Clinimetrics in rehabilitation medicine: current issues in developing and applying measurement instruments 1

Clinimetrics in rehabilitation medicine, i.e. the field of developing, evaluating and applying measurement instruments, has undergone considerable progress. Despite this progress, however, several issues remain. These include: (i) selection of an instrument out of the wide range available; (ii) using an instrument in a variety of diagnostic groups; (iii) using an instrument in individual patients, as opposed to a group of patients; and (iv) the use of instruments in clinical practice. This paper reviews these issues, as well as current attempts at resolving them. Illustrative examples are given. It is concluded that solutions seem to be available, but considerable research effort is required to make these a reality. Clinimetrics in rehabilitation medicine remains a field with challenging opportunities for researc

Reliability and Validity of the Disability Assessment Structured Interview (DASI): A Tool for Assessing Functional Limitations in Claimants

Objective The aim of this study is to investigate the reliability and validity of the Disability Assessment Structured Interview (DASI). The DASI is a semi-structured interview for assessing long-term functional limitations concerning the work disability assessment of claimants. Methods A randomized controlled trial was conducted. Patients applying for a work-disability pension after 21 months of sick leave were independently interviewed and examined either by two physicians who had completed a DASI training period (n = 32) or by two physicians from a control group (n = 30) without any DASI training. Agreement percentages within both groups of physicians, eligibility for a disability benefit, and differences between the groups in terms of the scores given on the work-limitation items from the Functional Ability List (FAL) were measured to investigate reliability and concurrent validity. To determine the content validity, the insurance physicians who completed DASI training (n = 8) were asked to fill out a questionnaire concerning their opinion of the DASI. Additionally, patients filled out a questionnaire to measure their satisfaction as to the behavioral aspects of the physicians. Results The groups showed no important differences in agreement percentages (mean percentage about 80%) and eligibility for a disability benefit. In 9 out of 21 items the physicians of the control group indicated fewer work limitations compared to physicians using the DASI. All physicians agreed on the fact that the DASI was an acceptable tool in daily practice, one that provided a realistic picture of the patient and provided sufficient information to assess functional limitations. In addition, between the two groups, no differences were found as to the satisfaction of patients concerning the behavioral aspects of the physicians. Conclusion The DASI is a tool with a reasonable to good inter-rater reliability and content validity, and it appears to be acceptable to both patients and physicians. It did not improve inter-observer agreement beyond that of usual interview procedures used in the Netherlands. The DASI would seem to be a worthwhile tool for collecting self-reported information in order to assess functional limitations in claimants

Mapping quantitative trait loci (QTL) in sheep. I. A new male framework linkage map and QTL for growth rate and body weight

A male sheep linkage map comprising 191 microsatellites was generated from a single family of 510 Awassi-Merino backcross progeny. Except for ovine chromosomes 1, 2, 10 and 17, all other chromosomes yielded a LOD score difference greater than 3.0 between the best and second-best map order. The map is on average 11% longer than the Sheep Linkage Map v4.7 male-specific map. This map was employed in quantitative trait loci (QTL) analyses on body-weight and growth-rate traits between birth and 98 weeks of age. A custom maximum likelihood program was developed to map QTL in half-sib families for non-inbred strains (QTL-MLE) and is freely available on request. The new analysis package offers the advantage of enabling QTL × fixed effect interactions to be included in the model. Fifty-four putative QTL were identified on nine chromosomes. Significant QTL with sex-specific effects (i.e. QTL × sex interaction) in the range of 0.4 to 0.7 SD were found on ovine chromosomes 1, 3, 6, 11, 21, 23, 24 and 26

Annual consultation prevalence of regional musculoskeletal problems in primary care: an observational study

