Discriminant validity, responsiveness and reliability of the rheumatoid arthritis-specific Work Productivity Survey (WPS-RA)

INTRODUCTION: The rheumatoid arthritis-specific Work Productivity Survey (WPS-RA) measures the impact of rheumatoid arthritis (RA) and treatment on patient productivity within and outside the home. It contains nine questions addressing employment status, productivity within and outside the home, and daily activities. The objective of this paper was to evaluate the discriminant validity, responsiveness, and reliability of the WPS-RA in patients with active RA. METHODS: Two hundred twenty subjects (mean age was 53.8 years, 83.6% were female, mean disease duration was 9.54 years, mean number of disease-modifying anti-rheumatic drugs failed was 2, and 38.6% were employed outside the home) in a phase III, 24-week, double-blind, placebo-controlled trial completed the WPS-RA at baseline and every 4 weeks until withdrawal/study completion. Validity was evaluated via known groups using baseline data (first and third quartiles of subjects' Health Assessment Questionnaire – Disability Index [HAQ-DI] scores and Short Form-36 health survey [SF-36] scores). To evaluate responsiveness, mean changes in WPS-RA at week 24 were compared between American College of Rheumatology 20% improvement criteria (ACR20) (or HAQ-DI) responders and non-responders. Standardized response mean (SRM) was also used to quantify responsiveness. All group comparisons were conducted using a non-parametric bootstrap-t method. RESULTS: Subjects with lower HAQ-DI or SF-36 scores generally had statistically greater RA-associated losses in productivity within and outside the home compared with subjects with higher scores (25 of 32 evaluations were statistically significant). Smallest differences between groupswere seen in work absenteeism and days with outside help. At week 24, ACR20 and HAQ-DI responders reported large improvements in productivity within and outside the home; non-responders reported mainly a worsening in productivity (P ≤ 0.05). Effect size for productivity changes in ACR20 or HAQ-DI responders was moderate to large for six out of eight items (SRM = 0.48 to 1.12). The effect size was small for work absenteeism and days with outside help. (SRM = 0.4 and 0.24, respectively). In non-responders, the magnitude of change was negligible (SRM < 0.1) or small (SRM < 0.3). CONCLUSIONS: The WPS-RA has demonstrated properties of discriminative validity, reliability, and responsiveness for the measurement of productivity within and outside the home in subjects with active RA

The validation of the Hungarian version of the ID-migraine questionnaire

Despite its high prevalence, migraine remains underdiagnosed and undertreated. ID-Migraine is a short, self-administrated questionnaire, originally developed in English by Lipton et al. and later validated in several languages. Our goal was to validate the Hungarian version of the ID-Migraine Questionnaire.Patients visiting two headache specialty services were enrolled. Diagnoses were made by headache specialists according to the ICHD-3beta diagnostic criteria. There were 309 clinically diagnosed migraineurs among the 380 patients. Among the 309 migraineurs, 190 patients had only migraine, and 119 patients had other headache beside migraine, namely: 111 patients had tension type headache, 3 patients had cluster headache, 4 patients had medication overuse headache and one patient had headache associated with sexual activity also. Among the 380 patients, 257 had only a single type headache whereas 123 patients had multiple types of headache. Test-retest reliability of the ID-Migraine Questionnaire was studied in 40 patients.The validity features of the Hungarian version of the ID-Migraine questionnaire were the following: sensitivity 0.95 (95% CI, 0.92-0.97), specificity 0.42 (95% CI, 0.31-0.55), positive predictive value 0.88 (95% CI, 0.84-0.91), negative predictive value 0.65 (95% CI, 0.5-0.78), missclassification error 0.15 (95% CI, 0.12-0.19). The kappa coefficient of the questionnaire was 0.77.The Hungarian version of the ID-Migraine Questionnaire had adequate sensitivity, positive predictive value and misclassification error, but a low specificity and somewhat low negative predictive value

Measuring the functional status and well-being of patients with migraine headache

