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Revision of the ICIDH Severity of Disabilities Scale by data linking and item response theory
The Severity of Disabilities Scale (SDS) of the ICIDH reflects the degree to which an individual's ability to perform a certain activity is restricted. This paper describes the application of two models from item response theory (IRT), the graded response model and the partial credit model, in order to derive a tentative proposal for a revised SDS. The key ingredient of the approach is to scale existing disability items obtained in different studies on a common scale by exploiting the overlap. Both IRT models are fitted to a linked data set containing items for measuring walking disability. Based on these solutions, a tentative SDS is constructed. The paper concludes with a discussion of the implications, limitations and advantages of the approach. Copyright © 2001 John Wiley & Sons, Ltd.
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[Abstract]
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Quality of life in elderly subjects with pain in the hip or knee
This study examines the quality of life (QOL) of community living elderly people aged 55-74 with chronic, episodic or sporadic pain in the hip or knee and of a reference group without pain (total n = 306). Firstly, it was hypothesized that the experienced QOL is lower in people with more chronic pain. Secondly, the potential mediating and moderating roles of disability and of coping with problems in general on the relationship between pain chronicity and QOL were assessed. A Visual Analogue Scale was used to assess global QOL. Physical as well as psychosocial disability was assessed with the Sickness Impact Profile (SIP). Coping with problems in general was assessed with the Utrecht Coping List. As expected, a significantly lower QOL was found in people with more chronic pain (p = 0.045). The difference in QOL between the group with chronic pain and a reference group without pain was 10%. A multivariate regression model showed that physical and especially psychosocial disability are mediators in the relationship between pain chronicity and QOL and that 'seeking social support' as a coping style is a more important predictor of the experienced QOL than either pain chronicity or physical disability. No moderating role of the style of coping with problems was found.
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[Abstract]
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Neonatal Facial Coding System for Assessing Postoperative Pain in Infants: Item Reduction is Valid and Feasible
Objective: The objectives of this study were to: (1) evaluate the validity of the Neonatal Facial Coding System (NFCS) for assessment of postoperative pain and (2) explore whether the number of NFCS facial actions could be reduced for assessing postoperative pain. Design: Prospective, observational study. Patients: Thirty-seven children (0-18 months old) undergoing major abdominal or thoracic surgery. Outcome Measures: The outcome measures were the NFCS, COMFORT "behavior" scale, and a Visual Analog Scale (VAS), as well as heart rate, blood pressure, and catecholamine and morphine plasma concentrations. At 3-hour intervals during the first 24 hours after surgery, nurses recorded the children's heart rates and blood pressures and assigned COMFORT "behavior" and VAS scores. Simultaneously we videotaped the children's faces for NFCS coding. Plasma concentrations of catecholamine, morphine, and its metabolite M6G were determined just after surgery, and at 6, 12, and 24 hours postoperatively. Results: All 10 NFCS items were combined into a single index of pain. This index was significantly associated with COMFORT "behavior" and VAS scores, and with heart rate and blood pressure, but not with catecholamine, morphine, or M6G plasma concentrations. Multidimensional scaling revealed that brow bulge, eye squeeze, nasolabial furrow, horizontal mouth stretch, and taut tongue could be combined into a reduced measure of pain. The remaining items were not interrelated. This reduced NFCS measure was also significantly associated with COMFORT "behavior" and VAS scores, and with heart rate and blood pressure, but not with the catecholamine, morphine, or M6G plasma concentrations. Conclusion: This study demonstrates that the NFCS is a reliable, feasible, and valid tool for assessing postoperative pain. The reduction of the NFCS to 5 items increases the specificity for pain assessment without reducing the sensitivity and validity for detecting changes in pain.
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[Abstract]
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Cesar-therapie tijdelijk effectiever dan standaardbehandeling door de huisarts bij patiënten met chronische aspecifieke lage rugklachten : gerandomiseerd, gecontroleerd en geblindeerd onderzoek met 1 jaar follow-up [Cesar therapy is temporarily more effective than a standard treatment from the general practitioner in patients with chronic aspecific lower back pain; randomized, controlled and blinded study with a I year follow-up]
Doel van dit onderzoek was het vaststellen van korte- en langetermijneffecten van Cesar-therapie op zelfgerapporteerd herstel en op houdingsverandering bij patiënten met chronische aspecifieke lage rugklachten. Patiënten met chronische aspecifieke lage rugklachten werden, nadat 'informed consent' was verkregen, 'at random' verdeeld over een groep die gedurende circa drie maanden Cesar-therapie kreeg en een controlegroep die de standaardbehandeling van de eigen huisarts kreeg. Uitkomstmaten waren zelfgerapporteerd herstel en houdingsverandering (thoracale en lumbale wervelkolom, bekken). Patiënten die met Cesar-therapie behandeld waren, gaven drie maanden na randomisatie significant vaker aan dat hun rugklachten verbeterd waren. Cesar-therapie blijkt significant effectiever dan standaardbehandeling bij patiënten met chronische lage rugklachten op een termijn van zes maanden na randomisatie.
