Latent class models for medical diagnostic tests in multicenter trials

Medical diagnostic tests must enjoy appropriate validity and high reliability in order to qualify as adequate assessment tools. Without a gold standard test, available medical diagnostic tests are not perfect; hence, the reliability of such tests must be evaluated precisely. Kappa coefficient statistics are often utilized to assess reliability of tests when there are two or more medical diagnostic tests. However, the statistics are imprecise for a typical case when the prevalence rate of a target disease is unknown. Although latent class models could be used to assess reliability, the models cannot estimate reliability in the case of two tests, due to unidentifiability or the lack of degrees of freedom. An alternative approach to assess reliability for the case of two tests is stratifying a two‐by‐two contingency table under the assumption that sensitivities and specificities between the two tests be equal over all strata and that prevalence rates in the strata be different from each other. Because stratification is basically a multi‐sample analysis, it should not be applied to the situation where subsamples (i.e., centers) are randomly selected from a larger population. In this article, a type of mixed‐effect model is proposed to evaluate the reliability of two tests for trials in randomly selected multiple centers. Several types of distributions for prevalence rates over subpopulations are considered. Simulation studies show that our proposed method performs nicely. Analysis of real data is also reported. Copyright © 2013 John Wiley & Sons, Ltd.     

Associations of coffee consumption with circulating level of adiponectin and leptin. A meta-analysis of observational studies

Abstract

The association between coffee consumption and the circulating level of adiponectin and leptin has been evaluated in several epidemiological studies with conflicting results. Therefore, the aim of this study was to examine the associations of coffee consumption with the circulating level of adiponectin and leptin. A comprehensive literature search up to January 2018, using PUBMED, EMBASE and Web of Science databases, was conducted to identify the relevant observational studies that examined the associations of coffee consumption with the circulating level of adiponectin and leptin. A total of twelve cross-sectional studies were included in this meta-analysis. According to the combined standard mean difference (SMD) between the highest and the lowest coffee intake category, coffee consumption was associated with a higher circulating adiponectin level (SMD?=?0.11, 95%CI: 0.06–0.17; P?<?.001). Subgroup analysis confirmed such findings in females (SMD?=?0.11, 95%CI: 0.02–0.20; P?=?.01), but not in males (SMD?=?0.03, 95%CI: ?0.08 to 0.14; P?=?.59). In addition, the combined SMD showed that coffee consumption was negatively associated with the circulating level of leptin (SMD?=??0.19, 95%CI: ?0.28 to ?0.10; P?<?.001). The results of this meta-analysis suggested that coffee consumption was associated with a higher circulating level of adiponectin. Additionally, we showed that coffee consumption was inversely associated with the circulating level of leptin. More well-designed prospective cohort studies and randomised controlled trials are needed to further elaborate the concerned issues.     

Graptopetalum paraguayense and resveratrol ameliorates carboxymethyllysine (CML)-induced pancreas dysfunction and hyperglycemia

Hyperglycemia is associated with advanced glycation end products (AGEs). Recently, AGEs were found to cause pancreatic damage, oxidative stress, and hyperglycemia through the AGE receptor. Carboxymethyllysine (CML) is an AGE but whether it induces pancreatic dysfunction remains unclear. Graptopetalum paraguayense, a vegetable consumed in Taiwan, has been used in folk medicine and is an antioxidant that protects against liver damage. We investigated the protective properties of G. paraguayense 95% ethanol extracts (GPEs) against CML-induced pancreatic damage. The results indicated that resveratrol, GPE, and gallic acid (the active compound of GPE) increased insulin synthesis via upregulation of pancreatic peroxisome proliferator activated-receptor-γ (PPARγ) and pancreatic-duodenal homeobox-1 (PDX-1) but inhibited the expression of CML-mediated CCAAT/enhancer binding protein-β (C/EBPβ), a negative regulator of insulin production. Moreover, resveratrol and GPE also strongly activated nuclear factor-erythroid 2-related factor 2 (Nrf2) to attenuate oxidative stress and improve insulin sensitivity in the liver and muscle of CML-injected C57BL/6 mice and resulted in reduced blood glucose levels. Taken together, these findings suggested that GPE and gallic acid could potentially be used as a food supplement to protect against pancreatic damage and the development of diabetes.     

