Treatment of nocturnal leg cramps. A crossover trial of quinine vs vitamin E.

OBJECTIVE: This study compared the efficacy and safety of quinine sulfate, vitamin E, and placebo in the treatment of nocturnal leg cramps. DESIGN: A random-order, double-blind, placebo-controlled crossover trial was performed. SETTING: The study was conducted at the Veterans Affairs Medical Center, White River Junction, Vt. PARTICIPANTS: Twenty-seven male veterans, aged 38 to 73 years, who experienced at least six leg cramps per month were recruited through the general medicine walk-in clinic or were referred from other clinics. Fifty-five subjects were contacted, 30 were enrolled consecutively, and 27 completed the study. INTERVENTION: Subjects received, in random order, quinine sulfate (200 mg at supper and 300 mg at bedtime), vitamin E (800 U at bedtime), or placebo for 4-week periods. These periods were separated by 4-week washout intervals. OUTCOME MEASURES: Patients reported cramp frequency, severity, and sleep disturbance caused by cramps. RESULTS: Compared with treatment with placebo, quinine reduced the frequency of cramps and sleep disturbance, but not the average cramp severity. Thirteen of 27 patients had at least a 50% reduction in the number of cramps while receiving quinine; the response was usually seen within 3 days. There was evidence of a mild increase in side effects while subjects received quinine. Vitamin E was not effective in reducing leg cramp frequency, severity, or sleep disturbance. CONCLUSIONS: Quinine sulfate, but not vitamin E, is superior to placebo in the treatment of nocturnal leg cramps.

The value of specialized tests in studies where ordered group means are expected.

The performances of three tests for ordered means (Bartholomew's, Williams' and a modified method of least significant differences) are compared with the performances of more general multiple comparison procedures. The tests are assessed using simulated data representing various patterns of results from a toxicological study with one (zero dose) control group and three treatment groups. The specialized tests are considerably more powerful than the general tests and their application is recommended whenever ordered group means are expected.

The choice between analysis of variance and analysis of covariance with special reference to the analysis of organ weights in toxicology studies.

The problem of when to include a covariate in the analysis of variance is considered in the special case of organ weight analysis in animal toxicology studies. The covariate is bodyweight prior to death, which may be subject to treatment effects. A simulation study is carried out to compare four rules for deciding whether or not to include the covariate. It is concluded that if there is background information which shows a linear relationship between variate and covariate it is advisable to adjust for the covariate, however weak the relationship may appear to be on the current set of data. Alternative procedures lead to unacceptably high Type I error rates.

The use of background data in the analysis of covariance.

The advantages and disadvantages of using extraneous information about the relationship between variate and covariate in analysis of covariance are examined. The problem is considered both theoretically and by a simulation study. It is found that the usefulness of extraneous information in increasing the precision of analysis of covariance can be assessed using simple formulae.

An evaluation of some statistical methods for analysing numbers of abnormalities found amongst litters in teratology studies.

Skeletal abnormalities in rabbit, rat and mouse foetuses are found to follow closely beta-binomial distributions rather than simple binomial distributions, i.e., foetuses from the same litter are found to have closer chances of being abnormal than foetuses from different litters. Control and treated groups of 12 litters were simulated using beta-binomial distributions and were used to compare the performances of three types of analysis on two-group teratological studies: Student's t test on the litter proportions, transformed or weighted where necessary; the Wilcoxon distribution-free on ranked litter proportions; and likelihood ratio tests assuming a beta-binomial distribution of abnormalities. It was found that the likelihood ratio tests do not have Type I errors equal to the nominal level and are not more powerful than the Student's t test or the Wilcoxon test. The latter two tests produce similar results but the Student's t test is marginally more powerful.