Content validity of visual analog scales to assess symptom severity of acute angioedema attacks in adults with hereditary angioedema: an interview study.

BACKGROUND: Hereditary angioedema (HAE) is a rare, debilitating, potentially life-threatening condition characterized by recurrent acute attacks of edema of the skin, face/upper airway, and gastrointestinal and urogenital tracts. During a laryngeal attack, people with HAE may be at risk of suffocation, while other attacks are often associated with intense pain, disfigurement, disability, and/or vomiting. The intensity of some symptoms is known only to the person experiencing them. Thus, interview studies are needed to explore such experience and patient-reported outcome measures (PROMs) are required for systematic assessment of symptoms in the clinical setting and in clinical trials of treatments for acute HAE attacks. OBJECTIVE: The aim of this interview study was to assess the content validity and suitability of four visual analog scale (VAS) instruments for use in clinical studies. The VAS instruments were designed to assess symptoms at abdominal, oro-facial-pharyngeal-laryngeal, peripheral, and urogenital attack locations. This is the first known study to report qualitative data about the patient's experience of the rare disorder, HAE. METHODS: Semi-structured exploratory and cognitive debriefing interviews were conducted with 27 adults with a confirmed clinical/laboratory diagnosis of HAE (baseline plasma level of functional plasma protein C1 esterase inhibitor [C1INH] <50% of normal without evidence for acquired angioedema). There were 17 participants from the US and 10 from Italy, with mean age 42.5 (SD 14.5) years, range 18-72 years, mean HAE duration 21.3 (SD 14.1) years, range 1-45 years, 67% female, and 44% VAS-naïve. Experience of acute angioedema attacks was first explored, noting spontaneous mentions by participants of HAE symptomatology. Cognitive debriefing of the VAS instruments was undertaken to assess the suitability, comprehensibility, and relevance of the VAS items. Asymptomatic participants completed the VAS instruments relevant to their angioedema experience, reporting as if they were experiencing an acute angioedema attack at the time. Interviews were conducted in the clinic setting in the US and Italy over an 8-month period. RESULTS: Participants mentioned spontaneously almost all aspects of acute angioedema attacks covered by the four VAS instruments, thus providing strong support for inclusion of nearly all VAS items, with no important symptoms missing. Predominant symptoms found to be associated with acute angioedema attacks were edema and pain, and there was evidence of varying degrees of disruption to everyday activities supporting the inclusion of an overall severity item reflecting the disabling effects of HAE symptoms. VAS item wording was understood by participants. CONCLUSION: This interview study explored and reported the patient experience of HAE attacks. It demonstrated the content validity of the four anatomical location HAE VAS instruments and their suitability for use in clinical trials of recombinant human C1INH (rhC1INH) treatment for ascertaining trial participants' assessments of the severity of acute angioedema symptoms.

Evaluation of new measures of the impact of hypothyroidism on quality of life and symptoms: the ThyDQoL and ThySRQ.

OBJECTIVES: This article reports the psychometric properties of two new condition-specific questionnaires: 1) the 18-item Underactive Thyroid-Dependent Quality of Life Questionnaire (ThyDQoL) individualized measure of perceived impact of hypothyroidism on quality of life (QoL); and 2) the 15-item Underactive Thyroid Symptom Rating Questionnaire (ThySRQ), in which patients rate symptom bother. METHODS: A cross-sectional survey was conducted of 110 adults with overt and subclinical hypothyroidism, 103 treated with thyroxine. Patients, the majority of whom (81%) were women, were recruited from primary care (57%) and from hospital clinics (43%). The mean age of patients was 55.1 (SD 14.3) years. Respondents rated personally applicable ThyDQoL life domains for importance and impact of hypothyroidism, and ThySRQ symptom bother. RESULTS: Completion rates were high (>98%). All 18 ThyDQoL domains were rated as negatively impacted by hypothyroidism and important for QoL. The ThyDQoL had high internal consistency reliability (Cronbach's alpha = 0.949 [N = 97]), factor analysis indicated that applicable domains could be combined into an overall Average Weighted Impact score, for which the sample mean, -3.11 (2.2), showed considerable negative impact of hypothyroidism on QoL (maximum possible range -9 to +3). There is good preliminary evidence to justify shortening the ThyDQoL to 14 domain-specific items. For the ThySRQ Cronbach's alpha was 0.808 (N = 95). Highest symptom bother ratings were for hair problems, weight gain, depression, cold, and tiredness. CONCLUSIONS: Both the ThyDQoL and ThySRQ are highly acceptable to patients with hypothyroidism and have good internal consistency reliability. Their sensitivity to change now needs to be evaluated in clinical trials.

