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Biomedical subjects

J Saper

Publications and source records attributed to J Saper.

At least 19 recordsLinked to original sources

The dimensions of insight in people with dementia.

This study aims to characterize the factors determining the retention or loss of insight in dementia through: (i). a comparison of assessment procedures previously used to quantify loss of insight and (ii). a qualitative analysis of interviews with patients and carers. Semi-structured interviews were carried out with thirty-two people with dementia and their carers, which incorporated assessments via clinical interview, discrepancy ratings between patient and carer on an Activities of Daily Living scale, and prediction of performance on a memory task. The results of these were compared and supplemented with themes arising from qualitative analysis of the interviews. Significant differences were found between insight as measured by a prediction of performance paradigm and other methods of assessment. This may reflect a distinction between implicit and explicit knowledge. Analysis of interviews identified the following factors as contributing to people's awareness of their difficulties: (1). short-term frustration or distress; (2). continuous discontent; (3). lack of concern; (4). normalization of problems; (5). worry and anxiety; (6). defensiveness; (7). explicit denial; and (8). priority given to other problems. We conclude that insight in dementia is a complex, multi-dimensional, and value-laden concept. Emotional and behavioural aspects need to be considered as well as the cognitive, which is emphasized by traditional methods of assessment based on quantitative ratings. Implicit awareness may be accessible through subjects' predictions of performance on cognitive tasks and should be further investigated. An adequate account of insight in dementia should incorporate both objective and subjective measures in order to determine the interrelationships between organic changes, personality factors, and psychological mechanisms. A generally accepted, reliable protocol for the assessment of insight needs to be developed.

Activities of Daily Living↗

A randomized trial of divalproex sodium extended-release tablets in migraine prophylaxis.

OBJECTIVE: To evaluate the efficacy and safety of extended-release divalproex sodium compared with placebo in prophylactic monotherapy treatment of migraine headache. METHODS: This was a double-blind, randomized, placebo-controlled, parallel-group study. Subjects with more than two migraine headache attacks during a 4-week baseline were randomly assigned in a 1:1 ratio at each center to receive either extended-release divalproex sodium or matching placebo once daily for 12 weeks. Subjects initiated treatment on 500 mg once daily for 1 week, and the dose was then increased to 1,000 mg once daily with an option, if intolerance occurred, to permanently decrease the dose to 500 mg during the second week. Reduction from baseline in 4-week migraine headache rate was the primary efficacy variable. Migraine headaches separated by a < 24-hour headache-free interval were counted as single migraines in calculating migraine headache rates. Tolerance and safety were also evaluated. RESULTS: The mean reductions in 4-week migraine headache rate were 1.2 (from a baseline mean of 4.4) in the extended-release divalproex sodium group and 0.6 (from a baseline mean of 4.2) in the placebo group (p = 0.006); reductions with extended-release divalproex sodium were significantly greater than with placebo in all three 4-week segments of the treatment period. No significant differences were detected between treatment groups in either the overall incidence or in the incidence of any specific treatment-emergent adverse event; 8% of subjects treated with extended-release divalproex sodium and 9% of those treated with placebo discontinued for adverse events. CONCLUSION: Extended-release divalproex sodium is an efficacious, well-tolerated, safe, and easy-to-use once-a-day prophylactic antimigraine medication.

Adolescent↗

Efficacy of gabapentin in migraine prophylaxis.

