Treatment sequence network meta-analysis in Crohn’s disease: a methodological case study

Objective: Several biologic therapies are available for the treatment of mild-to-moderate Crohn’s disease (CD). This network meta-analysis (NMA) aimed to assess the comparative efficacy of ustekinumab, adalimumab, vedolizumab and infliximab in the maintenance of clinical response and remission after 1?year of treatment.

Methods: A systematic literature search was performed to identify relevant randomized controlled trials (RCTs). Key outcomes of interest were clinical response (CD activity index [CDAI] reduction of 100 points; CDAI-100) and remission (CDAI score under 150 points; CDAI < 150). A treatment sequence Bayesian NMA was conducted to account for the re-randomization of patients based on different clinical definitions, the lack of similarity of the common comparator for each trial and the full treatment pathway from the induction phase onwards.

Results: Thirteen RCTs were identified. Ustekinumab 90?mg q8w was associated with statistically significant improvement in clinical response relative to placebo and vedolizumab 300?mg. For clinical remission, ustekinumab 90?mg q8w was associated with statistically significant improvement relative to placebo and vedolizumab 300?mg q8w. Findings from sub-population analyses had similar results but were not statistically significant.

Conclusions: The NMA suggest that ustekinumab is associated with the highest likelihood of reaching response or remission at 1?year compared with placebo, adalimumab and vedolizumab. Results should be interpreted with caution because this is a novel methodology; however, the treatment sequence analysis may be the most methodologically sound analysis to derive estimates of comparative efficacy in CD in the absence of head-to-head evidence.     

Older age is an adverse prognostic factor in stage I, favorable histology Wilms' tumor treated with vincristine monochemotherapy: a study by the United Kingdom Children's Cancer Study Group, Wilm's Tumor Working Group.

PURPOSE: To identify clinical prognostic factors in children with stage I, favorable histology (FH) Wilms' tumor treated with vincristine monochemotherapy after immediate nephrectomy to define subgroups for consideration of further reduction in treatment intensity. PATIENTS AND METHODS: During two consecutive trials of the United Kingdom Children's Cancer Study Group (UKW2 and UKW3, 1986 to 2001), 242 children with stage I FH Wilms' tumor were treated with immediate nephrectomy followed by 10 weekly injections of vincristine 1.5 mg/m2. Event-free survival (EFS) and overall survival (OS) were compared by age group. RESULTS: The 4-year EFS rate was 93.2%, 87.2%, and 71.3% for children less than 2 years old, 2 to 4 years old, and 4 years old or older at diagnosis, respectively (log-rank, P =.001); the corresponding 4-year OS rate was 98.1%, 95.0%, and 87.2% (log-rank, P =.01). There were no toxicity- or procedure-related deaths. In multivariate analysis, specimen weight was not of independent prognostic value (P =.66). Among the 186 children younger than 4 years at diagnosis, there were 17 relapses and five deaths, compared with 16 relapses and eight deaths among the 56 children at least 4 years old at diagnosis. OS after relapse was surprisingly poor (61.6% at 4 years). CONCLUSION: Treatment for stage I FH Wilms' tumor is generally successful using vincristine monotherapy after immediate nephrectomy, and therefore, the risks of dactinomycin hepatopathy can be avoided. However, age at least 4 years is a significant adverse prognostic factor. This treatment schedule should be considered in any trial of treatment reduction in very young children with stage I FH Wilms' tumor, regardless of tumor size, and we suggest that the upper age limit for the reduced therapy be set at 4 years.     

Measurements of Blood Pressure, Oedema and Proteinuria in a Pregnant Population of New Zealand

Summary: This is the first report of the largest study of blood pressure measurement in pregnancy in a New Zealand population using standardized definitions and methodology. Over 3,800 women who delivered in an 8-month period in the Wellington region were included in the study. Blood pressure measurement and the presence of oedema and proteinuria were recorded from booking until delivery and in the puerperium. Only 2.7% of women were unable to be contacted after delivery for details on outcomes. The results established normal ranges for blood pressure throughout pregnancy. The data show that Mood pressure greater than 140/90 until 35 weeks' gestation is outside 2 standard deviations at all gestations and justifies using these measurements as the definition of hypertension in pregnancy. The fall in blood pressure in the 2nd trimester was less than 1 mm Ffg per week in both the systolic and diastolic pressures. This fall was smaller than previously recorded in other studies. Gestational hypertension was the commonest blood pressure abnormality occurring in 15.2% of the population. This represented 69% of the pregnant women with a hypertensive disorder. The overall incidence of both gestational hypertension and preeclampsia was 18.5% which is higher than reported in other parts of the world. In this study obesity was significantly associated with hypertensive disorders in pregnancy. An arm circumference of >33 cm, one of the measurements of obesity, was found in 6.8% of the study population. Even after the effect of arm circumference was taken into account, hypertensive disorders were also more common in Pacific Island women. Ankle oedema was significantly associated with the development of both gestational hypertension and preeclampsia but the incidence of oedema was noted in only 11.9% of the subjects.     

