Analysis of medians under two-way model with and without interaction for Birnbaum-Saunders distributed response.

The Birnbaum-Saunders (BS) distribution, well-known as the fatigue-life distribution, has been used in numerous disciplines ranging from engineering to medical sciences. In this article, we develop a test for analysis of medians for BS distributed response to assess the impact of two interacting factors on the median, where no test is presently available. The proposed integrated likelihood ratio test (ILRT) eliminates the nuisance shape parameters by integrating them out. The second-order accurate asymptotic chi-square distribution of ILRT is derived. An in-depth simulation study strongly supports its excellent performance even under small group sizes. Furthermore, ILRT developed under the one-way model is found uniformly superior over its peers, is straightway extendable under general multiway setup, and has potential to be extended to other non-normal response variables. Its genuine need in industry, where non-normal responses are commonly encountered, is highlighted through analysis of three real data sets: ILRT strongly picked out the deposition time as influential factor in epitaxial layer experiment, revealed significant impact of spools on fiber life for the failure times of Kevlar 49 fiber data, and gave more accurate parameter estimates in delivery time data experiment, as assessed by various model adequacy tools, where its competitors failed to deliver desired results.

Association of hyperglycaemia with hospital mortality in nondiabetic COVID-19 patients: A cohort study.

OBJECTIVE: Diabetes is a known risk factor for mortality in Coronavirus disease 2019 (COVID-19) patients. Our objective was to identify prevalence of hyperglycaemia in COVID-19 patients with and without prior diabetes and quantify its association with COVID-19 disease course. RESEARCH DESIGN AND METHODS: This observational cohort study included all consecutive COVID-19 patients admitted to John H Stroger Jr. Hospital, Chicago, IL from March 15, 2020 to May 3, 2020 and followed till May 15, 2020. The primary outcome was hospital mortality, and the studied predictor was hyperglycaemia [any blood glucose ≥7.78 mmol/L (140 mg/dL) during hospitalization]. RESULTS: Of the 403 COVID-19 patients studied, 51 (12.7%) died; 335 (83.1%) were discharged while 17 (4%) were still in hospital. Hyperglycaemia occurred in 228 (56.6%) patients; 83 of these hyperglycaemic patients (36.4%) had no prior history of diabetes. Compared to the reference group no-diabetes/no-hyperglycaemia patients the no-diabetes/hyperglycaemia patients showed higher mortality [1.8% versus 20.5%, adjusted odds ratio 21.94 (95% confidence interval 4.04-119.0), P < 0.001]; improved prediction of death (P = 0.01) and faster progression to death (P < 0.01). Hyperglycaemia within the first 24 and 48 h was also significantly associated with mortality (odds ratio 2.15 and 3.31, respectively). CONCLUSIONS: Hyperglycaemia without prior diabetes was common (20.6% of hospitalized COVID-19 patients) and was associated with an increased risk of and faster progression to death. Development of hyperglycaemia in COVID-19 patients who do not have diabetes is an early indicator of progressive disease.

Therapy-related myeloid neoplasm after peptide receptor radionuclide therapy (PRRT) in 1631 patients from our 20 years of experiences: prognostic parameters and overall survival.

PURPOSE: To determine prognostic factors and overall survival (OS) in therapy-related myeloid neoplasm (t-MN) of patients after receiving peptide receptor radionuclide therapy (PRRT). METHODS: All patients treated from February 1999 until September 2019 at our center who had bone marrow biopsy-proven t-MN after PRRT were included. Patient characteristics, laboratory results, and all tumor-directed therapies before t-MN diagnosis were collected. Cox regression analysis was performed to identify parameters associated with OS. Receiver operating characteristic (ROC) curve analysis was used to define cutoff values as well as sensitivity and specificity of the parameters. RESULTS: Out of 1631 patients treated with PRRT, 30 patients developed t-MN comprising myelodysplastic syndrome (MDS) in 23 patients (77%) and acute myeloid leukemia (AML) in 7 patients (23%). The median OS of t-MN patients was 13 months (range 9.1-16.9 months): 6 months for AML and 15 months for the MDS subgroup, respectively. Higher platelet level was a significant prognostic parameter for longer OS (hazard ratio (HR): 0.99, P < 0.05). Using ROC analysis, the best cutoff value for thrombocyte count was 183.5 Gpt/L, resulting in a sensitivity of 92.3% and a specificity of 50%. Other factors, such as hemoglobin level, did not show a significant correlation with OS. CONCLUSION: Even rarely occurred, the OS is gravely compromised in t-MN patients after PRRT, and even less in the AML subgroup (6 months). Higher platelet value was a significant prognostic parameter for longer OS in t-MN patients.

