Functional Assessment Of Chronic Illness Therapy Research Articles

Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naive to complement inhibitors: the 301 study

AbstractRavulizumab (ALXN1210), a new complement C5 inhibitor, provides immediate, complete, and sustained C5 inhibition. This phase 3, open-label study assessed the noninferiority of ravulizumab to eculizumab in complement inhibitor–naive adults with paroxysmal nocturnal hemoglobinuria (PNH). Patients with lactate dehydrogenase (LDH) ≥1.5 times the upper limit of normal and at least 1 PNH symptom were randomized 1:1 to receive ravulizumab or eculizumab for 183 days (N = 246). Coprimary efficacy end points were proportion of patients remaining transfusion-free and LDH normalization. Secondary end points were percent change from baseline in LDH, change from baseline in Functional Assessment of Chronic Illness Therapy (FACIT)–Fatigue score, proportion of patients with breakthrough hemolysis, stabilized hemoglobin, and change in serum free C5. Ravulizumab was noninferior to eculizumab for both coprimary and all key secondary end points (Pinf < .0001): transfusion avoidance (73.6% vs 66.1%; difference of 6.8% [95% confidence interval (CI), −4.66, 18.14]), LDH normalization (53.6% vs 49.4%; odds ratio, 1.19 [0.80, 1.77]), percent reduction in LDH (−76.8% vs −76.0%; difference [95% CI], −0.83% [−5.21, 3.56]), change in FACIT-Fatigue score (7.07 vs 6.40; difference [95% CI], 0.67 [−1.21, 2.55]), breakthrough hemolysis (4.0% vs 10.7%; difference [95% CI], −6.7% [−14.21, 0.18]), and stabilized hemoglobin (68.0% vs 64.5%; difference [95% CI], 2.9 [−8.80, 14.64]). The safety and tolerability of ravulizumab and eculizumab were similar; no meningococcal infections occurred. In conclusion, ravulizumab given every 8 weeks achieved noninferiority compared with eculizumab given every 2 weeks for all efficacy end points, with a similar safety profile. This trial was registered at www.clinicaltrials.gov as #NCT02946463.

Fatigue Measurements in Systemic Lupus Erythematosus.

Fatigue is a frequent, disabling issue in systemic lupus erythematosus (SLE). It is, however, difficult to quantify. The Ad Hoc Committee on SLE Response Criteria for Fatigue in 2007 recommended using the Krupp Fatigue Severity Scale (FSS). Since then, the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale has also been validated in SLE. We performed a review of instruments used to measure fatigue in adult SLE patients from 2007 onward. We searched PubMed, Medline, and Embase (January 2008-October 2017), identifying clinical trials and observational studies in adult SLE, where fatigue was a specifically measured outcome. All English and French studies were reviewed to determine fatigue measures and results. Thirty-seven studies met inclusion criteria. Eight scales were used. The visual analog scale (VAS), FSS, and FACIT-Fatigue Scale were most frequent. FSS was the most often used instrument in both clinical trials and observational studies. Twenty-five of the 37 studies demonstrated a difference in fatigue that was statistically significant and clinically meaningful. Of the 12 studies that did not, 6 used FSS, 3 used VAS, 2 used the Multidimensional Assessment of Fatigue, and 1 used the Brief Fatigue Index. All 6 studies using the FACIT-Fatigue Scale detected clinically meaningful and statistically significant differences. VAS, FSS, and FACIT-Fatigue Scale were the most frequently used instruments in adult SLE studies from 2008 to 2017. Many studies detected clinically important changes in fatigue. Fatigue remains a key measure in both clinical trials and observational SLE studies.

RETRACTED ARTICLE: Content validity and psychometric evaluation of Functional Assessment of Chronic Illness Therapy-Fatigue in patients with psoriatic arthritis

BackgroundTo evaluate the measurement properties (e.g. content validity, reliability and ability to detect change) of the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale in patients with active psoriatic arthritis (PsA).MethodsOne-on-one semi-structured qualitative interviews with adult patients with active PsA evaluated the content validity of FACIT-Fatigue. Quantitative measurement properties were evaluated using data from phase III tofacitinib randomized controlled trials (RCTs) in PsA: OPAL Broaden (NCT01877668) and OPAL Beyond (NCT01882439).ResultsOf 12 patients included in the qualitative study, 2 (17%) had mild, 8 (67%) had moderate, and 2 (17%) had severe PsA disease activity; 7 (58%) attributed fatigue to PsA, and 7 (58%) rated fatigue as important or extremely important. Most patients considered the FACIT-Fatigue items relevant to their PsA experience and understood item content and response options as intended. In the psychometric analysis of RCT data, a second-order confirmatory factor model fit the data well (Bentler’s Comparative Fit Index ≥0.92). FACIT-Fatigue demonstrated good internal consistency (Cronbach’s coefficient α ≥ 0.90), test-retest reliability (Intraclass Correlation Coefficient ≥ 0.80) and a strong correlation with SF-36 Vitality (r > 0.80). A robust relationship between disease activity (based on Patient’s Global Assessment of Psoriasis and Arthritis) and FACIT-Fatigue was observed (effect sizes > 1.4), with clinically important difference for the FACIT-Fatigue total score estimated as 3.1 points, and the responder definition estimated as a 4-point improvement for FACIT-Fatigue total score.ConclusionFatigue was confirmed to be an important symptom to patients with PsA, and FACIT-Fatigue was found to be a reliable and valid measure in this population.

