BACKGROUND Oxaliplatin is a third‐generation platinum analog that is used to treat a variety of solid tumors, particularly colorectal carcinoma. Patients may develop hypersensitivity reactions, although this complication occurs infrequently. METHODS Three patients developed hypersensitivity reactions to oxaliplatin while undergoing treatment on a Phase I trial of oxaliplatin and capecitabine. An Entrez PUBMED search was performed to identify other cases. RESULTS Two patients experienced the abrupt onset of erythema alone or with pruritis during the 9th and 11th infusions of oxaliplatin, whereas the other patient developed fever and mild dyspnea a few hours after the 9th oxaliplatin infusion. All 3 patients were rechallenged successfully for at least 1 additional oxaliplatin infusion by using oral dexamethasone, 20 mg orally, 6 and 12 hours before the administration of oxaliplatin and by administering intravenously 125 mg of solumedrol, 50 mg of diphenhydramine, and 50 mg of cimetidine 30 minutes before oxaliplatin. The literature review suggests two distinct patterns of reactions: classic hypersensitivity (as experienced by the first two patients) and idiosyncratic reactions (as experienced by the third patient). CONCLUSIONS Patients who develop mild to moderate hypersensitivity to oxaliplatin may be pretreated with steroids and antagonists of Type 1 and 2 histamine receptors, whereas patients who develop severe reactions are unlikely to tolerate further therapy. Cancer 2003;97:2301–7. Published 2003 American Cancer Society. DOI 10.1002/cncr.11379

A new patient-reported outcome (PRO) instrument to measure fatigue symptoms and impacts in relapsing multiple sclerosis (RMS) was developed in a qualitative stage, followed by psychometric validation and migration from paper to an electronic format. Methods: Adult patients with relapsing-remitting multiple sclerosis (RRMS) were interviewed to elicit fatigue-related symptoms and impacts. A draft questionnaire was debriefed in cognitive interviews with further RRMS patients, and revised. Content confirmation interviews were conducted with patients with progressiverelapsing multiple sclerosis (PRMS) and relapsing secondaryprogressive multiple sclerosis (RSPMS). Psychometric analyses used data from adult patients with different RMS subtypes and matched non-RMS controls in a multicenter, observational study. After item reduction, the final instrument was migrated to a smartphone (eDiary) and usability was confirmed in interviews with additional adult RMS patients. Results: The qualitative stage included 37 RRMS, 5 PRMS, and 5 RSPMS patients. Saturation of concepts was reached during concept elicitation. Cognitive interviews confirmed that participants understood the instructions, items, and response options of the instrumentdnamed FSIQ-RMSdas intended. Psychometric validation included 164 RMS and 74 control patients. Internal consistency and testeretest reliability were demonstrated. The symptoms domain discriminated along the RMS symptom-severity continuum and between patients and controls. Patients were able to attribute fatiguerelated symptoms to RMS. Usability and conceptual equivalence of the eDiary were confirmed (n ¼ 10 participants). Conclusions: With 7 symptom items and 13 impact items (in 3 impacts subdomains: physical, cognitive and emotional, and coping) after item reduction, the FSIQ-RMS is a comprehensive, valid, and reliable measure of fatigue-related symptoms and impacts in RMS patients.