An international survey evaluating factors influencing the use of total intravenous anaesthesia.

The purpose of this study was to evaluate factors influencing the use of propofol-based total intravenous anaesthesia (TIVA)since despite TIVA being a well-established technique, it is used far less frequently than volatile anaesthesia. Questions were formulated after reviewing the literature for perceived disadvantages of TIVA and meeting with a focus group consisting of both senior and junior anaesthestists from our department. Once the survey had been formulated, specialist anaesthetists from professional colleges and societies from several countries were invited to complete the survey on an electronic web-based platform to allow evaluation of the respondent's rating of the importance of a range of factors in their decision not to use TIVA for a particular case. Basic descriptive statistics were determined using SPSS statistical software, while graphical depictions of data were handled using R for statistical analysis. A total of 763 survey responses were included in the final analysis and stratified according to the frequency of TIVA use. Among the infrequent users, issues such as additional effort, institutional preference, lack of real-time monitoring of propofol concentration, risk of missing drug delivery failure and increased turnaround time were among the top reasons mentioned. Interestingly, these issues were considered far less important among the frequent users when not choosing TIVA. We concluded that frequent and infrequent users respond quite differently to similar technical TIVA-related factors. Non-technical factors may play an important role in the infrequent user's decision not to use TIVA for a particular case.

Two sample comparisons including zero-inflated continuous data: A parametric approach with applications to microarray experiment.

Micro-array experiments are important fields in molecular biology where zero values mixed with a continuous outcome are frequently encountered leading to a mixed distribution with a clump at zero. Comparison of two mixed populations, e.g. of a control and a treated group; of two groups with different types of cancer, to name a few, are often encountered in these contexts. Fairly skewed distribution of the continuous part coupled with small sample sizes are issues of main concern to be attended for the quality of inference in such situations while popularly used nonparametric methods rely on asymptotic distribution of the underlying test statistics which are valid only under large sample sizes. We address the aforementioned issues via a newly proposed exact test for location-scale family distributions and Generalized pivot quantity (GPQ) based parametric test procedures for non-location-scale distributions. Simulation based assessment showed their superior performance with respect to size and power in comparison to the popular two-part tests (Wilcoxon rank sum, t-test, Kolmogrov-Smirnov, Ansari-Bradley and Sigel-Tukey) more prominently for small sample sizes.

[Pulmonary neuroendocrine neoplasms]. / Neuroendokrine Neoplasien der Lunge.

The pulmonary neuroendocrine neoplasms originate from the enterochromaffin cells which are diffusely distributed in the body. The incidence of these tumors has increased significantly in recent decades due to the available diagnostics. They make up about 1-2% of all lung tumors and 20-30% of all neuroendocrine neoplasms. The current WHO classification from 2004 divides them into typical carcinoids (TC), atypical carcinoids (AC), large cell neuroendocrine carcinomas (LCNEC) and small cell carcinomas (SCLC). The major neuroendocrine biomarkers are chromogranin A, synaptophysin and CD56. TC have a low mitotic rate of <2 mitoses/2mm(2) (10 HPF), whereas the mitotic rate of the AC is 2-10 mitoses/2 mm(2) (10 HPF). The Ki-67 staining is helpful to distinguish typical and atypical carcinoids from the highly malignant LCNEC and SCLC. Clinically, the patient presents usually with cough, hemoptysis or bronchial obstruction. The occurrence of a carcinoid or Cushing's syndrome and a tumor-associated acromegaly are rare. Surgical resection with radical lymph node dissection is the treatment of choice for achieving long-term survival. Endoscopic resection of the endobronchial tumor growth is a good alternative for inoperable endobronchially localized tumors. Peptide receptor radionuclide therapy (PRRT) is a promising treatment option for patients with metastatic or unresectable pulmonary neuroendocrine tumors. New targeted therapies using angiogenesis inhibitors, mTOR inhibitors, and tyrosine kinase inhibitors are being tested for their effectiveness in many previous studies. Typical carcinoid tumors metastasize less frequently than AC, the 5-year survival rate of patients with TC being over 90%. Patients with AC have a 5-year survival rate between 35% and 87%. The highly malignant LCNEC and SCLC, on the other hand, have a 5-year survival rate between 15% and 57%, and <5% respectively. The increasing number of therapeutic options and diagnostic procedures requires a multidisciplinary approach and decision-making in multidisciplinary tumor conferences to ensure a personalized treatment approach. Therefore patients with a neuroendocrine neoplasm of the lung should be treated in specialized centers.

