Measures Of Functional Status Research Articles

Differential Contribution of Alexithymia Factors to PTSD Severity in TBI

<h3>Research Objectives</h3> Traumatic brain injury (TBI) is commonly associated with neuropsychiatric symptoms, such as alexithymia and posttraumatic stress disorder (PTSD). However, the relation between these conditions is not well understood. Alexithymia, a dysfunction of affective and cognitive emotional processing, have been associated with TBI and PTSD. We examined the interaction of alexithymia factors and PTSD dimensions in Veterans with TBI. <h3>Design</h3> Cross-sectional. <h3>Setting</h3> Outpatient research unit. <h3>Participants</h3> Sixty veterans with mild TBI (medical records and clinical evaluation) and chronic cognitive (neuropsychological evaluation) and neuropsychiatric symptoms (clinical interview). <h3>Interventions</h3> Not applicable. <h3>Main Outcome Measures</h3> All participants were administered a series of standardized neuropsychiatric measures, including Toronto Alexithymia Scale-20 (TAS-20), PTSD Checklist (PCL-M), and standardized neuropsychological and functional status measures. <h3>Results</h3> Alexithymia levels were strongly associated with TBI and PTSD severity. PTSD severity was strongly related to alexithymia Factor 1 (difficulty describing feelings, p < .001) and Factor 2 (difficulty identifying feelings, p < .001), but not Factor 3. Alexithymia and PTSD severity were strongly related to cognitive (executive) dysfunction. However, further analyses demonstrated that alexithymia level was the strongest predictor of executive dysfunction. <h3>Conclusions</h3> These findings highlight the prevalence of alexithymia in veterans with TBI. Our results suggest that increased alexithymia level is associated with more severe levels of PTSD in TBI. In this study more severe alexithymia was also associated with cognitive dysfunction. These results underscore the importance of identification and treatment of alexithymia, as it may improve the quality of life and reduce disability in individuals with TBI. <h3>Author(s) Disclosures</h3> No disclosures

Functional status impairment at six-month follow-up is independently associated with child physical abuse mechanism

BackgroundChildren with abusive injuries have worse mortality, length-of-stay, complications, and healthcare costs compared to those sustaining an accidental injury. Long-term functional impairment is common in children with abusive head trauma but has not been examined in a cohort with heterogeneous body region injuries. ObjectiveTo assess for an independent association between child physical abuse and functional impairment at discharge and six-month follow-up. Participants and settingSeriously injured children (<15 years) treated at seven pediatric trauma centers. MethodsFunctional status was compared between child physical abuse and accidental injury groups at discharge and six-month follow-up. Functional impairment was defined at discharge (“new domain morbidity”) as a change from pre-injury ≥2 points in any of the six domains of the Functional Status Scale (FSS), and impairment at six-month follow-up as an abnormal total FSS score. ResultsChildren with abusive injuries accounted for 10.5% (n = 45) of the cohort. New domain morbidity was present in 17.8% (n = 8) of child physical abuse patients at discharge, with 10% (n = 3) of children having an abnormal FSS at six-months. There were no differences in new domain morbidity at hospital discharge between children injured by abuse and or accidental injury. However, children injured by physical abuse were 4.09 (2.15, 7.78) times more likely to have functional impairment at six months. ConclusionsChild physical abuse is an independent risk factor for functional impairment at six-month follow-up. Functional status measurement for this high-risk group of children should be routinely measured and incorporated into trauma center quality assessments.

Gender differences in characteristics and outcomes in heart failure patients referred for end-stage treatment.