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[Abstract]
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The effectiveness of graded activity for low back pain in occupational healthcare
A controlled trial was performed in a occupational healthcare setting to determine the effectiveness of graded activity as part of a multistage RTW programme. Workers (112) absent from work for more than eight weeks due to low back pain, were randomised to either graded activity (n = 55) or usual care (n = 57). The graded activity, a physical exercise programme aimed at RTW, was based on operant-conditioning behavioural principles. Main outcome measures were: number of days off work until first RTW for more then 28 days; total number of days on sick leave during follow u; functional status; severity of pain. Follow up was 26 weeks. Results showed, among others things, median time until RTW was equal to the total number of days on sick leave. It was 139 (IQR = 69) days in the graded activity group and 111 (IQR = 76) days in the usual care group (hazard ratio = 0.52, 95% CI 0.32 to 0.86). Graded activity did not improve pain or functional status clinically significantly. In is concluded that graded activity was not effective for any of the outcome measures. Different interventions combined can lead to a delay in RTW. Delay in referral to graded activity delays RTW. In implementing graded activity special attention should be paid to the structure and process of care.
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[Abstract]
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Is avoidant coping independent of disease status and stable over time in patients with ankylosing spondylitis?
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2004
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Author: |
Boonen, A.
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Heijde, D. van der
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Landewé, R.
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Chorus, A.
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Lankveld, W. van
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Miedema, H.
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Tempel, H. van der
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Linden, S. van der
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Keywords: |
age · ankylosing spondylitis · avoidance behavior · coping behavior · correlation analysis · disease activity · disease association · disease duration · education · gender · health status · immobilization · major clinical study · medical assessment · multivariate logistic regression analysis · physical activity · physical capacity · rigidity · time · Adaptation, Psychological · Adolescent · Adult · Cross-Sectional Studies · Female · Health Status Indicators · Humans · Longitudinal Studies · Male · Middle Aged · Pain · Pain Measurement · Questionnaires · Severity of Illness Index · Spondylitis, Ankylosing
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Objective: To determine whether avoidant coping in ankylosing spondylitis (AS) is independent of disease status and whether it is stable over time. Methods: 658 patients with AS completed a postal questionnaire on health status, including pain and stiffness (BASDAI), physical function (BASFI), and coping (CORS). In CORS, "decreasing activities to cope with pain" and "pacing to cope with limitations" reflect avoidant behavioural coping. Ninety patients continued in a longitudinal study and 70 completed the CORS after four years. The adjusted contribution of age, sex, disease duration, educational level, pain (BASDAI), and physical function (BASFI) to the two avoidant coping strategies at first assessment was determined by multiple linear regression. Agreement between coping at first assessment and four years later was determined by intraclass correlation, and the correlation between change in coping and change in disease status over time by Pearson's correlation. Results: At first assessment, worse physical function (BASFI) and more pain (BASDAI) were associated with "decreasing activities to cope with pain". Worse physical function, but not pain, was associated with "pacing to cope with limitations". The contribution of physical function or pain to the total explained variance in each of the coping strategies was small. Disease duration was not a determinant of avoidant coping, but greater age was associated with "pacing to cope with limitations". Change in avoidant coping strategies over time could not be explained by change in function or pain. Conclusions: In AS, avoidant coping at a particular time is largely independent of disease duration or status. Variability in avoidant coping over a limited period of four years cannot be explained by change in disease status.