The beneficial effect of L-thyroxine on cardiovascular risk factors, endothelial function, and quality of life in subclinical hypothyroidism: randomized, crossover trial.

CONTEXT: Subclinical hypothyroidism (SCH) is defined as raised serum TSH levels with circulating thyroid hormones within the reference range. It is uncertain whether treatment of SCH with L-thyroxine improves cardiovascular (CV) risk factors and quality of life. OBJECTIVE: The objective of the study was to assess CV risk factors and patient-reported outcomes after treatment. DESIGN: This was a randomized, double-blind, crossover study of L-thyroxine and placebo. SETTING: The study was conducted with community-dwelling patients. PATIENTS: One hundred patients [mean age (sd) 53.8 (12) yr, 81 females] with SCH [mean TSH 6.6 (1.3) mIU/liter] without previously treated thyroid or vascular disease. INTERVENTION: Intervention consisted of 100 microg L-thyroxine or placebo daily for 12 wk each. MEASUREMENTS: Primary parameters were total cholesterol (TC) and endothelial function [brachial artery flow-mediated dilatation (FMD)], an early marker of atherosclerosis. Patient-reported outcomes were also assessed. RESULTS: L-thyroxine treatment reduced TC (vs. placebo) from 231.6 to 220 mg/dl, P < 0.001; low-density lipoprotein cholesterol from 142.9 to 131.3 mg/dl, P < 0.05; waist to hip ratio from 0.83 to 0.81, P < 0.006; and improved FMD from 4.2 to 5.9%, P < 0.001. Multivariate analysis showed that increased serum free T(4) level was the most significant variable predicting reduction in TC or improvement in FMD. Furthermore, the symptom of tiredness improved on L-thyroxine therapy, but other patient-reported outcomes were not significantly different after correction for multiple comparisons. CONCLUSION: SCH treated by L-thyroxine leads to a significant improvement in CV risk factors and symptoms of tiredness. The CV risk factor reduction is related to the increased level of achieved free T(4) concentration.

Preliminary development of the new individualized HDQoL questionnaire measuring quality of life in adult hypopituitarism.

OBJECTIVES: The objectives were (1) to report the preliminary development of the Hormone Deficiency-dependent Quality of Life (HDQoL) questionnaire, a new individualized questionnaire in which respondents rate personally applicable domains for importance and impact of hormonal deficiency and its treatment; (2) to evaluate the HDQoL's psychometric properties for adults with hypopituitarism including growth hormone deficiency (GHD). METHODS: Internal consistency reliability, aspects of validity, and sensitivity to change of the HDQoL were investigated in: (1) a cross-sectional survey of 157 adults with treated or untreated GHD; (2) a randomized, placebo-controlled study of 3 months' growth hormone (GH) withdrawal from 12 of 21 GH-treated adults. RESULTS: Thirteen of the original 18 HDQoL domains were relevant and important for GH-deficient adults. The shorter 13-item HDQoL had excellent internal reliability (Cronbach's alpha coefficient = 0.914, n = 109), and was sensitive to sex differences (cross-sectional study): women perceived worse present QoL than men [t(149.8) = 2.33, P = 0.021]. The HDQoL was sensitive to change (GH-withdrawal study) with a significant between-group difference in change in domain scores for things I can do physically[t(16) = 2.47, P = 0.025, 2-tailed], patients withdrawn from GH reporting greater negative impact of hormone deficiency on this domain at end-point. Qualitative work resulted in the addition of seven new HDQoL domains, including energy and bodily pain. CONCLUSION: The HDQoL, although at an early stage of development, proved useful in identifying expected changes following GH withdrawal. The extended 20-item version is recommended for further evaluation in assessing the impact of hypopituitarism on QoL.