<p>Abstract</p> <p>Background</p> <p>Regional musculoskeletal pain such as back or shoulder pain are commonly reported symptoms in the community. The extent of consultation to primary care with such problems is unknown as a variety of labels may be used to record such consultations. The objective was to classify musculoskeletal morbidity codes used in routine primary care by body region, and to determine the annual consultation prevalence of regional musculoskeletal problems.</p> <p>Methods</p> <p>Musculoskeletal codes within the Read morbidity Code system were identified and grouped by relevant body region by four GPs. Consultations with these codes were then extracted from the recorded consultations at twelve general practices contributing to a general practice consultation database (CiPCA). Annual consultation prevalence per 10,000 registered persons for the year 2006 was determined, stratified by age and gender, for problems in individual regions and for problems affecting multiple regions.</p> <p>Results</p> <p>5,908 musculoskeletal codes were grouped into regions. One in seven of all recorded consultations were for a musculoskeletal problem. The back was the most common individual region recorded (591 people consulting per 10,000 registered persons), followed by the knee (324/10,000). In children, the foot was the most common region. Different age and gender trends were apparent across body regions although women generally had higher consultation rates. The annual consultation-based prevalence for problems encompassing more than one region was 556 people consulting per 10,000 registered persons and increased in older people and in females.</p> <p>Conclusions</p> <p>There is an extensive and varied regional musculoskeletal workload in primary care. Musculoskeletal problems are a major constituent of general practice. The output from this study can be used as a resource for planning future studies.</p

Costs of shoulder pain in primary care consulters: a prospective cohort study in The Netherlands

BACKGROUND: Shoulder pain is common in primary care, and has an unfavourable outcome in many patients. Information on the costs associated with health care use and loss of productivity in patients with shoulder pain is very scarce. The objective of this study was to determine shoulder pain related costs during the 6 months after first consultation in general practice METHODS: A prospective cohort study consisting of 587 patients with a new episode of shoulder pain was conducted with a follow-up period of 6 months. Data on costs were collected by means of a cost diary during 6 months. RESULTS: 84% of the patients completed all cost diaries. The mean consumption of direct health care and non-health related care was low. During 6 months after first consultation for shoulder pain, the mean total costs a patient generated were €689. Almost 50% of this total concerned indirect costs, caused by sick leave from paid work. A small proportion (12%) of the population generated 74% of the total costs. CONCLUSION: The total costs in the 6 months after first consultation for shoulder pain in primary care, mostly generated by a small part of the population, are not alarmingly high

Imaging Trans-Cellular Neurexin-Neuroligin Interactions by Enzymatic Probe Ligation

Neurexin and neuroligin are transmembrane adhesion proteins that play an important role in organizing the neuronal synaptic cleft. Our lab previously reported a method for imaging the trans-synaptic binding of neurexin and neuroligin called BLINC (Biotin Labeling of INtercellular Contacts). In BLINC, biotin ligase (BirA) is fused to one protein while its 15-amino acid acceptor peptide substrate (AP) is fused to the binding partner. When the two fusion proteins interact across cellular junctions, BirA catalyzes the site-specific biotinylation of AP, which can be read out by staining with streptavidin-fluorophore conjugates. Here, we report that BLINC in neurons cannot be reproduced using the reporter constructs and labeling protocol previously described. We uncover the technical reasons for the lack of reproducibilty and then re-design the BLINC reporters and labeling protocol to achieve neurexin-neuroligin BLINC imaging in neuron cultures. In addition, we introduce a new method, based on lipoic acid ligase instead of biotin ligase, to image trans-cellular neurexin-neuroligin interactions in human embryonic kidney cells and in neuron cultures. This method, called ID-PRIME for Interaction-Dependent PRobe Incorporation Mediated by Enzymes, is more robust than BLINC due to higher surface expression of lipoic acid ligase fusion constructs, gives stronger and more localized labeling, and is more versatile than BLINC in terms of signal readout. ID-PRIME expands the toolkit of methods available to study trans-cellular protein-protein interactions in living systems.National Institutes of Health (U.S.) (DP1 OD003961

How well do questionnaires on symptoms in neck-shoulder disorders capture the experiences of those who suffer from neck-shoulder disorders? A content analysis of questionnaires and interviews