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[Abstract]
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Effects of software programs stimulating regular breaks and exercises on work-related neck and upper-limb disorders
Objectives. This study evaluated the effects on work-related neck and upper-limb disorders among computer workers stimulated (by a software program) to take regular breaks and perform physical exercises. Possible effects on sick leave and productivity were studied as well. Methods. A randomized controlled design was used with cluster randomization. Altogether 268 computer workers with complaints in the neck or an upper limb from 22 office locations were randomized into a control group, one intervention group stimulated to take extra breaks and one intervention group stimulated to perform exercises during the extra breaks during an 8-week period. Questionnaires were administered before and after the intervention, and questions were generated by the software during the intervention period. Computer usage was recorded online. Results. The data on self-reported recovery suggested a favorable effect; more subjects in the intervention groups than in the control group reported recovery (55% versus 34%) from their complaints and fewer reported deterioration (4% versus 20%). However, a comparison between the reported pre- and postintervention scores on the severity and frequency of the complaints showed no significant differences in the change among the three groups. No effects on sick leave were observed. The subjects in the intervention groups showed higher productivity. Conclusions. The use of a software program stimulating workers to take regular breaks contributes to perceived recovery from neck or upper-limb complaints. There seems to be no additional effects from performing physical exercises during these breaks. This work is licensed under a Creative Commons Attribution 4.0 International License.
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[Abstract]
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The effectiveness of high-intensity versus low-intensity back schools in an occupational setting: A pragmatic randomized controlled trial
Study Design. Randomized controlled trial. Objectives. To compare high- and low-intensity back schools with usual care in occupational health care. Summary of Background Data. The content and intensity of back schools vary widely and the methodologic quality of randomized controlled trials is generally weak. Until now, no back school has proven to be superior for workers sick-listed because of subacute nonspecific low back pain. Methods. Workers (n = 299) sick-listed for a period of 3 to 6 weeks because of nonspecific low back pain were recruited by the occupational physician and randomly assigned to a high-intensity back school, a low-intensity back school, or care as usual. Outcome measures were days until return to work, total days of sick-leave, pain, functional status, kinesiophobia, and perceived recovery and were assessed at baseline and at 3 and 6 months of follow-up. Principal analyses were performed according to the intention-to-treat principle. Results. We randomly allocated 299 workers. Workers in the low-intensity back school returned to work faster compared with usual care and the high-intensity back school, with hazard ratios of 1.4 (P = 0.06) and 1.3 (P = 0.09), respectively. The comparison between high-intensity back school and usual care resulted in a hazard ratio of 1.0 (P = 0.83). The median number of sick-leave days was 68, 75, and 85 in the low-intensity back school, usual care, and high-intensity back school, respectively. Beneficial effects on functional status and kinesiophobia were found at 3 months in favor of the low-intensity back school. No substantial differences on pain and perceived recovery were found between groups. Conclusions. The low-intensity back school was most effective in reducing work absence, functional disability, and kinesiophobia, and more workers in this group scored a higher perceived recovery during the 6-month follow-up. ©2006, Lippincott Williams & Wilkins, Inc.
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[Abstract]
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What works best for whom? An exploratory, subgroup analysis in a randomized, controlled trial on the effectiveness of a workplace intervention in low back pain patients on return to work
STUDY DESIGN. Exploratory subgroup analysis in a randomized controlled trial (RCT). OBJECTIVE. To detect possible moderators in the effectiveness of a workplace intervention in a population of workers with sick leave due to sub acute nonspecific low back pain. SUMMARY OF BACKGROUND DATA. In a recently published RCT, a workplace intervention was effective on return to work, compared to usual care. Examining the heterogeneity of effect sizes within the population in this RCT (n = 196) can lead to information on the effectiveness of the intervention in subgroups of patients. METHODS. A subgroup analysis was performed by adding interaction terms to the statistical model. Before analysis the following possible moderators for treatment were identified: age, gender, pain, functional status, heavy work, and sick leave in the previous 12 months. Cox regression analyses were performed and survival curves were plotted. RESULTS. The interaction (P = 0.02) between age (dichotomized at the median value) and the workplace intervention indicates a modifying effect. The workplaceintervention is more effective for workers <44 years (HR, 95% CI = 2.5, [1.6, 4.1] vs. 1.2 [0.8, 1.8] for workers <44 years old). The interaction between sick leave in the previous 12 months and the workplace intervention is significant (P = 0.02). The intervention is more effective for workers with previous sick leave (HR, 95% CI = 2.8 [1.7, 4.9] vs. 1.3 [0.8, 2.0]). A modifying effect of gender, heavy work, and pain score and functional status on the effectiveness of this intervention was not found. CONCLUSION. The findings from these exploratory analyses should be tested in future RCTs. This workplace intervention seems very suitable for return to work of older workers and workers with previous sick leave. Gender, perceived heavy work, and baseline scores in pain and functional status should not be a basis for assignment to this intervention. © 2009 Lippincott Williams & Wilkins, Inc.