Psychometric evaluation of a new questionnaire measuring treatment satisfaction in hypothyroidism: the ThyTSQ.

OBJECTIVES: There is a clinical impression of dissatisfaction with treatment for hypothyroidism among some patients. Psychometric properties of the new ThyTSQ questionnaire are evaluated. The questionnaire, measuring patients' satisfaction with their treatment for hypothyroidism, has two parts: the seven-item ThyTSQ-Present and four-item ThyTSQ-Past, measuring satisfaction with present and past treatment, respectively, on scales from 6 (very satisfied) to 0 (very dissatisfied). METHODS: The questionnaire was completed once by 103 adults with hypothyroidism, age (mean [SD]) 55.2 [14.4], range 23-84 years (all treated with thyroxine). RESULTS: Completion rates were very high. Internal consistency reliability was excellent for both ThyTSQ-Present and ThyTSQ-Past (Cronbach's alpha = 0.91 and 0.90, respectively [N = 102 and 103]). Principal components analyses indicated that the seven items of the ThyTSQ-Present and the four items of the ThyTSQ-Past could be summed into separate Present Satisfaction and Past Satisfaction total scores. Mean Present Satisfaction was 32.5 (7.8), maximum range 0-42, and mean Past Satisfaction was 17.5 (6.1), maximum range 0-24, indicating considerable room for improvement. Patients were least satisfied with their present understanding of their condition, mean 4.2 (1.7) (maximum range 0-6), and with information provided about hypothyroidism around the time of diagnosis, mean 3.9 (1.8) (maximum range 0-6). CONCLUSIONS: The ThyTSQ is highly acceptable to patients with hypothyroidism (excellent completion rates), and has established internal consistency reliability. It will assist health professionals in considering psychological outcomes when treating people with hypothyroidism, and is suitable for clinical trials and routine clinical monitoring.

Psychometric properties of two measures of psychological well-being in adult growth hormone deficiency.

BACKGROUND: Psychometric properties of two measures of psychological well-being were evaluated for adults with growth hormone deficiency (GHD): the General Well-being Index, (GWBI)--British version of the Psychological General Well-being Index, and the 12-item Well-being Questionnaire (W-BQ12). METHODS: Reliability, structure and other aspects of validity were investigated in a cross-sectional study of 157 adults with treated or untreated GHD, and sensitivity to change in a randomised placebo-controlled study of three months' growth hormone (GH) withdrawal from 12 of 21 GH-treated adults. RESULTS: Very high completion rates were evidence that both questionnaires were acceptable to respondents. Factor analyses did not indicate the existence of useful GWBI subscales, but confirmed the validity of calculating a GWBI Total score. However, very high internal consistency reliability (Cronbach's alpha = 0.96, N = 152), probably indicated some item redundancy in the 22-item GWBI. On the other hand, factor analyses confirmed the validity of the three W-BQ12 subscales of Negative Well-being, Energy, and Positive Well-being, each having excellent internal reliability (alphas of 0.86, 0.86 and 0.88, respectively, N from 152 to 154). There was no sign of item redundancy in the highly acceptable Cronbach's alpha of 0.93 (N = 148) for the whole W-BQ12 scale. Whilst neither questionnaire found significant differences between GH-treated and non-GH-treated patients, there were correlations (for GH-treated patients) with duration of GH treatment for GWBI Total (r = -0.36, p = 0.001, N = 85), W-BQ12 Total (r = 0.35, p = 0.001, N = 88) and for all W-BQ12 subscales: thus the longer the duration of GH treatment (ranging from 0.5 to 10 years), the better the well-being. Both questionnaires found that men had significantly better overall well-being than women. The W-BQ12 was more sensitive to change than the GWBI in the GH-Withdrawal study. A significant between-group difference in change in W-BQ12 Energy scores was found [t(18) = 3.25, p = 0.004, 2-tailed]: patients withdrawn from GH had reduced energy at end-point. The GWBI found no significant change. CONCLUSION: The W-BQ12 is recommended in preference to the GWBI to measure well-being in adult GHD: it is considerably shorter, has three useful subscales, and has greater sensitivity to change.