Hyponatremia in systemic lupus erythematosus patients: Relation to disease activity and fatigue

Aim of the workTo investigate the relation of hyponatremia to disease activity and fatigue in systemic lupus erythematosus (SLE) patients. Patients and methodsThe present study included 30 SLE patients with hyponatremia and 70 with normal serum sodium (Na) level. SLE disease activity index and the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score were assessed. ResultsThe gender, age and disease duration of SLE patients with hyponatremia (26 females and 4 males; mean age 37.8 ± 9.3 years, 10.9 ± 5.1 years) were comparable with those without (60 females and 10 males; 36.9 ± 11.8 years, 11.1 ± 6.02; p = 0.71 and p = 0.9 respectively). SLE patients with hyponatremia showed significantly increased SLEDAI (14.2 ± 3.85 vs 3.86 ± 3.59; p < 0.001), ESR (55.2 ± 18.2 vs 14.70 ± 3.5 mm/1st h; p < 0.001) and CRP (30.97 ± 4.4 vs 5.17 ± 2.6 mg/dl; p < 0.001) and lower FACIT-Fatigue (21.99 ± 2.1 vs 35.87 ± 4.81; p < 0.001) compared to patients without. Serum Na levels significantly correlated with the FACIT-fatigue score (r = 0.99, p < 0.01), platelets (r = 0.22; p = 0.03), white blood cells count (r = 0.31, p < 0.001) and inversely with SLEDAI (r = −0.27, p = 0.01), ESR (r = −0.71; p < 0.001), CRP (r = −0.86, p < 0.001), anti-ds-DNA (r = 0.54, p < 0.001), C3 (r = −0.29, p = 0.01) and C4 (r = −0.2, p = 0.04). On regression, CRP (β = 0.3), SLEDAI (β = 0.28) and consumed C4 (β = −0.07) were significant independent risk factors for hyponatremia (p < 0.0001, p = 0.0005, p = 0.02 respectively). The optimal cut-off values to predict hyponatremia was a SLEDAI score ≥11 (90% sensitivity and 96% specificity), and ESR ≥ 17.5 mm/1st h (100% sensitivity and 80% specificity) and a CRP of ≥10.5 mg/dl (100% sensitivity and 97% specificity). ConclusionHyponatremia in SLE patients is associated with higher disease activity and more perceived fatigue. Hyponatremia could reflect severe inflammation and could be considered as one of the predisposing factors of fatigue.

A Phase 3 Study of Ravulizumab (ALXN1210) Versus Eculizumab in Adults with Paroxysmal Nocturnal Hemoglobinuria Naive to Complement Inhibitors: Results of a Subgroup Analysis with Patients Stratified By Baseline Hemolysis Level, Transfusion History, and Demographics

Background/Objective: Ravulizumab (ALXN1210) is an innovative C5 inhibitor with high C5 affinity and a half-life approximately 4 times longer than eculizumab. In the largest interventional clinical study of C5 inhibitor-naive patients with paroxysmal nocturnal hemoglobinuria (PNH) to date, ravulizumab administered every 8 weeks (q8w) was shown to be noninferior to eculizumab (every 2 weeks [q2w]) across 2 coprimary endpoints and 4 key secondary endpoints, due to its ability to provide immediate, complete, and sustained inhibition of complement C5 (Lee et al, EHA-2018). Because PNH is a rare disease, prospective evaluation of new agents for the treatment of this disease, with the exception of ravulizumab, has been limited to small populations. As a result, assessing the effect of treatment in patients with unique disease characteristics and gaining a full understanding of the benefit-to-risk profile of new therapies, has been challenging. The objective of this protocol-specified analysis was to evaluate the relative efficacy of ravulizumab and eculizumab in adult patients with PNH based upon baseline hemolysis level, transfusion history, and demographics.Methods: In this phase 3, randomized, open-label, noninferiority, multicenter study (NCT02946463), patients ≥18 years of age with confirmed diagnosis of PNH, naive to complement inhibitor therapy, with lactate dehydrogenase (LDH) level ≥1.5 times upper limit of normal (xULN), and ≥1 PNH-related sign/symptom at screening received ravulizumab or eculizumab over a 183 day study period. Coprimary efficacy endpoints were transfusion avoidance and LDH normalization. Secondary endpoints were percent change in LDH, change in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score, proportion of patients with breakthrough hemolysis, and proportion with stabilized hemoglobin levels. Subgroup analyses were performed on each of these endpoints, based on transfusion history (0, 1-14, or >14 units of packed red blood cells [pRBCs] in the year prior to the first dose of study drug), screening LDH levels (1.5-<3 or ≥3 xULN), sex, age, race, and geographical region. Descriptive statistics are provided with no formal hypothesis testing performed.Results: In total, 246 patients from countries across the Asia-Pacific region (n=124), Europe (n=91), North America (n=9), and South America (n=22) were randomized to ravulizumab (n=125) or eculizumab (n=121). For transfusion avoidance, the point estimates for 15/17 subgroups favored ravulizumab. The treatment effect favored ravulizumab irrespective of prior pRBC transfusion history and baseline LDH levels, as well as nearly all other demographic subgroups assessed (Panel A). With respect to LDH normalization, the point estimates for 11/17 subgroups favored ravulizumab. The treatment effect numerically favored ravulizumab among patients who received 1-14 and >14 pRBCs in the 12 months before randomization, both baseline LDH subgroups, and most of the demographic subgroups (Panel B). No sensitive subgroups were identified for either of the coprimary endpoints. Similarly, point estimates favored ravulizumab in the majority of patient subgroups across each of the key secondary endpoints, including: 8/17 of the subgroups on the assessment of percent change in LDH; 12/17 subgroups on the assessment of change in FACIT-Fatigue score; 13/17 subgroups on the assessment of breakthrough hemolysis; and 13/17 subgroups on the assessment of hemoglobin stabilization.Conclusions: Results of this prespecified analysis revealed point estimates favoring ravulizumab for the majority of the diverse subgroups of PNH patients analyzed. The consistency of these data across subgroups confirms the robustness of the results of this study. The benefit of ravulizumab in terms of transfusion avoidance and LDH normalization was retained across all subgroups. These results provide evidence supporting the use of ravulizumab for the treatment of complement inhibitor-naive patients with PNH regardless of transfusion history, baseline hemolysis level, sex, age, race, or geographic region. DisclosuresWeitz:Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria. Kulagin:Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria. Nakao:Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria; Novartis: Honoraria; Kyowa Hakko Kirin Co., Ltd.: Honoraria. Szer:Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Other: Travel Support , Research Funding. Rottinghaus:Alexion Pharmaceuticals, Inc.: Employment, Equity Ownership. Volles:Alexion Pharmaceuticals, Inc.: Employment, Equity Ownership. Damokosh:Alexion Pharmaceuticals, Inc.: Employment, Equity Ownership. Aguzzi:Alexion Pharmaceuticals, Inc.: Employment, Equity Ownership. Larratt:Alexion Pharmaceuticals, Inc.: Honoraria, Research Funding. Risitano:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Alnylam Pharmaceuticals, Inc.: Consultancy, Honoraria, Research Funding; Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Ra Pharmaceuticals, Inc.: Consultancy, Honoraria, Research Funding; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer Inc.: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amyndas Pharmaceuticals: Consultancy.