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[Abstract]
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The effect of physical activity in leisure time on neck and upper limb symptoms
Background. Little is known of the preventive effects of physical activity in leisure time on neck and upper limb symptoms. Methods. A cohort of 1742 employees was selected from a prospective cohort study with a follow-up period of 3 years. Independent variables were sporting activities and physically active commuting. Outcome measures were neck/shoulder symptoms and elbow/wrist/hand symptoms as well as sickness absence due to these symptoms. To analyze the data, the generalized estimating equation (GEE) method was used, with adjustment for individual characteristics, such as age, gender, lifestyle, and the outcome at baseline. Results. Practicing sports for at least 10 months a year decreased the risk of neck/shoulder symptoms (OR: 0.82; CI: 0.67-0.99), sickness absence (OR: 0.48; CI: 0.28-0.84), and long-term sickness absence (OR: 0.37; CI: 0.17-0.84) due to neck or upper limb symptoms. A high mean intensity (≥3 h per week) of sporting activities had less effect than the continuation of these activities throughout the year. Conclusion. Sustained sporting activities have a favorable effect on neck/shoulder symptoms and on sickness absence due to neck or upper limb symptoms. An effect of physically active commuting could not be demonstrated, although there was a tendency towards a favorable effect on sickness absence. © 2004 Elsevier Inc. All rights reserved.
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[Abstract]
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Physical and psychosocial disability in elderly subjects in relation to pain in the hip and/or knee
Objective. To determine physical and psychosocial disability in subjects aged 55 to 74 years living in the community, in relation to pain in the hip and/or knee, and to explore the relationships between pain, physical and psychosocial disability, and selected background variables. Methods. A subsample from a community based study on pain, disability, and radiological osteoarthritis (ROA) was used to identify groups with sporadic, episodic, and chronic pain and a reference group. Disability was assessed with the Sickness Impact Profile. Data were available for 306 subjects (response 83%). Results. The mean physical disability in the group with chronic (and more severe) pain (N=59) was 5.4 times and psychosocial disability was 3.6 times higher than those of a reference group (N=72). The body mass index, the existence of extra mobility problems, and ROA were independently positively related to physical disability. Male sex, having extra mobility problems, and moderate ROA were independently positively related to psychosocial disability. Conclusion. Subjects with more chronic (and severe) pain in the hip and/or knee had relatively high levels of physical as well as psychosocial disability, compared to a reference group without any signs of OA. Pain chronicity had no significant contribution to physical disability, if corrected for other factors. Both forms of disability in subjects with pain were better predicted by ROA and by problems other than pain in the hip or knee alone, than by the chronicity of the pain.
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[Abstract]
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The effects of a health educational and exercise program for older adults with osteoarthritis of the hip or knee
Objective. Evaluation of a self-management program for patients with osteoarthritis (OA) of the hip or knee. The program, which consisted of 6 weekly sessions of 2 hours, included health education by a peer and physical exercises taught by a physical therapist. Methods. Randomized controlled trial. Inclusion criteria were diagnosis of OA of the hip or knee according to ACR clinical and radiographic criteria and age 55 to 75 years. Exclusion criteria: on waiting list for joint replacement. There were pretest, posttest, and followup (6 months) assessments. The experimental group consisted of 56 patients, the control group 49. Outcome variables were pain, quality of life, activity restrictions, knowledge about OA, self-efficacy, body mass index (BMI), and mobility measures. Attention was also paid to effects on health care utilization and lifestyle behavior. Results. Significant MANOVA group x time effects (p < 0.05, one-sided) were found for pain, quality of life, strength of the left M. quadriceps, knowledge, self-efficacy, BMI, physically active lifestyle, and visits to the physical therapist. Most effects were moderate at posttest assessment and smaller at follow-up. No effects were found for range of motion and functional tasks. Conclusion. The program was reasonably effective, but more attention should be paid to proactive followup interventions and to the selection of participants.
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[Abstract]
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Lack of effect of doxycycline on disease activity and joint damage in patients with rheumatoid arthritis. A double blind, placebo controlled trial
article |
2001
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Author: |
Laan, W. van der
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Molenaar, E.
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Ronday, K.
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Verheijen, J.
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Breedveld, F.
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Greenwald, R.
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Dijkmans, B.
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Tekoppele, J.