The effects of growth hormone and/or testosterone in healthy elderly men: a randomized controlled trial.

CONTEXT: Declines in GH and testosterone (Te) secretion may contribute to the detrimental aging changes of elderly men. OBJECTIVE: To assess the effects of near-physiological GH with/without Te administration on lean body mass, total body fat, midthigh muscle cross-section area, muscle strength, aerobic capacity, condition-specific quality of life (Age-Related Hormone Deficiency-Dependent Quality of Life questionnaire), and generic health status (36-Item Short-Form Health Survey) of older men. DESIGN, SETTINGS, AND PARTICIPANTS: A 6-month, randomized, double-blind, placebo-controlled trial was performed on 80 healthy, community-dwelling, older men (age, 65-80 yr). INTERVENTIONS: Participants were randomized to receive 1) placebo GH or placebo Te, 2) recombinant human GH (rhGH) and placebo Te (GH), 3) Te and placebo rhGH (Te), or 4) rhGH and Te (GHTe). GH doses were titrated over 8 wk to produce IGF-I levels in the upper half of the age-specific reference range. A fixed dose of Te (5 mg) was given by transdermal patches. RESULTS: Lean body mass increased with GHTe (P = 0.008) and GH (P = 0.004), compared with placebo. Total body fat decreased with GHTe only (P = 0.02). Midthigh muscle (P = 0.006) and aerobic capacity (P < 0.001) increased only after GHTe. Muscle strength changes were variable; one of six measures significantly increased with GHTe. Significant treatment group by time interactions indicated an improved Age-Related Hormone Deficiency-Dependent Quality of Life questionnaire score (P = 0.007) in the GH and GHTe groups. Bodily pain increased with GH alone, as determined by the Short-Form Health Survey (P = 0.003). There were no major adverse effects. CONCLUSION: Coadministration of low dose GH with Te resulted in beneficial changes being observed more often than with either GH or Te alone.

Instruments used in measuring symptoms, health status and quality of life in hypothyroidism: a systematic qualitative review.

BACKGROUND: Symptoms of hypothyroidism are varied and nonspecific, thereby making clinical diagnosis impossible. Some patients report ongoing symptoms despite treatment. Measuring symptoms, health status and quality of life by using appropriate instruments, in addition to biochemical tests, is therefore vital to quantify disease severity and assess response to treatment. A number of instruments have been used in hypothyroidism, leading to lack of clarity about what exactly is being measured, and the rationale for the inclusion of particular measures is often uncertain. OBJECTIVES: To evaluate and compare instruments used in hypothyroidism in assessing patient-reported outcomes. DATA SOURCES AND STUDY SELECTION: All published literature on MEDLINE until March 2005 was searched using the keywords 'hypothyroidism', 'symptoms', 'quality of life' and 'health status'. Articles reporting controlled trials or instrument design and development were analysed to assess the instruments used and to ascertain whether they were measuring the stated outcome. DATA SYNTHESIS: Available tools to measure symptoms, health status and quality of life in diagnosis and management of hypothyroidism are discussed. We also describe how these tools have been described in published clinical trials along with the advantages and possible pitfalls of each of the commonly used tools. CONCLUSIONS: Some instruments reviewed have not been suited to the outcome being studied, thereby giving rise to questionable results. This review should be useful for clinicians, researchers and patient-support groups in understanding the principles behind these tools and the results obtained from their use in clinical practice, and in selecting measures for their own use.

Health status in patients with sub-clinical hypothyroidism.

