Multiplicity adjustment for multiple endpoints in clinical trials with multiple doses of an active treatment

Frequently, multiple doses of an active treatment and multiple endpoints are simultaneously considered in the designs of clinical trials. For these trials, traditional multiplicity adjustment procedures such as Bonferroni, Hochberg and Hommel procedures can be applied when treating the comparisons of different doses to the control on all endpoints at the same level. However, these approaches will not take into account the possible dose-response relationship on each endpoint, and therefore are less specific and may have lower power. To gain power, in this paper, we consider the problem as a two-dimensional multiplicity problem: one dimension concerns the multiple doses and the other dimension concerns the multiple endpoints. We propose procedures which consider the dose order to form the closure of the procedures and control the family-wise type I error rate in a strong sense. For this two-dimensional problem, numerical examples show that procedures proposed in this paper in general have higher power than the commonly used procedures (e.g. the regular Hochberg procedure) especially for comparing the higher dose to the control.     

Salt-losing syndrome in 2 infants with defective 18-dehydrogenation in aldosterone biosynthesis

Two infants presented with a salt-losing syndrome, the presenting features of which were subtle. One case appeared to be transient. Deficient production of aldosterone was shown by plasma renin activity and plasma aldosterone profile. Gas chromatography-mass spectrometry of urine indicated a defect in 18-dehydrogenation of 18-hydroxycorticosterone. Treatment with salt supplements and 9alpha-fludrocortisone reversed the salt-losing state and in one case treatment was later stopped. Although the disease may appear transient, the biochemical defect is persistent and for adequate growth a positive salt-balance is necessary.     

如何在医疗实践和言语表达中以患者为中心

以往,作医疗决策几乎都是由医生先诊断,然后RCC医生从可能的治疗方案中选出自认为恰当的措施,最后告之患者接受怎样的治疗.因此,医疗决策所有的权力都集中在医生手中.     

Italian Group for Lap-Band System®: Results of Multicenter Study on Patients with BMI ≤35 kg/m2

Background: The Lap-Band System? is the most common bariatric operation world-wide. Current selection criteria do not include patients with BMI ≤ 35. We report the Italian multicentre experience with BMI ≤ 35 kg/m² over the last 5 years. Patients and Methods: Data were obtained from 27 centres involved in the Italian Collaborative Study Group for Lap-Band System?. Detailed information was collected on a specially created electronic data sheet (MS Access 2000) on patients operated in Italy since January 1996. Items regarding patients with BMI ≤ 35 were selected. Data were expressed as mean ± SD except as otherwise indicated. Results: 225 (6.8%) out of 3,319 Lap-Band? patients were recruited from the data-base. 15 patients, previously submitted to another bariatric procedure (BIB =14; VBG= 1) were excluded. 210 patients were eligible for study (34M/176F, mean age 38.19±11.8, range 17-66 years, mean BMI 33.9±1.1, range 25.1-35 kg/m², mean excess weight 29.5±7.1, range 8-41). 199 comorbidities were diagnosed preoperatively in 55/210 patients (26.2%). 1 patient (0.4%) (35 F) died 20 months postoperatively from sepsis following perforation of dilated gastric pouch. There were no conversions to laparotomy. Postoperative complications presented in 17/210 patients (8.1%). Follow-up was obtained at 6, 12, 24, 36, 48 and 60 months. At these time periods, mean BMI was 31.1±2.15, 29.7±2.19, 28.7±3.8, 26.7±4.3, 27.9±3.2, and 28.2±0.9 kg/m² respectively. Co-morbidities completely resolved 1 year postoperatively in 49/55 patients (89.1%). At 60 months follow-up, only 1 patient (0.4%) has a BMI >30. Conclusions: Although surgical indications for BMI ≤ 35 remain questionable, the Lap-Band? in this study demonstrated that all but 1 patient achieved normal weight, and most lost their co-morbidities with a very low mortality rate.     

Peri-engraftment respiratory distress syndrome during autologous hematopoietic stem cell transplantation

From 1987 to 1998, 19 of 416 patients (4.6%) who underwent autologous hematopoietic stem cell transplantation experienced peri-engraftment (within 5 days of neutrophil recovery) respiratory distress syndrome (PERDS) not attributable to infection, fluid overload, or cardiac dysfunction. The median time from stem cell infusion to onset of PERDS was 11 days (range 4-25). Risk of PERDS or its outcome was not predicted by any pre- or peri-transplant clinical or laboratory feature. The respective median white blood cell and platelet counts at first symptoms were 1.3 x 10(9)/l and 25 x 10(9)/l. No patients had an infectious etiology by bronchoalveolar lavage. Six of the 19 patients had alveolar hemorrhage, which was significantly correlated with high neutrophil count. PERDS was directly implicated in four deaths (21%). Eleven patients received high-dose corticosteroid therapy, including five of the six who required mechanical ventilation. Ten of these patients experienced clinical improvement, which occurred within 24 h in five. The rapid response to corticosteroid treatment and the fact that such therapy was delayed until after intubation in all the mechanically ventilated cases point to a therapeutic benefit.     

Central venous catheter placement by an interventional radiology unit: An Australian experience

The aim of this retrospective study was to analyse the outcomes of central venous catheter (CVC) placement carried out by an interventional radiology unit. A review of our hospital records identified 331 consecutive patients who underwent insertion of a tunnelled or non‐tunnelled CVC between January 2000 and December 2004. Key outcome measures included the technical success rate of CVC insertion and the percentage of immediate (<24 h), early (24 h–30 days) and late (>30 days) complications. A total of 462 CVCs were placed under radiological guidance, with an overall success rate of 98.9%. Immediate complications included one pneumothorax, which was diagnosed 7 days after subclavian CVC insertion, and eight episodes of significant haematoma or bleeding within 24 h of CVC insertion. No cases were complicated by arterial puncture or air embolus. Catheter‐related sepsis occurred in 2% of non‐tunnelled CVC and 8.9% of tunnelled CVC. The overall incidence of catheter‐related sepsis was 0.17 per 100 catheter days. As the demand for chemotherapy and haemodialysis grows with our ageing population, interventional radiology suites are well placed to provide a safe and reliable service for the placement of central venous access devices.     

Tuberous sclerosis: A presentation of less‐commonly encountered stigmata

The protean manifestations of the tuberous sclerosis complex have lent this condition to extensive review in textbooks and in the medical literature. This condition generally presents by virtue of its neurological manifestations. Osseous stigmata, when encountered, are generally asymptomatic and do not require specific treatment owing to their benignity. We present the case of a young man with a slowly enlarging facial swelling for whom cosmetic surgery was considered. The swelling, present since childhood, had in time assumed disfiguring proportions. In what was hitherto considered an isolated facial deformity, a skull radiograph followed by CT revealed neurological stigmata of tuberous sclerosis. A large cerebellar hamartoma, proliferative soft tissue in the scalp adjacent to focal hyperostosis of the calvarium and the accompanying hemifacial changes seen in this patient constitute less commonly described features of tuberous sclerosis.