So different, yet so similar: meta-analysis and policy modeling of willingness to participate in clinical trials among Brazilians and Indians.

BACKGROUND: With the global expansion of clinical trials and the expectations of the rise of the emerging economies known as BRICs (Brazil, Russia, India and China), the understanding of factors that affect the willingness to participate in clinical trials of patients from those countries assumes a central role in the future of health research. METHODS: We conducted a systematic review and meta-analysis (SRMA) of willingness to participate in clinical trials among Brazilian patients and then we compared it with Indian patients (with results of another SRMA previously conducted by our group) through a system dynamics model. RESULTS: Five studies were included in the SRMA of Brazilian patients. Our main findings are 1) the major motivation for Brazilian patients to participate in clinical trials is altruism, 2) monetary reimbursement is the least important factor motivating Brazilian patients, 3) the major barrier for Brazilian patients to not participate in clinical trials is the fear of side effects, and 4) Brazilian patients are more likely willing to participate in clinical trials than Indians. CONCLUSION: Our study provides important insights for investigators and sponsors for planning trials in Brazil (and India) in the future. Ignoring these results may lead to unnecessary fund/time spending. More studies are needed to validate our results and for better understanding of this poorly studied theme.

Clinical traits of LRRK2-associated parkinson's disease in ireland: a link between familial and idiopathic PD

The role of genetics in parkinsonism has been confirmed over the last decade with the identification of genetic variation in seven genes, which are causative in familial forms of the disorder. A number of pathogenic mutations have been identified in the latest gene LRRK2, with a Gly2019Ser amino acid substitution identified in two siblings and one patient with idiopathic Parkinson's disease from Ireland. The clinical features resemble the idiopathic variant with a tremor predominant clinical picture shared by the siblings, slow progression of symptoms, and no observation of cognitive disturbance in all. The family and the sporadic individual were apparently not related and originated from different regions of Ireland, although haplotype analysis does suggest they share a common founder. The influence of the G2019S substitution on protein function and disease phenotype has yet to be fully resolved, but its elucidation will undoubtedly further our understanding of the mechanisms underlying Parkinson's disease.

Agreement between clinical and ultrasound biomicroscopy findings in different types of glaucoma

Purpose. To evaluate agreement between clinical examination (slit lamp examination and gonioscopy) and ultrasound biomicroscopy (UBM) in characterizing various features of the anterior chamber angle and adjacent structures. Methods. Twenty-eight patients (51 eyes) with open angle glaucoma (14), closed angle glaucoma (4), narrow angle and/or plateau iris (10), who had undergone UBM between March 94 and September 95 were studied. Evaluated parameters included angle width, iris configuration and presence of angle closure. The UBMs were reviewed in a masked fashion. Results. In 87.8% of cases there was agreement (within 10 degrees) between gonioscopic and UBM estimates of angle width. In all cases with greater than 10 degrees difference (12.2%) the angle size estimated by UBM was less than that estimated clinically. Iris configuration was graded identically in 51% of cases; the majority of disagreements (76.1%) occurred in cases graded as "regular" by gonioscopy and as "steep" by UBM. Angle closure was judged to be present more frequently by UBM. Conclusions. UBM and gonioscopy do not necessarily yield identical values for angle width, iris configuration, and presence of angle closure.

International differences in sport medicine access and clinical management

I undertook the 2012 ECOSEP travelling fellowship, sponsored by Bauerfeind, between May and August 2012, which involved visiting 5 European sport medicine centres and spending approximately one week in each centre. The 5 centres included: National Track and Field Centre, SEGAS, Thessaloniki, Greece; Professional School in Sport & Exercise Medicine, University of Barcelona, Spain; Sport Medicine Frankfurt Institute, Germany; Isokinetic Medical Group, FIFA Medical Centre of Excellence, Bologna, Italy, and Centre for Sports and Exercise Medicine, Barts and the London School of Medicine and Dentistry, Mile End Hospital, England. Throughout the fellowship, the clinical cases which were routinely encountered were documented. The following sections detail my experiences throughout the fellowship, the sports of the athletes and the injuries which were treated at each of the sport medicine centres during the fellowship visit and the different forms of management employed. © 2012, CIC Edizioni Internazionali

The two common polymorphic forms of human NRH-quinone oxidoreductase 2 (NQO2) have different biochemical properties