AimsDespite signals from clinical trials and mechanistic studies implying different resilience to heart failure (HF) depending on gender, the impact of gender on presentation and outcomes in patients with HF remains unclear. This study assessed the impact of gender on clinical presentation and outcomes in patients with HF referred to a specialised tertiary HF service.Methods and resultsConsecutive patients with HF referred to a specialised tertiary HF service offering advanced therapy options including left ventricular assist devices (LVAD) and heart transplantation were prospectively enrolled from August 2015 until March 2018. We assessed clinical characteristics at baseline and performed survival analyses and age‐adjusted Cox regression analyses in men vs. women for all‐cause death and a combined disease‐related endpoint comprising death, heart transplantation, and LVAD implantation. Analyses were performed for the overall study population and for patients with HF with reduced ejection fraction (HFrEF). Of 356 patients included, 283 (79.5%) were male. The median age was 58 years (interquartile range 50–67). Two hundred and fifty‐one (74.5%) patients had HFrEF. HF aetiology, ejection fraction, functional status measures, and most of the cardiac and non‐cardiac comorbidities did not differ between men and women. In a median follow‐up of 3.2 years, 50 patients died (45 men, 5 women), 15 patients underwent LVAD implantation, and 8 patients heart transplantation. While all‐cause death was not significantly different between both genders in the overall population [16.9 vs. 6.0%, P = 0.065, hazard ratio (HR) 2.29 (95% confidence interval 0.91–5.78), P = 0.078], in the HFrEF subgroup, a significant difference between men and women was observed [20.7% vs. 3.9%, P = 0.017, HR 3.67 (95% confidence interval 1.13–11.91), P = 0.031]. The combined endpoint was more often reached in men than in women in both the overall population [21.6% vs. 9.0%, P = 0.053, HR 2.51 (1.08–5.82), P = 0.032] and the HFrEF subgroup [27.1% vs. 7.7%, P = 0.015, HR 3.58 (1.29–9.94), P = 0.014].ConclusionsPatients referred to a specialised tertiary HF service showed a similar clinical profile without relevant gender differences. In the mid‐term follow‐up, more male than female patients died or underwent heart transplantation and LVAD implantation. These findings call for independent validation and for further research into gender‐specific drivers of HF progression.

Malnutrition, Frailty, and Sarcopenia in Patients With Cirrhosis: 2021 Practice Guidance by the American Association for the Study of Liver Diseases.

Malnutrition, Frailty, and Sarcopenia in Patients With Cirrhosis: 2021 Practice Guidance by the American Association for the Study of Liver Diseases.

Translation, cross-cultural adaptation and validation of the Upper Limb Functional Index (ULFI) into Brazilian Portuguese in patients with chronic upper limb musculoskeletal disorders

ObjectiveThe purpose of this study was to translate, cross-culturally adapt, and validate the Upper Limb Functional Index (ULFI) into Brazilian Portuguese (ULFI-Br). MethodsThe translation and cross-cultural adaptation of the ULFI was performed according to international recommendations. The ULFI-Br was applied to 190 patients with chronic upper limb musculoskeletal disorders to verify structural validity. The QuickDASH, the SF-36 and a Numerical Pain Scale (NPS) were completed by 180 patients to assess construct validity using the Spearman correlation (ρ). The internal structure of the ULFI-Br was evaluated by exploratory and confirmatory factor analysis with fit indices chi-square/degrees of freedom (DF), Root Mean Square Error of Approximation (RMSEA), Comparative Fit Index (CFI) and Tucker Lewis Index (TLI). A subsample of 51 patients was used to assess test-retest reliability using the intra-class correlation coefficient (ICC), standard error of measurement (SEM) and minimum detectable change at the 90th percentile (MDC90). Internal consistency was assessed by Cronbach's alpha (α). Floor and ceiling effects were also assessed. ResultsFactor analysis identified an uni-dimensional structure with acceptable fit indices (RMSEA = 0.063, CFI = 0.918, TLI = 0.910). The ULFI-Br showed excellent reliability (ICC = 0.909) and adequate internal consistency (α = 0.897). The SEM was 6.11% and the MDC90 was 14.26%. The ULFI-Br demonstrated high correlation with the QuickDASH (ρ = −0.721), and moderate to low correlation with other questionnaires. There were no floor or ceiling effects. ConclusionThe ULFI-Br showed adequate measurement properties in patients with chronic upper limb musculoskeletal disorders indicating its suitability for use as a measure of upper limb functional status in Brazil.

Chronic Nutrition Impact Symptoms Are Associated with Decreased Functional Status, Quality of Life, and Diet Quality in a Pilot Study of Long-Term Post-Radiation Head and Neck Cancer Survivors.

