Luigi Salmaso

Well-Being Therapy of Generalized Anxiety Disorder

Background: There is increasing awareness that the goal of treatment in generalized anxiety disorder (GAD) should not simply be a response, but restoration of normal function. The aim of this study was to apply a novel psychotherapeutic approach for increasing the level of remission in GAD. Methods: Twenty patients with DSM-IV GAD devoid of comorbid conditions were randomly assigned to 8 sessions of cognitive behavioral therapy (CBT) or the sequential administration of 4 sessions of CBT followed by other 4 sessions of well-being therapy (WBT). Assessment methods included the Anxiety and Depression Scales of Paykel’s Clinical Interview for Depression, Ryff’s Psychological Well-being Scales and Kellner’s Symptom Questionnaire. A one-year follow-up was undertaken. Results: Significant advantages of the CBT-WBT sequential combination over CBT only were observed with both observer and self-rated methods after treatment. Such gains were maintained at follow-up. Conclusions: These preliminary results suggest the feasibility and clinical advantages of adding WBT to the treatment of GAD. They lend support to a sequential use of treatment components for achieving a more sustained recovery.

Efficacy of Botulinum Toxin in Treating Myofascial Pain in Bruxers: A Controlled Placebo Pilot Study

Abstract The present investigation is a preliminary double-blind, controlled placebo, randomized clinical trial with a six month follow-up period. The study aimed to assess the efficacy of type A botulinum toxin (Botox, Allergan, Inc. Irvine, CA) to treat myofascial pain symptoms and to reduce muscle hyperactivity in bruxers. Twenty patients (ten males, ten females; age range 25-45) with a clinical diagnosis of bruxism and myofascial pain of the masticatory muscles were enrolled in a double-blind, controlled placebo, randomized clinical trial, with a treatment group (ten subjects treated with botulinum toxin injections- BTX-A) and a control group (ten subjects treated with saline placebo injections). A number of objective and subjective clinical parameters (pain at rest and during chewing; mastication efficiency; maximum nonassisted and assisted mouth opening, protrusive and laterotrusive movements; functional limitation during usual jaw movements; subjective efficacy of the treatment; tolerance of the treatment) were assessed at baseline time and at one week, one month, and six months follow-up appointments. Descriptive analysis showed that improvements in both objective (range of mandibular movements) and subjective (pain at rest; pain during chewing) clinical outcome variables were higher in the Botox treated group than in the placebo treated subjects. Patients treated with BTX-A had a higher subjective improvement in their perception of treatment efficacy than the placebo subjects. Differences were not significant in some cases due to the small sample size. Results from the present study supported the efficacy of BTX-A to reduce myofascial pain symptoms in bruxers, and provided pilot data which need to be confirmed by further research using larger samples.

A 35-year follow-up of a large cohort of patients with primary biliary cirrhosis seen at a single centre.

Background: The natural history of primary biliary cirrhosis (PBC) is still debated.

Finite-sample consistency of combination-based permutation tests with application to repeated measures designs

In several application fields, e.g. genetics, image and functional analysis, several biomedical and social experimental and observational studies, etc. it may happen that the number of observed variables is much larger than that of subjects. It can be proved that, for a given and fixed number of subjects, when the number of variables increases and the noncentrality parameter of the underlying population distribution increases with respect to each added variable, then power of multivariate permutation tests based on Pesarins combining functions [Pesarin, F. (2001), Multivariate Permutation Tests with Applications in Biostatistics, New York: Wiley, Chichester] is monotonically increasing. These results confirm and extend those presented by [Blair, Higgins, Karniski and Kromrey (1994), ‘A Study of Multivariate Permutation Tests which May Replace Hotellings T 2 Test in Prescribed Circumstances’, Multivariate Behavioral Research 29, 141–163]. Moreover, they allow us to introduce the property of finite-sample consistency for those kinds of combination-based permutation tests. Sufficient conditions are given in order that the rejection rate converges to one, for fixed sample sizes at any attainable α -values, when the number of variables diverges. A simulation study and a real case study are presented.

A review and some new results on permutation testing for multivariate problems

In recent years permutation testing methods have increased both in number of applications and in solving complex multivariate problems. When available permutation tests are essentially of an exact nonparametric nature in a conditional context, where conditioning is on the pooled observed data set which is often a set of sufficient statistics in the null hypothesis. Whereas, the reference null distribution of most parametric tests is only known asymptotically. Thus, for most sample sizes of practical interest, the possible lack of efficiency of permutation solutions may be compensated by the lack of approximation of parametric counterparts. There are many complex multivariate problems, quite common in empirical sciences, which are difficult to solve outside the conditional framework and in particular outside the method of nonparametric combination (NPC) of dependent permutation tests. In this paper we review such a method and its main properties along with some new results in experimental and observational situations (robust testing, multi-sided alternatives and testing for survival functions).

