Quantification methods were developed for selection bias by predictability of allocations with unequal block randomization.

BACKGROUND AND OBJECTIVE: A selection of patients for a controlled clinical trial may be biased because of prior knowledge of the treatment. With randomized blocks of known or guessed lengths, some allocations can be predicted with certainty. Previously described methods determine the proportion of predictable cases for blocks of equal lengths. It may be useful to make a calculation for unequal blocks as well to find a method that reduces this predictability. STUDY DESIGN AND SETTING: Quantification methods are developed for series of two and three unequal blocks, using the probability of identifying a long block when it comes before a short one if it starts with a sequence incompatible with the content of a short block. Results are compared with the recently described maximal allocation procedure. RESULTS: Predictability is not always reduced by unequal blocks and is even worse in some cases, compared to equal blocks. Predictability is not necessarily decreased with the maximal allocation procedure. CONCLUSIONS: Before choosing an allocation method, it is important to quantify the predictability of possible options to reduce selection bias. Several practical recommendations are formulated for choosing methods, taking this risk of bias into account.

[The domiciliary medication management review: is it possible in France?]. / La prise en charge médico-pharmaceutique: l'expérience australienne peut-elle être transposée en France?

From October 2001, the Australian healthcare system has made provision for, in predefined circumstances, a domiciliary medication review service. This pharmaceutical care service provides a medication review for outpatients encountering (or who may encounter) difficulties with their treatments, and who are referred by their physician. The pharmacist is chosen by the outpatient. Doctor and pharmacist gather the relevant elements of his/her medical file and work together, following procedures. After the consultation, the pharmacist passes his evaluation of the situation and his proposals to the doctor, who writes an action plan (shared with the pharmacist) and puts it into practice. This operational network is managed by the healthcare system. The 35000 consultations carried out confirm the interest in this service and make it possible to simplify the treatments. The cost of the operation is more than covered by the savings generated. This discussion proposes to specifically study the transposition of this service to France.

Pharmacokinetics and dialysability of naltrexone in patients undergoing hemodialysis.

The disposition of naltrexone (NLT) (REVIA), an opioid antagonist intended for patients with impaired renal function and with severe intractable itching refractory to regular antipruritic therapy, was characterized. Hemodialysis effects on both efficacy and elimination of NLT also were assessed. We developed a simple, sensitive and selective reverse-phase high-performance liquid chromatographic (HPLC) method for measuring NLT plasma concentration in hemodialysis patients treated to relieve pruritus. NLT and the internal standard, naloxone (NLX) were extracted from plasma using a solid-phase extraction method with sep-pack C18 cartridge. The method was employed to determine both naltrexone pharmacokinetics and dialysability parameters during 4-h in dialyzed patients with chronic renal impairment. Thus, seven patients (2 men, 5 women) with end-stage renal disease and pruritus on regular hemodialysis were included. They received one tablet of NLT (Revia, 50 mg) orally prior dialysis session. The Cmax at the inlet and at the outlet the dialyzer were higher (255+/-117 ng/mL and 206+/-137 ng/ml respectively) in comparison with healthy subjects (9 - 44 ng/mL). The decrease hepatic first-pass metabolism of NLT consecutive to end-stage renal disease and the renal impairment could explain the increased levels of the drug in plasma. Tmax before and after dialysis plates remain unchanged as healthy subjects (approximately 1h). With regard to dialysability, a high dialyzer extraction ratio averating 30 % was found with a low dialysis clearance of 58.70+/-17 mL/min. The amount removed by dialysis is only 1.27 mg. We concluded that hemodialysis has little effect on NLT blood levels, and consequently on drug pharmacokinetics, when the drug is delivered to dialyzed patients following oral route. Thus, dosage adjustement is not required in the presence of advanced dialysis-dependant renal failure. In patients with end-stage renal disease, hemodialysis does not result in clinically significant alterations in the disposition of NLT. Post-dialysis supplementation is not required. These data suggest that there is no pharmacokinetic basis for modification of the initial dosage, but in view of NLT plasma concentration levels in the patients, a clinician could determine whether dosage adjustment are necessary and, if so, make the required calculations accurately.