There are two common forms of NRH-quinone oxidoreductase 2 (NQO2) in the human population resulting from SNP rs1143684. One has phenylalanine at position 47 (NQO2-F47) and the other leucine (NQO2-L47). Using recombinant proteins, we show that these variants have similar steady state kinetic parameters, although NQO2-L47 has a slightly lower specificity constant. NQO2-L47 is less stable towards proteolytic digestion and thermal denaturation than NQO2-F47. Both forms are inhibited by resveratrol, but NQO2-F47 shows negative cooperativity with this inhibitor. Thus these data demonstrate, for the first time, clear biochemical differences between the variants which help explain previous biomedical and epidemiological findings. © 2014 Federation of European Biochemical Societies.

New approaches for the diagnosis of human papillomavirus infection:relevance for clinical practice and cancer prevention

Tese de doutoramento, Biologia (Microbiologia), Universidade de Lisboa, Faculdade de Ciências, 2014

Immunological mechanism of action and clinical profile of disease-modifying treatments in multiple sclerosis.

Multiple sclerosis (MS) is a life-long, potentially debilitating disease of the central nervous system (CNS). MS is considered to be an immune-mediated disease, and the presence of autoreactive peripheral lymphocytes in CNS compartments is believed to be critical in the process of demyelination and tissue damage in MS. Although MS is not currently a curable disease, several disease-modifying therapies (DMTs) are now available, or are in development. These DMTs are all thought to primarily suppress autoimmune activity within the CNS. Each therapy has its own mechanism of action (MoA) and, as a consequence, each has a different efficacy and safety profile. Neurologists can now select therapies on a more individual, patient-tailored basis, with the aim of maximizing potential for long-term efficacy without interruptions in treatment. The MoA and clinical profile of MS therapies are important considerations when making that choice or when switching therapies due to suboptimal disease response. This article therefore reviews the known and putative immunological MoAs alongside a summary of the clinical profile of therapies approved for relapsing forms of MS, and those in late-stage development, based on published data from pivotal randomized, controlled trials.

The Swiss Systemic lupus erythematosus Cohort Study (SSCS) - cross-sectional analysis of clinical characteristics and treatments across different medical disciplines in Switzerland.

OBJECTIVES: To describe disease characteristics and treatment modalities in a multidisciplinary cohort of systemic lupus erythematosus (SLE) patients in Switzerland. METHODS: Cross-sectional analysis of 255 patients included in the Swiss SLE Cohort and coming from centres specialised in Clinical Immunology, Internal Medicine, Nephrology and Rheumatology. Clinical data were collected with a standardised form. Disease activity was assessed using the Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI), an integer physician's global assessment score (PGA) ranging from 0 (inactive) to 3 (very active disease) and the erythrocyte sedimentation rate (ESR). The relationship between SLE treatment and activity was assessed by propensity score methods using a mixed-effect logistic regression with a random effect on the contributing centre. RESULTS: Of the 255 patients, 82% were women and 82% were of European ancestry. The mean age at enrolment was 44.8 years and the median SLE duration was 5.2 years. Patients from Rheumatology had a significantly later disease onset. Renal disease was reported in 44% of patients. PGA showed active disease in 49% of patients, median SLEDAI was 4 and median ESR was 14 millimetre/first hour. Prescription rates of anti-malarial drugs ranged from 3% by nephrologists to 76% by rheumatologists. Patients regularly using anti-malarial drugs had significantly lower SELENA-SLEDAI scores and ESR values. CONCLUSION: In our cohort, patients in Rheumatology had a significantly later SLE onset than those in Nephrology. Anti-malarial drugs were mostly prescribed by rheumatologists and internists and less frequently by nephrologists, and appeared to be associated with less active SLE.

Effect of Different Forms of Poly o-Toluidine /Poly Vinyl Chloride Composites on Dielectric Propertiesin the Microwave Field

In this paper we report the preparation and dielectric properties of poly o-toluidine:poly vinyl chloride composites in pellet and film forms. The composites were prepared using ammonium persulfate initiator and HCl dopant. The characterization is done by TGA and DSC. The dielectric properties including dielectric loss, conductivity, dielectric constant, dielectric heating coefficient, absorption coefficient, and penetration depth were studied in the microwave field. An HP8510 vector network analyzer with rectangular cavity resonator was used for the study. Sbands (2-4 GHz), C band (5-8 GHz), and X band (8-12 GHz) frequencies were used in the microwave field. Comparisons between the pellet and film forms of composites were also included. The result shows that the dielectric properties in the microwave field are dependent on the frequency and on the method of preparation.

