Torquil Watt

Tests of data quality, scaling assumptions, and reliability of the Danish SF-36.

We used general population data (n = 4084) to examine data completeness, response consistency, tests of scaling assumptions, and reliability of the Danish SF-36 Health Survey. We compared traditional multitrait scaling analyses to analyses using polychoric correlations and Spearman correlations. The frequency of missing values was low, except for elderly people and people with lower levels of education. Response consistency was high and compared well with results for the U.S. SF-36. For respondents with computable scales in all eight domains, scaling assumptions (item internal consistency, item discriminant validity, equal item-own scale correlations, and equal variances) were satisfactory in the total sample and in all subgroups. The SF-36 could discriminate between levels of health in all subgroups, but there were skewness, kurtosis, and ceiling effects in many subgroups (elderly people and people with chronic diseases excepted). Concerning correlation methods, we found interesting differences indicating advantages of using methods that do not assume a normal distribution of answers as an addition to traditional methods.

Fatigue in the Danish general population. Influence of sociodemographic factors and disease

OBJECTIVE To measure the levels of fatigue in the general population, and to examine how disease and sociodemographic factors influence fatigue. DESIGN Cross sectional questionnaire study in the Danish general population. SUBJECTS A random, age stratified sample of 1608 people aged 20–77 with an equal gender distribution (response rate 67%). MAIN OUTCOME MEASURES Five fatigue scales from the questionnaire Multidimensional Fatigue Inventory: General Fatigue, Physical Fatigue, Reduced Activity, Reduced Motivation and Mental Fatigue. RESULTS Fatigue scores were skewed towards absence of fatigue. The General Fatigue and Physical Fatigue scales showed the highest fatigue levels while the Reduced Motivation scale showed lowest levels. Gender differences in fatigue scores were small, but the variability among women was higher—that is, more women had high scores. A multiple linear regression analysis showed that respondents of low social status and respondents with a depression had high fatigue scores on all scales, independent of other factors. Chronic somatic disease had an independent direct effect on Mental Fatigue, but for the rest of the scales, the effect of somatic disease depended on age, gender and/or whether the person was living alone. For example, General and Physical Fatigue decreased with age among healthy people, whereas scores on these scales increased with age among those with a somatic disease. CONCLUSIONS Physical and mental diseases play essential parts for the level of fatigue and as modulators of the associations between sociodemographic factors and fatigue. These interactions should be taken into account in future research on fatigue and sociodemographic factors and when data from clinical studies are compared with normative data from the general population.

Quality of life in the Danish general population - normative data and validity of WHOQOL-BREF using Rasch and item response theory models

Background: The main objective of this study was to investigate the construct validity of the WHOQOL-BREF by use of Rasch and Item Response Theory models and to examine the stability of the model across high/low scoring individuals, gender, education, and depressive illness. Furthermore, the objective of the study was to estimate the reference data for the quality of life questionnaire WHOQOL-BREF in the general Danish population and in subgroups defined by age, gender, and education. Methods: Mail-out-mail-back questionnaires were sent to a randomly selected sample of the Danish general population. The response rate was 68.5%, and the sample reported here contained 1101 respondents: 578 women and 519 men (four respondents did not indicate their genders). Results: Each of the four domains of the WHOQOL-BREF scale fitted a two-parameter IRT model, but did not fit the Rasch model. Due to multidimensionality, the total score of 26 items fitted neither model. Regression analysis was carried out, showing a level of explained variance of between 10 and 14%. The mean scores of the WHOQOL-BREF are reported as normative data for the general Danish population. Conclusion: The profile of the four WHOQOL-BREF domains is a more adequate expression of quality of life than the total score of all 26 items. Although none of the subscales are statistically sufficient measures of their domains, the profile scores seem to be adequate approximations to the optimal score.