Background: As a result of tumor location and treatment that is aggressive, head and neck cancer (HNC) survivors experience an array of symptoms impacting the ability and desire to eat termed nutrition impact symptoms (NISs). Despite increasing cancer survival time, the majority of research studies examining the impact of NISs have been based on clinical samples of HNC patients during the acute phase of treatment. NISs are often chronic and persist beyond the completion of treatment or may develop as late side effects. Therefore, our research team examined chronic NIS complications on HNC survivors’ functional status, quality of life, and diet quality. Methods: This was a cross-sectional study of 42 HNC survivors who were at least 6 months post-radiation. Self-reported data on demographics, NISs, quality of life, and usual diet over the past year were obtained. Objective measures of functional status included the short physical performance battery and InBody© 270 body composition testing. NISs were coded so a lower score indicated lower symptom burden, (range 4–17) and dichotomized as ≤10 vs. >10, the median in the dataset. Wilcoxon rank sum tests were performed between the dichotomized NIS summary score and continuous quality of life and functional status outcomes. Diet quality for HNC survivors was calculated using the Healthy Eating Index 2015 (HEI-2015). Wilcoxon rank sum tests examined the difference between the HNC HEI-2015 as compared to the National Health and Nutrition Examination Survey (NHANES) data calculated using the population ratio method. Results: A lower NIS score was statistically associated with higher posttreatment lean muscle mass (p = 0.002). A lower NIS score was associated with higher functional (p = 0.0006), physical (p = 0.0007), emotional (p = 0.007), and total (p < 0.0001) quality of life. Compared to NHANES controls, HNC survivors reported a significantly lower HEI-2015 diet quality score (p = 0.0001). Conclusions: Lower NIS burden was associated with higher lean muscle mass and functional, physical, emotional, and total quality of life in post-radiation HNC survivors. HNC survivors reported a significantly lower total HEI-2015 as compared to healthy NHANES controls, providing support for the hypothesis that chronic NIS burden impacts the desire and ability to eat. The effects of this pilot study were strong enough to be detected by straight forward statistical approaches and warrant a larger longitudinal study. For survivors most impacted by NIS burden, multidisciplinary post-radiation exercise and nutrition-based interventions to manage NISs and improve functional status, quality of life, and diet quality in this survivor population are needed.

Immunotherapy in elderly patients

In the recent years the growing life expectancy of the population and increasing cancer burden in elderly patients substantiate the urgent need for the search of optimal cancer treatment strategies. This article provides an overview of the current literature on the efficacy and safety of checkpoint inhibitors in the elderly population. A literature search for published studies using Medline (PubMed) and Elibrary databases was performed. All studies containing data on treatment results including tumor response criteria, treatment response rate, tumor control rate, overall survival were included. Case studies, animal studies and studies containing duplicate results were excluded from the analysis. In elderly patients with cancer there is a substantial number of comorbid conditions and functional disorders, which may decrease the efficacy and modulate the tolerability of immune checkpoint inhibitors (ICI). Besides, different changes associated with immunologic ageing, including thymolysis, increase of the number of memory B-cells and a decrease of hematopoesis intensity are observed. Several studies performed a comparative analysis of efficacy and toxicity of ICIs in elderly and younger patients. In most cases similar results for efficacy and toxicity were demonstrated. To evaluate the toxicity and the influence of treatment on functional status and other important measures in geriatric population further studies of factors, influencing the tolerability and treatment response of newer ICI in elderly cancer patients are needed, including additional adverse events associated with treatment.

Socioeconomic Disparities in Functional Status in a National Sample of Patients With Rheumatoid Arthritis

Little is known about the association of poverty with functional status (FS) in patients with rheumatoid arthritis (RA) who use rheumatology care. To examine the association between socioeconomic status (SES) and FS among patients with RA and to evaluate the association between SES and functional declines over time in patients who received at least some rheumatology care. This cohort study used data from the American College of Rheumatology's Rheumatology Informatics System for Effectiveness (RISE) registry between January 1, 2016, and December 31, 2018. Analyses included all adult patients with a confirmed RA diagnosis (ie, had ≥2 encounters associated with RA International Classification of Diseases codes ≥30 days apart) and at least 1 FS score documented between 2016 and 2018 seen at participating rheumatology practices. Data analysis was conducted from April to December 2020. The Area Deprivation Index (ADI), a zip code-based indicator of neighborhood poverty, was used as a proxy for SES. ADI scores were categorized into quintiles. FS measures included Multidimensional Health Assessment Questionnaire (MDHAQ), Health Assessment Questionnaire Disability index, and Health Assessment Questionnaire-II. Cross-sectionally, mean FS scores were compared across ADI quintiles. Longitudinally, among patients with at least 2 FS scores, multilevel multivariate regression computed the probability of functional decline, defined as a change greater than the minimum clinically important difference, across ADI quintiles. In a subgroup analysis, whether disease activity mediated the association between SES and functional decline was examined. Of the 83 965 patients included in the study, 66 649 (77%) were women, and 60 037 (72%) were non-Hispanic White. Mean (SD) age was 63.4 (13.7) years. MDHAQ was the most reported FS measure (56 928 patients [67.8%]). For all measures, mean (SD) FS score was worse at lower SES levels (eg, for MDHAQ quintile 1: 1.79 [1.87]; quintile 5: 2.43 [2.17]). In longitudinal analyses, the probability of functional decline was 14.1% (95% CI, 12.5%-15.7%) in the highest SES quintile and 18.9% (95% CI, 17.1%-20.7%) in the lowest SES quintile. The association between SES and functional decline was partially mediated (7%; 95% CI, 4%-22%) by disease activity. In this cohort study of patients with RA, worse FS and faster declines in functioning over time were observed in patients with lower SES. These findings provide a framework for monitoring disparities in RA and for generating evidence to spur action toward achieving health equity.

