Vito M. R. Muggeo

Improvement of wound healing after hemorrhoidectomy : A double-blind, randomized study of botulinum toxin injection

PURPOSEHemorrhoidectomy is usually associated with significant pain during the postoperative period. The spasm of the internal sphincter seems to play an important role in the origin of pain. This study was designed to evaluate the effectiveness of intrasphincter injection of botulinum toxin after hemorrhoidectomy in reducing the maximum resting pressure of the anal canal, accelerating wound healing, and decreasing postoperative pain when resting and during defecation.METHODSThirty patients with hemorrhoids of third and fourth degree were included in the study and randomized in two groups. Anorectal manometry was performed preoperatively and 5 and 30 days afterward in all patients undergoing Milligan-Morgan hemorrhoidectomy. One group received an injection of 0.4 ml of saline into the internal anal sphincter, the other group were injected with 0.4 ml of solution containing 20 units of botulinum toxin.RESULTSAfter five days from hemorrhoidectomy, maximum resting pressure decreased in the group injected with botulinum toxin and increased in the placebo group. The time of healing and postoperative pain when resting and during defecation significantly decreased in the group treated with an injection of botulinum toxin.CONCLUSIONSBotulinum toxin injection into internal anal sphincter after hemorrhoidectomy is effective in reducing maximum resting pressure, time of healing, and postoperative pain both on resting and during defecation in absence of complications or side effects.

Modeling temperature effects on mortality: multiple segmented relationships with common break points

We present a model for estimation of temperature effects on mortality that is able to capture jointly the typical features of every temperature-death relationship, that is, nonlinearity and delayed effect of cold and heat over a few days. Using a segmented approximation along with a doubly penalized spline-based distributed lag parameterization, estimates and relevant standard errors of the cold- and heat-related risks and the heat tolerance are provided. The model is applied to data from Milano, Italy.

Animal Perception of Seasonal Thresholds: Changes in Elephant Movement in Relation to Rainfall Patterns

Background The identification of temporal thresholds or shifts in animal movement informs ecologists of changes in an animal’s behaviour, which contributes to an understanding of species’ responses in different environments. In African savannas, rainfall, temperature and primary productivity influence the movements of large herbivores and drive changes at different scales. Here, we developed a novel approach to define seasonal shifts in movement behaviour by examining the movements of a highly mobile herbivore (elephant; Loxodonta africana), in relation to local and regional rainfall patterns. Methodology/Principal Findings We used speed to determine movement changes of between 8 and 14 GPS-collared elephant cows, grouped into five spatial clusters, in Kruger National Park, South Africa. To detect broad-scale patterns of movement, we ran a three-year daily time-series model for each individual (2007–2009). Piecewise regression models provided the best fit for elephant movement, which exhibited a segmented, waveform pattern over time. Major breakpoints in speed occurred at the end of the dry and wet seasons of each year. During the dry season, female elephant are constrained by limited forage and thus the distances they cover are shorter and less variable. Despite the inter-annual variability of rainfall, speed breakpoints were strongly correlated with both local and regional rainfall breakpoints across all three years. Thus, at a multi-year scale, rainfall patterns significantly affect the movements of elephant. The variability of both speed and rainfall breakpoints across different years highlights the need for an objective definition of seasonal boundaries. Conclusions/Significance By using objective criteria to determine behavioural shifts, we identified a biologically meaningful indicator of major changes in animal behaviour in different years. We recommend the use of such criteria, from an animal’s perspective, for delineating seasons or other extrinsic shifts in ecological studies, rather than arbitrarily fixed definitions based on convention or common practice.

Estimating growth charts via nonparametric quantile regression: a practical framework with application in ecology

We discuss a practical and effective framework to estimate reference growth charts via regression quantiles. Inequality constraints are used to ensure both monotonicity and non-crossing of the estimated quantile curves and penalized splines are employed to model the nonlinear growth patterns with respect to age. A companion R package is presented and relevant code discussed to favour spreading and application of the proposed methods.

