Multivariate modelling of responses to conditional items: New possibilities for latent class analysis

Questionnaire data may contain missing values because certain questions do not apply to all respondents. For instance, questions addressing particular attributes of a symptom, such as frequency, triggers or seasonality, are only applicable to those who have experienced the symptom, while for those who have not, responses to these items will be missing. This missing information does not fall into the category ‘missing by design’, rather the features of interest do not exist and cannot be measured regardless of survey design. Analysis of responses to such conditional items is therefore typically restricted to the subpopulation in which they apply. This article is concerned with joint multivariate modelling of responses to both unconditional and conditional items without restricting the analysis to this subpopulation. Such an approach is of interest when the distributions of both types of responses are thought to be determined by common parameters affecting the whole population. By integrating the conditional item structure into the model, inference can be based both on unconditional data from the entire population and on conditional data from subjects for whom they exist. This approach opens new possibilities for multivariate analysis of such data. We apply this approach to latent class modelling and provide an example using data on respiratory symptoms (wheeze and cough) in children. Conditional data structures such as that considered here are common in medical research settings and, although our focus is on latent class models, the approach can be applied to other multivariate models. Copyright © 2009 John Wiley & Sons, Ltd.     

Greater curve approach for laparoscopic gastric bypass: total stapler gastrojejunostomy

BACKGROUND: Gastric bypass is an established bariatric procedure that has undergone multiple modifications to improve its effectiveness. The side-to-side stapled technique is well recognized, but closure of the gastrotomy/enterotomy by the stapler can potentially narrow the Roux limb. Because of this, many surgeons will hand suture the closure of the gastrotomy/enterotomy. To obviate this difficulty, we inserted the linear stapler from the stomach's greater curvature, using a double-stapled anastomosis that minimized the need for hand suturing. METHODS: We performed a retrospective analysis of 307 patients undergoing this technique for laparoscopic gastric bypass. The weight loss and 30-day morbidity and mortality were tabulated and compared with those in other published series. RESULTS: Of the 307 patients, none died postoperatively. The overall 30-day morbidity rate was 15%. Two leaks from the gastrojejunostomy and 2 from the jejunojejunostomy (1.2%) developed. The mean percentage of excess weight loss was 34% at 3 months, 52% at 6 months, 73% at 1 year, 71% at 2 years, and 69% at 3 years. CONCLUSION: The greater curve approach avoids Roux limb obstruction, minimizes the need for hand suturing, and uses standard trocar incisions. Our short-term follow-up results are similar to those of series of other techniques.     

One‐ and two‐stage design proposals for a phase II trial comparing three active treatments with control using an ordered categorical endpoint

Phase II clinical trials are performed to investigate whether a novel treatment shows sufficient promise of efficacy to justify its evaluation in a subsequent definitive phase III trial, and they are often also used to select the dose to take forward. In this paper we discuss different design proposals for a phase II trial in which three active treatment doses and a placebo control are to be compared in terms of a single‐ordered categorical endpoint. The sample size requirements for one‐stage and two‐stage designs are derived, based on an approach similar to that of Dunnett. Detailed computations are prepared for an illustrative example concerning a study in stroke. Allowance for early stopping for futility is made. Simulations are used to verify that the specified type I error and power requirements are valid, despite certain approximations used in the derivation of sample size. The advantages and disadvantages of the different designs are discussed, and the scope for extending the approach to different forms of endpoint is considered. Copyright © 2008 John Wiley & Sons, Ltd.     

Measurement in clinical trials: A neglected issue for statisticians?

Biostatisticians have frequently uncritically accepted the measurements provided by their medical colleagues engaged in clinical research. Such measures often involve considerable loss of information. Particularly, unfortunate is the widespread use of the so‐called ‘responder analysis’, which may involve not only a loss of information through dichotomization, but also extravagant and unjustified causal inference regarding individual treatment effects at the patient level, and, increasingly, the use of the so‐called number needed to treat scale of measurement. Other problems involve inefficient use of baseline measurements, the use of covariates measured after the start of treatment, the interpretation of titrations and composite response measures. Many of these bad practices are becoming enshrined in the regulatory guidance to the pharmaceutical industry. We consider the losses involved in inappropriate measures and suggest that statisticians should pay more attention to this aspect of their work. Copyright © 2009 John Wiley & Sons, Ltd.     

Is the political system really related to health?