Multidisciplinary Care after Acute Care for Stroke: A Prospective Comparison between a Multidisciplinary Post-Acute Care Group and a Standard Group Matched by Propensity Score.

In this large-scale prospective cohort study, a propensity score matching method was applied in a natural experimental design to investigate how post-acute care (PAC) after stroke affects functional status and to identify predictors of functional status. The main objective of this study was to examine longitudinal changes in various measures of functional status in stroke patients and predictors of scores for these measures before and after PAC. A group of patients who had received PAC for stroke at one of two medical centers (PAC group, n = 273) was compared with a group who had received standard care for stroke at one of four hospitals (three regional hospital and one district hospital; non-PAC group, n = 273) in Taiwan from March, 2014, to October, 2018. The patients completed the functional status measures before rehabilitation, the 12th week and the 1st year after rehabilitation. Generalized estimating equations were used to estimate differences-in-differences models for examining the effects of PAC. The average age was 68.0 (SD = 8.1) years, and males accounted for 57.9%. During the follow-up period, significant risk factors for poor functional outcomes were advanced age, hemorrhagic stroke, and poor function scores before rehabilitation (p < 0.05). Between-group comparisons at subsequent time points revealed significantly higher functional status scores in the PAC group versus the non-PAC group (p < 0.001). Notably, for all functional status measures, between-group differences in total scores significantly increased over time from baseline to 1 year post-rehabilitation (p < 0.001). The contribution of this study is its further elucidation of the clinical implications and health policy implications of rehabilitative care after stroke. Specifically, it improves understanding of the effects of PAC in stroke patients at different follow-up times. Therefore, a policy implication of this study is that standard care for stroke should include intensive rehabilitative PAC to maximize recovery of overall function.

Patients, caregivers, and clinicians differ in performance status ratings: Implications for pediatric cancer clinical trials.

The Lansky Play-Performance Scale (LPPS) is often used to determine a child's performance status for cancer clinical trial eligibility. Differences between clinician and caregiver LPPS ratings and their associations with child-reported functioning have not been evaluated. Children aged 7 to 18 years who were receiving cancer treatment and their caregivers were recruited from 9 pediatric cancer centers. Caregivers and clinicians reported LPPS scores, and children completed Patient-Reported Outcomes Measurement Information System (PROMIS) pediatric functioning and symptom measures before treatment (time 1 [T1]) and after treatment (time 2 [T2]). t tests and mixed-linear models were used to assess differences in caregiver and clinician LPPS scores; polyserial correlations quantified associations between PROMIS and LPPS scores. Of 482 children, 281 had matched caregiver- and clinician-reported LPPS T1/T2 scores. Caregivers rated children significantly worse on the LPPS than clinicians at both T1 (mean, 73.3 vs 87.4; P < .01) and T2 (mean, 67.9 vs 83.1; P < .01). These differences were not related to a child's age (P = .89), diagnosis (P = .17), or sex (P = .64) or to the time point (P = .45). Small to moderate associations existed between caregiver- and clinician-reported LPPS ratings and child-reported PROMIS scores for mobility (caregiver T1/T2 r = 0.51/0.45; P < .01; clinician T1/T2 r = 0.40/0.35; P < .01), fatigue (caregiver T1/T2 r = -0.46/-0.37; P < .01; clinician T1/T2 r = -0.26/-0.27; P < .01), and pain interference (caregiver T1/T2 r = -0.32/-0.30; P < .01; clinician T1/T2 r = -0.17/-0.31; P < .01). Caregivers and clinicians assigned significantly lower LPPS scores at T2 (caregiver Δ = -5.37; P < .01; clinician Δ = -4.20; P < .01), whereas child-reported PROMIS scores were clinically stable. Significant differences between clinician and caregiver LPPS ratings of child performance were sustained over time; their associations with child reports were predominantly small to moderate. These data suggest that clinician-reported LPPS ratings by themselves are inadequate for determining clinical trial eligibility and should be supplemented by appropriate measures of a child's functional status reflecting the child and caregiver perspectives.