OBJECTIVE: Sub-clinical hypothyroidism (SCH) is a common disorder. People with this condition may have symptoms which could affect their perception of health. Therefore, the perceived health status of people with SCH was assessed and compared with population-matched norms. DESIGN: A prospective cross-sectional survey. METHODS: Seventy-one adults with SCH, age range 18-64 years were studied. Perceived health status was measured by the Short Form-36 (SF-36) version 2 questionaire, which has been validated in a UK population setting. The SF-36 has eight scales measuring physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health. Their SF-36 scores were compared with UK normative data after matching for age and sex and are reported as z-scores. RESULTS: Scores of all eight SF-36 scales were significantly lower in people with SCH compared with the normative population. A negative score (compared with zero of the normative population) indicates worse health status. The most significantly impaired aspects of health status were vitality and role limitations due to physical problems (role physical scale) with z-scores (95% confidence intervals) of -1.01 (-0.74 to -1.29) and -0.73 (-0.43 to -1.04) respectively. Thyroid autoimmunity did not influence the results. CONCLUSION: Perceived health status is significantly impaired in people with SCH when compared with UK normative population scores. This needs to be taken into consideration by clinicians when managing patients with this disease.

+Psychometric evaluation of the MacDQoL individualised measure of the impact of macular degeneration on quality of life.

BACKGROUND: The MacDQoL is an individualised measure of the impact of macular degeneration (MD) on quality of life (QoL). There is preliminary evidence of its psychometric properties and sensitivity to severity of MD. The aim of this study was to carry out further psychometric evaluation with a larger sample and investigate the measure's sensitivity to MD severity. METHODS: Patients with MD (n = 156: 99 women, 57 men, mean age 79 +/- 13 years), recruited from eye clinics (one NHS, one private) completed the MacDQoL by telephone interview and later underwent a clinic vision assessment including near and distance visual acuity (VA), comfortable near VA, contrast sensitivity, colour recognition, recovery from glare and presence or absence of distortion or scotoma in the central 10 degrees of the visual field. RESULTS: The completion rate for the MacDQoL items was 99.8%. Of the 26 items, three were dropped from the measure due to redundancy. A fourth was retained in the questionnaire but excluded when computing the scale score. Principal components analysis and Cronbach's alpha (0.944) supported combining the remaining 22 items in a single scale. Lower MacDQoL scores, indicating more negative impact of MD on QoL, were associated with poorer distance VA (better eye r = -0.431 p < 0.001; worse eye r = -0.350 p < 0.001; binocular vision r = -0.419 p < 0.001) and near VA (better eye r = -0.326 p < 0.001; worse eye r = -0.226 p < 0.001; binocular vision r = -0.326 p < 0.001). Poorer MacDQoL scores were associated with poorer contrast sensitivity (better eye r = 0.392 p < 0.001; binocular vision r = 0.423 p < 0.001), poorer colour recognition (r = 0.417 p < 0.001) and poorer comfortable near VA (r = -0.283, p < 0.001). The MacDQoL differentiated between those with and without binocular scotoma (U = 1244 p < 0.001). CONCLUSION: The MacDQoL 22-item scale has excellent internal consistency reliability and a single-factor structure. The measure is acceptable to respondents and the generic QoL item, MD-specific QoL item and average weighted impact score are related to several measures of vision. The MacDQoL demonstrates that MD has considerable negative impact on many aspects of QoL, particularly independence, leisure activities, dealing with personal affairs and mobility. The measure may be valuable for use in clinical trials and routine clinical care.

The development of a new measure of quality of life for young people with diabetes mellitus: the ADDQoL-Teen.

