Usability of daily SF36 questionnaires to capture the QALD variation experienced after vaccination with AS03A-adjuvanted monovalent influenza A (H5N1) vaccine in a safety and tolerability study.

BACKGROUND: This study aims to describe the short-term reactogenicity of the AS03-adjuvanted H5N1 vaccine expressed through adverse events (AEs) and quality-adjusted life-day (QALD) scores. The AEs are likely to be short-term and therefore the quality of life (QoL) questionnaire, SF-36v2, was administered daily to record changes over seven days. A more sensitive application of this instrument should allow for a better understanding of short-term tolerability of adjuvanted vaccines. METHODS: Participants (N = 50) received a 2-dose vaccination schedule. Solicited (collected daily: days 0 to 7 [post dose 1] and 21 to 28 [post dose 2]) and unsolicited (collected weekly until day 21) AEs were collected via diary cards. The QoL questionnaires were completed daily (days 0-6) and weekly (days 0, 6, 21, 27) after dose one. Questionnaire data were transformed into SF-6D scores to report QALDs. It was hypothesized post-hoc that the QALD and daily AEs scores should correlate if discrete QoL-changes were captured. RESULTS: Pain (92%) and muscle ache (66%) were the most commonly reported solicited local and general AEs respectively, neither increased in intensity nor in frequency after dose 2. No safety concerns were identified during the study. A correlation between the daily AEs and QALD scores existed (correlation coefficient, - 0.97 (p < 0.001)). The impact of the AEs scores on the QALD was marginal (- 0.02 max for one day). CONCLUSION: Similarly with other H5N1 studies, no safety concern was identified throughout the study. Some time-limited variations in QALD-scores were reported. Our results imply that daily administration of the SF-36v2 captures changes in QALD-scores. TRIAL REGISTRATION: ClinicalTrials.gov . NCT01788228. Registered 11 February 2013.

Psychological targeting as an effective approach to digital mass persuasion.

People are exposed to persuasive communication across many different contexts: Governments, companies, and political parties use persuasive appeals to encourage people to eat healthier, purchase a particular product, or vote for a specific candidate. Laboratory studies show that such persuasive appeals are more effective in influencing behavior when they are tailored to individuals' unique psychological characteristics. However, the investigation of large-scale psychological persuasion in the real world has been hindered by the questionnaire-based nature of psychological assessment. Recent research, however, shows that people's psychological characteristics can be accurately predicted from their digital footprints, such as their Facebook Likes or Tweets. Capitalizing on this form of psychological assessment from digital footprints, we test the effects of psychological persuasion on people's actual behavior in an ecologically valid setting. In three field experiments that reached over 3.5 million individuals with psychologically tailored advertising, we find that matching the content of persuasive appeals to individuals' psychological characteristics significantly altered their behavior as measured by clicks and purchases. Persuasive appeals that were matched to people's extraversion or openness-to-experience level resulted in up to 40% more clicks and up to 50% more purchases than their mismatching or unpersonalized counterparts. Our findings suggest that the application of psychological targeting makes it possible to influence the behavior of large groups of people by tailoring persuasive appeals to the psychological needs of the target audiences. We discuss both the potential benefits of this method for helping individuals make better decisions and the potential pitfalls related to manipulation and privacy.

The French-Canadian validation of a disease-specific, patient-reported outcome measure for lupus.