OBJECTIVE: To compare gabapentin with placebo for use as a prophylactic agent in patients with migraine (with or without aura). STUDY DESIGN AND TREATMENT: After screening, a 4-week, single-blind, placebo baseline period was followed by a 12-week, double-blind, treatment period. The 12-week treatment period consisted of a 4-week titration phase and an 8-week stable-dosing phase. During the 4-week titration phase, patients were started on one 300-mg capsule of gabapentin or matching placebo. Patients were titrated weekly from 900 mg/day (end of week 1) to 2400 mg/day (end of week 4) and had to be receiving a stable dose of study medication by the end of the titration period. Study medication was to be given on a three-times-a-day dosing regimen. METHODS: The study hypothesis was defined a priori as a lower 4-week migraine rate during the second stabilization period for the gabapentin-treated patients as compared with the placebo-treated patients. The analyses were performed with the 4-week migraine rate at baseline as a covariate and center as a blocking factor. RESULTS: At seven participating centers, 143 patients with migraine were randomized in a 2:1 ratio and received either gabapentin (n = 98) or matching placebo (n = 45). Thirty-three patients (24.1%) discontinued prematurely from the study, including 24 (24.5%) of 98 gabapentin-treated patients and 9 (20.0%) of 45 placebo-treated patients; the majority of patients discontinued due to adverse events (16 [16.3%] of 98 gabapentin-treated patients; 4 [8.9%] of 45 placebo-treated patients). Patients included in the analysis were evenly balanced for age, sex, race, weight, and height. The majority of these patients were white (80 [92.0%] of 87) and women (72 [82.8%] of 87), with a mean age of approximately 39.4 years and a history of migraine episodes for a mean of about 21 years. At the end of the 12-week treatment phase, the median 4-week migraine rate was 2.7 for the gabapentin-treated patients maintained on a stable dose of 2400 mg/day and 3.5 for the placebo-treated patients (P =.006), compared with 4.2 and 4.1, respectively, during the baseline period. Additionally, 26 (46.4%) of 56 patients receiving a stable dose of 2400 mg/day gabapentin and 5 (16.1%) of 31 patients receiving placebo showed at least a 50% reduction in the 4-week migraine rate (P =.008). The average number of days per 4 weeks with migraine was also statistically significant and favored gabapentin (P =.006) during stabilization period 2. The median change in 4-week headache rate was statistically significant as well (P =.013). The most frequently reported adverse events for both treatment groups were asthenia, dizziness, somnolence, and infection. Adverse events determined by the investigator to be associated with study drug resulted in patient withdrawal in 13 (13.3%) of 98 gabapentin-treated patients and 3 (6.7%) of 45 placebo-treated patients. Somnolence and dizziness accounted for many of the premature withdrawals among those taking gabapentin. CONCLUSION: Gabapentin is an effective prophylactic agent for patients with migraine. In addition, gabapentin appears generally well tolerated with mild to moderate somnolence and dizziness.

Acetates↗

Botulinum toxin type A as a migraine preventive treatment. For the BOTOX Migraine Clinical Research Group.

OBJECTIVE: To assess the safety and efficacy of botulinum toxin type A (BOTOX; Allergan, Inc) in the prevention of migraine. BACKGROUND: Current migraine preventive therapies are often unsatisfactory because of their limited efficacy, adverse effects, and drug interactions. Botulinum toxin type A injections often reduce the pain associated with conditions such as cervical dystonia, achalasia, rectal fissures, and myofascial pain syndrome. An open-label, noncontrolled study of botulinum toxin type A suggested benefits for patients with migraine. DESIGN AND METHODS: This was a double-blind, vehicle-controlled study of 123 subjects with a history of two to eight moderate-to-severe migraine attacks per month, with or without aura. Participants were randomized to receive single administrations of vehicle or botulinum toxin type A, 25 U or 75 U, injected into multiple sites of pericranial muscles at the same visit. During a 1-month baseline period and for 3 months following injection, subjects kept daily diaries in which they recorded migraine frequency, migraine severity, and the occurrence of migraine-associated symptoms. RESULTS: Compared with vehicle treatment, subjects in the 25-U botulinum toxin type A treatment group showed significantly fewer migraine attacks per month, a reduced maximum severity of migraines, a reduced number of days using acute migraine medications, and reduced incidence of migraine-associated vomiting. Both the 25-U and 75-U botulinum toxin type A groups were significantly better than the vehicle group on subject global assessment. Botulinum toxin A treatment was well tolerated, with only the 75-U treatment group exhibiting a significantly higher rate of treatment-related adverse events than vehicle. CONCLUSIONS: Pericranial injection of botulinum toxin type A, 25 U, was found to be a safe treatment that significantly reduced migraine frequency, migraine severity, acute medication usage, and associated vomiting.

