Increasing value and reducing waste by optimizing the development of complex interventions: Enriching the development phase of the Medical Research Council (MRC) Framework

This is the final version of the article. Available from Elsevier via the DOI in this record.Background In recent years there has been much emphasis on ‘research waste’ caused by poor question selection, insufficient attention to previous research results, and avoidable weakness in research design, conduct and analysis. Little attention has been paid to the effect of inadequate development of interventions before proceeding to a full clinical trial. Objective We therefore propose to enrich the development phase of the MRC Framework by adding crucial elements to improve the likelihood of success and enhance the fit with clinical practice Methods Based on existing intervention development guidance and synthesis, a comprehensive iterative intervention development approach is proposed. Examples from published reports are presented to illustrate the methodology that can be applied within each element to enhance the intervention design. Results A comprehensive iterative approach is presented by combining the elements of the MRC Framework development phase with essential elements from existing guidance including: problem identification, the systematic identification of evidence, identification or development of theory, determination of needs, the examination of current practice and context, modelling the process and expected outcomes leading to final element: the intervention design. All elements are drawn from existing models to provide intervention developers with a greater chance of producing an intervention that is well adopted, effective and fitted to the context. Conclusion This comprehensive approach of developing interventions will strengthen the internal and external validity, minimize research waste and add value to health care research. In complex interventions in health care research, flaws in the development process immediately impact the chances of success. Knowledge regarding the causal mechanisms and interactions within the intended clinical context is needed to develop interventions that fit daily practice and are beneficial for the end-user

Brace technology thematic series: the dynamic derotation brace

<p>Abstract</p> <p>Background</p> <p>The dynamic derotation brace (DDB) was designed in Greece in 1982, as a modification of the Boston brace. It is a custom-made, underarm spinal orthosis featuring aluminium blades set to produce derotating and anti-rotating effects on the thorax and trunk of patients with scoliosis. It is indicated for the non-operative correction of most curves, barring the very high thoracic ones, (when the apex vertebra is T5 or above). The purpose of this article is to familiarize physicians with the DDB, analyze the rationale behind its design, and present the published results of its application.</p> <p>Description & Principles</p> <p>The key feature of the DDB is the addition of the aluminium-made derotating blades posteriorly. These function as a force couple, which is added to the side forces exerted by the brace itself. Corrective forces are also directed through pads. One or more of previously proposed pathomechanical models of scoliosis may underline the corrective function of the DDB: it may act directly on the apical intervertebral disc, effecting correction through the Heuter-Volkman principle; the blades may produce an anti-rotatory element against the deforming "spiral composite muscle trunk rotator"; or it may alter the neuro-motor response by constantly providing new somatosensory input to the patient.</p> <p>Results</p> <p>Based on measurements of the Cobb and Perdriolle angles, up to 82% of patients remained stable or improved with the use of the DDB. Results have varied, though, depending on the type/location of the deformity. The overall results showed that 35% of the curves improved, 46% remained stable and 18% became worse, as assessed by measuring the Cobb angle. The DDB has also been shown to improve cosmesis (except for right thoracic curves) and leave several aspects of patient quality of life unaffected during use.</p> <p>Conclusion</p> <p>Conservative treatment of idiopathic scoliosis using the DDB has shown favorable results. Thoracic curves appear more resistant to both angular and rotatory correction. The published outcome data on the DDB support our belief that the incorporation of aluminium blades to other orthoses would likely improve their efficacy.</p

Methodology of evaluation of morphology of the spine and the trunk in idiopathic scoliosis and other spinal deformities - 6th SOSORT consensus paper

<p>Abstract</p> <p>Background</p> <p>Comprehensive evaluation of the morphology of the spine and of the whole body is essential in order to correctly manage patients suffering from progressive idiopathic scoliosis. Although methodology of clinical and radiological examination is well described in manuals of orthopaedics, there is deficit of data which clinical and radiological parameters are considered in everyday practise. Recently, an increasing tendency to extend scoliosis examination beyond the measure of the Cobb angle can be observed, reflecting a more patient-oriented approach. Such evaluation often involves surface parameters, aesthetics, function and quality of life.</p> <p>Aim of the study</p> <p>To investigate current recommendations of experts on methodology of evaluation of the patient with spinal deformity, essentially idiopathic scoliosis.</p> <p>Methods</p> <p>Structured Delphi procedure for collecting and processing knowledge from a group of experts with a series of questionnaires and controlled opinion feedback was performed. Experience and opinions of the professionals - physicians and physiotherapists managing scoliosis patients - were studied. According to Delphi method a Meeting Questionnaire (MQ) has been developed, resulting from a preliminary Pre-Meeting Questionnaire (PMQ) which had been previously discussed and approved on line. The MQ was circulated among the SOSORT experts during Consensus Session on "Measurements" which took place at the Annual Meeting of the Society, totally 23 panellists being engaged. Clinical, radiological and surface topography parameters were checked for agreement.</p> <p>Results</p> <p>90% agreement or more was reached in 35 items and superior than 75% agreement was reached in further 25 items. An evaluation form was proposed to be used by clinicians and researchers.</p> <p>Conclusion</p> <p>The consensus was reached on evaluation of the morphology of the patient with idiopathic scoliosis, comprising clinical, radiological and, to less extend, surface topography assessment. Considering the variety of parameters indicated by the panellists, the Cobb angle, yet the gold standard, can be seen neither as the unique nor the only decisive parameter in the management of patients with idiopathic scoliosis.</p

School screening for scoliosis: can surface topography replace examination with scoliometer?

