[Definition of low threshold volumes for quality assurance: conceptual and methodological issues involved in the definition and evaluation of thresholds for volume outcome relations in clinical care]. / Mindestmengen zur Qualitätssicherung: Konzeptionelle und methodische Uberlegungen zur Festlegung und Evaluation von Fallzahlgrenzwerten für die klinische Versorgung.

In a large number of mostly retrospective association studies, a statistical relationship between volume and quality of health care has been reported. However, the relevance of these results is frequently limited by methodological shortcomings. In this article, criteria for the evidence and definition of thresholds for volume-outcome relations are proposed, e.g. the specification of relevant outcomes for quality indicators, analysis of volume as a continuous variable with an adequate case-mix and risk adjustment, accounting for cluster effects and considering mathematical models for the derivation of cut-off values. Moreover, volume thresholds are regarded as surrogate parameters for the indirect classification of the quality of care, whose diagnostic validity and effectiveness in improving health care quality need to be evaluated in prospective studies.

Sequentially adjusted randomization to force balance in controlled trials with unknown prevalence of covariates: application to alcoholism research.

AIMS: In treatment outcome studies with small to medium sample sizes (n < 200), the balance of groups with regard to important factors, which sometimes occur at low prevalence, is indispensable for adequate interpretation. This study tested a method for use in clinical alcoholism research, an uncomplicated procedure for satisfactory randomization of patients to different treatments, taking into account relevant background variables. METHODS: An easily applicable modification of Efron's biased coin method for the randomization of treatments within strata of unknown but low prevalence was compared with the original approach and alternative methods by computer simulation (10,000 runs). An application example for a clinical trial in alcoholism research is given. RESULTS: The sequentially adjusted randomization procedure revealed results similar to Efron's approach without the necessity for monitoring the assignment history throughout the trial. The new method was slightly superior to Efron's approach in randomizing subjects in strata with n < or = 20, whereas strata with n > 20 favoured randomization with Efron's approach. Taking into account all results from simulation, the new approach reached a proportion of acceptable balanced randomization > 95% in all stratum sizes. CONCLUSIONS: The approach, a special case of the standard urn design, provides three major advantages in clinical trials: (i) it can be easily implemented in any trial without technical equipment; (ii) it works with high accuracy in trials with a priori unknown but low numbers of subjects (4 < or = n < or = 20) in prognostic relevant strata; and (iii) a deterministic assignment tendency is completely avoided, as a random process takes place throughout the assignment procedure. The modified biased coin method can be recommended as one possible strategy for special purposes, particularly in alcoholism research.

Combination treatment with nefazodone and cognitive-behavioral therapy for relapse prevention in alcohol-dependent men: a randomized controlled study.

BACKGROUND: This study evaluated the serotonergic antidepressant nefazodone versus placebo and specific cognitive-behavioral therapy (CBT) versus nondirective group counseling (GC) for relapse prevention in alcohol dependence in a large prospective, randomized, and placebo-controlled double-blind study at 3 German university centers. METHOD: 242 male patients fulfilling at least 5 criteria for alcohol dependence according to DSM-IV and ICD-10 were eligible, after detoxification, for one of the following treatment combinations: nefazodone + CBT, nefazodone + GC, placebo + CBT, and placebo + GC. Either nefazodone or placebo was administered throughout the evaluation period of 15 months. Either CBT or GC was applied during the first 12 weeks as group therapy according to operationalized manuals. The main outcome measures (assessed at 3 and 12 months of treatment) were the cumulative number of abstinent days, the amount of ethanol consumed during specified evaluation periods of 3 and 12 months, the number of relapses, and the duration of time until first relapse. RESULTS: After 12 weeks of treatment, no statistically significant differences were observed between the 4 treatment combinations in any outcome measure. After 52 weeks, the only significant difference was observed in the amount of ethanol consumed, with the nefazodone + GC group showing higher alcohol intake than the other 3 groups. CONCLUSIONS: The results from this carefully designed clinical trial suggest that the 4 treatment combinations do not differ substantially in their efficacy for relapse prevention in nondepressed, severely alcohol-dependent patients. Nefazodone might even increase the risk of consuming a larger amount of ethanol per relapse in a subset of patients. CBT as performed in this study was associated with little additional benefit compared with structured GC.

