophrenia participating in a clinical trial comparing clozapine and haloperidol (VA Cooperative Study in Health Services #17) were evaluated using multiple measures of health-related quality of life (Lehman Quality of Life Interview; Heinrichs-Carpenter-Hanlon Quality of Life Scale; Strauss-Carpenter Level of Function scale, and clinical response.) The Quality of Life Interview showed less sensitivity to change and treatment effect, as well as lower correlations with all other measures than the Quality of Life Scale and the Level of Function scale. The latter scales showed high sensitivity to both change and treatment effect, and moderate-high correlations with other measures and with each other. The Quality of Life Scale and the Level of Function scale rater assessments appeared to be substantially more sensitive to subtle change and treatment effects than the patient-reported Quality of Life Interview for clinical trials. Health-related quality of life in schizophrenia is a more heterogeneous concept than previously appreciated.

Adult↗
PubMed2000

Effect of levetiracetam on epilepsy-related quality of life. N132 Study Group.

PURPOSE: To evaluate the short-term effect of levetiracetam (LEV; UCB L059) as add-on therapy on health-related quality of life in the treatment of refractory partial-onset seizures. METHODS: Patients were enrolled in protocol UCB N132 if they had >/=12 partial-onset seizures with or without secondary generalization during the 12-week baseline period with a minimum of two seizures every 4 weeks. Randomization was made to placebo, LEV 1,000 mg, or LEV 3,000 mg, with sample size based on seizure frequency reduction. The 31-item Quality of Life in Epilepsy (QOLIE-31) questionnaire was completed by 246 patients at the end of baseline and at 18-week follow-up, or earlier if withdrawn. RESULTS: Significant differences were found among the three treatment groups for Seizure Worry (p = 0. 0003), Overall Quality of Life (p = 0.04), and Cognitive Functioning domains (p = 0.01), as well as the Total Score (p = 0.009). Responders (>/=50% partial onset seizure reduction) had significant improvements in all areas, except Medication Effect, compared with nonresponders (all p > 0.006). Clinically noticeable improvement (>/=10% change from baseline to follow-up) was perceived by LEV 3, 000 mg responders in all areas, except Emotional Well-Being, by LEV 1,000 mg responders in 5 of 9 areas, and by placebo responders in 2 of 9 areas. CONCLUSIONS: Addition of LEV to standard medication seems to have a positive impact on health-related quality of life, particularly among responders in this short-term study. These exploratory analyses require additional studies to evaluate long-term changes in a larger population.

Adult↗
PubMed1999

Alcohol exposure during the first two trimesters equivalent alters granule cell number and neurotrophin expression in the developing rat olfactory bulb.

Although alcohol has been shown to affect brain development adversely, the underlying mechanism of alcohol's actions are poorly understood. The present study addressed the hypothesis that alcohol affects growth factor availability during critical periods of neural growth by measuring the mRNA expression of brain-derived neurotrophic factor (BDNF), a potent developmental growth factor. Multiple offspring of timed-pregnant rat dams given alcohol (6.0 g/kg per day) or control treatments during gestation were sacrificed at either embryonic (E) day 21 or E33 (usually postnatal day 10) when their olfactory bulbs were processed for molecular analyses or neuron counting. BDNF mRNA levels were measured by reverse-transcription-polymerase chain reaction, and DNA methylation of the BDNF gene was quantified by Southern blot analyses following digestion with methylation-sensitive enzymes. Estimates of total granule cell number were obtained by counting those cells using unbiased stereological techniques. There was a significant decrease in BDNF mRNA levels in the alcohol-exposed offspring of both ages compared with controls. In addition, the number of olfactory bulb granule cells significantly decreased in the E33 but not the E21 rat pups exposed to alcohol compared with their appropriate aged controls. Finally, BDNF DNA of alcohol-exposed animals was less susceptible to digestion with the methylation-sensitive enzyme HpaII compared with controls, suggesting that the DNA of the alcohol exposed pups was hypermethylated. Our results indicate that exposure to alcohol during early brain development in the rat, a period equivalent to the first two trimesters in humans, can have a detrimental effect on normal development of the olfactory bulb by reducing the number of BDNF-synthesizing neurons. Although the exact mechanism for the alcohol-induced neuronal loss is unknown, the inappropriate transcription of the BDNF gene is one mechanism that may account for the complexity of effects observed in offspring exposed to heavy alcohol exposure in utero.

Animals↗
PubMed1999

Phase I trial of the selective mitochondrial toxin MKT077 in chemo-resistant solid tumours.

BACKGROUND: MKT077 is a rhodacyanine dye analogue which preferentially accumulates in tumour cell mitochondria. It is cytotoxic to a range of tumours. In this phase I study, MKT077 was administered as a five-day infusion once every three weeks. PATIENTS AND METHODS: Ten patients, median age 59 (38-70) years, with advanced solid cancers were treated at three dose levels: 30, 40 and 50 mg/m2/day for a total of 18 cycles. 31Phosphorus magnetic resonance spectroscopy (MRS) was used to evaluate the effect of MKT077 on skeletal muscle mitochondrial function. RESULTS: The predominant toxicity was recurrent reversible functional renal impairment (grade 2, two patients). One patient with renal cancer attained stable disease and the remainder progressive disease. There were no MRS changes in the first or second treatment cycles but one patient received 11 treatment cycles and developed changes consistent with a mitochondrial myopathy. Mean values for all pharmacokinetic parameters were at sub micromolar levels and did not exceed IC50 values (> or = 1 microM). CONCLUSIONS: Because of the renal toxicity, and animal studies showing MKT077 causes eventual irreversible renal toxicity, further recruitment was halted. The study shows, however, that it is feasible to target mitochondria with rhodacyanine analogues, if drugs with higher therapeutic indices could be developed.

Adult↗