Replicated Risk Index of Patient Functional Status Prior to Allogeneic Hematopoietic Cell Transplantation Predicts Healthcare Utilization and Survival

Poor physical functioning is associated with adverse outcomes after allogeneic hematopoietic cell transplantation (alloHCT). Analytic tools to predict mortality in alloHCT recipients include the HCT Comorbidity Index (HCT-CI) based on comorbidities and the Disease Risk Index (DRI) based on disease and disease status. We developed and replicated a risk model for overall survival (OS), early mortality (ie, death from any cause at or before day +100), initial hospital length of stay (LOS), and percentage of inpatient days within the first year post-alloHCT. In this study, we incorporated a physical therapy (PT) assessment with the HCT-CI and DRI to improve outcome predictions. The well-defined and feasible measure of functional status for assessing risk includes (1) the number of sit-to-stands performed in 30 seconds, (2) performance of 25 step-ups on the right/left side with (3) oxygen saturation recovery and (4) heart rate recovery, (5) weight-bearing ability, (6) assistance with ambulation, (7) motor and grip strength, (8) sensory and coordination impairment (eg, self-reported peripheral neuropathy, imbalance), (9) self-reported pain, and (10) limited endurance (ie, inability to complete step-ups and/or sit-to-stands). Our training cohort (TC) included 349 consecutive alloHCT recipients at Roswell Park treated between 2010 and 2016 and a subsequent replication cohort (RC; n=163) treated between 2016 and 2019. Four of the 10 metrics-self-reported pain, limited endurance, self-reported neuropathy, and <10 sit-to-stands in 30 seconds-were identified as significant predictors and were included in the multivariable models with the HCT-CI and DRI to create a new risk index (HCT-PCDRI: HCT-physical, comorbidity, and DRI) for outcomes. Models were tested in the RC. Shorter OS was associated with self-reported pain, limited endurance, higher HCT-CI, and higher DRI. At a median follow-up of 34 months, the 3-year OS based on the HCT-PCDRI was 30% for the very-high-risk group, 54% for the high-risk group, 49% for the intermediate-risk group, and 80% for the low-risk group. The number of patients identified as very high risk increased from 55 using HCT-CI alone to 120 with the new HCT-PCDRI, whereas the number in the low-risk group decreased from 91 to 45. Early mortality and a higher percentage of inpatient days within the first year post-alloHCT (a proxy for poor quality of life and high healthcare utilization) were associated with self-reported pain, higher HCT-CI, and higher DRI. A shorter initial LOS (ie, initial low healthcare utilization) was associated with performance of >10 sit-to-stands in 30 seconds, no self-reported neuropathy, and lower HCT-CI. These PT metrics combined with the HCT-CI and DRI created the HCT-PCDRI, which resulted in more patients being categorized accurately as high risk versus low risk. The HCT-PCDRI results were replicated in an independent cohort. Pre-alloHCT PT metrics with self-reported symptoms (pain and neuropathy) were associated with survival post-alloHCT and prolonged hospital LOS. The HCT-PCDRI scoring system for risk stratification of alloHCT recipients more accurately identifies patients at potential risk of poor outcomes. The HCT-PCDRI can be tested in <15 minutes to identify patients for intervention before or during treatment to potentially improve outcomes.

Medical Care Situation of People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in Germany.

Background and Objective: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a severe illness with the hallmark symptom of Post-Exertional Malaise (PEM). Currently, no biomarkers or established diagnostic tests for ME/CFS exist. In Germany, it is estimated that over 300,000 people are affected by ME/CFS. Research from the United States and the UK shows that patients with ME/CFS are medically underserved, as they face barriers to medical care access and are dissatisfied with medical care. The first aim of the current research was to investigate whether patients with ME/CFS are medically underserved in Germany in terms of access to and satisfaction with medical care. Second, we aimed at providing a German-language version of the DePaul Symptom Questionnaire Short Form (DSQ-SF) as a tool for ME/CFS diagnostics and research in German-speaking countries. Materials and Methods: The current research conducted an online questionnaire study in Germany investigating the medical care situation of patients with ME/CFS. The questionnaire was completed by 499 participants who fulfilled the Canadian Consensus Criteria and reported PEM of 14 h or longer. Results: Participants frequently reported geographic and financial reasons for not using the available medical services. Furthermore, they reported low satisfaction with medical care by the physician they most frequently visited due to ME/CFS. The German version of the DSQ-SF showed good reliability, a one-factorial structure and construct validity, demonstrated by correlations with the SF-36 as a measure of functional status. Conclusions: Findings provide evidence that patients with ME/CFS in Germany are medically underserved. The German-language translation of the DSQ-SF provides a brief, reliable and valid instrument to assess ME/CFS symptoms to be used for research and clinical practice in German-speaking countries. Pathways to improve the medical care of patients with ME/CFS are discussed.

