Measurement properties of quantitative urine benzoylecgonine in clinical trials research

Psychometric data are presented which examine the validity of using the concentration of benzoylecgonine in urine, a major metabolite of cocaine, as a measure of drug use, in studies of drug abuse treatments. In such research the standard biological indicator of drug use is usually a qualitative urine drug test, which merely indicates the presence or absence of a drug or its metabolite. A quantitative (i.e. continuous) outcome measure, such as the concentration of a drug or its metabolite in a biological fluid, has substantially more statistical power than a dichotomous measure and should, therefore, prove a more sensitive measure of drug use when viewed from a measurement perspective. Data from two placebo-controlled clinical trials of fluoxetine as an adjunct to treatment for cocaine abuse are analyzed to address this issue. Results indicate that urine benzoylecgonine level is closely related to self-reports of drug use and is independent of levels of anxiety, depression and hopelessness.     

Collagenous colitis: Clinical and histological spectrum in ten patients

Collagenous colitis is characterized by the presence of a thick subepithelial collagen band in the colonic mucosa. The condition was diagnosed on rectal biopsy in 10 patients (one male, nine females) who presented with watery diarrhoea. Although rectal mucosal erythema was present in three and ulceration in two, the mucosa was of normal endoscopic appearance in five of the patients. There was marked variability in the thickness of the submucosal collagen band, both between and within individuals. Empirical drug therapy included sulphasalazine, glucocorticoids and antidiarrhoeals. All patients reported symptomatic improvement.     

The effect of fluconazole and ketoconazole on the metabolism of sulphamethoxazole

1 Cytochrome P450-mediated bioactivation of sulphamethoxazole to a hydroxylamine has been implicated in the hypersensitivity reactions associated with co-trimoxazole administration. Inhibiting the formation of the hydroxylamine may be one method of preventing the high frequency of toxicity which is observed in HIV-infected patients. Therefore, in this study, we have investigated the ability of fluconazole and ketoconazole, known cytochrome P450 inhibitors, to inhibit the formation of sulphamethoxazole hydroxylamine.
2 Ten healthy male volunteers were given co-trimoxazole (800  mg sulphamethoxazole and 160  mg trimethoprim) alone or 1  h after either fluconazole (150  mg) or ketoconazole (200  mg) in a randomized fashion with a washout period of at least 1 week between each phase. Urine was collected for 24  h, and sulphamethoxazole and its metabolites were quantified by electrospray LC-MS.
3 Ketoconazole had no effect on the urinary recovery of sulphamethoxazole or any of its metabolites. In contrast, fluconazole significantly ( P <0.001) inhibited the formation of sulphamethoxazole hydroxylamine by 50.0±15.1%. Fluconazole also inhibited the oxidation of sulphamethoxazole to the 5-methylhydroxy and 5-methylhydroxy acetate metabolites by 69.9±15.8% and 64.0±12.0%, respectively, but had no effect on the amount of sulphamethoxazole, N₄-acetyl sulphamethoxazole, or sulphamethoxazole N₁-glucuronide excreted in urine.
4 The potential clinical benefit of using fluconazole to prevent hypersensitivity to co-trimoxazole in patients with AIDS needs to be assessed in a prospective study using both metabolite formation and the clinical occurrence of adverse reactions as end-points.     

Do Electrode and Lead Design Differences for Permanent Cardiac Pacing Translate into Clinically Demonstrable Differences? (Comparison of Sintered Platinum and Activated Vitreous and Porous Carbon Electrodes)

A randomized prospective study was undertaken to compare the electrical performances of three permanent, endocardial, tined pacing leads with different electrode designs--sintered platinum, vitreous carbon, and porous carbon. Ninety-nine patients received one of the leads (S80 31; 423S 32; S100 36). Acute R wave amplitude and ST elevation of the native endocardial electrogram, voltage threshold, impedance, and current flow at four pulse durations (0.25-1.0 msec) were measured. Voltage thresholds were measured noninvasively at each of four pulse durations at 2 days and 1, 3, and 6 months after implantation. No significant differences were found in sensing properties, or current flow at threshold at 0.5 msec pulse duration. The 423S lead had a significantly higher impedance at threshold and both a higher impedance and lower current flow at 5 V. No significant differences in threshold voltages were found between the three leads at any pulse duration, at any of the assessed times after implantation. Six-month thresholds for the S80, 423S, and S100 leads were 1.18 +/- 0.35, 1.17 +/- 0.29, and 1.06 +/- 0.38 V respectively at 0.5 msec pulse duration. Differences between 'high performance' pacing leads need to be of a greater order of magnitude before they can be exploited to give any real clinical advantage to patients.     

Effects of Age, Parity, and Adherence on Pelvic Muscle Response to Exercise

OBJECTIVE: To examine factors that affect pelvic muscle response to 12 weeks of pelvic muscle exercise. DESIGN: Repeated measures design in which intravaginal pressures during pelvic muscle contractions were recorded at baseline and after four exercise levels. SETTING: College of Nursing research site in Gainesville, Florida. PARTICIPANTS: Eighty-five parous, community-dwelling women, aged 35-78 years and without incontinence as a primary concern. INTERVENTIONS: A 12-week graded program of regular (three times per week, every other day) pelvic muscle exercise at home. MAIN OUTCOME MEASURES: The hypotheses were that younger age, lower parity, higher baseline intravaginal pressures, and adherence to the pelvic muscle exercise program each would result in significant improvement in maximum intravaginal pressures. RESULTS: The only factor showing significance in predicting a successful outcome was age (t = -2.29, df = 41, one-tail probability = .0136). CONCLUSIONS: Regular, graded exercise over several weeks is needed to build pelvic muscles, and some women who exercise do not improve. Although the reasons for not improving are unclear, age is a significant factor.     

Assessment of Aortic Coarctation and Collateral Circulation By Biplane Transesophageal Echocardiography

Our experience in using biplane transesophageal echocardiography in the assessment of coarctation of the aorta is described.     

Postnatal classes on prevention of sleeplessness in young children

Parents of young babies attended evening classes on prevention of sleeping problems in pre-school children. The aim was to test the consumer-appeal of this preventative approach. Content focused on individual behavioural differences in babies as well as adaptation of parenting strategies to avoid some of the common pitfalls in the management of sleep-related behaviours. Parents' views were obtained and were favourable. Results are discussed in terms of the timing and format of similar prevention programmes.     

Non-prescribed drug use during methadone treatment by clinic- and community-based patients

We investigated the efficacy of methadone maintenance treatment in clinic-based (n= 10) and community-based (n= 10) patients by studying the relationships between dose, plasma concentrations of methadone and non-prescribed drug-use using logistic regression. We found that clinic-based patients had significantly reduced odds of having a urine sample test positive for illicit drugs when compared to community-based patients (OR = 0.20; 95% confidence interval 0.10–0.38: p < 0.001). There was no relationship between either methadone dose or plasma methadone concentration and testing positive for non-prescribed drugs (including cocaine, cannabis, amphetamine, ecstasy, benzodiazepines). We looked specifically at the misuse of opiate drugs. Location was again important and clinic-based patients had significantly reduced odds of having a urine sample test positive for opiate drugs (OR= 0.36, 95% confidence internal 0.13–0.71: p～0.004). Opiate drug use in our patients was also significantly related to plasma methadone concentration, increasing noticeably when the drug concentration < 0.48 nmol/L (p～0.04). We found no relationship between methadone dose and odds of having a positive urine drug test in either clinic- or community-based patients.