Quality assessment by expert opinion in melanoma pathology: experience of the pathology panel of the Dutch Melanoma Working Party.

Some cutaneous melanocytic lesions are notoriously difficult to diagnose by histopathology. For that reason, the Pathology Panel of the Dutch Melanoma Working Party was instituted and is regularly approached to provide an expert opinion on problem cases. In order to identify the most common diagnostic problems, 1069 consecutive referral cases of submitted lesions (1992 to 1994 inclusive) were analysed. About 60 per cent of the requests came from small laboratories, with up to three consultant pathologists. Two-thirds of the lesions reviewed concerned women and nearly 50 per cent of the patients were 30 years of age or younger. In 8 per cent of the cases, the referring pathologists felt unable to make a confident diagnosis; in 14 per cent, melanoma was suspected; and in 12 per cent, a differential diagnosis only had been formulated. The panel felt able to provide an unequivocal diagnosis in 93 per cent of the requests. Of the 158 lesions classified as 'invasive melanoma' by the referring pathologists, 22 were considered to be benign by the panel. Conversely, 108 invasive melanomas (panel diagnosis) had originally been considered as benign lesions, dysplastic naevi or melanoma in situ. These high numbers of discordancies reflect the intrinsic difficulty of the differential diagnoses in this selected material submitted to the panel. Diagnostic difficulties were most often encountered with Spitz naevi and dysplastic naevi. Although the rate of overdiagnosis and underdiagnosis is quite high, in the majority of cases the diagnosis of the referring pathologist matched the diagnosis of the panel. This may reflect a proper awareness of difficult melanocytic lesions in pathology practice. The activities of the Pathology Panel of the Dutch Melanoma Working Party contribute to the improvement of the quality of diagnosis in cutaneous melanocytic lesions, as they increase the number of unequivocal diagnoses and reduce the number of incorrect diagnoses. On the basis of the systematic comparison of the diagnosis by the referring pathologist and the panel, postgraduate teaching and quality control can be more focused on specific diagnostic problems.

Randomised controlled trial of hydroquinine in muscle cramps.

BACKGROUND: Although quinine and hydroquinine are commonly prescribed for muscle cramps, controlled clinical trials of these drugs have reported mixed findings about efficacy. We investigated hydroquinine therapy in otherwise healthy adults who had frequent, ordinary muscle cramps. METHODS: This randomised, double-blind, placebo-controlled, parallel-group trial consisted of three consecutive 2-week periods: qualification, treatment, and washout, 68 women and 44 men who had at least three muscle cramps per week were enrolled. During the treatment period, participants were randomly assigned 300 mg daily dose of hydroquinine hydrobromide dihydrate (54 participants) or placebo (58). The frequency, severity (1-10), duration, and location of muscle cramps, as well as any side-effects, were recorded by participant in daily diaries. The primary outcome measures were the number of muscle cramps and the number of days during which the participants had muscle cramps (cramp-days). FINDINGS: We excluded five participants from both groups from the analysis. Thus, data from 49 hydroquinine-group participants and 53 placebo-group participants were analysed. In both groups the total number of muscle cramps and the number of cramp-days decreased during the treatment period compared with the qualification period. However, these improvements were greater in the hydroquinine group than in the placebo group. The hydroquinine-group participants reported a median of 8 (95% CI 7-12) fewer cramps and median of 3 (1-4) fewer cramp-days, whereas those on placebo reported only 3 (0-5) fewer cramps and 1 (0-5) fewer cramp-days. 32 (65%) of participants in the hydroquinine group had a 50% or greater reduction in the number of muscle cramps. After the onset of cramps, hydroquinine did not reduce the severity or duration of cramps. We also found a sustained effect after treatment had stopped. Hydroquinine was well tolerated, and resulted in only mild side-effects. INTERPRETATION: In our study, 300 mg hydroquinine was safe to take in the short-term and significantly more effective than placebo in the prevention of frequent, ordinary muscle cramps. This therapeutic effect outlasted the duration of treatment.

Efficacy of hydroquinine in preventing frequent ordinary muscle cramp outlasts actual administration.

In order to compare the efficacy of a daily dose of 300 mg hydroquinine hydrobromide and placebo in preventing frequent ordinary muscle cramp, we designed a randomized, double-blind, placebo-controlled study of three consecutive 2-week periods viz. a qualification period, a medication period and a wash-out period. Twenty healthy adult volunteers experiencing at least 3 muscle cramps a week (6 men, 14 women aged 38-78 yrs) were enrolled into this study, and 19 of them completed it. Hydroquinine hydrobromide (300 mg/day) was administered to group 1 (10 women) and placebo to group 2 (4 women, 6 men). The frequency, severity, duration and location of muscle cramps as well as short-term adverse drug effects were recorded in daily diaries. Compared with placebo the decrease in the mean number of muscle cramps (16.1 or 58%) in the active drug treatment group during the medication period was highly significant (Wilcoxon test p = 0.004). During the wash-out period this decrease partly persisted (8.9 or 33%). In this study a daily dose of 300 mg hydroquinine hydrobromide was effective in preventing frequent ordinary muscle cramp in healthy female volunteers. The effects of hydroquinine outlasted its administration. The drug was well tolerated.