Dimensions of Post-Stroke Fatigue: A Two-Year Follow-Up Study

Background: The aim of this study was to examine the course of poststroke fatigue in a cohort of first-time stroke patients compared to the general population, and to identify clinically relevant features of post-stroke fatigue. Methods: We performed a follow-up study of 165 patients with first-time stroke admitted to acute stroke units at the Aarhus University Hospital, Denmark. A reference group of 1,069 persons was sampled from the general population. Fatigue was assessed using the Multidimensional Fatigue Inventory (MFI-20) covering five scales of fatigue (General Fatigue, Physical Fatigue, Reduced Activity, Reduced Motivation, and Mental Fatigue). Results: Compared to the general population, stroke patients reported higher levels of Physical Fatigue. Minor or no differences were found for the other fatigue scales. Pathological fatigue, defined as a score ≧12 on the General Fatigue scale, was reported by 59% (95% CI: 51–66%), 44% (95% CI: 36–51%), 38% (95% CI: 31–46%), and 40% (95% CI: 32–48%) of stroke patients 10 days, 3 months, 1 year, and 2 years following hospitalization for stroke, respectively. Post-stroke fatigue levels decreased after three months and remained stable throughout the remainder of follow-up. Poor functional outcome was consistently associated with increased levels of fatigue. Conclusions: Post-stroke fatigue is a common condition primarily characterized by increased levels of Physical Fatigue. The pathological mechanisms underlying post-stroke fatigue and its clinical implications require further study.

Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism

BACKGROUND The use of levothyroxine to treat subclinical hypothyroidism is controversial. We aimed to determine whether levothyroxine provided clinical benefits in older persons with this condition. METHODS We conducted a double‐blind, randomized, placebo‐controlled, parallel‐group trial involving 737 adults who were at least 65 years of age and who had persisting subclinical hypothyroidism (thyrotropin level, 4.60 to 19.99 mIU per liter; free thyroxine level within the reference range). A total of 368 patients were assigned to receive levothyroxine (at a starting dose of 50 μg daily, or 25 μg if the body weight was <50 kg or the patient had coronary heart disease), with dose adjustment according to the thyrotropin level; 369 patients were assigned to receive placebo with mock dose adjustment. The two primary outcomes were the change in the Hypothyroid Symptoms score and Tiredness score on a thyroid‐related quality‐of‐life questionnaire at 1 year (range of each scale is 0 to 100, with higher scores indicating more symptoms or tiredness, respectively; minimum clinically important difference, 9 points). RESULTS The mean age of the patients was 74.4 years, and 396 patients (53.7%) were women. The mean (±SD) thyrotropin level was 6.40±2.01 mIU per liter at baseline; at 1 year, this level had decreased to 5.48 mIU per liter in the placebo group, as compared with 3.63 mIU per liter in the levothyroxine group (P<0.001), at a median dose of 50 μg. We found no differences in the mean change at 1 year in the Hypothyroid Symptoms score (0.2±15.3 in the placebo group and 0.2±14.4 in the levothyroxine group; between‐group difference, 0.0; 95% confidence interval [CI], ‐2.0 to 2.1) or the Tiredness score (3.2±17.7 and 3.8±18.4, respectively; between‐group difference, 0.4; 95% CI, ‐2.1 to 2.9). No beneficial effects of levothyroxine were seen on secondary‐outcome measures. There was no significant excess of serious adverse events prespecified as being of special interest. CONCLUSIONS Levothyroxine provided no apparent benefits in older persons with subclinical hypothyroidism. (Funded by European Union FP7 and others; TRUST ClinicalTrials.gov number, NCT01660126.)

Agalsidase beta treatment is associated with improved quality of life in patients with Fabry disease: Findings from the Fabry Registry

Disclosure: The Fabry Registry is sponsored by Genzyme Corporation. U.F.-R., K.S., R.J.H., M.B., A.M., and A.P.B. serve on the Genzyme-sponsored Fabry Registry Boards of Advisors. D.B.-J. and F.O.B. are full-time employees of Genzyme Corporation. T.W. has received unrestricted grants from Genzyme for other research projects.Purpose: To evaluate the effect of agalsidase beta on longitudinal health-related quality of life in patients with Fabry disease.Methods: The SF-36® Health Survey was used to measure health-related quality of life in Fabry Registry patients. Seventy-one men and 59 women who were treated with agalsidase beta (median dose: 1.0 mg/kg/2 weeks) and who had baseline and at least 2 yearly posttreatment health-related quality of life measurements were included in these analyses. A repeated measures model was used to analyze change in score from baseline.Results: Men improved in the physical component summary and in all eight scales of the SF-36 after 1 and 2 years and in the mental component summary after 1 year of agalsidase beta treatment (P < 0.05). Women improved in the mental component summary and in six of the eight scales after 1 and/or 2 years of treatment. Patients whose baseline SF-36 scores were below the median showed the greatest improvements. These responses were comparable with or greater than the published effects of various treatments for multiple sclerosis, rheumatoid arthritis, central neuropathic pain, and Gaucher disease.Conclusion: Long-term treatment with agalsidase beta resulted in substantial improvements in health-related quality of life in both men and women; the effect was more pronounced in men.