[The relevance of PET/CT for the surgical management of neuroendocrine neoplasms]. / Bedeutung der PET/CT für die Chirurgie neuroendokriner Neoplasien.

Neuroendocrine neoplasms (NEN) are rare malignancies with a wide spectrum of metastatic potential which originate from the endocrine cells of the body and express somatostatin receptors. The (68)gallium somatostatin receptor positron emission tomography-computed tomography (PET/CT) technique is the most sensitive method of assessment of well-differentiated NENs and for the detection of cancer of unknown primary (CUP syndrome) NENs. Imaging with 18F-fluorodeoxyglucose (18F-FDG PET/CT) is indicated in poorly differentiated neuroendocrine carcinomas. The receptor-dependent imaging of NENs has a decisive impact on further management.

Waist circumference is genetically correlated with incident Type 2 diabetes in Mexican-American families.

AIMS: We aimed to determine the genetic and environmental correlation between various anthropometric indexes and incident Type 2 diabetes with a focus on waist circumference. METHODS: We used the data on extended Mexican-American families (808 subjects, 7617.92 person-years follow-up) from the San Antonio Family Heart Study and estimated the genetic and environmental correlations of 16 anthropometric indexes with the genetic liability of incident Type 2 diabetes. We performed bivariate trait analyses using the solar software package. RESULTS: All 16 anthropometric indexes were significantly heritable (range of heritabilities 0.24-0.99). Thirteen indexes were found to have significant environmental correlation with the liability of incident Type 2 diabetes. In contrast, only anthropometric indexes consisting of waist circumference (waist circumference, waist-hip ratio and waist-height ratio) were significantly genetically correlated (genetic correlation coefficients: 0.45, 0.55 and 0.44, respectively) with the liability of incident Type 2 diabetes. We did not observe such a correlation for BMI. CONCLUSIONS: Waist circumference as a predictor of future Type 2 diabetes is supported by the finding that they share common genetic influences.

Efficacy trial of Camouflage Syringe to reduce dental fear and anxiety.

AIM: Dental fear and anxiety in early childhood are widely prevalent and contribute to dental problems and behaviour in adulthood. Novel ways to reduce dental fear and anxiety in children are needed. Our aim was to conduct an efficacy trial of a novel Camouflage Syringe to reduce dental fear and anxiety in children. STUDY DESIGN: randomised controlled trial of efficacy of the Camouflage Syringe. We designed a Camouflage Syringe with a toy-like appearance that veils the conventional syringe to permit topical application and injection of local anaesthesia and ensure more involvement of the patient in the treatment process. We conducted a concurrent parallel, randomised controlled trial (NCT01398007) on the efficacy of this Camouflage Syringe to reduce the dental fear and anxiety in children seeking dental treatment who required the use of local anaesthesia. RESULTS: Using Venham's clinical rating scale, Venham's picture test, parental stress questionnaire and recall questionnaire, the efficacy of the Camouflage Syringe to reduce dental fear and anxiety ranged from 82% to 97% for various outcomes and from 60% to 100% for prevention of related adverse outcomes. For all outcomes, the number needed to treat was close to unity. CONCLUSION: Our results strongly favour the use of Camouflage Syringe to reduce dental fear and anxiety in children.

Efficiency and mechanism of intracellular paclitaxel delivery by novel nanopolymer-based tumor-targetes delivery system, Nanoxel

INTRODUCTION: An increasing research interest has been directed toward nanoparticle-based drug delivery systems for their advantages. The appropriate amalgamation of pH sensitivity and tumor targeting is a promising strategy to fabricate drug delivery systems with high efficiency, high selectivity and low toxicity. MATERIALS AND METHODS: A novel pH sensitive Cremophor-free paclitaxel formulation, Nanoxel(TM), was developed in which the drug is delivered as nanomicelles using a polymeric carrier that specifically targets tumors. The efficiency and mechanism of intracellular paclitaxel delivery by Nanoxel(TM) was compared with two other commercially available paclitaxel formulations: Abraxane(TM) and Intaxel(TM), using different cell lines representing target cancers [breast, ovary and non-small cell lung carcinoma (NSCLC)] by transmission electron microscopy and quantitative intracellular paclitaxel measurements by high performance liquid chromatography. RESULTS: The data obtained from the present study revealed that the uptake of nanoparticle-based formulations Nanoxel(TM) and Abraxane(TM) is mediated by the process of endocytosis and the uptake of paclitaxel was remarkably superior to Intaxel(TM) in all cell lines tested. Moreover, the intracellular uptake of paclitaxel in Nanoxel(TM)- and Abraxane(TM)-treated groups was comparable. Hence, the nanoparticle-based formulations of paclitaxel (Nanoxel(TM) and Abraxane(TM)) are endowed with higher efficiency to deliver the drug to target cells as compared to the conventional Cremophor-based formulation. CONCLUSION: Nanoxel(TM) appears to be of great promise in tumor targeting and may provide an advantage for paclitaxel delivery into cancer cells (AU)

Vandetanib therapy in medullary thyroid cancer.

