Population pharmacokinetics of cyclophosphamide in patients with thalassemia major undergoing HSCT

CY in combination with BU is a widely used conditioning regimen for haematopoietic SCT (HSCT). The aim of this study was to evaluate the pharmacokinetics (PK) of CY and its major metabolite 4-hydroxyCY (HCY) in patients with thalassemia undergoing HSCT. A total of 55 patients received BU (16 mg/kg) followed by CY (160-200 mg/kg) both over 4 days before HSCT. A population PK model was developed to describe the disposition of CY and HCY and the inter-individual (IIV) and inter-occasion variability (IOV). The model was also used to determine the effects covariates including: demographics, Lucarelli classification and polymorphisms in enzymes involved in the metabolism or biotransformation of CY had on CY and HCY disposition. Overall, 17-114% IIV and 12-103% IOV in CY and HCY PK parameters were observed. Body weight and age were the main covariates, which explained the largest portion of the IIV. In addition, CYP2C9*2 explained a significant portion of the IIV in the clearance (P<0.002) and thus the area under the concentration curve (P<0.05) of CY. This covariate model may be used to design and plan targeted dose therapy in this group of pediatric patients, if clinical outcome association with CY PK are proved and target range established.     

Recruitment and retention of women for clinical leiomyoma trials

BackgroundSubject recruitment and retention in clinical leiomyoma trials is challenging. We evaluated strategies to increase patient enrollment and completion in leiomyoma trials.Materials and methodsRandomized trials for treatment of symptomatic leiomyoma published from 2000 through 2008 were evaluated and thirteen trials were selected. Subject enrollment and completion rates, recruitment methods and reasons for patient drop-out were assessed.ResultsRecruitment by study personnel or clinic staff during evaluation for symptomatic leiomyoma was the most common strategy for enrollment. Additional methods included local media, internet postings and physician referrals. Seven to 85% of patients enrolled after screening, with a median enrollment of 70%. Sixty-five to 100% of patients completed the study after enrollment with a median completion rate of 89%. Reasons for drop-out at the screening stage included failure to meet inclusion criteria, patient refusal and patient preference for specific treatment. Commonly reported reasons for drop-out after enrollment were refusal of treatment following randomization, adverse reaction to study intervention and non-compliance with study protocol or follow-up visits.ConclusionWomen with symptomatic uterine leiomyomas may be attracted to participate in leiomyoma trials, however desire for specific treatment and persistent symptoms following intervention may hinder their participation. Randomization to placebo treatment and stringent inclusion criteria appear to adversely impact accrual. A wide range of recruiting tactics is needed and media sources or direct mailings may prove particularly effective to improve subject recruitment and retention in clinical leiomyoma trials.     

"Tension-free" hernioplasty with prosthesis: comparison of 2 techniques

The paper evaluates the results of the surgical therapy of primary inguinal hernia in adult subjects performed in our Institution from 1994 to 2000. The Trabucco and Lichtenstein procedures were compared. Two hundred and fifteen patients--123 Trabucco and 92 Lichtenstein--were enrolled in the study. A file was created for each patient with details of personal data, procedures, anaesthesia and postoperative course. A form regarding the present state of each patient was filled in, mainly by phone, but sometimes by physical examination, if patients complained of problems. The results were evaluated statistically using the Fisher f and X2 tests. Only four parameters showed significant differences: wound swelling, constipation and days off work were less frequent with the Trabucco procedure, while there was less loss of the foreign body sensation in the Lichtenstein patients (6.7% vs. 18.3%). No recurrences were detected. The results of the two procedures can be considered comparable.     

Minimal clinically important improvement and patient acceptable symptom state for subjective outcome measures in rheumatic disorders

The concepts of minimal clinically important improvement (MCII) and patient acceptable symptomatic state (PASS) could help in interpreting results of trials involving patient-reported outcomes by translating the response at the group level (change in mean scores) into more clinically meaningful information by addressing the patient level as "therapeutic success (yes/no)." The aims of the special interest group (SIG) at OMERACT 8 were to discuss specific issues concerning the MCII and PASS concepts, especially the wording of the external anchor questions used to determine the MCII and PASS estimates, and to move toward a consensus for the cutoff values to use as the MCII and PASS in the different outcome criteria. The purpose of this SIG at OMERACT 8 was to inform participants of the MCII and PASS concepts and to agree on MCII and PASS values for pain, patient global assessment, and functional impairment.     