Statistical analysis of clinical, radiographic, and histologic features of temporomandibular arthropathy

For a variety of reasons, the past few years have brought about a tremendous emphasis on conditions affecting the temporomandibular joint and associated structures. Although important advances are being made relative to the diagnosis and treatment of these conditions, a myriad of problems remain for the practitioner who tries to sort through the literature or who attends courses in order to determine a means for properly diagnosing and treating these patients. This article attempts to develop correlations between certain clinical and radiographic findings documented by histologic evaluation as a beginning guide to more sound diagnosis.     

Perfusion imaging

The term perfusion has varied connotations in different situations. The word perfusion comes from the Latin to pour or diffuse through or over. Myocardial perfusion depends on (a) coronary artery or vessel flow, and (b) myocardial or muscle flow. The factors which determine perfusion at rest and during stress in coronary vessels and within the myocardium are clearly related but not with a predictable linear relationship. In animals there is extensive literature concerning the regulation of coronary flow and perfusion obtained by many sophisticated methods. In contrast, the techniques that are applicable to humans are relatively crude. To date, the clinical data available suggests that the normal control of coronary flow in man and in dogs is fairly similar but that models of pathology in animals bear little relation to the compensatory changes found in the coronary circulation in man. Although the data available is limited and subject to many technical inaccuracies, this article is confined to the assessment of myocardial perfusion in clinical practice.     

Retroperitoneal Laparoscopic Nephrectomy in Children

Retroperitoneal pediatric laparoscopic nephrectomy is described in 3 patients requiring 3 to 5 hours with an estimated blood loss of 10 to 60 cc. The children returned to school within 7 days postoperatively. Advantages of this procedure include the avoidance of intraoperative repositioning of the patient and easy conversion to an open lumbodorsal approach, if necessary; early laparoscopic visualization of the renal artery; applicability in cases of previous abdominal surgery, and avoidance of intraperitoneal adhesion.     

Fine needle aspiration cytology: an in vitro study of cell yield

To investigate the effect of needle size and number of passes into a tumour mass on the cell yield from a fine needle aspirate, an in vitro study was undertaken in 19 consecutive tumours removed surgically for biopsy. Different needle sizes (23G, 21G, 19G) passed in random order, five, ten and fifteen times into the tumours, were compared. The type of tumour, needle size and number of passes independently and significantly influenced cell yield. A 21G(green) needle passed into the tumour at least 10 times was the most efficient in obtaining cells. This in vitro study could explain the variation in the reported accuracy of fine needle aspiration cytology from groups using different techniques and is perhaps one reason why the highest diagnostic accuracy and the lowest rate of unsatisfactory aspirates comes from a centre which uses a 21G needle and at least 10 passes through the tumour.     

Rediscovery and redefinition of Malcolm Smith's Trimeresurus kanburiensis in Thailand, with a report of envenoming.

Three specimens of an apparently rare pit viper, Trimeresurus kanburiensis, previously known only from the holotype collected in 1928, were found near Kanchanaburi in western Thailand. One of the snakes had bitten a young woman on the foot. She experienced severe local pain, swelling that involved the whole of the bitten limb and beyond, local bruising, recurrent shock, peripheral leucocytosis and a mild coagulopathy, but she recovered despite the lack of specific treatment. The severity of envenoming augurs ill for a young or debilitated patient bitten by this species. During the last 20 years, the name T. kanburiensis has been used incorrectly for the medically more important species, T. purpureomaculatus. Conversely, the name T. purpureomaculatus has been misapplied to specimens of a species of viper from southern Thailand which we consider very similar to T. kanburiensis, but for which a new specific name, 'T. venustus', has been suggested recently. The rediscovery and redefinition of T. kanburiensis should prevent further confusion.