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Keywords: |
Health · Biomedical Research · Doxycycline · Pyridinolines · Rheumatoid arthritis · deoxypyridinoline · doxycycline · placebo · pyridinoline · clinical examination · clinical trial · controlled clinical trial · controlled study · crossover procedure · disease activity · double blind procedure · erythrocyte sedimentation rate · foot radiography · hand radiography · joint destruction · joint stiffness · laboratory test · major clinical study · randomized controlled trial · scoring system · Adolescent · Adult · Aged · Aged, 80 and over · Analysis of Variance · Arthritis, Rheumatoid · Chi-Square Distribution · Cross-Over Studies · Dose-Response Relationship, Drug · Double-Blind Method · Doxycycline · Drug Administration Schedule · Female · Follow-Up Studies · Humans · Male · Middle Aged · Pain Measurement · Reference Values · Severity of Illness Index · Treatment Failure · Treatment Outcome
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Objective. To investigate the effects of doxycycline on disease activity and joint destruction in patients with rheumatoid arthritis (RA). Methods. A 36 week double blind, placebo controlled crossover trial was conducted. Patients (n = 66) received 50 mg doxycycline or placebo twice a day during 12, 24, or 36 weeks. Patient assessments were performed before the treatment was administered, at 6, 12, 24 and 36 weeks of treatment, and finally at 4 weeks after cessation of treatment. Patient assessments, swollen and tender joint counts, duration of morning stiffness, erythrocyte sedimentation rate, and Modified Disease Activity Score were used as measures of disease activity. Effects on joint destruction were assessed by urinary excretion of the pyridinolines hydroxylysylpyridinoline and lysylpyridinoline and by scoring radiographic damage of hands and feet before and after treatment. Results. The changes of clinical or laboratory disease activity measures, pyridinoline excretion, or progression of radiographic joint damage during doxycycline or placebo treatment did not differ significantly. Conclusion. The results indicate that 50 mg doxycycline twice a day provided no therapeutic benefit for patients with RA.
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[Abstract]
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Feasibility and reliability of a mailed questionnaire to obtain visual analogue scale valuations for health states defined by the health utilities index mark 3
article |
2004
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Author: |
Raat, H.
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Bonsel, G.J.
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Hoogeveen, W.C.
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Essink-Bot, M.L.
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Gemke, R.J.B.J.
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Krabbe, P.F.M.
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Moll, H.A.
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Suijlekom van-Smit, L.W.A.
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Verrips, E.
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Keywords: |
Health · Activities of Daily Living · Adolescent · Adult · Age Distribution · Attitude to Health · Canada · Child · Child Welfare · Child, Preschool · Feasibility Studies · Female · France · Health Status Indicators · Humans · Male · Netherlands · Pain Measurement · Parents · Pediatrics · Postal Service · Questionnaires · Reference Values · Reproducibility of Results · Sex Distribution · Socioeconomic Factors · Children · Feasibility · Health utilities index mark 3 (HUI, HUI3) · Health-related quality of life · Mailed questionnaire · Preferences · Reliability · Visual analogue scale (VAS) · Age distribution · Classification · Comparative study · Daily life activity · Evaluation · Health survey · Instrumentation · Pain assessment · Postal mail · Preschool child · Psychological aspect · Reference value · Reproducibility · Sex ratio · Socioeconomics · Standard · Validation study
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To establish the generalizability (external validity) of the Health Utilities Index Mark 3 (HUI3) as a single-summary score generic outcome measure in numerous countries/subgroups (including children), repeated studies of community preferences should be performed in various settings. In performing multiple HUI3 studies, a mailed questionnaire approach, if feasible and reliable, might be substituted for oral interviews. In the present study, we assessed the feasibility and reliability of a mailed questionnaire approach originally developed for the EQ-5D, for the purpose of collecting Visual Analogue Scale (VAS) valuations from parents as surrogate responders for 65 pediatric HUI3 health states and for the state of being dead Untransformed mean VAS scores of the health states and scores converted into preliminary Standard Gamble (SG)-utilities were compared with Canadian and French multiattribute utility estimates. A random sample of 1920 parents of schoolchildren (aged 4 to 13) received a mailed questionnaire. Each parent was asked to rate 6 HUI3 health states on a 0 to 100 VAS. Response was 70%. Mean completion time was 20 minutes (SD 9). The questionnaire was rated difficult by only 9%. The current format was, however, inappropriate for valuing the state of being dead. Interrater reliability of health state valuations was .87. Spearman's rank correlations, Pearson-R correlations and intra class correlation coefficients (ICCs) between untransformed VAS valuations and Canadian/French utility estimates were =.87. However, preliminary SG-utilities showed diminished ICCs (.71 to .72). The data support the feasibility and reliability of mailed HUI3 valuation questionnaires to a considerable extent, but further methodological studies regarding other formats and different populations are recommended. Copyright 2003 by Lippincott Williams & Wilkins.