Evaluation of the preventative effects exerted by Lactobacillus fermentum in an experimental model of septic shock induced in mice

The preventative effects of the probiotic Lactobacillus fermentum CECT5716 were evaluated in the lipopolysaccharide (LPS) model of septic shock in mice. The probiotic was administered suspended in drinking water at the final concentration of 108 colony-forming units/ml for 2 weeks before the induction of an endotoxic shock by an intraperitoneal injection of LPS (400 microg/200 microl per mouse). Blood and different organs were collected after 24 h to evaluate the severity of the endotoxic shock and the preventative effects of the probiotic. L. fermentum reduced TNF-alpha levels in blood, which promotes the major alterations observed during septic shock, as well as the infiltration of activated neutrophils into the lungs. Furthermore, free radical overproduction and oxidative stress were associated with a significant decrease in hepatic glutathione levels in septic mice, and with an excessive NO production attributed to the induction of the inducible isoform of NO synthase (iNOS). In fact, hepatic glutathione levels were significantly increased in the group of mice receiving the probiotic, and the increased iNOS expression both in the colon and lungs was down-regulated in those mice treated with L. fermentum. Finally, pre-treatment with L. fermentum may also exert its protective action modulating the expression of different cytokines in splenocyte-derived T cells such us IL-2, IL-5, IL-6 or IL-10. In conclusion, pre-treatment with L. fermentum may exert its protective action against LPS-induced organ damage in mice by a combination of several actions including its antioxidant properties and by reduction of the synthesis of the pro-inflammatory TNF-alpha and IL-6.     

Short report: edematous Mycobacterium ulcerans infection (Buruli ulcer) on the face: a case report

We report a case of a four-year-old Angolan boy with the edematous form of Buruli ulcer on the face and scalp, who was treated at a rural hospital in the Bas-Congo Province, Democratic Republic of Congo. Treatment consisted of a series of surgical interventions and antimycobacterial chemotherapy (rifampin and ciprofloxacin) for two months. This case demonstrates the diagnostic and management difficulties of an edematous lesion of BU on the face and suggests an enhancement of healing and limitation of extent of excision by specific antibiotherapy. The outcome in this patient also underscores the importance of prompt referral of suspected cases and training of health professionals in the early diagnosis of BU.     

The portuguese version of the personal health scale: a validation study in southern Brazil

The Personal Health Scale is a concise instrument for comprehensive culture-informed and self-rated assessment of general health status and well-being. It is composed of 10 questions that appraise different health dimensions collated from the international literature, including aspects ranging from somatic and psychological domains to social functioning and insight. PURPOSE: In this investigation, results of a study conducted in Southern Brazil to test and validate the Portuguese version of the Personal Health Scale (PHS-Pt) are presented. Method: This study analyzes data from a sample of 120 Brazilian volunteers (90 patients and 30 health care professionals). All patients completed the Portuguese version of the Personal Health Scale under a minimal guidance by trained examiners, who followed standardized instructional procedures. RESULTS: The internal consistency of the PHS-Pt attained a Cronbach's a of 0.75 among patients and of 0.69 among health care professionals. The test-retest reliability correlation coefficient yielded a score of 0.82. Furthermore, the PHS-Pt was able to detect a significant discriminating validity between the 2 evaluated samples (P < .001). CONCLUSIONS: The original English version of the Personal Health Scale was successfully adapted to Portuguese as methodologically demonstrated herein. The PHS-Pt constitutes a reliable and trustworthy research instrument for evaluating health status in Brazil, since it is appropriately designed to distinguish different groups of volunteers regarding their health status.     

Tolerance and efficacy of combined diethylcarbamazine and albendazole for treatment of Wuchereria bancrofti and intestinal helminth infections in Haitian children

This randomized, placebo-controlled trial investigated the tolerance, efficacy, and nutritional benefit of combining chemotherapeutic treatment of intestinal helminths and lymphatic filariasis. Children were infected with Ascaris (30.7%), Trichuris (53.4%), and hookworm (9.7%) with 69.9% having more than one of these parasites. A total of 15.8% of the children had Wuchereria bancrofti microfilariae. Children were randomly assigned treatment with placebo, albendazole (ALB), diethylcarbamazine (DEC), or combined therapy. The combination of DEC/ALB reduced microfilarial density compared with placebo, ALB, or DEC (P < or = 0.03). Albendazole and DEC/ALB reduced the prevalence of Ascaris, Trichuris, and hookworm more than placebo or DEC (P < or = 0.03). Among Trichuris-infected children, those receiving ALB and DEC/ALB demonstrated greater gains in weight compared with placebo (P < or = 0.05). Albendazole and DEC/ALB were equally efficacious in treating intestinal helminths and for children with W. bancrofti microfilaremia, DEC/ALB was more effective than DEC, with no increase in severity of adverse reactions.