Adolescent↗

A randomized, double-blind, placebo-controlled study of sumatriptan nasal spray in the treatment of acute migraine in adolescents.

OBJECTIVE: To compare the efficacy and tolerability of sumatriptan nasal spray (NS; 5 mg, 10 mg, and 20 mg) with placebo for the treatment of acute migraine in adolescents. METHODS: A randomized, double-blind, placebo-controlled, single-attack study was conducted in 653 US adolescents (12-17 years of age). Patients with at least a 6-month history of migraine, who met International Headache Society criteria for migraine (with or without aura) were eligible for participation. Headache relief 2 hours postdose, complete relief, presence or absence of associated symptoms, headache recurrence, and use of rescue medications were recorded. The primary efficacy endpoint was headache relief 2 hours postdose sumatriptan NS (20 mg) versus placebo. Safety and tolerability were assessed by examining adverse events, changes in electrocardiograms, vital signs, physical examinations, and clinical laboratory tests. RESULTS: Headache relief 1 hour postdose was significantly greater for patients using 10 mg (56%) and 20 mg (56%) of sumatriptan NS compared with placebo (41%). Headache relief 2 hours postdose was significantly greater for patients using 5 mg of sumatriptan NS (66%) compared with placebo (53%), and approached statistical significance for 20 mg (63%) compared with placebo (53%). Complete relief 2 hours postdose was significantly greater for patients using 20 mg of sumatriptan NS compared with placebo (36% vs 25%, respectively). Each dose of sumatriptan (5 mg, 10 mg, and 20 mg) was superior to placebo with respect to the cumulative percentages of patients first reporting headache relief within 2 hours of dosing (Kaplan-Meier). The sumatriptan 20-mg dose was superior to placebo with respect to the cumulative percentages of patients first reporting complete relief within 2 hours of dosing (Kaplan-Meier). Photophobia and phonophobia were significantly reduced 2 hours postdose for sumatriptan NS (20 mg), compared with placebo (36% vs 48% and 25% vs 44%, respectively). Taste disturbance was the most commonly reported adverse event (2%, 19%, 30%, and 26% for placebo, 5 mg, 10 mg, and 20 mg, respectively). No drug-related serious adverse events or clinically relevant changes in laboratory parameters, electrocardiograms, or vital signs were reported. CONCLUSIONS: Sumatriptan NS is effective and well-tolerated for the treatment of acute migraine in adolescents, with the 20-mg dose providing the best overall efficacy and tolerability profiles.

Acute Disease↗

Efficacy and safety of acetaminophen, aspirin, and caffeine in alleviating migraine headache pain: three double-blind, randomized, placebo-controlled trials.