A Single Infusion of Iron Isomaltoside 1000 Allows a More Rapid Hemoglobin Increment Than Multiple Doses of Iron Sucrose with a Similar Safety Profile in Patients with Iron Deficiency Anemia

▪Introduction: Iron deficiency anemia (IDA) is prevalent and associated with reduced quality of life (QoL) and worsened disease outcomes. Oral iron administration remains the front line standard but its use is associated with an unacceptably high incidence of gastrointestinal side effects and low adherence. Further, in many conditions associated with blood loss, iron losses may exceed the capacity for oral iron absorption. Use of intravenous (IV) iron, especially if given in a single dose, may result in better compliance, fewer visits to the medical practitioner, and overall improvement in QoL. To date, no product has been licensed in the USA for single visit complete replacement dosing. To address this issue, this trial compared the safety and efficacy of iron isomaltoside 1000 with the most commonly prescribed IV formulation, iron sucrose, in patients intolerant of, or unresponsive to oral iron or likely to receive a blood transfusion.Methods: This was a randomized, open-label, comparative, multi-center trial conducted in the USA. Patients with IDA were randomized 2:1 to either iron isomaltoside administered as a single dose of 1000 mg infused over 20 min at baseline or iron sucrose administered as 200 mg IV injections according to label and repeated up to 5 times. The primary endpoints were adjudicated serious or severe hypersensitivity events starting on or after the first dose of treatment (if the upper bound of the 95 % CI was <3 %, the safety objective was met) and change in hemoglobin (Hb) from baseline to week 8.Results: A total of 1512 patients were enrolled of whom 26 % had gastrointestinal and 50 % gynecologic blood loss. The mean (standard deviation [SD]) age was 44 (15) years. The mean (SD) cumulative dose of iron was 975 (145) mg and 905 (217) mg in the iron isomaltoside and iron sucrose group, respectively. All required 1 visit for iron correction with iron isomaltoside and 4 to 5 visits for iron sucrose.The frequency of subjects with serious or severe hypersensitivity reactions was 0.3% in the iron isomaltoside group versus 0.4 % in the iron sucrose group (95% CI: 0.88 for iron isomaltoside and 1.45 for iron sucrose), meeting the primary safety endpoint.The treatment groups had statistically similar adverse drug reactions (ADRs), 12.5 % in the iron isomaltoside group and 12.8 % in the iron sucrose group. Only 0.2 % of patients in iron isomaltoside group and 0.4 % in iron sucrose group experienced serious ADRs. There were no related fatalities. The frequency of composite cardiovascular safety endpoint was 0.8 % in the iron isomaltoside group and 1.2 % in the iron sucrose group (p = 0.57). The frequency of hypophosphatemia (s-phosphate <2 mg/dL) was low and similar in the 2 groups (3.9 % in the iron isomaltoside and 2.3 % in the iron sucrose group). No patients had s-phosphate <1 mg/dL.The primary efficacy endpoint of non-inferiority in Hb change from baseline to week 8 was met. Iron isomaltoside lead to a significantly more rapid and increased Hb response in the first 2 weeks. This was reflected in both Hb change from baseline and proportion of responders with Hb increases ≥2 g/dL. Hb increased with least square means of 0.70 and 0.44 g/dL at week 1 (p <0.0001) and 1.48 and 1.19 g/dL at week 2 (p <0.0001) for iron isomaltoside and iron sucrose respectively, and the proportion of responders were 5.3 and 2.5 % at week 1 (p = 0.0077) and 32.6 and 20.8 % at week 2 (p <0.0001) for iron isomaltoside and iron sucrose respectively. Larger improvement in Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scores were observed with iron isomaltoside at week 1 (p = 0.04). A faster and greater response with iron isomaltoside was also observed for s-ferritin and transferrin saturation.Conclusion: Iron isomaltoside 1000 administered as 1000 mg in a single visit resulted in a faster and more pronounced hematological response and improvement in fatigue compared to iron sucrose which requires multiple visits. The safety profile was similar with a low frequency of hypersensitivity reactions, cardiovascular events, and serious ADRs. The frequency of hypophosphatemia was low in both treatment groups and no patients had s-phosphate <1 mg/dL. DisclosuresAuerbach:AMAG Pharmaceuticals: Research Funding; Pharmacosmos A/S: Research Funding. Lykke:Pharmacosmos A/S: Employment.