BACKGROUND: This study evaluated the psychometric properties of the ADDQoL-Teen, an innovative individualised, patient-centred questionnaire measuring perceived impact of diabetes mellitus on quality of life (QoL) of teenagers. Respondents rate all 30 life domains for frequency, and personally applicable domains for 'bother'. Two overview items measure present QoL and diabetes-dependent QoL. ADDQoL-Teen design was based on the ADDQoL (for adults with diabetes). METHODS: Interviews and discussion groups were conducted with 23 teenagers aged 13-16 years, during work to design the ADDQoL-Teen. The new questionnaire was then completed by 152 young people, (mean age 16.4 +/- 2.4 years), attending diabetes clinics at six UK centres. RESULTS: Five domains detracted from the measure's reliability and factor structure, four of which were analysed separately and one deleted. The 25-domain ADDQoL-Teen had high internal consistency reliability [Cronbach's alpha = 0.91, (N = 133)] and could be summed into an overall Average Weighted Impact score. There were two subscales: a 10-item Impact-Self subscale (measuring impact of diabetes and its treatment on the individual) and a 15-item Impact-Other subscale (measuring impact on interactions with others and the external world). Both subscales had good internal consistency reliability, [Cronbach's alpha coefficients of 0.82 (N = 142) and 0.88 (N = 138) respectively]. Domains reported as most severely (and negatively) impacted by diabetes were (mean weighted impact +/- SD): lie in bed (-3.68 +/- 3.41), interrupting activities (-3.5 +/- 3.23), worry about the future (-3.45 +/- 3.28), career (-3.43 +/- 3.15) and sweets (-3.24 +/- 3.24), (maximum range -9 to +3). Analysis of the overview items showed that although 72.5% considered that their present QoL was good or brilliant, 61.8% felt that having diabetes had a negative impact on QoL, but 35.6% reported no impact and 2.6% reported a positive impact on QoL. CONCLUSIONS: The ADDQoL-Teen is a new measure of perceived impact of diabetes and its treatment on QoL of teenagers. It will help healthcare professionals and parents consider QoL issues as well as medical outcomes when caring for young people with diabetes. It may be used in clinical trials and for routine clinical monitoring in a context of continuing evaluation.

Preliminary development of a new individualised questionnaire measuring quality of life in older men with age-related hormonal decline: the A-RHDQoL.

BACKGROUND: There is increasing interest in hormone replacement therapy to improve health and quality of life (QoL) of older men with age-related decline in hormone levels. This paper reports the preliminary development and evaluation of the psychometric properties of a new individualised questionnaire, the A-RHDQoL, measuring perceived impact of age-related hormonal decline on QoL of older men. A-RHDQoL design was based on the HDQoL for people with growth hormone (GH) deficiency and the ADDQoL (for diabetes). METHODS: Internal consistency reliability and some aspects of validity of the A-RHDQoL were investigated in a cross-sectional survey of 128 older men (age range: 64 - 80 yrs), being screened for inclusion in a trial of GH and testosterone (T) replacement, and who completed the A-RHDQoL once. Respondents rated personally applicable life domains for importance and impact of their hormonal decline. A single overview item measured present QoL. Serum levels of Insulin-like Growth Factor-I and total T were measured. RESULTS: Of the 24 A-RHDQoL domains, 21 were rated as relevant and important for older men. All domains were perceived as negatively impacted by hormonal decline. The most negatively impacted domains were: memory (-4.54 +/- 3.02), energy (-4.44 +/- 2.49), sex life (-4.34 +/- 3.08) and physical stamina (-4.29 +/- 2.41), (maximum range -9 to +9). The shorter 21-domain A-RHDQoL had high internal consistency reliability (Cronbach's alpha coefficient = 0.935, N = 103) and applicable domains could be weighted and summed into an overall Average Weighted Impact score. The questionnaire was acceptable to the majority of respondents and content validity was good. The single overview item measuring present QoL correlated significantly with total T levels [r = 0.26, p <0.01, N = 114]. CONCLUSION: The new 21-item A-RHDQoL is an individualised questionnaire measuring perceived impact of age-related hormonal decline on the QoL of older men. The internal consistency reliability and content validity of the A-RHDQoL are established, but the measure is at an early stage of its development and its sensitivity to change and other psychometric properties need now to be evaluated in clinical trials of hormone replacement in older men.