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R E Weeks

Publications and source records attributed to R E Weeks.

12 recordsLinked to original sources

Differentiating the efficacy of 5-HT(1B/1D) agonists.

OBJECTIVE: To examine, for a set of published clinical trials of serotonin (5-HT(1B/1D)) agonists as acute treatments for migraine, whether transformation of efficacy data into therapeutic gain (TG) or number needed to treat (NNT) is useful. BACKGROUND: Pivotal clinical trials of 5-HT(1B/1D) agonists in migraine use a primary end point of change in pain score from 3 or 2 to 1 or 0. Placebo response rates among such studies are variable. Meta-analytic comparisons of 5-HT(1B/1D) agonists often employ TG and NNT as efficacy measures. METHODS: Data from US product labeling or published sources were converted into TG (TG = active response rate [%] - placebo response rate [%]) and NNT (NNT = 1/TG). Pivotal clinical trial data were compared before and after transformation. RESULTS: Therapeutic gain ranged from 17.5% to 51%. The transformation of TG into NNT yielded no clinically significant difference in efficacy estimate for the range of 17.5% to 47% (N = 29 clinical trials). However, NNT and TG had a nonlinear relationship for some secondary end points. When the relationship between the standard primary and secondary end points was compared, the correlation of TG with clinical disability (Pearson coefficient R = 0.93) was stronger than for NNT. Placebo response rates correlated more strongly with NNT (R = 0.66) than active response rates (R = 0.42; N = 29 clinical trials), although both TG and NNT were sensitive to placebo response rate. CONCLUSIONS: Transforming efficacy rates into TG or NNT adds no new information to placebo-controlled trials. The variables, TG and NNT, should not be used to compare members of this class of drugs. Migraine therapies can only be compared using well-designed head-to-head studies and not by meta-analysis. Broader measures of efficacy should be used to describe and compare 5-HT(1B/1D) efficacy.

Acute Disease↗

Characteristics of migraine visual aura.

Visual auras (VAs) of 100 patients with migraine with aura were studied by questionnaire. Visual auras accompanied the patients' first headache (HA) in 39% of patients. Only 19% had VAs with every attack. Patients with VAs over the entire HA history had a high frequency (greater than 50%) of attacks with VA; patients with VA during only part of the HA history had a low frequency (less than 50%) of attacks with VA. The auras occurred exclusively prior to the HA in 57%. The free interval between the end of the VA and the start of the HA was usually (75%) shorter than 30 minutes. Most (59%) patients had VAs that lasted from 1 to 30 minutes. They started in the periphery of the visual fields in 56%. The most common phenomena described were: small bright dots (42%), flashes of light (39%), "blind spots" (32%), and "foggy vision" (27%). Fortification spectra was reported by only 20%. Although most (65%) patients had a combination of phenomena, the majority (72%) had only one uniform constellation of manifestations. There was no clear-cut relationship between side of VA and side of HA. Migraine VA is a pleomorphic and complex symptom. Many patients not qualifying for the diagnostic criteria of migraine with aura, as proposed by the International Headache Society (IHS), unequivocally present with visual phenomena that strongly suggest this diagnosis.

Adolescent↗

Early and transient side effects of repetitive intravenous dihydroergotamine.

Side effects associated with administration of repetitive intravenous dihydroergotamine (DHE) were prospectively studied in 72 patients with chronic daily headache who were hospitalized in a dedicated inpatient headache treatment program. All patients received 11 consecutive doses of DHE, starting with 0.25 mg and increasing by 0.25 mg up to a maximum dose of 1.25 mg, depending on side effects and/or headache relief. The adverse events were recorded after each dose administered. The great majority of patients (91.6%) reported at least one side effect. The most common were: nausea (72.2%), increase in previous headache (47.2%), lightheadedness (33.3%), "new" headache (27.8%), and leg cramps (23.6%). The overall number of side effect complaints did not increase proportionally with the strength of the dose of DHE administered. These complaints declined from the earlier to the later doses of DHE, except for leg cramps, which were more common with the later doses. Side effects determined the strength of subsequent doses of DHE in only 18.1% of patients. Only four patients had to have a decrease in dosage and none required termination of DHE due to side effects. Although repetitive intravenous DHE causes frequent side effects, they are usually mild and transient and decrease with subsequent doses, even at higher doses.