OBJECTIVE: To assess the effectiveness of the nonprescription combination of acetaminophen, aspirin, and caffeine in alleviating migraine headache pain. DESIGN: Three double-blind, randomized, parallel-group, single-dose, placebo-controlled studies. SETTING: Private practice, referral centers, and general community. PATIENTS: Migraineurs with moderate or severe headache pain who met International Headache Society diagnostic criteria for migraine with aura or without aura. The most severely disabled segment of migraineurs, including those whose attacks usually required bed rest, or who vomited 20% or more of the time, were excluded. Of the 1357 enrolled patients, 1250 took study medication and 1220 were included in the efficacy-evaluable data set. INTERVENTION: Two tablets of the nonprescription combination of acetaminophen, aspirin, and caffeine or placebo taken orally as a single-dose treatment of 1 eligible acute migraine attack. MAIN OUTCOME MEASURES: Pain intensity difference from baseline; percentage of patients with pain reduced to mild or none. RESULTS: Significantly greater reductions in migraine headache pain intensity 1 to 6 hours after dose were seen in patients taking the acetaminophen, aspirin, and caffeine combination than in those taking placebo in each of the 3 studies. Pain intensity was reduced to mild or none 2 hours after dose in 59.3% of the 602 drug-treated patients compared with 32.8% of the 618 placebo-treated patients (P< .001; 95% confidence interval [CI], 55%-63% for drug, 29%-37% for placebo); at 6 hours after dose, 79% vs 52%, respectively, had pain reduced to mild or none (P<.001; 95% CI, 75%-82% vs 48%-56%). In addition, by 6 hours after dose, 50.8% of the drug-treated patients were pain free compared with 23.5% of the placebo-treated patients (P<.001; 95% CI, 47%-55% for drug, 20%-27% for placebo). Other migraine headache characteristics, such as nausea, photophobia, phonophobia, and functional disability, were significantly improved 2 to 6 hours after treatment with the acetaminophen, aspirin, and caffeine combination compared with placebo (P< or =.01). CONCLUSIONS: The nonprescription combination of acetaminophen, aspirin, and caffeine was highly effective for the treatment of migraine headache pain as well as for alleviating the nausea, photophobia, phonophobia, and functional disability associated with migraine attacks. This drug combination also has an excellent safety profile and is well tolerated.

Acetaminophen↗

A double-blind study of subcutaneous dihydroergotamine vs subcutaneous sumatriptan in the treatment of acute migraine.

OBJECTIVE: To assess the efficacy and tolerability of subcutaneous dihydroergotamine mesylate (DHE-45) vs subcutaneous sumatriptan succinate (Imitrex) for the treatment of acute migraine with or without aura. DESIGN: Double-blind, randomized trial with parallel treatment arms. SETTING: Clinics and private neurology practices. SUBJECTS: Patients of either sex, with migraine with or without aura, between the ages of 18 and 65 years. INTERVENTIONS: Patients with moderate or severe head pain were randomized to receive either 1 mg of subcutaneous dihydroergotamine mesylate or 6 mg of subcutaneous sumatriptan succinate. Patients rated head pain, functional ability, nausea, and vomiting at baseline and at 0.5, 1, 2, 4, and 24 hours after the injection. Presence or absence of headache at 3 hours was calculated from collected data. If pain persisted after 2 hours, a second injection of the same study medication was allowed, and self-ratings were repeated 30 and 60 minutes later. Follow-up data were collected at 24 hours. MAIN OUTCOME MEASURES: Relief of head pain and recurrence of successfully treated headache. RESULTS: There were 295 evaluable patients. At 2 hours, 73.1% of the patients treated with dihydroergotamine and 85.3% of those treated with sumatriptan had relief (P = .002). There was no statistical difference in headache relief between the groups at 3 or 4 hours. Headache relief was achieved by 85.5% of those treated with dihydroergotamine and by 83.3% of those treated with sumatriptan by 4 hours. By 24 hours 89.7% of dihydroergotamine-treated patients and 76.7% of sumatriptan-treated patients had relief (P = .004). Headache recurred within 24 hours after treatment in 45% of the sumatriptan-treated patients and in 17.7% of the dihydroergotamine-treated patients (P < or = .001). CONCLUSIONS: Both sumatriptan and dihydroergotamine were effective in aborting migraine headaches. Headache recurrence was two and a half time as likely with sumatriptan as with dihydroergotamine.

Acute Disease↗

Treatment of migraine with BMS180048: response at 2 hours. North American BMS180048 Study Group.