OBJECTIVES: The objective of this paper is to perform the cross-cultural validation of the French version of the LupusPRO, a disease-targeted patient-reported outcome measure, among systemic lupus erythematosus (SLE) patients in Canada. METHODS: The French version of the LupusPRO and the MOS SF-36 were administered; demographic, clinical and serological characteristics were obtained. Disease activity (SELENA-SLEDAI and the Lupus Foundation of America definition of flare) and damage (SLICC/ACR SDI) were assessed. Physician disease activity and damage assessments were ascertained using visual analog scales. Internal consistency reliability (ICR), test-retest reliability (TRT), convergent and discriminant validity (against corresponding domains of the SF-36), criterion validity (against disease activity, damage or health status) and known group validity were tested. RESULTS: A total of 99 French-Canadian SLE patients participated (97% women, mean (SD) age 45.2 (14.5) years). The median (IQR) SELENA-SLEDAI and SDI were 3.5 (6.0) and 1.0 (2.0), respectively. The ICR of the LupusPRO domains ranged from 0.81 to 0.93 (except for lupus symptoms, procreation and coping), while TRT ranged from 0.72 to 0.95. Convergent and discriminant validity, criterion validity and known group validity against disease activity, damage and health status measures were observed. Confirmatory factor analysis showed a good fit. CONCLUSION: The LupusPRO has fair psychometric properties among French-Canadian patients with SLE.

Postpartum reversibility of impaired incretin effect in gestational diabetes mellitus.

The potential reversibility of a reduced incretin effect is unclear. We investigated the incretin effect during third trimester and 3 to 4months postpartum in women with and without gestational diabetes mellitus (GDM). Ten women with GDM (plasma glucose (PG) concentration at 120min after 75g-oral glucose tolerance test (OGTT) (PG120min): 10.1±0.6mmol/l (mean±SEM)) and eight women with normal glucose tolerance (NGT; PG120min: 7.0±0.1mmol/l) were investigated on four occasions: 4h 50g-OGTT and isoglycaemic intravenous glucose infusion during third trimester and 3 to 4months postpartum. In women with GDM, the incretin effect increased significantly postpartum (31±6 vs. 56±6%, p=0.02), whereas the increment in women with NGT was insignificant (35±12 vs. 56±9%, p=0.08). Similarly, the gastrointestinal-mediated glucose disposal (GIGD=100%×(glucoseOGTT-glucoseIIGI)/glucoseOGTT) was reduced to diabetic levels in women with GDM (37±3%), but increased (p=0.030) to normal levels post partum (58±6%). GIGD did not change significantly in NGT women (48±3 vs. 57±6%, p=0.94). Women with GDM exhibit a reduced incretin effect which is fully reversible alongside the restoration of normal glucose homeostasis, whereas the reduction in incretin effect during pregnancy in women with NGT was insignificant. Our results suggest that decreased incretin effect in women with GDM is a fully reversible phenomenon.

Spanish LupusPRO: cross-cultural validation study for lupus.

PURPOSE: LupusPRO is a disease-targeted, patient-reported, outcome measure that was developed and validated among US patients with systemic lupus erythematosus (SLE). To expand the availability and use of the tool, we undertook a cross-cultural adaptation and validation study of the Spanish-translated version of the LupusPRO. METHOD: Forward and back translations of the 43-item English LupusPRO were undertaken and pretested in five individuals. The finalized Spanish version was administered to 211 SLE patients of Hispanic ancestry from the US and Latin America. Short Form-36 (Spanish) and Spanish LupusPRO were also administered. Disease activity was ascertained using the systemic lupus erythematosus disease activity index. A Spanish LupusPRO questionnaire that could be completed within 2-3 days was mailed to SLE patients of Hispanic ancestry and they mailed it back. Internal consistency reliability, test-retest reliability, criterion validity (against disease activity or health status) and convergent validity were tested. All reported p values are two-tailed. RESULTS: A total of 211 Spanish-speaking SLE patients (90% women) participated. Test-retest reliability of LupusPRO domains ranged from 0.80-0.95, while internal consistency reliability of the domains ranged from 0.71-0.96. Convergent validity with corresponding domains of the SF-36 was present. All health-related quality of life domains of the LupusPRO (except procreation) performed well against disease activity measures, establishing its criterion validity. Confirmatory factor analysis showed a good fit. CONCLUSION: The Spanish LupusPRO has fair psychometric properties and is now available to be included in clinical trials and in longitudinal studies for testing of responsiveness to change.

Qualitative validation of the FACIT-fatigue scale in systemic lupus erythematosus.