Factors related to alexithymia in patients with systemic sclerosis: a tight relationship with facial image dissatisfaction.

To assess clinical and psychosocial factors related to alexithymia in systemic sclerosis (SSc). We enrolled 40 consecutive SSc patients in a cross-sectional study evaluating alexithymia with Toronto Alexithymia scale (TAS-20). We measured Beck Depression inventory (BDI), Hamilton Anxiety rating scale (HAM-H), 36-Items Short-Form Healthy Survey (SF-36), Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue, Visual Analog Scale (VAS) pain, Pittsburgh Sleep Quality Index (PSQI), Satisfaction with Appearance Scale (SWAP), and Mouth Handicap in Systemic Sclerosis (MHISS). The prevalence of alexithymia was 42%. Alexithymic patients presented increased depressive (p = ≤ 0.001) and anxiety symptoms (p = ≤ 0.001), sleep disorders (p = 0.03), pain (p = 0.02), esthetic concerns (p = 0.03), disability in activities (p = 0.03) and reduced scores of SF-36 in mental components summary (MCS) (p = ≤ 0.001) and physical components summary (PCS) (p = 0.01). We found significant correlations with sleep disorders (r = 0.41, p = ≤ 0.001), BID (r = 0.35, p = 0.04), facial image dissatisfaction (r = 0.35, p = 0.04), mouth disability (r = 0.51, p = 0.005), depressive (r = 0.6, p = ≤ 0.001), and anxiety symptoms (r = 0.48, p = ≤ 0.001), fatigue (r = - 0.45 p = 0.005), SF-36 PCS (r = - 0.51, p = ≤ 0.001) and MCS (r = - 0.65, p = ≤ 0.001). In multiple linear regression analysis, SWAP facial was the only variable associated with TAS-20 [0.99 (0.48) p = 0.05]. Alexithymia correlates with several psychosocial factors but seems strongly related to facial image dissatisfaction.

Simplified Chinese translation of 13 adult item banks from the Quality of Life in Neurological Disorders (Neuro-QoL)

BackgroundThe Quality of Life in Neurological Disorders (Neuro-QoL) item banks evaluate and monitor the physical, mental, and social health of individuals with neurological conditions. Neuro-QoL items can be administered via short form or computerized adaptive testing. This paper describes the English-to-Simplified Chinese translation of 299 items from 13 adult item banks, which are publicly available.MethodsItems were translated according to the Functional Assessment of Chronic Illness Therapy (FACIT) method, including forward and backward translation, reconciliation, expert reviews, and cognitive debriefing with both general and clinical populations in China.ResultsMost of the 299 Simplified Chinese items were well understood by the respondents. Revisions were made on a small number of items after cognitive debriefing. Although some difficulties were encountered in the translation process, all 13 item banks were linguistically validated with acceptable translations.ConclusionAll Chinese adult Neuro-QoL measures are linguistically equivalent to their English sources. Future work includes psychometric validation of these measures in order to create a final version of the item banks. The translation methodology used in this study can serve as a blueprint for researchers in other countries interested in translating the Neuro-QoL.

Questionnaires measuring quality of life and satisfaction of patients and their relatives in a palliative care setting-German translation of FAMCARE-2 and the palliative care subscale of FACIT-Pal.

The evaluation of quality of life (QoL) and satisfaction with care in palliative care patients and their relatives is an important aspect of palliative care research, likewise important to get a direct feedback for the success of treatment. Here, questionnaires are important tools for measuring outcomes of care in medicine. Several validated, predominantly English, questionnaires already exist. These have been translated in different languages but German. The Functional Assessment of Chronic Illness Therapy (FACIT) is an established tool for the evaluation of QoL in cancer patients. The FACIT-Pal, a 46-itemquestionnaire of this group of questionnaires, measures the QoL in palliative care patients. It includes a new palliative care subscale which is not yet available in German. The FAMCARE-2, a 17-item-questionnaire, evaluates the relatives' satisfaction with the care and support they received from palliative care team. The translation process followed a protocol including multiple independent translators as well as a forth and back translation. A German version of FAMCARE-2 and FACIT-Pal was translated based on the original questionnaire. Relevant differences between the English original versions and the back translations weren't revealed by the original scale developers. The final versions of the German translations have been authorized by the scale developers. The FAMCARE-2 and the FACIT-Pal are now available in German and can be used for research and quality control purposes.

