Sample Size Requirements for Calibrated Approximate Credible Intervals for Proportions in Clinical Trials

In Bayesian analysis of clinical trials data, credible intervals are widely used for inference on unknown parameters of interest, such as treatment effects or differences in treatments effects. Highest Posterior Density (HPD) sets are often used because they guarantee the shortest length. In most of standard problems, closed-form expressions for exact HPD intervals do not exist, but they are available for intervals based on the normal approximation of the posterior distribution. For small sample sizes, approximate intervals may be not calibrated in terms of posterior probability, but for increasing sample sizes their posterior probability tends to the correct credible level and they become closer and closer to exact sets. The article proposes a predictive analysis to select appropriate sample sizes needed to have approximate intervals calibrated at a pre-specified level. Examples are given for interval estimation of proportions and log-odds

Bayesian Set Estimation with Alternative Loss Functions: Optimality and Regret Analysis

Decision-theoretic interval estimation requires the use of loss functions that, typically, take into account the size and the coverage of the sets. We here consider the class of monotone loss functions that, under quite general conditions, guarantee Bayesian optimality of highest posterior probability sets. We focus on three specific families of monotone losses, namely the linear, the exponential and the rational losses whose difference consists in the way the sizes of the sets are penalized. Within the standard yet important set-up of a normal model we propose: 1) an optimality analysis, to compare the solutions yielded by the alternative classes of losses; 2) a regret analysis, to evaluate the additional loss of standard non-optimal intervals of fixed credibility. The article uses an application to a clinical trial as an illustrative example

On the predictive performance of a non-optimal action in hypothesis testing

In Bayesian decision theory, the performance of an action is measured by its pos- terior expected loss. In some cases it may be convenient/necessary to use a non- optimal decision instead of the optimal one. In these cases it is important to quantify the additional loss we incur and evaluate whether to use the non-optimal decision or not. In this article we study the predictive probability distribution of a relative measure of the additional loss and its use to define sample size determination criteria in a general testing set-up

Marked efficacy of Rituximab in multifocal motor neuropathy associated with chronic lymphocytic leukemia

The authors describe a patient who presented a multifocal motor neuropathy (MMN) associated with a high anti-ganglioside antibody (anti-GM1 and anti-GD1) titer at the clinical onset of a B-cell chronic lymphocytic leukemia (B-CLL). Immunomodulation (IVIg plus cyclosporine) resulted in a neurological improvement and reduced anti-ganglioside antibody titers, both of which remained stable for at least six years. After this period, the patient had a severe relapse of the neuropathy, which was independent of the clinical course of the B-CLL. Both IVIg and cyclophosphamide were ineffective, and the patient became tetraplegic within six months; in the meantime, the patient displayed an increased antiganglioside antibody titer. Treatment with rituximab (RTX), which is designed to selectively inhibit B cell function, resulted in a dramatic, prompt and long-lasting neurological improvement as well as a reduced anti-ganglioside antibody titer. Although there are no previous reports of MMN in patients with B-CLL, the efficacy of RTX in the treatment of MMN in this patient may be considered remarkable. The expansion of B-cell clones may be a prerequisite for RTX effectiveness in MMN, and in dysimmune neuropathies in general

Marked efficacy of rituximab in multifocal motor neuropathy associated with chronic lymphocytic leukemia

The authors describe a patient who presented a multifocal motor neuropathy (MMN) associated with a high anti-ganglioside antibody (anti-GM1 and anti-GD1) titer at the clinical onset of a B-cell chronic lymphocytic leukemia (B-CLL). Immunomodulation (IVIg plus cyclosporine) resulted in a neurological improvement and reduced anti-ganglioside antibody titers, both of which remained stable for at least six years. After this period, the patient had a severe relapse of the neuropathy, which was independent of the clinical course of the B-CLL. Both IVIg and cyclophosphamide were ineffective, and the patient became tetraplegic within six months; in the meantime, the patient displayed an increased antiganglioside antibody titer. Treatment with rituximab (RTX), which is designed to selectively inhibit B cell function, resulted in a dramatic, prompt and long-lasting neurological improvement as well as a reduced antiganglioside antibody titer. Although there are no previous reports of MMN in patients with B-CLL, the eficacy of RTX in the treatment of MMN in this patient may be considered remarkable. The expansion of B-cell clones may be a prerequisite for RTX effectiveness in MMN, and in dysimmune neuropathies in general

Mechanisms of altered bone remodeling in children with type 1 diabetes

Bone loss associated with type 1 diabetes mellitus (T1DM) begins at the onset of the disease, already in childhood, determining a lower bone mass peak and hence a greater risk of osteoporosis and fractures later in life. The mechanisms underlying diabetic bone fragility are not yet completely understood. Hyperglycemia and insulin deficiency can affect the bone cells functions, as well as the bone marrow fat, thus impairing the bone strength, geometry, and microarchitecture. Several factors, like insulin and growth hormone/insulin-like growth factor 1, can control bone marrow mesenchymal stem cell commitment, and the receptor activator of nuclear factor-kappa B ligand/osteoprotegerin and Wnt-b catenin pathways can impair bone turnover. Some myokines may have a key role in regulating metabolic control and improving bone mass in T1DM subjects. The aim of this review is to provide an overview of the current knowledge of the mechanisms underlying altered bone remodeling in children affected by T1DM

Determination of Commercial Animal and Vegetable Milks’ Lipid Profile and Its Correlation with Cell Viability and Antioxidant Activity on Human Intestinal Caco-2 Cells

none9openantonella aresta; Stefania De Santis; Alessia Carocci; Alexia Barbarossa; Andrea Ragusa; Nicoletta De Vietro; Maria Lisa Clodoveo; Filomena Corbo; Carlo ZAMBONINAresta, Antonella; De Santis, Stefania; Carocci, Alessia; Barbarossa, Alexia; Ragusa, Andrea; De Vietro, Nicoletta; Lisa Clodoveo, Maria; Corbo, Filomena; Zambonin, Carl