OBJECTIVE: Fatigue in systemic lupus erythematosus (SLE) is burdensome and must be assessed using validated scales. Although the psychometric properties of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale in SLE have been evaluated previously, its content validity in this disease remains to be evaluated. The study objective was, therefore, to evaluate content validity of the FACIT-Fatigue in SLE. METHODS: Three SLE focus groups (n=21) in the United States were conducted using semi-structured interviews. Participant comments were categorized by response type, and relative response strength was qualitatively assessed. RESULTS: Participants were mostly female (90%; n=19), white (57%; n=12) with a mean age of 43.7 years (range=28-70). Most scale items were considered relevant with the exception of four items for which participant interpretations varied. Consistent with the scale's measurement model, "listless" on item 3 ("I feel listless ('washed out')") was interpreted as physical or mental impairment. Participant responses to item 8 ("I am able to do my usual activities") sometimes included influence of other health conditions, which is acceptable because it is difficult to separate disease-specific and general fatigue. Some participants found item 7 ("I have energy") irrelevant and most could not relate to item 10 ("I am too tired to eat"). However, both items were intended to capture the extreme ends of fatigue (item 7, ceiling; item 10, floor). CONCLUSIONS: From a content perspective, items of the FACIT-Fatigue scale were relevant for measuring fatigue in SLE.

Cross-cultural validation of a disease-specific patient-reported outcome measure for lupus in Philippines.

OBJECTIVE: LupusPRO is a disease-targeted patient-reported outcome measure that was developed and validated among US patients with systemic lupus erythematosus (SLE). We report the cross-cultural validation results of the LupusPRO English-language version among Filipino SLE patients. METHOD: The 43-item LupusPRO was pretested in 15 SLE individuals, then administered to 106 SLE patients, along with short-form SF36 and the EQ5D visual analogue scale. A mail/drop-back LupusPRO and change in health status item survey were returned within two to three days. Demographics, clinical and serological characteristics, disease activity and damage measured by PGA, SELENA-SLEDAI, LFA Flare, and SLICC-ACR SLE damage index (SDI) were collected. Internal consistency reliability (ICR), test-retest reliability (TRT), convergent validity (corresponding SF36 domains) and criterion validity (against general health and disease activity measures) were tested. Reported p values are two tailed. RESULTS: A total of 121 Filipino SLE subjects (95% women, median age 31.0 ± 16 years) with at least a high school level of English instruction participated. Median (IQR) PGA, SLEDAI and SDI were 0.0 (1.0), 2.0 (10) and 0 (1), respectively. ICR exceeded 0.7 for all domains except the lupus symptoms domain. TRT was greater than 0.85 for all LupusPRO domains. Convergent and criterion validity were observed against corresponding SF36 domains and disease activity measures. The tool was well received by patients. Confirmatory factor analysis showed good fit. CONCLUSION: English LupusPRO has fair psychometric properties among SLE patients in the Philippines, and is now available for inclusion in clinical trials and longitudinal studies to test responsiveness to change.

18F-FLT and 125I-IdUrd uptake increase in human tumour cell lines induced by the thymidylate synthase inhibitor FdUrd.