Kidney Function in Heart Failure

Objective. The purpose of this investigation was to improve a rankit ordinal model for evaluating and validating dichotomized tests in a prospective Nordic project. Material and methods. The model is based on the assumption that the S‐shaped curve of fractions of positive for increasing concentrations can be de‐convoluted to a histogram and thereby used to calculate the parameters for a ln‐Gaussian distribution. In a Nordic survey, four urine samples with known concentrations of hCG (human chorionic gonadotrophin) and nitrites were distributed to more than 2500 practitioners' offices. Results. The results are presented as parameters (geometric mean and CV) for the components urine‐hCG and urine‐nitrites, together with fractions of positive for clinical critical values (5 and 40?IU/L for hCG), for which fractions should be below 0.01 and above 0.99, respectively, and 7?µmol/L for nitrites. Furthermore, the concentration intervals of varying fractions of positive from 0.01 to 0.99 are estimated as grey zones. The parameters and grey zones for different kits are compared. No urine‐hCG kit fulfilled the low clinical criterion, whereas all fulfilled the high criterion. Seven of the eight nitrites kits had fractions of positive above 0.9 for the company confirmation limit, but varying fractions for the clinically important limit of 7?µmol/L (fractions from 0.06 to 0.83). Conclusions. The present model makes it easy to estimate parameters for the kits, and also to estimate the fractions of measured positives for specified concentrations. It is thus suited for external quality assessment as well as for manufacturers' method validation.     

Insulin sensitivity (Si) assessment in lean and overweight subjects using two different protocols and updated software

Abstract

Background. The standard frequently-sampled intravenous glucose tolerance test (FSIVGTT) is an alternative procedure to the clamp technique for estimating the insulin sensitivity (Si) parameter. The goal of this study was to compare Si in lean and overweight individuals in addition to assessing intra-individual reproducibility using two different protocols and updated software. Methods. FSIVGTT was carried out in 14 lean (BMI ≤ 25 kg/m²) and 14 overweight (BMI>25 kg/m²) subjects using two different protocols; full (29 samples) and short (12 samples). For reproducibility assessment four normal subjects (triplicate on three and twice on one) were recruited to undergo the same procedure at 1-week intervals. Data analysis was performed using COMAL and Minmod Millennium software. Results. Mean Si (10^?4min^?1[pmol/l]^?1) values were significantly different between lean and overweight subjects (p < 0.001) but not between the two protocols using both software packages. For the full and short protocols, Si values were more closely related in lean versus overweight subjects using either COMAL (r = 0.98, p < 0.001), (r = 0.89, p < 0.001) or Minmod Millennium (r = 0.99, p < 0.001), (r = 0.85, p < 0.001) software respectively. The intra-individual reproducibility (%CV) of Si (COMAL) in full versus short protocol was 18.3 ± 11.1% and 13.7 ± 1.9% respectively. Reproducibility values for Si (Minmod Millenium) in full versus short protocols were 14.3 ± 3.8 and 14.9 ± 1.9% respectively. Conclusions. Si can be assessed accurately by a short protocol FSIVGTT in normal individuals. The short protocol may give less acceptable results for insulin sensitivity in individuals who have normal glucose tolerance but high BMI.     

Incidence of diabetes and serum adipokines in Catalonian men. The ADIPOCAT study

Aims. To investigate the relationship of body mass index and serum adipokines with incidence of diabetes in men. Material and methods. Ten-year cohort study of a random population sample of 1011 men aged 35–69 years from the MONICA-Catalonia survey (1986–1988). WHO-MONICA protocol and the US Hispanic NHANES diabetes questionnaire were applied. Fasting serum glucose and lipids were measured by enzymatic methods, adipokines and insulin by Luminex xMAP technology,and hs-CRP by nephelometry in stored baseline samples (–80°C). Type2 diabetes was defined as fasting glucose ≥?7.0 mmol/L or diagnosed diabetes. Incident diabetes was defined as absence of these criteria at baseline but presence at re-examination. Cox regression analysis was used. Results. Incidence of diabetes (n =?85) was 10.3/1000 person-years, increasing significantly with BMI but decreasing by quartiles of adiponectin. Incidence increased above median BMI and glucose (45.3/1000 person-years, OR =?19.97). Log-adiponectin associated with reduced risk of diabetes after multivariate adjustment (HR =?0.24, 95% CI 0.08–0.72), with significant modification of this effect by baseline glycaemia. C-reactive protein was not a significant factor. Leptin lost strength when adjusted for BMI. Conclusions. In a population with relatively high diabetes incidence, BMI and glucose were strong risk factors, while adiponectin protected against diabetes, especially in men with high glycaemic level.     