Molecular breakdown of different forms of natural rubber and its influence on properties of their mixes and vulcanizates

The forms of natural rubber studied were sheet [RSS 4 and RSS 5], ISNR 20 and EBC. In the case of the latter two forms samples from estate and nonestate sectors were included. The samples were collected from different locations at specified intervals, for a particular period. The effect of the extent of mastication on raw rubber properties as well as the properties of the compounds and vulcanizates also studied. The consistency in raw rubber properties and breakdown behavior of skim rubber were studied by collecting samples periodically from selected processing units. The effect of incorporation of skim with ISNR 20 has also been investigated

The effects of different forms of advice on the control of a simulated complex system

Three experiments examine the effect of different forms of computer-generated advice on concurrent and subsequent performance of individuals controlling a simulated intensive-care task. Experiment 1 investigates the effect of optional and compulsory advice and shows that both result in an improvement in subjects' performance while receiving the advice, and also in an improvement in subsequent unaided performance. However, although the advice compliance displayed by the optional advice group shows a strong correlation with subsequent unaided performance, compulsory advice has no extra benefit over the optional use of advice. Experiment 2 examines the effect of providing users with on-line explanations of the advice, as well as providing less specific advice. The results show that both groups perform at the same level on the task as the advice groups from Experiment 1, although subjects receiving explanations scored significantly higher on a written post-task questionnaire. Experiment 3 investigates in more detail the relationship between advice compliance and performance. The results reveal a complex relationship between natural ability on the task and the following of advice, in that people who use the advice more tend to perform either better or worse than the more moderate users. The theoretical and practical implications of these experiments are discussed.

A comparison of three different models for estimating relative risk in meta-analysis of clinical trials under unobserved heterogeneity

We focus on the comparison of three statistical models used to estimate the treatment effect in metaanalysis when individually pooled data are available. The models are two conventional models, namely a multi-level and a model based upon an approximate likelihood, and a newly developed model, the profile likelihood model which might be viewed as an extension of the Mantel-Haenszel approach. To exemplify these methods, we use results from a meta-analysis of 22 trials to prevent respiratory tract infections. We show that by using the multi-level approach, in the case of baseline heterogeneity, the number of clusters or components is considerably over-estimated. The approximate and profile likelihood method showed nearly the same pattern for the treatment effect distribution. To provide more evidence two simulation studies are accomplished. The profile likelihood can be considered as a clear alternative to the approximate likelihood model. In the case of strong baseline heterogeneity, the profile likelihood method shows superior behaviour when compared with the multi-level model. Copyright (C) 2006 John Wiley & Sons, Ltd.

Clinical test responses to different orthoptic exercise regimes in typical young adults

Purpose The relative efficiency of different eye exercise regimes is unclear, and in particular the influences of practice, placebo and the amount of effort required are rarely considered. This study measured conventional clinical measures after different regimes in typical young adults. Methods 156 asymptomatic young adults were directed to carry out eye exercises 3 times daily for two weeks. Exercises were directed at improving blur responses (accommodation), disparity responses (convergence), both in a naturalistic relationship, convergence in excess of accommodation, accommodation in excess of convergence, and a placebo regime. They were compared to two control groups, neither of which were given exercises, but the second of which were asked to make maximum effort during the second testing. Results Instruction set and participant effort were more effective than many exercises. Convergence exercises independent of accommodation were the most effective treatment, followed by accommodation exercises, and both regimes resulted in changes in both vergence and accommodation test responses. Exercises targeting convergence and accommodation working together were less effective than those where they were separated. Accommodation measures were prone to large instruction/effort effects and monocular accommodation facility was subject to large practice effects. Conclusions Separating convergence and accommodation exercises seemed more effective than exercising both systems concurrently and suggests that stimulation of accommodation and convergence may act in an additive fashion to aid responses. Instruction/effort effects are large and should be carefully controlled if claims for the efficacy of any exercise regime are to be made.