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[Abstract]
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Intestinal Fungal Dysbiosis Is Associated With Visceral Hypersensitivity in Patients With Irritable Bowel Syndrome and Rats
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2017
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Author: |
Botschuijver, S.
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Roeselers, G.
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Levin, E.
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Jonkers, D.M.
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Welting, O.
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Heinsbroek, S.E.M.
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Weerd, H.H. de
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Boekhout, T.
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Fornai, M.
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Masclee, A.A.
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Schuren, F.H.J.
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Jonge, W.J. de
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Seppen, J.
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Wijngaard, R.M. van den
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Keywords: |
Biology · Dectin-1 · Immune Response · Mycobiota · Yeast · Protein kinase inhibitor · Protein kinase Syk · Syk protein, rat · Abdominal pain · Separation anxiety · Abdominal Pain · Adult · Animals · Antifungal Agents · Anxiety, Separation · Behavior, Animal · Beta-Glucans · Case-Control Studies · Cell Degranulation · Cell Line · Disease Models, Animal · Dysbiosis · Fecal Microbiota Transplantation · Feces · Female · Fungi · Gastrointestinal Microbiome · Humans · Hyperalgesia · Intestines · Irritable Bowel Syndrome · Male · Mast Cells · Maternal Deprivation · Middle Aged · Pain Measurement · Pain Perception · Pain Threshold · Protein Kinase Inhibitors · Rats, Long-Evans · Syk Kinase · Biomedical Innovation · Healthy Living · Life · MSB - Microbiology and Systems Biology · ELSS - Earth, Life and Social Sciences
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Background & Aims Visceral hypersensitivity is one feature of irritable bowel syndrome (IBS). Bacterial dysbiosis might be involved in the activation of nociceptive sensory pathways, but there have been few studies of the role of the mycobiome (the fungal microbiome) in the development of IBS. We analyzed intestinal mycobiomes of patients with IBS and a rat model of visceral hypersensitivity. Methods We used internal transcribed spacer 1-based metabarcoding to compare fecal mycobiomes of 18 healthy volunteers with those of 39 patients with IBS (with visceral hypersensitivity or normal levels of sensitivity). We also compared the mycobiomes of Long-Evans rats separated from their mothers (hypersensitive) with non-handled (normally sensitive) rats. We investigated whether fungi can cause visceral hypersensitivity using rats exposed to fungicide (fluconazole and nystatin). The functional relevance of the gut mycobiome was confirmed in fecal transplantation experiments: adult maternally separated rats were subjected to water avoidance stress (to induce visceral hypersensitivity), then given fungicide and donor cecum content via oral gavage. Other rats subjected to water avoidance stress were given soluble β-glucans, which antagonize C-type lectin domain family 7 member A (CLEC7A or DECTIN1) signaling via spleen-associated tyrosine kinase (SYK), a SYK inhibitor to reduce visceral hypersensitivity, or vehicle (control). The sensitivity of mast cells to fungi was tested with mesenteric windows (ex vivo) and the human mast cell line HMC-1. Results α diversity (Shannon index) and mycobiome signature (stability selection) of both groups of IBS patients differed from healthy volunteers, and the mycobiome signature of hypersensitive patients differed from that of normally sensitive patients. We observed mycobiome dysbiosis in rats that had been separated from their mothers compared with non-handled rats. Administration of fungicide to hypersensitive rats reduced their visceral hypersensitivity to normal levels of sensitivity. Administration of cecal mycobiomes from rats that had been separated from their mothers (but not non-handled mycobiome) restored hypersensitivity to distension. Administration of soluble β-glucans or a SYK inhibitor reduced visceral hypersensitivity, compared with controls. Particulate β-glucan (a DECTIN-1 agonist) induced mast cell degranulation in mesenteric windows and HMC-1 cells responded to fungal antigens by release of histamine. Conclusions In an analysis of patients with IBS and controls, we associated fungal dysbiosis with IBS. In studies of rats, we found fungi to promote visceral hypersensitivity, which could be reduced by administration of fungicides, soluble β-glucans, or a SYK inhibitor. The intestinal fungi might therefore be manipulated for treatment of IBS-related visceral hypersensitivity. © 2017 AGA Institute. Chemicals/CAS: protein kinase Syk, 138674-26-7; Antifungal Agents; beta-Glucans; Protein Kinase Inhibitors; Syk Kinase; Syk protein, rat
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[Abstract]
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