BMS180048 is a 5HT agonist that was well-tolerated in early phase II trials. This study utilized a double-blind, parallel-group dose ranging format, comparing BMS180048 in doses of 25, 50, or 75 mg to placebo in effectiveness of treatment of a single migraine headache. To assess tolerability of BMS180048, patients received a test dose of the medication they would receive for a headache in the clinic under observation. If no significant side effects occurred, patients were allowed to treat a headache. Headaches were moderate or severe in intensity before treatment, and response at 2 hours was tabulated. Reduction to mild or no headache was the criteria for successful response. Response rates at 2 hours were as follows: placebo--19 of 53 subjects (35.8%); 25 mg--21 of 53 subjects (40.3%); 50 mg--34 of 53 subjects (64.2%); 75 mg--35 of 55 subjects (63.6%) The improvement for subjects treated with 50 or 75 mg of BMS180048 when compared to placebo was highly significant (P < .01). Nausea, photophobia, and phonophobia improved 35% to 50% for BMS180048-treated subjects and 20% to 24% in the placebo group. The improvement in these symptoms in comparison to placebo was statistically significant only for nausea in those treated with 75 mg of BMS180048 (P = .02). Side effects were mild for the most part, and no serious adverse events occurred. The study suggests BMS180048 is effective in acute symptomatic therapy of migraine.

Adult↗

Dihydroergotamine nasal spray for the acute treatment of migraine.

We conducted a multicenter, double-blind, parallel-group study to compare the efficacy and safety of dihydroergotamine (DHE) nasal spray and placebo over 4 hours in the treatment of migraine. Of the 112 patients enrolled, 100 were included in the "intent-to-treat" efficacy analysis. The patients self-administered either 2.0 mg DHE (0.5 mg per nostril, repeated after 15 minutes) or placebo at the onset of two separate headaches and rated hourly the drugs' effects on pain severity, pain relief, nausea, and vomiting. The physicians assessed the overall effectiveness of the drugs in relieving headache pain, nausea, and vomiting. Both the patients' and physicians' ratings indicated that DHE was significantly superior to placebo in improving headache and nausea; according to the patients' ratings, these between-group differences were already significant at the first (hour 1) evaluation. There were no significant differential treatment effects with respect to relief of vomiting. Most adverse events were mild or moderate, confined to the nasopharyngeal area, and probably related to the route of administration. We conclude that DHE nasal spray is a safe and effective treatment for the pain and nausea of migraine attacks.

Administration, Intranasal↗

Dose ranging efficacy and safety of subcutaneous sumatriptan in the acute treatment of migraine. US Sumatriptan Research Group.

Sumatriptan, a specific serotonin1-like receptor agonist, was studied in the acute treatment of migraine. Two hundred forty-two adult migraineurs participated in a randomized, double-blind study in which one dose of 1, 2, 3, 4, 6, or 8 mg of subcutaneous sumatriptan succinate was evaluated in sequential ascending fashion. At each dose level, a placebo group was included. Efficacy was defined as reduction of moderate or severe pain to mild or no pain, without the use of rescue medication. Headache relief rates showed an approximate dose-response relationship and at 1 hour were as follows: placebo, 24%; 1 mg, 43%; 2 mg, 57%; 3 mg, 57%; 4 mg, 50%; 6 mg, 73%; and 8 mg, 80%. Relief of nausea and improvement in clinical disability were also approximately dose related. Adverse events were dose related; the most common types were injection site reactions and tingling. The 6-mg dose was as effective as the 8-mg dose but was associated with fewer adverse effects and so is optimal.

Adult↗

A follow-up study of patients treated for benzodiazepine dependence.

By interviewing and administering questionnaires to 63 patients one to five years after treatment for benzodiazepine dependence the long-term success rate was examined together with factors associated with outcome. Fifty-four per cent of patients had permanently withdrawn from medication at follow-up. Most of those who were successful continued to experience psychiatric symptoms after discharge. Significantly more women than men managed to withdraw from medication. Outcome was not related to previous benzodiazepine regimen, psychiatric history or experiences of withdrawal. It is argued that psychological adjuncts should be included in the treatment of benzodiazepine dependence in order to prevent relapse.

Adult↗