Modified-Release Recombinant Human TSH (MRrhTSH) Augments the Effect of 131I Therapy in Benign Multinodular Goiter: Results from a Multicenter International, Randomized, Placebo-Controlled Study

BACKGROUND Recombinant human TSH (rhTSH) can be used to enhance (131)I therapy for shrinkage of multinodular goiter (MG). OBJECTIVE, DESIGN, AND SETTING The objective of the study was to compare the efficacy and safety of 0.01 and 0.03 mg modified-release (MR) rhTSH as an adjuvant to (131)I therapy, vs. (131)I alone, in a randomized, placebo-controlled, international, multicenter study. PATIENTS AND INTERVENTION Ninety-five patients (57.2 ± 9.6 yr old, 85% females, 83% Caucasians) with MG (median size 96.0, range 31.9-242.2 ml) were randomized to receive placebo (group A, n = 32), MRrhTSH 0.01 mg (group B, n = 30), or MRrhTSH 0.03 mg (group C, n = 33) 24 h before a calculated activity of (131)I. MAIN OUTCOME MEASURES The primary end point was a change in thyroid volume (by computerized tomography scan, at 6 months). Secondary end points were the smallest cross-sectional area of the trachea; thyroid function tests; Thyroid Quality of Life Questionnaire; electrocardiogram; and hyperthyroid symptom scale. RESULTS Thyroid volume decreased significantly in all groups. The reduction was comparable in groups A and B (23.1 ± 8.8 and 23.3 ± 16.5%, respectively; P = 0.95). In group C, the reduction (32.9 ± 20.7%) was more pronounced than in groups A (P = 0.03) and B. The smallest cross-sectional area of the trachea increased in all groups: 3.8 ± 2.9% in A, 4.8 ± 3.3% in B, and 10.2 ± 33.2% in C, with no significant difference among the groups. Goiter-related symptoms were effectively reduced and there were no major safety concerns. CONCLUSION In this dose-selection study, 0.03 mg MRrhTSH was the most efficacious dose as an adjuvant to (131)I therapy of MG. It was well tolerated and significantly augmented the effect of (131)I therapy in the short term. Larger studies with long-term follow-up are warranted.

Establishing construct validity for the thyroid-specific patient reported outcome measure (ThyPRO): an initial examination

ObjectiveTo establish a reliable and valid scale structure of a patient-reported outcome measuring thyroid-specific quality of life.MethodsThe 98-item ThyPRO questionnaire was administered to patients with benign thyroid diseases at two university hospitals. Multi-trait scaling was performed, evaluating lack of convergent validity (item-own scale polyserial correlation <0.40) or lack of discriminant validity (item-other scale correlation higher than item-own scale correlation) of the hypothesized scale structure. Analyses were repeated in clinical and sociodemographic subgroups and with Pearson correlations. Reliability was estimated by Cronbach’s α, both conventionally and with polychoric correlations.ResultsIn total, 904 patients (69%) responded. Initial multitrait scaling analysis identified 25 scaling errors. Twelve items were omitted from the scale structure, and a re-analysis showed complete convergent validity and only two instances of lack of discriminant validity. Pearson correlations yielded similar results. Across all subgroups, convergent validity was complete, and discriminant validity was found in 99.2% of tests. Lack of discriminant validity was mainly between physical symptoms and psychological and disease-impact scales. Cronbach’s α was acceptable (>0.70, >0.80 with polychoric correlations) for all 13 scales.ConclusionA reliable scale structure displaying complete convergent and almost complete discriminant validity was established in general analyses and in distinct clinical subgroups of patients with benign thyroid diseases.