Ensuring cultural sensitivity for Muslim patients in the Australian ICU: Considerations for care

Australia is a diverse and multicultural nation, made up of a population with a predominant Christian faith. Islam, the second largest religion in the world, has demonstrated significant growth in Australia in the last decade. Coming from various countries of origin and cultural backgrounds, Muslim beliefs can range from what is considered ‘traditional’ to very ‘liberal’.It is neither possible nor practical for every intensive care clinician to have an intimate understanding of Islam and Muslim practices, and cultural variations amongst Muslims will mean that not all beliefs/practices will be applicable to all Muslims. However, being open and flexible in the way that care is provided and respectful of the needs of Muslim patients and their families is essential to providing culturally sensitive care.This discussion paper aims to describe the Islamic faith in terms of Islamic teachings, beliefs and common practices, considering how this impacts upon the perception of illness, the family unit and how it functions, decision-making and care preferences, particularly at the end of life in the intensive care unit.     

Hormone-based therapies in the regulation of fuel metabolism and body weight

Background: The integrated central actions of hormones secreted from pancreatic islets, the gut and adipocytes regulate both energy homeostasis and body weight. Dysregulation in these neurohormonal pathways probably contributes to pathogenesis of obesity and type 2 diabetes. Objective: To examine hormone-based therapies targeting these interrelated pathways as potential treatments for obesity and diabetes. Methods: Preclinical and clinical data on therapies based on hormones secreted from the pancreas (glucagon, insulin, amylin and pancreatic polypeptide), gut (glucagon-like peptide-1, glucose dependent insulinotropic polypeptide, cholecystokinin and peptide YY) and adipose tissue (leptin and adiponectin) as potential treatments for diabetes and obesity are reviewed. Results/conclusions: In diabetes, hormone-based treatments have translated into new clinical platforms including insulin analogs, the GLP-1-like peptide receptor agonist exenatide and amylinomimetic pramlintide, which due to their complex interplay and the progressive nature of diabetes, can be utilized in different settings. Various peptide hormones and agonists/antagonists are currently under investigation as new approaches to treatment of obesity and diabetes.     

Impaired laryngopharyngeal sensitivity in patients with COPD: The association with swallow function

Abstract

Research indicates that patients with Chronic Obstructive Pulmonary Disease (COPD) have increased aspiration risk. Several factors may pre-dispose a patient to aspiration including a reduction in laryngopharyngeal sensitivity (LPS). Reduced LPS has been associated with increased aspiration risk in pathologies including stroke; however, this has not been examined in COPD. This study aims to explore possible associations between LPS and swallowing function in COPD patients, and determine whether a LPS predictive value may be used as a method of evaluating dysphagia risk in this patient population. Twenty participants with COPD underwent LPS discrimination testing, respiratory function testing, self-reporting swallowing questionnaire, clinical swallowing examination, and fibre-optic endoscopic evaluation of swallowing (FEES). Participants with COPD demonstrated impaired LPS defined by elevated laryngeal adductor reflex thresholds and high incidence of pharyngeal residue on FEES. Positive correlations were identified between their clinical swallowing examination and FEES results for the presence of laryngeal penetration/aspiration (p < 0.04), vallecular residue (p < 0.01), and piriform residue (p < 0.01). In conclusion, COPD patients have reduced laryngopharyngeal mechanosensitivity and impaired swallowing function characterized primarily by pharyngeal stasis. The combination of these deficits may place patients with COPD at increased aspiration risk due to lack of detection of pharyngeal residue and subsequent inhalation of pharyngeal contents.     

超敏C反应蛋白在健康体检中的意义

[目的]探讨超敏C反应蛋白（HS-CRP）作为心、脑血管疾病的常规筛查指标,在正常人群健康体检中的意义。[方法]选取本院健康体检者310例,排除能引起C反应蛋白升高的炎性疾病,在OlympusAU2700全自动生化分析仪上,用乳胶增强免疫透射比浊法测定血清中的HS-CRP,同步测定血清总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）等4项血脂指标,并进行对比分析。[结果]单纯血脂检测,高脂血症者108例,心、脑血管疾病危险因素的检出率为34.8%;单纯HS-CRP检测,升高者86例,检出率27.7%;血脂与HS-CRP同时检测,异常者145例,检出率46.7%。血脂、HS-CRP单独检测与两者同时检测比较,P值均〈0.01,差异具有非常显著性意义。[结论]HS-CRP与血脂同时检测,能筛查出30%~40%用常规血脂检测未发现的具有心、脑血管疾病的潜在危险者。HS-CRP在心、脑血管疾病预测中具有重要价值。应作为血脂的补充检测指标,用于健康人群体检中,以提高心、脑血管疾病的预报率。