The U.S. Food and Drug Administration (FDA) approved vandetanib in April 2011 for the treatment of unresectable, locally advanced or metastatic medullary thyroid cancer (MTC). In Europe it was approved in March 2012, but only for the treatment of aggressive and symptomatic MTC. This small molecule is a tyrosine kinase inhibitor of several growth factors involved in cellular proliferation and angiogenesis, including the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor receptors 2 and 3 (VEGFR-2, VEGFR-3). In addition, vandetanib is an inhibitor of the RET (rearranged during transfection) gene, a proto-oncogene often mutated in familial MTC. Since MTC is a rare disease, for which no previous medical therapies are approved, vandetanib is the first drug shown to be effective in a large phase III trial treating patients with metastatic or locally advanced MTC. Common adverse events are diarrhea, nausea, hypertension, headache and QT prolongation that are manageable and are commonly outweighed by the benefits of vandetanib in terms of delaying disease progression and inducing tumor response.

Even partial reduction of biomass fuel use may improve the respiratory health of rural women in Central India.

Routine use of biomass fuels in cooking adversely affects respiratory health, but whether partial abolition of the biomass use is also detrimental is unknown. We conducted a cross-sectional study of 760 women in rural central India: 283 used non-biomass fuels (Group A), 225 biomass and other fuels (Group B), while 252 exclusively used biomass fuels (Group C). Robust multivariate analyses adjusted for age, daily cooking time, cooking experience, marital status, overcrowding and education showed that only Group C, and not Group B, had poor respiratory health. Our results indicate that even partial abolition of biomass use may be beneficial.

Bilateral optic neuritis due to isoniazid (INH).

Optic nerve involvement is a rare side effect of isoniazid (INH) and has not been described in children. We describe this adverse reaction in a 10-year-old boy, who was treated for tuberculous meningitis. The patient showed almost complete resolution following withdrawal of INH and administration of pyridoxine and steroids.

Bone recovery after zoledronate therapy in thalassemia-induced osteoporosis: a meta-analysis and systematic review.

UNLABELLED: Zoledronate is a promising bisphosphonate that improves the bone mineral density by 0.69 standard deviations in thalassemia-induced osteoporosis, but the entire range of its actions and side effects is currently not fully understood. INTRODUCTION: Zoledronate is a promising bisphosphonate for the treatment of thalassemia-induced osteoporosis; however, a quantitative summary of its beneficial effect and its effects on the markers of bone turnover are not established. METHODS: We conducted a meta-analysis of the published randomized controlled trials using standardized mean difference and a random effects model for improvement in bone mineral density (BMD). We also conducted a systematic review for the influence of zoledronate on markers of bone turnover and bone pain. RESULTS: We found that zoledronate improves the baseline BMD by 0.69 (95% confidence interval 0.47-0.90) standard deviations-an effect that was more pronounced when BMD was measured at the lumbar spine. However, the mechanistic interpretations of the effects on the markers of bone turnover are not completely clear. CONCLUSION: Sufficient evidence exists to demonstrate that 4 mg zoledronate given every 3 months markedly improves the BMD; however, more qualitative and quantitative evidence is required to understand the mechanisms of its action and the potential side effects.

A new method for interval estimation of the mean of the Gamma distribution.

The two parameter Gamma distribution is widely used for modeling lifetime distributions in reliability theory. There is much literature on the inference on the individual parameters of the Gamma distribution, namely the shape parameter k and the scale parameter theta when the other parameter is known. However, usually the reliability professionals have a major interest in making statistical inference about the mean lifetime mu, which equals the product thetak for the Gamma distribution. The problem of inference on the mean mu when both parameters theta and k are unknown has been less attended in the literature for the Gamma distribution. In this paper we review the existing methods for interval estimation of mu. A comparative study in this paper indicates that the existing methods are either too approximate and yield less reliable confidence intervals or are computationally quite complicated and need advanced computing facilities. We propose a new simple method for interval estimation of the Gamma mean and compare its performance with the existing methods. The comparative study showed that the newly proposed computationally simple optimum power normal approximation method works best even for small sample sizes.