The effects of geriatric assessment on oncologist-patient communication regarding functional status and physical performance in older adults with cancer: A secondary analysis of a 541-subject nationwide URCC NCORP (NCI Community Oncology Research Program) cluster randomized trial.

12010 Background: Despite high prevalence of functional status (FS) and physical performance (PP) impairments among older adults with cancer, standardized assessments and interventions are not routinely used in oncology care. This study characterized how oncologist knowledge of Geriatric Assessment (GA) results influenced conversations and GA-guided recommendations addressing FS and PP concerns. Methods: Data were from a NCORP funded (UG1CA189961) nationwide cluster randomized controlled trial (ClinicalTrials.gov: NCT02107443; PI: Mohile), with inclusion criteria: age ≥70, stage III/IV solid tumor or lymphoma with palliative treatment intent, and ≥1 GA domain impairment. All subjects underwent baseline GA including standardized FS ([instrumental] activities of daily living) and PP (Timed Up and Go, Short Physical Performance Battery, Older Americans Resources and Services Physical Health scale, falls in past 6 months) measures. Oncologists in Intervention arm practices received full GA results and validated recommendations for each patient, while those in the usual care (UC) arm were only notified of depression or severe cognitive impairment. One clinical encounter per patient within 4 weeks of GA was audio-recorded, transcribed and blind coded using a priori content-analysis scheme to categorize conversations and oncologist response (dismissed, acknowledged, or addressed with recommendation) by GA domain. Frequencies, raw and adjusted (for site using generalized linear mixed models) proportions were compared using the Chi square test. Results: 541 patients (mean age: 77, range 70-96) were included. More FS and PP conversations occurred in Intervention (PP=532, FS=164) than UC (PP=183, FS=87) arm (p&lt;.0001). The adjusted proportion of all patients having one or more FS or PP conversations reached 85.8% in the Intervention arm but only 58.6% in UC (p&lt;.0001). Intervention oncologists were more likely to address FS and PP concerns than UC oncologists (42.6% vs 16.5%, p=0.0003), and to use referrals (Intervention=23.5%, UC=5.0%, p&lt;.0001) or information (Intervention=22.3%, UC=3.8%, p=0.0006) to address them. Conclusions: Providing oncologists a GA report with recommended interventions enhances oncologist-patient communication regarding FS and PP-related concerns in older adults with advanced cancer. FS and PP-related issues were more likely to be addressed by those oncologists receiving the GA report, demonstrating the utility of GA as a tool in creating tailored interventions for FS and PP concerns. Our findings support use of GA as an important tool in caring for patients with impairments in physical performance and function. Funding: NIH/NCI UG1CA189961, T32CA102618. Clinical trial information: NCT02107443.

Digital measurement of functional status of patients with glioblastoma.

2016 Background: Among the primary aims of new therapies for glioblastoma (GBM) are the reduction of morbidity and restoration or preservation of quality of life (QoL). Selinexor (SEL) is a first-in class, oral, selective inhibitor of nuclear export which blocks exportin 1 (XPO1), forcing the nuclear retention and reactivation of tumor suppressor proteins, ultimately causing cell death in cancer cells. SEL is approved for the treatment of previously treated multiple myeloma and DLBCL. XPORT-GBM-029 (NCT04421378) is a phase 1 dose finding study followed by an open-label randomized phase 2, 3-arm trial to evaluate SEL in combination with standard therapies for newly diagnosed and recurrent GBM: Arm A (ndGBM, uMGMT) – radiation +/- SEL; Arm B (ndGBM, mMGMT) – radiation and temozolomide +/- SEL; Arm C (rGBM) – lomustine +/- SEL at first relapse. We look to identify sensitive, reliable, and clinically meaningful digital assessments of the functional status of ndGBM and rGBM patients via a patient-centric approach. Methods: XPORT-GBM-029 incorporates standard clinical and imaging evaluations of GBM progression with novel digital tools that objectively measure motor and cognitive function. The study is conducted at 50 sites globally with the aim of enrolling 350 patients with newly diagnosed and recurrent GBM. Following discussions with KOLs and patient advocacy partners at EndbrainCancer, we surveyed GBM patients and their caregivers to identify disease manifestations critical to patients’ QoL. The survey revealed four key areas impacting patients’ QoL that can be affected by GBM therapies and can be objectively monitored: cognitive function, lateralization, fatigue, and sleep. In this trial we use objective measurements to evaluate SEL’s effects on GBM patients’ QoL. Patients wear inertial sensors to measure their activity and sleep and complete a cognitive battery at baseline and before each MRI. Results: Associations between objective digital measures of activity, gait, fatigue, sleep, and cognition will be examined with respect to clinical assessments including physical examinations, modified Response Assessment in Neuro-Oncology (mRANO), Neurologic Assessment in Neuro-Oncology (NANO), Karnofsky Performance Score (KPS) and Patient Reported Outcome (PRO) QoL questionnaires. Descriptive summary statistics and plots are employed in exploratory data analysis, and other advanced data mining methods may also be considered. Conclusions: XPORT-GBM-029 trial is probably the first large, prospective, longitudinal study in GBM patients employing digital markers and may provide useful information regarding the utility of wearable and mobile devices for measuring functional outcomes in clinical trials. Clinical trial information: NCT04421378.