The chronic autoimmune thyroiditis quality of life selenium trial (CATALYST): study protocol for a randomized controlled trial

BackgroundPatients with chronic autoimmune thyroiditis have impaired health-related quality of life. The thyroid gland has a high selenium concentration, and specific selenoprotein enzyme families are crucial to immune function, and catalyze thyroid hormone metabolism and redox processes in thyroid cells. Previous randomized controlled trials have found that selenium supplementation decreases thyroid-disease-specific antibody levels. We hypothesize that selenium might be beneficial in the treatment of chronic autoimmune thyroiditis.Methods/DesignThe CATALYST trial is an investigator-initiated randomized, blinded, multicentre clinical trial of selenium supplementation versus placebo in patients with chronic autoimmune thyroiditis. Inclusion criteria: age ≥18 years; serum thyroid peroxidase antibody level ≥100 IU/ml within the previous 12 months; treatment with levothyroxine and written informed consent. Exclusion criteria: previous diagnosis of toxic nodular goitre, Graves’ hyperthyroidism, postpartum thyroiditis, Graves’ orbitopathy; previous antithyroid drug treatment, radioiodine therapy or thyroid surgery; immune-modulatory or other medication affecting thyroid function; pregnancy, planned pregnancy or breastfeeding; allergy towards any intervention or placebo component; intake of selenium supplementation >55 μg/day; inability to read or understand Danish or lack of informed consent. The trial will include 2 × 236 participants. The experimental intervention and control groups will receive 200 μg selenium-enriched yeast or matching placebo tablets daily for 12 months. The experimental supplement will be SelenoPrecise®. The primary outcome is thyroid-related quality of life assessed by the Thyroid Patient-Reported Outcome (ThyPRO) questionnaire. Secondary outcomes include serum thyroid peroxidase antibody concentration; serum triiodothyronine/thyroxine ratio; levothyroxine dosage; adverse reactions and serious adverse reactions and events.DiscussionIn this pragmatic trial, participating patients follow their usual treatment at their usual hospitals. In order to collect high-quality data on the clinical course and quality of life, and to minimize missing data, an elaborate trial management system has been designed. 12 months intervention duration was selected in consideration of the primary outcome, thyroid-related quality of life.Trial registrationClinicalTrials.gov ID: NCT02013479.

Disease-Specific as Well as Generic Quality of Life Is Widely Impacted in Autoimmune Hypothyroidism and Improves during the First Six Months of Levothyroxine Therapy

Background Hypothyroidism is often diagnosed, and subsequently treated, due to health-related quality of life (HRQL) issues. However, HRQL following treatment has never previously been assessed in longitudinal descriptive studies using validated instruments. Objective To investigate disease-specific (ThyPRO) and generic (SF-36) HRQL, following levothyroxine therapy in patients with hypothyroidism due to autoimmune thyroiditis. Methods This prospective cohort study was set at endocrine outpatient clinics at two Danish university hospitals. Seventy-eight consecutive patients were enrolled and completed HRQL questionnaires before, six weeks, and six months after initiation of levothyroxine therapy. Normative ThyPRO (n = 739) and SF-36 (n = 6,638) data were available for comparison and changes in HRQL following treatment were estimated and quantified. Results Prior to treatment, all ThyPRO scales were significantly impacted (p<0.0001), compared to the general population sample. The same was observed for seven of eight SF-36 scales, the exception being Bodily Pain. Tiredness (ThyPRO) and Vitality (SF-36) were the most markedly impacted scales. After six weeks of treatment, nine of thirteen ThyPRO scales had significantly improved. ThyPRO improvements were consistent at six months, where five of eight SF-36 scales had also significantly improved, but deficits persisted for a subset of both ThyPRO and SF-36 scales. Conclusions In this population of hypothyroid patients, HRQL was widely affected before treatment, with tiredness as the cardinal impairment according to both ThyPRO and SF-36. Many aspects of HRQL improved during the first six months of LT4 therapy, but full recovery was not obtained. Our results may help clinicians inform patients about expected clinical treatment effects.