Multi-aspect permutation tests in shape analysis with small sample size

Inferential methods known in the shape analysis literature make use of configurations of landmarks optimally superimposed using a least-squares procedure or analyze matrices of interlandmark distances. For example, in the two independent sample case, a practical method for comparing the mean shapes in the two groups is to use the Procrustes tangent space coordinates, if data are concentrated, calculate the Mahalanobis distance and then the Hotelling T^2-test statistic. Under the assumption of isotropy, another simple approach is to work with statistics based on the squared Procrustes distance and then consider the Goodall F-test statistic. Despite their widespread use, on the one hand it is well known that Hotellings T^2-test may not be very powerful unless there are a large number of observations available, and on the other hand the underlying model required by Goodalls F-test is very restrictive. For these reasons, an extension of the nonparametric combination (NPC) methodology to shape analysis is proposed. Focussing on the two independent sample case, through a comparative simulation study and an application to the Mediterranean monk seal skulls dataset, the behaviour of some nonparametric permutation tests has been evaluated, showing that the proposed tests are very powerful, for both balanced and unbalanced sample sizes.

Temporomandibular joint click sound and magnetic resonance-depicted disk position: Which relationship?

AIMS The aim of this work was to evaluate the agreement between temporomandibular joint click sound and MR diagnoses of different disk positions. METHODS One hundred ninety-four (N=194) patients seeking treatment for temporomandibular disorders at the TMD Clinic, Department of Maxillofacial Surgery, University of Padova, Italy, underwent a bilateral magnetic resonance of the temporomandibular joints. The presence of click sounds was clinically assessed according to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) and put into relation with different magnetic resonance (MR) diagnoses of disk-condyle position by means of permutation tests. RESULTS The proportion of joints with reducing and non-reducing disk displacement which provided a click sound during the clinical assessment was similar (45.6% vs. 48.9%, respectively), while the prevalence of the two MR diagnoses in joints with click sound were strongly different (25.3% vs. 40.1%, respectively. Thus, the MR diagnosis which appears to be more positively associated with click sounds is disk displacement without reduction. CONCLUSION There is a weak form of dependence between click and MR diagnosis, and the MR diagnosis of DDNR seems to be more positively associated with the presence of click sounds than the other categories, which did not show significant positive associations with click (i.e. there is negative association between click presence and normal disk position and no association between click presence and DDR joints.

Treatment Effectiveness of Arthrocentesis Plus Hyaluronic Acid Injections in Different Age Groups of Patients With Temporomandibular Joint Osteoarthritis

PURPOSE To investigate for treatment effectiveness in different age groups of patients with temporomandibular joint osteoarthritis who underwent a cycle of 5 weekly arthrocenteses plus hyaluronic acid injections. MATERIALS AND METHODS We implemented a retrospective study on 76 patients followed up for 1 year. Outcome variables were pain levels at rest and during chewing, subjective masticatory efficiency, functional limitation, perceived efficacy, and jaw range of motion. Three age groups of patients were identified, and treatment effectiveness was compared among groups by means of a multistrata permutation test. RESULTS All the partial P values of the subtests related to the age groups, adjusted according to the close testing method for controlling multiplicity, were significant: P = .009 (aged <45 years), P = .001 (aged 45-65 years), and P = .001 (aged >65 years). For the younger age group, the treatment had a significant effect only on the pain at mastication and on the subjective efficacy. For the other age groups, the treatment effectiveness was evident with regard to almost all the considered symptoms. CONCLUSIONS Our findings suggested that the treatment protocol was more effective in patients older than 45 years, thus having important clinical implications regarding attempts to define tailored treatment protocols for patients with temporomandibular disorders.

Synchronized Permutation Tests in 2 k Factorial Designs

Abstract In this article, based on the notion of synchronized permutations (Salmaso, L. (2000). Orthogonal Two-Level Factorial Designs and Permutation Tests for Effects. Ph.D. thesis, Department of Statistics, University of Padova.), we provide a new full exact solution for testing effects in replicated 2 k factorial designs within a nonparametric framework. Synchronized permutations allow for testing separately all effects by shuffling the appropriate set of sufficient statistics. Such tests are exact, unbiased, and consistent. Furthermore, they are uncorrelated to each other and asymptotically at least as powerful as the parametric solution when the latter is appropriate. A simulation study shows that also for small sample sizes their power is close to that of parametric counterparts based on normality of errors. This approach preserves the exchangeability of error components for testing all 2 k -1effects.

Testing marginal homogeneity against stochastic order in multivariate ordinal data.

SUMMARY Many assessment instruments used in the evaluation of toxicity, safety, pain, or disease progression consider multiple ordinal endpoints to fully capture the presence and severity of treatment effects. Contingency tables underlying these correlated responses are often sparse and imbalanced, rendering asymptotic results unreliable or model fitting prohibitively complex without overly simplistic assumptions on the marginal and joint distribution. Instead of a modeling approach, we look at stochastic order and marginal inhomogeneity as an expression or manifestation of a treatment effect under much weaker assumptions. Often, endpoints are grouped together into physiological domains or by the body function they describe. We derive tests based on these subgroups, which might supplement or replace the individual endpoint analysis because they are more powerful. The permutation or bootstrap distribution is used throughout to obtain global, subgroup, and individual significance levels as they naturally incorporate the correlation among endpoints. We provide a theorem that establishes a connection between marginal homogeneity and the stronger exchangeability assumption under the permutation approach. Multiplicity adjustments for the individual endpoints are obtained via stepdown procedures, while subgroup significance levels are adjusted via the full closed testing procedure. The proposed methodology is illustrated using a collection of 25 correlated ordinal endpoints, grouped into six domains, to evaluate toxicity of a chemical compound.