Chronic post-stroke fatigue: It may no longer be about the stroke itself

ObjectivePost-stroke fatigue (PSF) is a debilitating complication of stroke recovery. Contributing risk factors, whether they are modifiable, and if they change over time remain understudied. We determine factors associated with PSF and how they evolve from the subacute through chronic phases of recovery. Patients and methodsA consecutive series of patients presenting to our comprehensive stroke center with acute stroke were seen in follow-up within 6 months of infarct and administered the Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scale to evaluate for PSF. It was re-administered >6 months post-infarct. Demographics, stroke characteristics (NIH Stroke Scale [NIHSS], infarct size and location), medical comorbidities, and outcomes (modified Rankin Scale [mRS]) were also recorded. Regression analyses were used to determine factors associated with FACIT scores and PSF at each time point. Results203 patients were administered the FACIT a mean 1.6 months post-stroke; 128 underwent re-administration (mean 13.9 months post-event). In adjusted models, stroke severity (follow-up NIHSS [p < 0.001], mRS [p = 0.005]) and posterior circulation localization (p = 0.012) were associated with lower FACIT scores (increased fatigue) in the subacute setting, while medical comorbidities (hypertension [p = 0.024], obstructive sleep apnea [p = 0.020]) and medication use (anticonvulsants [p = 0.021]) were associated with lower scores chronically. Baseline depression (p < 0.001, p = 0.029) was associated with lower scores at both time points. ConclusionEarly PSF appears to be largely attributable to stroke severity, while chronic fatigue occurs in the setting of medical comorbidities and medication use. This has significant clinical implications when considering management strategies at different stages of recovery.

Abstract A55: A prospective geriatric breast cancer cohort study to define unique features and outcomes in older breast cancer patients

Abstract Background: Adults over age 65 are the fastes- growing segment of the US population. However, clinicians have less evidence of how to treat older adults, because they are underrepresented in clinical trials, and studies designed specifically for older adults are rare. Therefore, clinicians have to extrapolate from trials conducted in younger, healthier populations when developing treatment plans for older adults. Over 40% of new breast cancer diagnoses in the US occur in women aged over 65 years. In general, breast cancer in the older woman has distinct biologic features, including less aggressive characteristics and greater expression of estrogen receptor and progesterone receptor. Increasing age is associated with higher rates of comorbidity and frailty, which has been shown to potentially reduce the survival advantage of more aggressive breast cancer therapies. We are conducting a prospective cohort study of adults &amp;gt; or = 65 years with a new diagnosis of breast cancer (OSU-16153) in order to better understand the complex health issues faced by this population, and to collect data with which to support future studies designed to improve the management of these patients. Specific Aims: 1) To assess overall and progression-free survival of breast cancer patients ages 65 and older seen in the Breast Medical Oncology clinics at the Stefanie Spielman Comprehensive Breast Center at The Ohio State University; 2) to examine the association of demographic, diagnostic, and treatment data with patient outcomes, such as progression-free and overall survival, within this patient population; 3) to evaluate the unique needs of breast cancer patients ages 65 and older by implementing a Comprehensive Geriatric Assessment (CGA) within the Breast Medical Oncology clinics at The Ohio State University. Methods: The study will enroll patients &amp;gt; or = 65 years with a new diagnosis of breast cancer. Participants will complete a brief baseline questionnaire, including items addressing demographics, lifestyle, and health history. Patients will then be asked to complete a Comprehensive Geriatric Assessment (CGA) at the time of enrollment, and approximately every six months while on follow-up. The CGA contains both performance-based assessments of patients’ function, completed by study staff, as well as the patients’ self-reports of symptoms and quality of life. The CGA contains a multifaceted battery of clinical instruments including the PROMIS Global Short Form, Functional Assessment of Cancer Therapy-Breast (FACT-B), Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale, The Pittsburgh Sleep Quality Index, Geriatric Depression Scale, The James Supportive Care Screening Tool, Timed Up &amp; Go Test, Grip Strength, Blessed Orientation-Memory-Concentration Test, Mini-Cog Test, Charlson Comorbidity Index, Mini Nutritional Assessment, Katz Index of Independence in Activities of Daily Living, and Instrumental Activities of Daily Living. Participant medical records will be reviewed every three months to assess survival, disease progression, and treatment changes. All questionnaire data will be completed using iPads, and will be directly recorded into the REDCap database. Electronic medical records will be reviewed by research staff, and relevant data will be manually entered into the REDCap database. The aim is to enroll 1,000 participants, and the recruitment period will be five years from study initiation. Participants will be followed for five years from the time of enrollment, resulting in a total study length of ten years. The study opened to accrual on 18 April 2017. To date 3 patients have been enrolled and have completed baseline assessments. Citation Format: Anne M. Noonan, Janine A. Overcash, Anupama Suresh, Laura K. Flora, Julie Stephens, Geetika Bhatt, Raquel Reinbolt, Nicole O. Williams, Robert Wesolowski, Jeffrey B. VanDeusen, Sagar D. Sardesai, Maryam B. Lustberg, Bhuvaneswari Ramaswamy. A prospective geriatric breast cancer cohort study to define unique features and outcomes in older breast cancer patients [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr A55.