Adolescent↗

Subcutaneous sumatriptan in a clinical setting: the first 100 consecutive patients with acute migraine in a tertiary care center.

The first 100 consecutive patients at our center receiving subcutaneous sumatriptan (6 mg) were evaluated over a total of 455 migraine attacks. Parameters included overall efficacy, average time to relief, recurrence rate, average time to recurrence, adverse events, comparison to previous abortive agents, and subjective global ratings. Overall efficacy (defined as headache severity reduction from severe or moderate to mild or none) was 84%. Average time to relief was 40 minutes. Nine percent failed to respond at all. Recurrence rate was 46.5% with 36% of patients having no recurrence. Fourteen percent of patients reported 100% recurrence (minimum 3 attacks; average 5.4 attacks). Time to recurrence varied widely, but averaged 9.1 hours. Eighty-one percent rated the drug better or much better than previous abortive medications in terms of sumatriptan's ability to abort the attack. Seventy-seven percent reported some adverse event (generally mild and transient) with 23% reporting no adverse events. Sixty-nine percent reported a global rating of Good to Excellent and 31% rated Poor or Fair. The rate of recurrence and average time to recurrence were the most significant factors affecting the global ratings. These parameters were further evaluated with respect to a variety of subgroups: 1) migraine alone 2) migraine with co-existent tension-type headache 3) drug-induced headache (analgesic rebound headache) 4) posttraumatic headache 5) preventive versus no preventive medication 6) presence or absence of adverse events 7) presence or absence of recurrence and 8) average duration of migraine with no medication.

Acute Disease↗

Participation by internists in primary care; Results of a survey of Mayo clinical alumni.

In late 1972, a survey of Mayo Graduate School alumni was undertaken to determine if changes were needed to make the internal medicine residency program more relevant to such medical practice in the 1970s. Responses were obtained from 783 of the 1,109 former residents in internal medicine to whom questionnaries were sent. Althought nearly half of the responders indicated a subspecialty component to their practice,73% indicated they spend more than half of their time in the delivery of parimary car; and additional 15% reported that primary care occupied from 20% to 50% of their professional time. There was agreement that more general internists are needed and that better geographic distribution of physicians would improve health care delivery.

Delivery of Health Care↗

Excretory urographic localization of adrenal cortical tumors and pheochromocytomas.

An excretory urographic evaluation of 124 surgically proved adrenal tumors comprising 65 pheochromocytomas, 36 cortical adenomas and 23 cortical carcinomas is reported. The addition of linear tomography improved the diagnostic accuracy over conventional excretory urography. All types of tomographic examinations demonstrated at least 70% of adrenal tumors. Excretory urographic procedures are relatively safe, simple and economical and should be used as the initial step in attempting to localize clinically suspected and chemically diagnosed adrenal tumors.

Adenoma↗

Primary aldosteronism and malignant adrenocortical neoplasia.

Our experience indicates that although adrenal carcinoma is not a common cause of primary aldosteronism, 4 to 5% of patients in a single large series may have a malignant adrenocortical tumor. The magnitude of the hypokalemia and the hyperaldosteronuria tends to be greater in patients with malignant tumors, but these patients cannot be clearly separated from those with benign tumors or hyperplasia on this basis. Patients who have malignant tumors may have no chemical evidence of adrenocortical dysfunction other than excessive aldosterone secretion. Finally, a good response to spironolactone for months does not exclude adrenal carcinoma as the cause of primary aldosteronism.

Adenoma↗

Biosynthesis of monensin.

The biosynthesis of monensin by Streptomyces cinnamonensis was studied by using (14)C-labeled glucose, acetate, propionate, butyrate, and methionine. The results indicated that the antibiotic is synthesized from five acetate, seven propionate, and one butyrate molecules. The o-methyl group of monensin is derived from methionine, whereas the terminal hydroxymethyl group is incorporated from acetate.

Anti-Bacterial Agents↗