<p>Abstract</p> <p>Background</p> <p>Clinical examination with the use of scoliometer is a basic method for scoliosis detection in school screening programs. Surface topography (ST) enables three-dimensional back assessment, however it has not been adopted for the purpose of scoliosis screening yet. The purpose of this study was to assess the usefulness of ST for scoliosis screening.</p> <p>Methods</p> <p>996 girls aged 9 to 13 years were examined, with both scoliometer and surface topography. The Surface Trunk Rotation (STR) was introduced and defined as a parameter allowing comparison with scoliometer Angle of Trunk Rotation taken as reference.</p> <p>Results</p> <p>Intra-observer error for STR parameter was 1.9°, inter-observer error was 0.8°. Sensitivity and specificity of ST were not satisfactory, the screening cut-off value of the surface topography parameter could not be established.</p> <p>Conclusions</p> <p>The study did not reveal advantage of ST as a scoliosis screening method in comparison to clinical examination with the use of the scoliometer.</p

Evaluation of SOVAT: An OLAP-GIS decision support system for community health assessment data analysis

Background. Data analysis in community health assessment (CHA) involves the collection, integration, and analysis of large numerical and spatial data sets in order to identify health priorities. Geographic Information Systems (GIS) enable for management and analysis using spatial data, but have limitations in performing analysis of numerical data because of its traditional database architecture. On-Line Analytical Processing (OLAP) is a multidimensional datawarehouse designed to facilitate querying of large numerical data. Coupling the spatial capabilities of GIS with the numerical analysis of OLAP, might enhance CHA data analysis. OLAP-GIS systems have been developed by university researchers and corporations, yet their potential for CHA data analysis is not well understood. To evaluate the potential of an OLAP-GIS decision support system for CHA problem solving, we compared OLAP-GIS to the standard information technology (IT) currently used by many public health professionals. Methods. SOVAT, an OLAP-GIS decision support system developed at the University of Pittsburgh, was compared against current IT for data analysis for CHA. For this study, current IT was considered the combined use of SPSS and GIS ("SPSS-GIS"). Graduate students, researchers, and faculty in the health sciences at the University of Pittsburgh were recruited. Each round consisted of: an instructional video of the system being evaluated, two practice tasks, five assessment tasks, and one post-study questionnaire. Objective and subjective measurement included: task completion time, success in answering the tasks, and system satisfaction. Results. Thirteen individuals participated. Inferential statistics were analyzed using linear mixed model analysis. SOVAT was statistically significant (α = .01) from SPSS-GIS for satisfaction and time (p < .002). Descriptive results indicated that participants had greater success in answering the tasks when using SOVAT as compared to SPSS-GIS. Conclusion. Using SOVAT, tasks were completed more efficiently, with a higher rate of success, and with greater satisfaction, than the combined use of SPSS and GIS. The results from this study indicate a potential for OLAP-GIS decision support systems as a valuable tool for CHA data analysis. © 2008 Scotch et al; licensee BioMed Central Ltd

Genome-wide analysis of ivermectin response by Onchocerca volvulus reveals that genetic drift and soft selective sweeps contribute to loss of drug sensitivity

Treatment of onchocerciasis using mass ivermectin administration has reduced morbidity and transmission throughout Africa and Central/South America. Mass drug administration is likely to exert selection pressure on parasites, and phenotypic and genetic changes in several Onchocerca volvulus populations from Cameroon and Ghana-exposed to more than a decade of regular ivermectin treatment-have raised concern that sub-optimal responses to ivermectin's anti-fecundity effect are becoming more frequent and may spread.Pooled next generation sequencing (Pool-seq) was used to characterise genetic diversity within and between 108 adult female worms differing in ivermectin treatment history and response. Genome-wide analyses revealed genetic variation that significantly differentiated good responder (GR) and sub-optimal responder (SOR) parasites. These variants were not randomly distributed but clustered in ~31 quantitative trait loci (QTLs), with little overlap in putative QTL position and gene content between the two countries. Published candidate ivermectin SOR genes were largely absent in these regions; QTLs differentiating GR and SOR worms were enriched for genes in molecular pathways associated with neurotransmission, development, and stress responses. Finally, single worm genotyping demonstrated that geographic isolation and genetic change over time (in the presence of drug exposure) had a significantly greater role in shaping genetic diversity than the evolution of SOR.This study is one of the first genome-wide association analyses in a parasitic nematode, and provides insight into the genomics of ivermectin response and population structure of O. volvulus. We argue that ivermectin response is a polygenically-determined quantitative trait (QT) whereby identical or related molecular pathways but not necessarily individual genes are likely to determine the extent of ivermectin response in different parasite populations. Furthermore, we propose that genetic drift rather than genetic selection of SOR is the underlying driver of population differentiation, which has significant implications for the emergence and potential spread of SOR within and between these parasite populations