Content and Face Validity and Feasibility of 5 Candidate Instruments for Psoriatic Arthritis Randomized Controlled Trials: The PsA OMERACT Core Set Workshop at the GRAPPA 2017 Annual Meeting.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-Outcome Measures in Rheumatology (OMERACT) Psoriatic Arthritis (PsA) Core Set working group is in the process of selecting core instruments for PsA clinical trials. During a 2-h workshop and breakout group discussions at the GRAPPA 2017 annual meeting in Amsterdam, the Netherlands, participants discussed the first set of candidate instruments to be taken through the OMERACT Filter 2.1 instrument selection process: 66/68 swollen/tender joint count (66/68JC), Spondyloarthritis Consortium of Canada (SPARCC) enthesitis index, patient's global assessment (GRAPPA and OMERACT formulations), Health Assessment Questionnaire-Disability Index (HAQ-DI), Psoriatic Arthritis Impact of Disease (PsAID) questionnaires 9 and 12, and Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue. Based on the assessment of domain match (content and face validity) and feasibility according to the OMERACT instrument selection criteria, the working group recommends continuing with appraisal of construct validity and discrimination for 66/68JC, SPARCC, PsAID 9 and 12, HAQ-DI, and FACIT-Fatigue. In addition, it recommends repeating the OMERACT Filter 2.1 process for patient global instruments because of insufficient votes. Additional sets of candidate instruments for the PsA core instrument set will be evaluated in a similar process.

General Population Norms for the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale

BackgroundThe Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale is an internationally used validated measure. General population–based age- and sex-specific percentile norms are, however, not published to date, although these are needed as reference for the interpretation of clinical research data. ObjectivesTo assess the FACIT-Fatigue Scale in a large representative sample of the German general population to examine psychometric characteristics and factorial structure and to provide population-based norms. MethodsA nationally representative face-to-face household survey was conducted in Germany using the FACIT-Fatigue Scale. Item characteristics were examined. Internal consistency was determined using the Cronbach α. Dimensionality was analyzed using confirmatory factor analysis (CFA) and bifactor analysis. Scale score differences relating to sex and age were assessed. Sex- and age-specific percentiles were computed for the entire scale range. ResultsOf 2426 participants, 55.7% were women, and the mean age was 49.8 ± 17.4 years. The FACIT-Fatigue Scale mean was 43.5 ± 8.3. Cronbach α was high at 0.92. Although fit indices of the CFA were below desired levels (root mean squared error of approximation = 0.144, comparative fit index = 0.846, and Tucker-Lewis index = 0.815), item loadings in the CFA and bifactor analysis confirm the scale’s unidimensionality. Women were more fatigued than men, and participants who were 70 years or older showed higher fatigue scores than younger respondents. Thus, sex- and age-specific population-based percentiles were provided. ConclusionsReliability and validity of the German translation of the FACIT-Fatigue Scale were confirmed. This study provides general population–based sex- and age-specific FACIT-Fatigue Scale percentile norms for the first time, thereby contributing to a meaningful interpretation of clinical research data.

Evaluation of Quality of Life: Functional Assessment of Chronic Illness Therapy after Thoracic Sympathectomy for Palmar Hyperhidrosis.

Primary hyperhidrosis is a condition that significantly decreases the quality of life (QOL). Thoracic sympathectomy is safe and efficient method of treatment in palmar hyperhidrosis. The aim of the study was to evaluate the change in QOL in patients with palmar hyperhidrosis who underwent thoracic sympathectomy. The study includes 149 patients (37 men and 112 women) who were treated with bilateral thoracoscopic sympathectomy for primary palmar hyperhidrosis. Subjective and objective evaluation of hyperhidrosis were performed prior to the surgery, 3 and 12 months after the treatment. Control group consists of 305 healthy volunteers (118 men and 187 women). The QOL was measured using Functional Assessment of Chronic Illness Therapy (FACIT) scale. The average level of palmar hyperhidrosis in the study group prior to surgery was 224.69 ± 179.20 mg/min/m2. General QOL (FACIT total) before the surgery was significantly lower in the study group when compared with the control group (66.57 ± 16.33 vs. 91.29 ± 11.13; p < 0.05). Three months after surgery level of hyperhidrosis decreased significantly and remained at similar level 12 months after the procedure (13.55 ± 15.41 mg/min/m2 p < 0.05 and 14.41 ± 18.19 mg/min/m2 p < 0.05, respectively). After thoracoscopic sympathectomy, the QOL increased and did not differ when compared with the control group 3 and 12 months after the surgery (90.28 ± 11.13 vs. 91.29 ± 11.13; p = 0.55 and 89.59 ± 11.34 vs. 91.29 ± 11.13; p = 0.84, respectively). The highest increase was observed in functional well-being domain (32.25%); however, it was also noticeable in other domains. Thoracic sympathectomy is an efficient method of treatment in palmar hyperhidrosis which significantly increases patients' QOL especially in a functional domain.