Symptom-triggered versus standard chlormethiazole treatment of inpatient alcohol withdrawal: clinical implications from a chart analysis.

To evaluate clinical effectiveness and safety of 2 different detoxification treatment protocols, a chart analysis of hospital inpatients consecutively admitted for alcohol withdrawal during one year was undertaken. Records of 33 patients receiving symptom-triggered treatment (using a modified version of the revised Clinical Institute Withdrawal Assessment for Alcohol Scale) were compared with those of patients treated by applying a fixed-dose regimen (n = 32). Patients (45.3 +/- 9.8 years, 21% female) of both groups were comparable regarding illness severity, epidemiologic parameters as well as complications during the observed treatment period. Under symptom-triggered therapy, chlormethiazole (CMZ) treatment duration (4.2 +/- 3.5 vs. 7.5 +/- 3.3 days, Mann-Whitney U test: p = 0.0003) and cumulative CMZ dosage (4352 +/- 4589 vs. 9921 +/- 6599 mg, Mann-Whitney U test: p = 0.0004) were significantly reduced. The daily CMZ dose was significantly lower at days 1-5 in the group receiving symptom-triggered treatment. There was no influence of age on the outcome parameters of either treatment group. In conclusion, an individualized symptom-triggered treatment of alcohol withdrawal with CMZ seems to be equally safe but more efficient than a scheduled regimen.

Dose-related effects of amisulpride on five dimensions of psychopathology in patients with acute exacerbation of schizophrenia.

The present analysis investigated symptom-specific dose-response relationships of the atypical antipsychotic amisulpride (AMI) in schizophrenic patients. The effects of different AMI doses on five different symptom dimensions of the Brief Psychiatric Rating Scale (BPRS) were analyzed. Results on global efficacy and safety parameters have been previously published. Four AMI doses (100 mg/day [AMI100], 400 mg/day [AMI400], 800 mg/day [AMI800], 1200 mg/day) were compared with 16 mg haloperidol (HAL16) in a multicenter, double-blind, randomized, parallel-group, 4-week trial. A total of 319 patients with acute exacerbation of schizophrenia (DSM-III-R) were included. AMI100 was compared with the other AMI doses, and HAL16 was compared with all AMI dosage groups. Response on BPRS factors defined as > or = 40% improvement and ORs were computed. An optimal AMI dose was calculated for each BPRS factor based on linear and quadratic regression. For all BPRS factors, inverted u-shaped dose-response curves emerged (r2 > 95%). The estimated AMI dose optimum for the BPRS factors activation/ agitation (760 mg), thought disturbances (716 mg), and hostility/suspiciousness (694 mg) was higher than that for anergia/negative symptoms (584 mg) and depression/anxiety (672 mg). Significant differences (p < 0.05) were found for AMI400/800 versus AMI100 (thought disturbances, hostility/ suspiciousness), for AMI400/800 versus HAL16 (depression/anxiety, thought disturbances, hostility/suspiciousness), and for AMI400 versus HAL16 (anergia/negative symptoms). ORs for response of the BPRS factors depression/anxiety, anergia/negative symptoms, and hostility/suspiciousness were highest under treatment with AMI400 compared to AMI100 and HAL16. For the BPRS factors thought disturbances and activation/agitation, the highest response chance emerged under AMI800 compared to AMI100 or HAL16. AMI seems to show the best clinical efficacy in acutely schizophrenic patients in a moderate dose (400-800 mg/day), with a somewhat lower dose optimum for negative than for positive symptoms. The present finding of distinct dose-response relationships of AMI regarding the BPRS dimensions is in accordance with studies on the mechanism of action of AMI and provides a useful rationale for the clinical treatment of schizophrenic patients with AMI.