OBJECTIVE: Compare adult migraineurs\u27 health related quality of life to adults in the general U.S. population reporting no chronic conditions, and to samples of patients with other chronic conditions. METHODS: Subjects (n = 845) were surveyed 2-6 months after participation in a placebo-controlled clinical trial and asked to complete a questionnaire including the SF-36 Health Survey, a migraine severity measurement scale and demographics. Results were adjusted for severity of illness and comorbidities. Scores were compared with responses to the same survey by the U.S. sample and by patients with other chronic conditions. RESULTS: Response rate was 67%. After adjustment for comorbid conditions, SF-36 scale scores were significantly (P 0.001) lower in migraineurs, relative to age and sex-adjusted norms for the U.S. sample with no chronic conditions. Some health dimensions were more affected by migraine than other chronic conditions, while other dimensions were less affected by migraine. Measures of bodily pain, role disability due to physical health and social functioning discriminated best between migraineurs, the U.S. sample, and patients with other chronic conditions. Patients reporting moderate, severe and very severe migraines scored significantly (P \u3c or = 0.001) lower on five of the eight SF-36 scales than the U.S. sample. CONCLUSIONS: Migraine has a unique, significant quality of life burden

Determining minimally important changes in generic and disease-specific health-related quality of life questionnaires in clinical trials of rheumatoid arthritis

OBJECTIVE: To define clinically meaningful changes in 2 widely used health-related quality of life (HQL) instruments in studies of patients with rheumatoid arthritis (RA). METHODS: Patients with RA (n = 693) who were enrolled in 2 double-blind, placebo-controlled clinical trials completed the Short Form 36 (SF-36) modified health survey and the Health Assessment Questionnaire (HAQ) disability index at baseline and 6-week followup assessments. Data on 5 RA severity measures were also collected at baseline and at 6 weeks (patient and physician global assessments, joint swelling and tenderness counts, and global pain assessment). Comparison of changes in the SF-36 scales and HAQ scores was made between groups of patients known to differ in the level of change on each RA severity measure. RESULTS: With few exceptions, changes in the SF-36 and HAQ scores were different between patients who differed in the level of change on each RA severity measure. Changes in the SF-36 and HAQ scores were more strongly related to changes in the patient and physician global assessments and patient pain assessment than to changes in the joint swelling and tenderness counts. CONCLUSION: Based on these results, minimally important changes in the SF-36 scales and HAQ disability scores were determined, which will be useful in interpreting HQL results in clinical trials

Intranasal H5N1 vaccines, adjuvanted with chitosan derivatives, protect ferrets against highly pathogenic influenza intranasal and intratracheal challenge

We investigated the protective efficacy of two intranasal chitosan (CSN and TM-CSN) adjuvanted H5N1 Influenza vaccines against highly pathogenic avian Influenza (HPAI) intratracheal and intranasal challenge in a ferret model. Six groups of 6 ferrets were intranasally vaccinated twice, 21 days apart, with either placebo, antigen alone, CSN adjuvanted antigen, or TM-CSN adjuvanted antigen. Homologous and intra-subtypic antibody cross-reacting responses were assessed. Ferrets were inoculated intratracheally (all treatments) or intranasally (CSN adjuvanted and placebo treatments only) with clade 1 HPAI A/Vietnam/1194/2004 (H5N1) virus 28 days after the second vaccination and subsequently monitored for morbidity and mortality outcomes. Clinical signs were assessed and nasal as well as throat swabs were taken daily for virology. Samples of lung tissue, nasal turbinates, brain, and olfactory bulb were analysed for the presence of virus and examined for histolopathological findings. In contrast to animals vaccinated with antigen alone, the CSN and TM-CSN adjuvanted vaccines induced high levels of antibodies, protected ferrets from death, reduced viral replication and abrogated disease after intratracheal challenge, and in the case of CSN after intranasal challenge. In particular, the TM-CSN adjuvanted vaccine was highly effective at eliciting protective immunity from intratracheal challenge; serologically, protective titres were demonstrable after one vaccination. The 2-dose schedule with TM-CSN vaccine also induced cross-reactive antibodies to clade 2.1 and 2.2 H5N1 viruses. Furthermore ferrets immunised with TM-CSN had no detectable virus in the respiratory tract or brain, whereas there were signs of virus in the throat and lungs, albeit at significantly reduced levels, in CSN vaccinated animals. This study demonstrated for the first time that CSN and in particular TM-CSN adjuvanted intranasal vaccines have the potential to protect against significant mortality and morbidity arising from infection with HPAI H5N1 virus