Frailty, a Dimension of Impaired Functional Status in Advanced COPD: Utility and Clinical Applicability.

Background and Objectives: In advanced chronic obstructive pulmonary disease (COPD), functional status is significantly impaired mainly as a result of disease related respiratory symptoms such as dyspnea or as a result of fatigue, which is the extra-respiratory symptom the most prevalent in this setting. “Physical” frailty, considered to be an aging phenotype, has defining traits that can also be considered when studying impaired functional status, but little is known about this relationship in advanced COPD. This review discusses the relevance of this type of frailty in advanced COPD and evaluates it utility and its clinical applicability as a potential outcome measure in palliative care for COPD. Materials and Methods: A conceptual review on the functional status as an outcome measure of mortality and morbidity in COPD, and an update on the definition and traits of frailty. Results: Data on the prognostic role of frailty in COPD are rather limited, but individual data on traits of frailty demonstrating their relationship with mortality and morbidity in advanced COPD are available and supportive. Conclusions: Frailty assessment in COPD patients is becoming a relevant issue not only for its potential prognostic value for increased morbidity or for mortality, but also for its potential role as a measure of functional status in palliative care for advanced COPD.

Trajectories in early rheumatoid arthritis related fatigue over 10 years: results from the ESPOIR cohort.

In a cohort of early rheumatoid arthritis (RA) patients, we aimed to determine and characterise fatigue trajectories over 10 years of follow-up and identify predictors of trajectory membership. We selected patients fulfilling the 2010 ACR/EULAR criteria for RA included in the ESPOIR cohort. We used a cluster analysis to obtain fatigue (assessed by fatigue visual analogue scale) trajectories over the course of 10 years from enrolment. Chi-square tests or ANOVA were performed to evaluate differences of baseline variables between fatigue trajectories. Using a multinomial logistic regression we were able to identify predictors of trajectory membership. We analysed 598 patients with mean disease duration at enrolment of 26.2±40.9 days. Cluster analysis revealed 3 trajectories: high (18%), moderate (52%) and low fatigue (30%). Compared to patients with moderate or low fatigue trajectory, patients with high fatigue trajectory were predominantly women and reported significantly higher duration and intensity of morning stiffness, HAQ score, tender joints count, levels of pain, number of awakenings due to arthritis, frequency of fibromyalgic RA, levels of physician and patient global assessment, more frequent sleep problems, and increased psychological distress. Female patients with pain, psychological distress and presence of sicca symptoms had a higher risk of being in the high trajectory group. These findings suggest that levels of fatigue are rather stable over time in each trajectory. Baseline clinical measures and baseline patient-reported measures of functional status better distinguished the three fatigue trajectories. We did not find any differences between trajectories in baseline laboratory measures. Inflammatory activity was not a predictor of being in the high trajectory fatigue group.

Exploring Factors Associated with Functional Change and Predictors of Participation Improvement-A Two Years Follow-Up on People with Depression.

The purpose of this study is to understand the functional status distribution and to explore the factors associated with changes in functional status and social participation in people with depression using two-year follow-up data. Subjects were selected from the Taiwan Databank of Persons with Disabilities (TDPD) if they had an evaluation date between July 2012 and 31 December 2017. We used data for 1138 individuals with multiple evaluation records and who were diagnosed with depression. The WHO Disability Assessment Schedule 2.0 (WHODAS 2.0) was the primary functional status measure. Other factors selected from the TDPD included social demographic data, living situation, employment status, economic status, and educational level. The results show scores in all dimensions of the WHODAS 2.0 declined over two years, especially in the domains of cognition, household activities, social participation, and total WHODAS 2.0 score. Aging groups showed poor recovery in cognition, getting along with others, and household activities. People living in suburban areas showed poorer recovery than people living in rural and urban areas in cognition, self-care, and general function (total score of WHODAS 2.0). Employment was also strongly associated with functional recovery in household activities, social participation, and general function. The original scores for cognition and getting along with others showed a significant negative relationship with social participation improvement. Our results can be used by policy makers to provide resources and conduct investigations, and by clinicians when making rehabilitation plans.