We analyze whether the political system and its stability are related to cross-country differences in health. We apply factor analysis on various national health indicators for a large sample of countries over the period 2000–2005 and use the outcomes of the factor analysis to construct two new health measures, i.e., the health of individuals and the quality of the health care sector. Using a cross-country structural equation model with various economic and demographic control variables, we examine the relationship between the type of regime and political stability on the one hand and health on the other. The political variables and the control variables are measured as averages over the period 1980–1999. Our results suggest that democracy has a positive relationship with the health of individuals, while regime instability has a negative relationship with the health of individuals. Government instability is negatively related to individual health via its link with the quality of the health care sector, while democracy is positively related with individual health through its link with income. Our main findings are confirmed by the results of a panel model and various sensitivity tests.     

Foot Polydactyly and Polysyndactyly: Genetic Implications in Two Families

The purpose of this study was to determine the genetic characteristics of foot polydactyly and identify its inheritance pattern by analyzing familial pedigree. Five cases from 2 Korean families were studied: 1 is a family whose members have been affected for 4 generations and the other for 2 generations. Using peripheral blood samples, we performed chromosomal analysis using the banding technique with Giemsa stain and karyotyping. We investigated the shape and structure of 46 chromosomes, looking for translation, deletion, inversion, ring chromosome, and isochromosome abnormalities. All peripheral blood samples demonstrated no chromosomal abnormalities, though the genetic nature of foot polydactyly and a new genetic locus was identified recently by other studies. Familial pedigree analysis suggested that polydactyly was inherited as an autosomal dominant trait in the first family. The mode of inheritance for the second family could not be determined due to an insufficient number of family members. The result of this study brought us to the conclusion that, while genetic factors play a major role in polydactyly, other factors may contribute to its occurrence.     

胃粘膜癌前病变的形态定量研究——胃粘膜核腺比值的定量分析

应用自动化图象分析仪对131个胃粘膜肠型病灶(单纯性肠化27个;异型增生:轻度30,中度35个,重度20个;肠型胃癌19个)进行定量分析。以单个腺管内细胞核总面积与细胞面积之比(ING)作为反映细胞核大小、数量及覆层排列程度的客观定量指标。结果发现:单纯性肠化(对照组)0.165±0.025,轻度异型增生0.21±0.023,中度异型增生0.259±0.026,重度异型增生0.32±0.028,分化型胃癌0.371±0.052,各组ING值呈正态,各组间的均值有非常显著的差异(P<0001)。因而,ING可作为胃粘膜癌前病变诊断的指标。     

Characterization of peptide components in the venom of the scorpion Liocheles australasiae (Hemiscorpiidae).

Scorpion venoms are composed of a number of neurotoxic peptides. A variety of toxins have been isolated from the venoms of scorpions of the family Buthidae, however, little interest has been paid to non-Buthidae scorpions. In this study, we examined the toxicity of the venom of Liocheles australasiae (Hemiscorpiidae) to mice and crickets, and characterized the peptide components by HPLC and mass spectrometry. Over 200 components were detected in the L. australasiae venom by LC/MS analysis, with components of molecular masses ranging from 500 to 5000 Da being particularly abundant. A number of peptides contained two to four disulfide bridges, which was estimated based on the mass difference after derivatization of Cys residues. A peptide having a monoisotopic molecular mass of 7781.6 Da and four disulfide bridges was isolated from the venom. The peptide has a primary structure similar in terms of the position of eight Cys residues to those observed in several peptides found from scorpions, ticks and insects, although biological roles of these peptides are unknown.     

Stereophotogrammetric measurement of the nasolabial fold in repose: a study of age and posture-related changes

The nasolabial fold is a significant facial landmark. Its size, shape, and symmetry are important in facial reanimation surgery, while effacement is an important goal in rejuvenation surgery. However, quantitative data for the nasolabial fold volume (NLFV) and depth is still unavailable. We present a new method of measurement using 3D color speckle stereophotogrammetry and its application in the assessment of NLFV. The VECTRA-3D system was validated to determine its minimum resolution and accuracy. Normal volunteers aged 13–84 years (n = 87) were imaged in repose. Mother–daughter pairs (n = 15, aged 13–61) were imaged in the upright and supine positions. All data were processed using custom software and analyzed by linear regression and nonparametric tests as appropriate. NLFV varied from 0.0026 to 0.2306 ml. There was significant correlation between NLFV and age (r = 0.7269, p < 0.0001). Men had significantly higher NLFV than women across all ages. There was no significant difference between the left and right NLFV. NLFV altered significantly from upright to supine in all subjects (p = 0.0012). However, the mothers increased their NLFV by 32% from supine to upright postures, which was a greater change than observed in their daughters. We have demonstrated a rapid, objective, and non-invasive assessment tool for facial reanimation and rejuvenation surgery. We have quantified the effects of age and posture on NLFV, and the efficacy and longevity of rejuvenation procedures are currently under investigation.