AIM: 5-fluoro-2'-deoxyuridine (FdUrd) depletes the endogenous 5'-deoxythymidine triphosphate (dTTP) pool. We hypothesized whether uptake of exogenous dThd analogues could be favoured through a feedback enhanced salvage pathway and studied the FdUrd effect on cellular uptake of 3'-deoxy-3'-18F-fluorothymidine (18F-FLT) and 5-125I-iodo-2'-deoxyuridine (125I-IdUrd) in different cancer cell lines in parallel. METHODS: Cell uptake of 18F-FLT and 125I-IdUrd was studied in 2 human breast, 2 colon cancer and 2 glioblastoma lines. Cells were incubated with/without 1 µmol/l FdUrd for 1 h and, after washing, with 1.2 MBq 18F-FLT or 125I-IdUrd for 0.3 to 2 h. Cell bound 18F-FLT and 125I-IdUrd was counted and expressed in % incubated activity (%IA). Kinetics of 18F-FLT cell uptake and release were studied with/without FdUrd modulation. 2'-3H-methyl-fluorothymidine (2'-3H-FLT) uptake with/without FdUrd pretreatment was tested on U87 spheroids and monolayer cells. RESULTS: Basal uptake at 2 h of 18F-FLT and 125I-IdUrd was in the range of 0.8-1.0 and 0.4-0.6 Bq/cell, respectively. FdUrd pretreatment enhanced 18F-FLT and 125I-IdUrd uptake 1.2-2.1 and 1.7-4.4 fold, respectively, while co-incubation with excess thymidine abrogated all 18F-FLT uptake. FdUrd enhanced 18F-FLT cellular inflow in 2 breast cancer lines by factors of 1.8 and 1.6, respectively, while outflow persisted at a slightly lower rate. 2'-3H-FLT basal uptake was very low while uptake increase after FdUrd was similar in U87 monolayer cells and spheroids. CONCLUSIONS: Basal uptake of 18F-FLT was frequently higher than that of 125I-IdUrd but FdUrd induced uptake enhancement was stronger for 125I-IdUrd in five of six cell lines. 18F-FLT outflow from cells might be an explanation for the observed difference with 125I-IdUrd.

68Ga-NODAGA-RGDyK for αvß3 integrin PET imaging. Preclinical investigation and dosimetry.

AIM: To visualize neovasculature and/or tumour integrin αvß3 we selected the binding moiety Arg-Gly-Asp-D-Tyr-Lys (RGDyK) coupled to NODAGA for labeling with 68Ga. METHODS: NODAGA-RGDyK (ABX) was labeled with the 68Ga eluate from the 68Ge generator IGG100 using the processor unit PharmTracer. Biodistribution was measured in female Hsd mice sacrificed 10, 30, 60 and 90 min after i.v. injection of 68Ga-NODAGA-RGDyK for OLINDA dosimetry extrapolated to humans. Tumour targeting was studied in SCID mice bearing A431 and other tumour transplants using microPET and biodistribution measurements. RESULTS: Effective half-life of 68Ga-NODAGA-RGDyK was ~25 min for total body and most organs except liver and spleen that showed stable activity retention. With a bladder voiding interval of 0.5 h the calculated effective dose (ED) was 0.012 and 0.016 mSv/MBq for males and females, respectively. Rapid uptake within 10 min was observed in A431 tumours with dynamic PET followed by a slow release. Biodistribution measurements showed a 68Ga-NODAGA-RGDyK uptake in A431 tumours of 3.4±0.4 and 2.7±0.3%ID/g at 1 and 2 h, respectively. Similar uptakes were observed in a mouse and human breast and ovarian cancer xenografts. Co-injection of excess (5 mg/kg) unlabeled NODAGA-RGDyK with the radiotracer reduced tumour uptake at one hour to 0.23±0.01%ID/g, but similarly decreased uptake in normal organs as well. When unlabeled peptide was injected 15 min after 68Ga-NODAGA-RGDyK, uptake diminished particularly in tumour and adrenals, suggestive of a different binding mode compared with other normal tissues. CONCLUSION: NODAGA-RGDyK was reliably labeled with 68Ga and revealed a predicted ED of 0.014 mSv/MBq. Tumour uptake was rapid and significant and was chased with unlabeled RGDyK in a similar manner as adrenal uptake.

Fluorodeoxyuridine mediated cell cycle synchronization in S-phase increases the Auger radiation cell killing with 125I-iododeoxyuridine.