Estimated pre-morbid IQ effects on cognitive and functional outcomes in Alzheimer disease: a longitudinal study in a treated cohort

Abstract Background Cognitive reserve is thought to influence the degree of neuropathology needed for diagnosis of Alzheimer disease (AD). Cognitive reserve can be operationally defined as the hypothesized capacity of the mature adult brain to sustain the effects of disease or injury without manifesting clinical symptoms of AD, but sufficient to cause clinical dementia in an individual possessing less cognitive reserve. Its effect on the subsequent course of AD is less clear. Pre-morbid IQ is a useful measure of cognitive reserve. Methods We studied 659 consecutive patients with AD at a tertiary referral memory clinic. Patients were assessed on six cognitive tests at baseline. Activities of Daily Living (ADL) were measured on the Instrumental Activities of Daily Living (IADL) scale and Physical Self-Maintenance Scale (PSMS). The National Adult Reading Test (NART) was used to estimate pre-morbid IQ. Patients were followed up after starting a cholinesterase inhibitor over 78 weeks. Mixed general linear models estimated the effects of NART on cognition and ADL. Results Three hundred and fifty-five patients had NART scored with a mean estimated pre-morbid IQ of 104.7 (standard deviation 18.5). NART increased overall cognitive ability by 2.7% for every 10 IQ points (p Conclusion Our data support the hypothesis that cognitive reserve continues to have a limited influence on cognition after AD has been diagnosed and thus, indirectly, has an impact on ADL.</p

A geographical population analysis of dental trauma in school-children aged 12 and 15 in the city of Curitiba-Brazil

<p>Abstract</p> <p>Background</p> <p>The study presents a geographical analysis of dental trauma in a population of 12 and 15 year-old school-children, in the city of Curitiba, Brazil (n = 1581), using a database obtained in the period 2005-2006. The main focus is to analyze dental trauma using a geographic information system as a tool for integrating social, environmental and epidemiological data.</p> <p>Methods</p> <p>Geostatistical analysis of the database and thematic maps were generated showing the distribution of dental trauma cases according to Curitiba's Health Districts and other variables of interest. Dental trauma spatial variation was assessed using a generalized additive model in order to identify and control the individual risk-factors and thus determine whether spatial variation is constant or not throughout the Health Districts and the place of residence of individuals. In addition, an analysis was made of the coverage of dental trauma cases taking the spatial distribution of Curitiba's primary healthcare centres.</p> <p>Results</p> <p>The overall prevalence of dental trauma was 37.1%, with 53.1% in males and 46.7% in females. The spatial analysis confirms the hypothesis that there is significant variation in the occurrence of dental trauma, considering the place of residence in the population studied (Monte Carlo test, p = 0,006). Furthermore, 28.7% of cases had no coverage by the primary healthcare centres.</p> <p>Conclusions</p> <p>The effect of the place of residence was highly significant in relation to the response variable. The delimitation of areas, as a basis for case density, enables the qualification of geographical territories where actions can be planned based on priority criteria. Promotion, control and rehabilitation actions, applied in regions of higher prevalence of dental trauma, can be more effective and efficient, thus providing healthcare refinement.</p

Effectiveness of Chêneau brace treatment for idiopathic scoliosis: prospective study in 79 patients followed to skeletal maturity

<p>Abstract</p> <p>Background</p> <p>Progressive idiopathic scoliosis can negatively influence the development and functioning of 2-3% of adolescents, with health consequences and economic costs, placing the disease in the centre of interest of the developmental medicine. The aim of this study was to evaluate the effectiveness of Chêneau brace in the management of idiopathic scoliosis.</p> <p>Methods</p> <p>A prospective observational study according to SOSORT and SRS recommendations comprised 79 patients (58 girls and 21 boys) with progressive idiopathic scoliosis, treated with Chêneau brace and physiotherapy, with initial Cobb angle between 20 and 45 degrees, no previous brace treatment, Risser 4 or more at the final evaluation and minimum one year follow-up after weaning the brace. Achieving 50° of Cobb angle was considered surgical recommendation.</p> <p>Results</p> <p>At follow-up 20 patients (25.3%) improved, 18 patients (22.8%) were stable, 31 patients (39.2%) progressed below 50 degrees and 10 patients (12.7%) progressed beyond 50 degrees (2 of these 10 patients progressed beyond 60 degrees). Progression concerned the younger and less skeletally mature patients.</p> <p>Conclusion</p> <p>Conservative treatment with Chêneau orthosis and physiotherapy was effective in halting scoliosis progression in 48.1% of patients. The results of this study suggest that bracing is effective in reducing the incidence of surgery in comparison with natural history.</p