Effect of filgotinib, a selective JAK 1 inhibitor, with and without methotrexate in patients with rheumatoid arthritis: patient-reported outcomes

BackgroundThe aim was to assess patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA) treated with filgotinib during two phase 2b, 24-week, randomized, placebo-controlled studies.MethodsPatients with moderate-to-severe active RA and an inadequate response to methotrexate (MTX) were randomized to daily placebo or filgotinib 50 mg, 100 mg, or 200 mg as add-on therapy to MTX (NCT01888874) or as monotherapy (NCT01894516). At week 12, nonresponders receiving filgotinib 50 mg in both studies or placebo in the add-on study, and all patients receiving placebo as monotherapy, were re-assigned to filgotinib 100 mg. PROs were measured using the Health Assessment Questionnaire - Disability Index (HAQ-DI) including Patient Pain assessed by visual analog scale, and the Patient Global Assessment of Disease Activity (Patient Global), the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale (Version 4), and the 36-Item Short Form Health Survey (SF-36).ResultsAt week 12, improvements in all PROs, apart from the SF-36 mental component in the add-on study, were statistically better with filgotinib than placebo; some improvements were noted as early as the first assessment time point (week 1 or week 4). Filgotinib improved HAQ-DI by 0.58–0.84 points, FACIT-Fatigue by 6.9–11.4 points, Patient Global by 25.2–35.6 mm, and Pain by 24.2–37.9 mm; scores were maintained or improved to week 24. Across all PROs, more patients achieved minimal clinically important differences and normative values with filgotinib 200 mg than placebo. Patients re-assigned to filgotinib 100 mg at week 12 experienced improvements in PROs between weeks 12 to 24.ConclusionsFilgotinib as MTX add-on therapy or as monotherapy demonstrated rapid and sustained (to 24 weeks) improvements in health-related quality of life and functional status in patients with active RA.Trial registrationMTX add-on study: ClinicalTrials.gov, NCT01888874. Registered on 28 June 2013. Monotherapy study: ClinicalTrials.gov, NCT01894516. Registered on 10 July 2013.

Association Between Anemia and Fatigue in Hospitalized Patients: Does the Measure of Anemia Matter?

To assess multiple Hb-based measures of anemia in hospitalized patients and test whether these are associated with fatigue. Prospective observational study. Urban, academic medical center. Hospitalized general medicine patients, age =50 years, with any Hb < 9 g/dL. Measures of anemia were created for each patient based on the Hb values from their hospitalization (mean, median, minimum, maximum, admission, and discharge). Fatigue was measured using the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue subscale. Seven hundred eighty-four patients participated. Minimum Hb was strongly associated with fatigue. Patients with a minimum Hb of < 8 g/dL had higher fatigue levels (mean FACIT [standard deviation] Hb < 7 g/dL: 25 [13], 7 g/ dL = Hb <8 g/dL: 25 [14] Hb =8 g/dL: 29 [14], P = 0.001) and were more likely to report high levels of fatigue (FACIT-Fatigue < 27) (56% vs 41%; P = 0.002). Mean Hb had a less robust association with fatigue than minimum Hb, and no other measure of Hb was associated with patients' fatigue levels. Minimum Hb is associated with fatigue while hospitalized and may help identify patients for interventions to address anemia-related fatigue.

A structured group exercise program for patients with metastatic cancer receiving chemotherapy and CTNNB1 (β-catenin) as a biomarker of exercise efficacy.

IntroductionExercise can improve the symptoms of cancer. However, is it a cancer treatment? We tested the feasibility of group exercise for metastatic cancer patients while on chemotherapy. A biomarker for exercise efficacy in colorectal cancer (CRC), β-catenin, was tested.MethodsPatients undergoing palliative chemotherapy were eligible for a pre–post, single-arm study comprising an indefinite, weekly group exercise intervention using strength and aerobic training. The Functional Assessment of Chronic Illness Therapy (FACIT) and Piper Fatigue Scale (PFS) questionnaires were administered, and aerobic capacity assessed using the 6-minute walk test. Selection bias, as measured by invitation rate, as well as participation, compliance, and attrition rates, was measured. CRC patients had surgical sections stained for β-catenin and correlated to survival. The statistical analysis was primarily exploratory and hypothesis generating.ResultsOf the 124 eligible patients, 53 (43%) patients were invited and 35 (28%) patients participated. The median number of classes attended was 16, the compliance rate was 73.1% (95% confidence interval [CI] 67.0–79.4), and the modified attrition rate was 24%. There were no injuries. No significant improvements were seen in the FACIT or PFS at 30 weeks. Aerobic capacity significantly improved at 30 weeks. Participation of CRC patients in the exercise pilot vs nonparticipation was not associated with a change in survival (hazard ratio [HR] =0.98, 95% CI 0.32–2.97). For all CRC patients, strong nuclear staining for β-catenin, compared to weak, suggested a lower risk of mortality (HR =0.54, 95% CI 0.14–1.96). However, CRC participants in the exercise program with weak nuclear staining for β-catenin had a trend to lower mortality (HR =0.39, 95% CI 0.025–6.1).ConclusionExercise for patients with metastatic cancer receiving chemotherapy is feasible and safe. β-Catenin is a potential biomarker for exercise anticancer effect in CRC.