AIM: 125I-iododeoxyuridine is a potential Auger radiation therapy agent. Its incorporation in DNA of proliferating cells is enhanced by fluorodeoxyuridine. Here, we evaluated therapeutic activities of 125I-iododeoxyuridine in an optimized fluorodeoxyuridine pre-treatment inducing S-phase synchronization. METHODS: After S-phase synchronization by fluorodeoxyuridine, cells were treated with 125I-iododeoxyuridine. Apoptosis analysis and S-phase synchronization were studied by flow cytometry. Cell survival was determined by colony-forming assay. Based on measured growth parameters, the number of decays per cell that induced killing was extrapolated. RESULTS: Treatment experiments showed that 72 to 91% of synchronized cells were killed after 0.8 and 8 kBq/ml 125I-iododeoxyuridine incubation, respectively. In controls, only 8 to 38% of cells were killed by corresponding 125I-iododeoxyuridine activities alone and even increasing the activity to 80 kBq/ml gave only 42 % killing. Duplicated treatment cycles or repeated fluorodeoxyuridine pre-treatment allowed enhancing cell killing to >95 % at 8 kBq/ml 125I-iododeoxyuridine. About 50 and 160 decays per S-phase cells in controls and S-phase synchronization, respectively, were responsible for the observed cell killing at 0.8 kBq/ml radio-iododeoxyuridine. CONCLUSION: These data show the successful application of fluorodeoxyuridine that provided increased 125I-iododeoxyuridine Auger radiation cell killing efficacy through S-phase synchronization and high DNA incorporation of radio-iododeoxyuridine.

Nanomedicines for active targeting: physico-chemical characterization of paclitaxel-loaded anti-HER2 immunonanoparticles and in vitro functional studies on target cells.

Paclitaxel (Tx)-loaded anti-HER2 immunonanoparticles (NPs-Tx-HER) were prepared by the covalent coupling of humanized monoclonal anti-HER2 antibodies (trastuzumab, Herceptin) to Tx-loaded poly (dl-lactic acid) nanoparticles (NPs-Tx) for the active targeting of tumor cells that overexpress HER2 receptors. The physico-chemical properties of NPs-Tx-HER were compared to unloaded immunonanoparticles (NPs-HER) to assess the influence of the drug on anti-HER2 coupling to the NP surface. The immunoreactivity of sulfo-MBS activated anti-HER2 mAbs and the in vitro efficacy of NPs-Tx-HER were tested on SKOV-3 ovarian cancer cells that overexpress HER2 antigens. Tx-loaded nanoparticles (NPs-Tx) obtained by a salting-out method had a size of 171+/-22 nm (P.I.=0.1) and an encapsulation efficiency of about of 78+/-10%, which corresponded to a drug loading of 7.8+/-0.8% (w/w). NPs-Tx were then thiolated and conjugated to activated anti-HER2 mAbs to obtain immunonanoparticles of 237+/-43 nm (P.I.=0.2). The influence of the activation step on the immunoreactivity of the mAbs was tested on SKOV-3 cells using 125I-radiolabeled mAbs, and the activity of the anti-HER2 mAbs was minimally affected after sulfo-MBS functionalization. Approximately 270 molecules of anti-HER2 mAbs were bound per nanoparticle. NPs-Tx-HER exhibited a zeta potential of 0.2+/-0.1 mV. The physico-chemical properties of the Tx-loaded immunonanoparticles were very similar to unloaded immunonanoparticles, suggesting that the encapsulation of the drug did not influence the coupling of the mAbs to the NPs. No drug loss was observed during the preparation process. DSC analysis showed that encapsulated Tx is in an amorphous or disordered-crystalline phase. These results suggest that Tx is entrapped in the polymeric matrix and not adsorbed to the surface of the NPs. In vitro studies on SKOV-3 ovarian cancer cells demonstrated the greater cytotoxic effect of NPs-Tx-HER compared to other Tx formulations. The results showed that at 1 ng Tx/ml, the viability of cells incubated with drug encapsulated in NP-Tx-HER was lower (77.32+/-5.48%) than the viability of cells incubated in NPs-Tx (97.4+/-12%), immunonanoparticles coated with Mabthera, as irrelevant mAb (NPs-Tx-RIT) (93.8+/-12%) or free drug (92.3+/-9.3%).

Evaluation of the meaningfulness of health-related quality of life improvements as assessed by the SF-36 and the EQ-5D VAS in patients with active Crohn's disease.