BackgroundRegulators and clinical experts increasingly recognize the importance of incorporating patient-reported outcomes (PROs) in clinical studies of therapies for pulmonary arterial hypertension (PAH). No PAH-specific instruments have been developed to date in accordance with the 2009 FDA guidance for the development of PROs as endpoints in clinical trials. A qualitative research study was conducted to develop a new instrument assessing PAH symptoms and their impacts following the FDA PRO guidance.MethodsA cross-sectional study was conducted at 5 centers in the US in symptomatic PAH patients aged 18–80 years. Concept elicitation was based on 5 focus group discussions, after which saturation of emergent concepts was reached. A PRO instrument for PAH symptoms and their impacts was drafted. To assess the appropriateness of items, instructions, response options, and recall periods, 2 rounds of one-on-one cognitive interviews were conducted, with instrument revisions following each round. Additional interviews tested the usability of an electronic version (ePRO). PRO development considered input from an international Steering Committee, and translatability and lexibility assessments.ResultsFocus groups comprised 25 patients (5 per group); 20 additional patients participated in cognitive interviews (10 per round); and 10 participated in usability interviews. Participants had a mean ± SD age of 53.1 ± 15.8 years, were predominantly female (93 %), and were diverse in race/ethnicity, WHO functional class (FC I/II: 56 %, III/IV: 44 %), and PAH etiology (idiopathic: 56 %, familial: 2 %, associated: 42 %). The draft PRO instrument (PAH-SYMPACT®) was found to be clear, comprehensive, and relevant to PAH patients in cognitive interviews. Items were organized in a draft conceptual framework with 16 symptom items in 4 domains (respiratory symptoms, tiredness, cardiovascular symptoms, other symptoms) and 25 impact items in 5 domains (physical activities, daily activities, social impact, cognition, emotional impact). The recall period is the past 24 h for symptoms, and the past 7 days for impacts.ConclusionsThe PAH-SYMPACT® was shown to capture symptoms and their impacts relevant to PAH patients, demonstrating content saturation, concept validity, and ePRO usability. Final content and psychometric validation of the instrument will be based on the results of an ongoing Phase IIIb clinical trial in PAH patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-016-0388-6) contains supplementary material, which is available to authorized users.

Background and Purpose— In this analysis of data from a large clinical trial in aneurysmal subarachnoid hemorrhage, the impact of angiographic vasospasm (aVSP) on specific patient outcomes and inpatient healthcare resource use was assessed. Methods— This was a post hoc analysis of exploratory end points collected for 409 patients with aneurysmal subarachnoid hemorrhage in the Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage (CONSCIOUS-1) trial. Central reviewers graded severity of aVSP as none, mild, moderate, or severe based on comparison of catheter angiograms obtained at baseline and 7 to 11 days after aneurysmal subarachnoid hemorrhage. Assessments of cognitive status (Mini-Mental State Examination) and patient-relevant outcomes (EuroQol total score and visual analog scale and Functional Status Examination) were administered at Week 12. The relationship between severity of aVSP and these end points as well as inpatient healthcare resource use (intensive care, general ward, and total hospital lengths of stay) was assessed using univariate and multivariate analyses. Results— Cognitive status and all patient-relevant outcome measures varied significantly ( P <0.0001) with severity of aVSP (mean for severe aVSP versus no aVSP, respectively: Mini-Mental State Examination, 18.0 versus 27.6; EuroQol total, 0.38 versus 0.74; EuroQol visual analog scale, 50.9 versus 75.5; Functional Status Examination, 20.5 versus 11.7). A significant inverse relationship with severity of aVSP was observed for total hospital days ( P =0.008) and days in the intensive care unit ( P <0.0001). On average, patients with severe aVSP stayed in the hospital 5 days longer than those with no aVSP. Conclusions— Severe aVSP is associated with poor cognition, worse patient-relevant outcomes, and greater inpatient healthcare resource use. Future studies assessing new aVSP treatments should include outcome measures that evaluate quality of recovery among survivors.

Access to medical services is a concern for this population. Patients were dissatisfied with the waiting time for their first specialist appointment and with decreased access to allied health professionals. Patients travelling longer distances were more satisfied with their health care provider's care, suggesting that good patient-care giver relationships helped to ameliorate the difficulties of travelling to their appointments. Copyright © 2016 John Wiley & Sons, Ltd.

The CDI-DaySyms captures symptoms relevant to patients undergoing CDI, demonstrating initial content validity. Final content and psychometric validity are being evaluated in a substudy comprising patients from two ongoing international clinical trials (ClinicalTrials.gov identifiers NCT01987895 and NCT01983683).