<p>Abstract</p> <p>Background</p> <p>Previous research has indicated neck-shoulder disorders to have a fluctuating course incorporating a variety of symptoms. These findings awoke our interest to make a comparison between symptoms experienced by people affected with the disorder and the content of questionnaires that assess pain and other symptoms in neck-shoulder disorders. Thus the aims of this study were: -to explore the symptoms experienced by people with non-specific neck-shoulder problems, as well as experiences of nuances and temporal variations (fluctuations) of symptoms; -to investigate which sources were used in the development of ten questionnaires for assessing pain and other symptoms in the neck-shoulder; -to analyse the item content of the questionnaires; -to analyse the correspondence between the item content of the questionnaires and the symptoms described by the informants.</p> <p>Methods</p> <p>Content analysis of interviews with 40 people with non-specific neck-shoulder pain, and 10 questionnaires used to assess pain and other symptoms in neck-shoulder disorders.</p> <p>Results</p> <p>The interviews revealed a variety of symptoms indicating a bodily, mental/cognitive, and emotional engagement, and more general and severe symptoms than are usually considered in neck-shoulder questionnaires. Taking all questionnaires together many of the symptoms were considered, but most questionnaires only included a few of them. The informants were able to distinguish fluctuation of symptoms, and a variety of different qualities which were not usually considered in the questionnaires. Only two questionnaires had made use of the opinions of affected people in the development.</p> <p>Conclusion</p> <p>Few of the questionnaires had made use of the experiences of affected people in the development. The correspondence between the symptoms expressed by those affected and the content of the questionnaires was low. A variety of symptoms were expressed by the interviewees, and the participants were also able to distinguish nuances and fluctuations of symptoms. The present study points to the importance of other aspects than just pain and physical functioning as clinical trial outcome measures related to neck-shoulder disorders. To develop a condition-specific questionnaire, it is important to decide on the specific symptoms for the condition. Using the experiences of those affected, in combination with relevant research and professional knowledge, can enhance the validity of the questionnaires.</p

Involvement of mast cells in monocrotaline-induced pulmonary hypertension in rats

Background: Mast cells (MCs) are implicated in inflammation and tissue remodeling. Accumulation of lung MCs is described in pulmonary hypertension (PH); however, whether MC degranulation and c-kit, a tyrosine kinase receptor critically involved in MC biology, contribute to the pathogenesis and progression of PH has not been fully explored.Methods: Pulmonary MCs of idiopathic pulmonary arterial hypertension (IPAH) patients and monocrotaline-injected rats (MCT-rats) were examined by histochemistry and morphometry. Effects of the specific c-kit inhibitor PLX and MC stabilizer cromolyn sodium salt (CSS) were investigated in MCT-rats both by the preventive and therapeutic approaches. Hemodynamic and right ventricular hypertrophy measurements, pulmonary vascular morphometry and analysis of pulmonary MC localization/counts/activation were performed in animal model studies.Results: There was a prevalence of pulmonary MCs in IPAH patients and MCT-rats as compared to the donors and healthy rats, respectively. Notably, the perivascular MCs were increased and a majority of them were degranulated in lungs of IPAH patients and MCT-rats (p < 0.05 versus donor and control, respectively). In MCT-rats, the pharmacological inhibitions of MC degranulation and c-kit with CSS and PLX, respectively by a preventive approach (treatment from day 1 to 21 of MCT-injection) significantly attenuated right ventricular systolic pressure (RVSP) and right ventricular hypertrophy (RVH). Moreover, vascular remodeling, as evident from the significantly decreased muscularization and medial wall thickness of distal pulmonary vessels, was improved. However, treatments with CSS and PLX by a therapeutic approach (from day 21 to 35 of MCT-injection) neither improved hemodynamics and RVH nor vascular remodeling.Conclusions: The accumulation and activation of perivascular MCs in the lungs are the histopathological features present in clinical (IPAH patients) and experimental (MCT-rats) PH. Moreover, the accumulation and activation of MCs in the lungs contribute to the development of PH in MCT-rats. Our findings reveal an important pathophysiological insight into the role of MCs in the pathogenesis of PH in MCT- rats