BACKGROUND: Crohn's disease (CD) is a chronic inflammatory illness characterized by episodic abdominal pain, diarrhoea, fever, bleeding and obstruction. While the Crohn's Disease Activity Index (CDAI) remains the most commonly accepted measure for assessing the disease status in clinical trials, patient-reported outcome (PRO) instruments are being utilized more frequently to provide information about health-related quality of life (HRQOL). To facilitate interpretation of results, it is common to identify a meaningful unit of PRO score change, such as a minimal clinically important difference (MCID). AIM: To define and apply MCID estimates for the SF-36 and EuroQol-5D visual analogue scale (EQ-5D VAS) for use in CD treatment evaluation. METHODS: Data from two phase III randomized controlled trials of certolizumab pegol were utilized. MCID estimates were computed from one trial using anchor-based and distribution-based methods. These estimates were applied to data from the other trial. RESULTS: SF-36 PCS and MCS MCID estimates ranged from 1.6 to 7.0 and 2.3 to 8.7 respectively, depending on approach. EQ-5D VAS MCID estimates ranged from 4.2 to 14.8. CONCLUSIONS: For the first time, the MCID values provided interpretation guidelines for PRO results in CD. This research demonstrates that patients treated with certolizumab pegol benefit from meaningful and sustained HRQOL improvements.

GARDASIL: prophylactic human papillomavirus vaccine development--from bench top to bed-side.

GARDASIL (Merck, Whitehouse Station, NJ) is a non-infectious recombinant, quadrivalent vaccine prepared from the highly purified virus-like particles (VLPs) of the major capsid proteins of human papillomavirus (HPV) types 6, 11, 16, and 18. GARDASIL is the first vaccine approved for use in women aged 9-26 years for the prevention of cervical cancer and genital warts, as well as vulvar and vaginal precancerous lesions. This report describes some of the key preclinical efforts, achievements in pharmaceutical development, in vivo animal evaluation, and clinical trial data.

Long-term complete responses after 131I-tositumomab therapy for relapsed or refractory indolent non-Hodgkin's lymphoma.

We present the long-term results of 18 chemotherapy relapsed indolent (N = 12) or transformed (N = 6) NHL patients of a phase II anti-CD20 (131)I-tositumomab (Bexxar) therapy study. The biphasic therapy included two injections of 450 mg unlabelled antibody combined with (131)I-tositumomab once as dosimetric and once as therapeutic activity delivering 75 or 65 cGy whole-body radiation dose to patients with normal or reduced platelet counts, respectively. Two patients were not treated due to disease progression during dosimetry. The overall response rate was 81% in the 16 patients treated, including 50% CR/CRu and 31% PR. Median progression free survival of the 16 patients was 22.5 months. Median overall survival has not been reached after a median observation of 48 months. Median PFS of complete responders (CR/CRu) has not been reached and will be greater than 51 months. Short-term side effects were mainly haematological and transient. Among the relevant long-term side effects, one patient previously treated with CHOP chemotherapy died from secondary myelodysplasia. Four patients developed HAMA. In conclusion, (131)I-tositumomab RIT demonstrated durable responses especially in those patients who achieved a complete response. Six of eight CR/CRu are ongoing after 46-70 months.

Endovascular isolated hepatic perfusion under pneumoperitoneum.