HEART (Heart Evaluation After Radiation Therapy): Novel Detection of Cardiotoxicity in Breast Cancer Patients

Sensitive and reliable tools for the detection and quantification of subclinical cardiotoxicity are critical following RT for primary breast cancer. We prospectively evaluated the association between breast RT and several contemporary measures of cardiac and global cardiovascular function, including cardiopulmonary exercise testing (CPET), in a uniformly-treated cohort with locally-advanced breast cancer. Sixteen patients with HER-2 negative, stage II or III breast cancer were enrolled following completion of neoadjuvant dose-dense anthracycline-containing chemotherapy and mastectomy with immediate reconstruction. Two pre-defined cohorts were analyzed: (1) patients receiving multi-beam IMRT to 50Gy to the reconstructed chest wall and regional nodes (RT) and (2) control group that did not receive RT (No RT). Study assessments were: (1) echocardiogram with speckle tracking (strain), 2) endothelial function - flow-mediated dilatation by brachial artery, (3) CPET, (4) cardiac biomarkers, and 5) Functional Assessment of Cancer Therapy-Breast (FACT-B) and Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue questionnaires. Study assessments were performed at baseline (0-4 weeks prior to RT or 4-8 weeks after mastectomy) and follow-up (2-4 weeks post RT or 15-20 weeks after mastectomy). Differences between baseline and follow-up measurements were assessed using the t-test and the Wilcoxon signed-rank test. A total of 11 patients (9 RT, 2 No RT) had complete data sets and were evaluable for the primary endpoints. Median age was 46 yrs (range: 30-63 yrs). In the RT group, median mean heart dose was 4.66 Gy (3.95 Gy for 5 right-sided and 7.73 Gy for 4 left-sided breast plans). For the entire cohort, there were no significant differences in the mean values between baseline and follow-up ejection fraction (61% vs 63%; p=.07), global longitudinal strain (-19.6 vs -20.0; p=.23), FACT-B scores (111 vs 115; p=.67), and FACIT-Fatigue scores (40 vs 38, p=.40). In the RT group, the mean baseline VO2peak and percent age-predicted VO2peak were significantly higher at follow-up (23.8 vs 25.8, p=.03) (89.5% vs 96.2%; p=.03). Results for cardiac biomarkers and flow-mediated dilatation will be reported at the time of presentation. In this signal-seeking study, breast RT was not associated with detrimental changes in any parameter. Conversely, VO2peak significantly increased from pre- to post-RT. These findings require validation of CPET as a predictor of cardiotoxicity after breast RT in a larger cohort.

Impact of tocilizumab monotherapy on patient-reported outcomes in patients with rheumatoid arthritis from two randomised controlled trials

ObjectiveTwo randomised controlled trials, AMBITION (NCT00109408) and ADACTA (NCT01119859), showed tocilizumab (TCZ) monotherapy superior to methotrexate (MTX) and adalimumab (ADA) monotherapy, respectively, for improving rheumatoid arthritis (RA) disease activity. This...

Clinical benefit of eculizumab in patients with no transfusion history in the International Paroxysmal Nocturnal Haemoglobinuria Registry.

Eculizumab reduces intravascular haemolysis and improves disease symptoms in patients with paroxysmal nocturnal haemoglobinuria (PNH). To characterise, in a real-world setting, the effect of eculizumab in patients with haemolytic PNH (lactase dehydrogenase (LDH) ≥ 1.5 upper limit of normal) and no history of red blood cell transfusion, including those with high disease activity (HDA). Three populations from the International PNH Registry were studied: (i) non-transfused, untreated; (ii) non-transfused, eculizumab-treated and (iii) transfused, eculizumab-treated (≥1 transfusions in 6 months prior to eculizumab initiation). Using multivariate linear regression, the primary outcome was mean absolute change from baseline to 6 months in LDH (U/L) in non-transfused patients who were treated with eculizumab versus those who remained untreated. Secondary outcomes were mean changes in functional assessment of chronic illness therapy (FACIT)-Fatigue and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ)-C30 Fatigue scores from baseline to last available assessment. The study population included (i) 144 non-transfused, untreated patients; (ii) 45 non-transfused, eculizumab-treated patients and (iii) 105 transfused, eculizumab-treated patients. Of these, 136/144, 43/45 and 99/105 had HDA respectively. Compared with untreated patients, non-transfused, treated patients had greater absolute reduction in LDH (-1318.8 vs -39.4; P < 0.001) and greater percentage reduction in LDH (-69.9 vs -1.6%; P < 0.001). Clinically meaningful improvements in FACIT-Fatigue (73.7 vs 24.6%, respectively) and in EORTC-QLQ-C30 (84.2 vs 33.3%, respectively) were observed. Non-transfused, treated patients with HDA had significantly reduced LDH levels (P < 0.001) and clinically meaningful improvements in FACIT-Fatigue (P = 0.003) and EORTC-QLQ-C30 (P = 0.020) versus untreated patients. Significant LDH reduction and clinically meaningful improvement in fatigue were observed in patients with PNH and HDA treated with eculizumab versus untreated patients, irrespective of transfusion history.