Objectives: Fatigue is an important symptom for multiple sclerosis (MS) patients. Qualitative research supported initial content validity of the FSIQ-RMS™,1 the first patient-reported outcome (PRO) measure of fatigue in relapsing (R)MS developed according to the 2009 FDA PRO guidance. To confirm appropriateness, validity, and reliability of the FSIQ-RMS, further psychometric analyses were required. MethOds: The FSIQ-RMS™ with 9 Symptom items (daily recall period, 1 subdomain) and 14 Impact items (weekly recall period, 3 subdomains) was administered over 3 months (three 7-day intervals) in a multicenter, noninterventional, US-based, IRB-approved study to adult patients with different RMS subtypes (relapsing remitting, secondary progressive, progressive relapsing) and a subset of matched healthy controls (week 1 only). Data analyses included: item response and dimensionality; content and construct validity; internal consistency and test-retest reliability; as well as attribution of fatigue to RMS. Evaluations were supported by those from a cross-sectional, multicenter study, in which RMS patients completed the FSIQ-RMS™ Symptoms domain. Results: The psychometric validation study included 164 RMS patients (mean age 45 [range 19-65] years; 76% female) and 74 controls (40 [18-65] years; 73% female). Two redundant Symptom items were deleted, leaving 7; Impact items were unchanged. A 0-100 scoring algorithm was developed for the FSIQ-RMS™ (sub)domains. Internal consistency (Cronbach's alpha 0.87-0.97) and test-retest reliability (intraclass correlation coefficient [ICC] 0.92-0.95) of all (sub)domains exceeded pre-specified thresholds (alpha> 0.70; ICC≥ 0.70). The Symptoms domain discriminated along the symptom-severity continuum of RMS patients and between patients and healthy controls. Patients were able to attribute fatigue-related symptoms to RMS (14-point difference vs. controls; P< 0.0001). Findings were supported by those from the cross-sectional study (N= 154). cOnclusiOns: Content and measurement validity of the revised final FSIQ-RMS™ were confirmed. Responsiveness of the PRO will be evaluated in a Phase III trial. 1Value Health 2014;17(3):A195-6.

A569 chemotherapy treatment decision-making. Methods: We embedded the validated Decisional Conflict Scale (DCS) into our discrete choice experiment survey examining preferences for chemotherapy treatment in early BrCa. Of the 1004 general population participants, 200 completed the DCS before (DCS-1; no GEP test score in scenario) and after (DCS-2; GEP test score added to scenario) the discrete choice experiment. The 16-item DCS was scored from 0-100 with five subscores. Mean total and subscores, standard deviations and change in scores were calculated, with significance based on matched pairs t-tests (p< 0.05). We anticipated GEP would decrease decisional conflict in individuals unsure of their chemotherapy treatment decision. Results: As anticipated, total score and all subscores (uncertainty, informed, values clarity, support, and effective decision) decreased significantly (all p< 0.05) in the group of respondents (n= 33) who indicated uncertainty about taking chemotherapy in DCS-1 but changed to no chemotherapy after receiving a GEP test score in DCS-2. In the group of respondents (n= 25) who indicated they would undergo chemotherapy in DCS-1 but changed to unsure in DCS-2, their effective decision subscore increase significantly (24.5 to 34.5, p< 0.05). In the overall sample (n= 200), total decisional conflict decreased from DCS-1 to DCS-2 by 0.5 (p= 0.3) and all subscores had non-significant decreases with the exception of effective decision, which had a non-significant increase. ConClusions: GEP influences chemotherapy treatment decisional conflict in individuals who are initially unsure in their treatment decision-making. However, we do not observe this effect in individuals who do not change their chemotherapy treatment decisions.objeCtives: Individuals with BrCa have high decisional conflict with respect to treatment decisions. GEP of tumours informs risk prediction, potentially affecting decisions about adjuvant chemotherapy in early BrCa, where only 15% will experience recurrence. We aimed to examine whether GEP reduces decisional conflict in