AIMS: Isolated hepatic perfusion (IHP) allows loco-regional administration of high drug doses for cancer treatment. Minimally invasive endovascular occlusion techniques can be used for IHP, but control of leakage remains a major drawback. We hypothesized that the increased intraabdominal pressure generated by a CO(2)-pneumoperitoneum (PP) can reduce the leakage rate of hypoxic endovascular IHP by mechanical compression of the capillary beds connecting the liver to the systemic circulation. METHODS: IHP was performed on adult pigs through laparotomy using a fenestrated double balloon-catheter placed into the retrohepatic vena cava to collect the hepatic outflow which was reinfused into the hepatic artery through an extracorporeal circulation system. Each pig underwent IHP during four consecutive phases: abdomen open (Phase I), abdomen closed under a 15 and 20 mmHg pneumoperitoneum (Phase II and III, respectively) and abdomen re-opened (Phase IV). The leakage rate from the liver to the systemic circulation was continuously monitored using a nuclear medicine technique. The systemic arterial pressure, the IHP inflow and outflow pressures and the flow rate were recorded. RESULTS: Leakage from the hepatic extracorporeal circulation to the systemic circulation occurred in all animals during Phase I. Under PP (Phases II and III), two leakage profiles were observed: (1) a major increase of the leakage rate in two animals with a high differential pressure (>50 mmHg) between the IHP inflow and the systemic pressures; (2) no change or a decrease of the leakage rate in the other three animals who had a low or negative differential pressure (<30 mmHg). Leakage was undetectable in all animals after exsufflation of the PP (Phase IV). CONCLUSIONS: IHP under PP is feasible. Leakage is not reduced during PP. A high gradient between the IHP inflow and the systemic pressure increases systemic leakage during PP. Upon release of the PP, the leakage is most likely redirected towards the volume depleted low resistance portal territory.

The responsiveness of headache impact scales scored using 'classical' and 'modern' psychometric methods: a re-analysis of three clinical trials.

BACKGROUND: While item response theory (IRT) offers many theoretical advantages over classical test theory in the construction and scoring of patient based measures of health few studies compare scales constructed from both methodologies head to head. OBJECTIVE: Compare the responsiveness to treatment of migraine specific scales scored using summated rating scale methods vs. IRT methods. METHODS: The data came from three clinical studies of migraine treatment that used the Migraine Specific Quality of Life Questionnaire (MSQ). Five methods of quantifying responsiveness were used to evaluate and compare changes from pre- to post-treatment in MSQ scales scored using Likert and IRT scaling methods. RESULTS: Changes in all MSQ scale scores from pre- to post-treatment were highly significant in all three studies. A single index scored from the MSQ using IRT methods was determined to be more responsive than any one of the MSQ subscales across the five methods used to quantify responsiveness. Across 13 of the 15 tests (5 responsiveness methods * 3 studies) conducted, the single index scored from the MSQ using IRT methods was the most responsive measure. CONCLUSIONS: IRT methods increased the responsiveness of the MSQ to the treatment of migraine. The results agree with the psychometric evidence that suggest that it is feasible to score a single index from the MSQ using IRT methods. This approach warrants further testing with other measures of migraine impact.

A six-item short-form survey for measuring headache impact: the HIT-6.

BACKGROUND: Migraine and other severe headaches can cause suffering and reduce functioning and productivity. Patients are the best source of information about such impact. OBJECTIVE: To develop a new short form (HIT-6) for assessing the impact of headaches that has broad content coverage but is brief as well as reliable and valid enough to use in screening and monitoring patients in clinical research and practice. METHODS: HIT-6 items were selected from an existing item pool of 54 items and from 35 items suggested by clinicians. Items were selected and modified based on content validity, item response theory (IRT) information functions, item internal consistency, distributions of scores, clinical validity, and linguistic analyses. The HIT-6 was evaluated in an Internet-based survey of headache sufferers (n = 1103) who were members of America Online (AOL). After 14 days, 540 participated in a follow-up survey. RESULTS: HIT-6 covers six content categories represented in widely used surveys of headache impact. Internal consistency, alternate forms, and test-retest reliability estimates of HIT-6 were 0.89, 0.90, and 0.80, respectively. Individual patient score confidence intervals (95%) of app. +/-5 were observed for 88% of all respondents. In tests of validity in discriminating across diagnostic and headache severity groups, relative validity (RV) coefficients of 0.82 and 1.00 were observed for HIT-6, in comparison with the Total Score. Patient-level classifications based in HIT-6 were accurate 88.7% of the time at the recommended cut-off score for a probability of migraine diagnosis. HIT-6 was responsive to self-reported changes in headache impact. CONCLUSIONS: The IRT model estimated for a 'pool' of items from widely used measures of headache impact was useful in constructing an efficient, reliable, and valid 'static' short form (HIT-6) for use in screening and monitoring patient outcomes.