Parenteral iron supplementation for the treatment of iron deficiency anemia in children

Abstract. Iron-deficiency anemia impairs growth and intellectual development in children, which can be reversed only by early diagnosis and iron supplementation. Oral supplementation can efficiently replace stores, but in many cases parenteral iron is needed. Unfortunately some adverse reactions have limited its use in children. We compared the efficacy and safety of intramuscular and intravenous administration in 33 evaluable children with severe iron deficiency and/or iron-deficiency anemia who failed to respond to oral iron supplementation. Nineteen children received intravenous infusion and 14 intramuscular injections. All children showed recovery from iron-deficiency anemia, with statistically similar improvement in hemoglobin levels. The duration of treatment was longer in those receiving intramuscular injection. Parenteral iron therapy for the treatment of iron-deficiency anemia is a rapid, easy, and definitive solution to a long-troubling situation. We suggest the use of parenteral iron, in particular intravenous iron, in children who do not recover from severe iron-deficiency anemia after oral therapy. We should consider the physical and neuropsychological sequelae of long-lasting iron deficiency in children and the fact that oral supplementation is less likely to replace iron stores.

Segmented mixed models with random changepoints: a maximum likelihood approach with application to treatment for depression study

We present a simple and effective iterative procedure to estimate segmented mixed models in a likelihood based framework. Random effects and covariates are allowed for each model parameter, including the changepoint. The method is practical and avoids the computational burdens related to estimation of nonlinear mixed effects models. A conventional linear mixed model with proper covariates that account for the changepoints is the key to our estimating algorithm. We illustrate the method via simulations and using data from a randomized clinical trial focused on change in depressive symptoms over time which characteristically show two separate phases of change.

Upregulation of cytokines and IL-17 in patients with hereditary angioedema.

aPatologia Clinica Presidio Ospedaliero V. Cervello, Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy (until March 2010). *Corresponding author: Enrico Cillari, Department of Clinical Pathology, Ospedali Riuniti Villa Sofia-Cervello, Cervello Hospital, Palermo, Italy, E-mail: enrico.cillari@tiscali.it Francesco Arcoleo, Marilisa Salemi and Antonio La Porta: Ospedali Riuniti Villa Sofia-Cervello, Cervello Hospital, Clinical Pathology Laboratories, Palermo, Italy Valentina Selvaggio: Tempor Agengy, Genova, Italy Vitalba Mandalà and Vito Muggeo: University of Palermo, Department of Statistical and Mathematical Sciences “Vianelli”, Palermo, Italy Gabriella Misiano, Salvatore Milano and Giuseppina Colonna Romano: University of Palermo, Department of Pathobiology and Medical and Forensic Biotechnologies, Palermo, Italy

Quantifying Treatment Effects When Flexibly Modeling Individual Change in a Nonlinear Mixed Effects Model

A core task in analyzing randomized clinical trials based on longitudinal data is to find the best way to describe the change over time for each treatment arm. We review the implementation and estimation of a flexible piecewise Hierarchical Linear Model (HLM) to model change over time. The flexible piecewise HLM consists of two phases with differing rates of change. The breakpoints between these two phases, as well as the rates of change per phase are allowed to vary between treatment groups as well as individuals. While this approach may provide better model fit, how to quantify treatment differences over the longitudinal period is not clear. In this paper, we develop a procedure for summarizing the longitudinal data for the flexible piecewise HLM on the lines of Cook et al. (2004). We focus on quantifying the overall treatment efficacy using the area under the curve (AUC) of the individual flexible piecewise HLM models. Methods are illustrated through data from a placebo-controlled trial in the treatment of depression comparing psychotherapy and pharmacotherapy.

Quantile regression via iterative least squares computations

We present an estimating framework for quantile regression where the usual L 1-norm objective function is replaced by its smooth parametric approximation. An exact path-following algorithm is derived, leading to the well-known ‘basic’ solutions interpolating exactly a number of observations equal to the number of parameters being estimated. We discuss briefly possible practical implications of the proposed approach, such as early stopping for large data sets, confidence intervals, and additional topics for future research.

The “Three Plus One” Likelihood-Based Test Statistics: Unified Geometrical and Graphical Interpretations

The presentations of the well-known likelihood ratio, Wald and score test statistics in textbooks appear to lack a unified graphical and geometrical interpretation. We present two simple graphical representations on a common scale for these three test statistics, and also the recently proposed gradient test statistic. These unified graphical displays may favor better understanding of the geometrical meaning of the likelihood-based statistics and provide useful insights into their connections.