Sarcopenia is a strong predictive factor of clinical and oncological outcomes following curative colorectal cancer resection.

Skeletal muscle depletion and subsequent functional loss is common in gastrointestinal malignancy. Usual markers of nutritional status may not be part of routine workup. The predictive value of sarcopenia was assessed and compared with clinically utilized factors. The aim of this was to assess the association between computed tomography assessed sarcopenia with outcomes in colorectal cancer resection. A total of 228 consecutive patients who underwent curative colorectal cancer resection were included. Skeletal muscle area was measured at L3, with pre-defined gender-specific cut-offs applied to a height standardized index. Albumin, body mass index and Subjective Global Assessment scores were recorded alongside measures of comorbidity. Predictors of complications, mortality, and recurrence were identified through multivariate logistic regression. Computed tomography assessed sarcopenia was significantly associated with longer stays, complications, 30-day mortality, readmissions and recurrence at 1 year. Specific associations with major, respiratory and cardiac complications were seen. It independently predicted overall complications (odds ratio 2.96, confidence interval 1.19-7.35 P=0.019), recurrence at 1 year (odds ratio 8.00, confidence interval 1.45-44.21, P=0.017) and an increase in comprehensive complication index of 14 (P=0.002). Subgroup analysis found sarcopenia predicted overall complications in rectal surgery and major complications in colonic surgery. American Society of Anesthesiologists predicted complications but not major complications while cancer stage also predicted recurrence rates. Sarcopenia presents an objective, available predictive factor that may be superior to current biochemical and clinical measures of nutritional and functional status. This study found it to be predictive of complication rates and recurrence after curative in colorectal cancer resection.

Gait Speed and Instrumental Activities of Daily Living in Older Adults After Hospitalization: A Longitudinal Population-Based Study.

Hospitalization can impair physical and functional status of older adults, but it is unclear whether these deficits are transient or chronic. This study determined the association between hospitalization of older adults and changes in long-term longitudinal trajectories of 2 measures of physical and functional status: gait speed (GS) and instrumental activities of daily living measured with Functional Activities Questionnaire (FAQ). Linear mixed-effects models assessed the association between hospitalization (nonelective vs elective, and surgical vs medical) and outcomes of GS and FAQ score in participants (older than 60 years) enrolled in the Mayo Clinic Study of Aging who had longitudinal assessments. Of 4902 participants, 1879 had ≥1 hospital admission. Median GS at enrollment was 1.1 m/s. The slope of the annual decline in GS before hospitalization was -0.015 m/s. The parameter estimate (95% CI) for additional annual change in GS trajectory after hospitalization was -0.009 (-0.011 to -0.006) m/s, p < .001. The accelerated GS decline was greater for medical versus surgical hospitalizations (-0.010 vs -0.003 m/s, p = .005), and nonelective versus elective hospitalizations (-0.011 vs -0.006 m/s, p = .067). The odds of a worsening FAQ score increased on average by 4% per year. Following hospitalization, odds of FAQ score worsening further increased (multiplicative annual increase in odds ratio per year [95% CI] following hospitalization was 1.05 [1.03, 1.07], p < .001). Hospitalization of older adults is associated with accelerated long-term decline in GS and functional limitations, especially after nonelective admissions and those for medical indications. However, for most well-functioning participants, these changes have little clinical significance.

Association of Performance Status With Survival in Patients With Advanced Non–Small Cell Lung Cancer Treated With Pembrolizumab Monotherapy

Despite approximately 40% of patients having Eastern Cooperative Oncology Group (ECOG) performance status (PS) scores of at least 2 in the real world, most landmark clinical trials that led to the use of pembrolizumab as standard of care in advanced non-small cell lung cancer (NSCLC) excluded this group. To evaluate whether an ECOG PS score of at least 2 at the start of therapy is associated with progression-free survival (PFS) and overall survival (OS) in advanced NSCLC treated with pembrolizumab monotherapy. This cohort study included all consecutive patients with advanced NSCLC who underwent treatment with palliative pembrolizumab monotherapy from February 2016 to October 2019 at a single academic cancer center, with data censoring on January 15, 2020. ECOG PS score at start of therapy, with 0 and 1 indicating fully active or restricted in strenuous activity and scores of 2 and higher indicating increasing disability. PFS and OS, measured from initiation of pembrolizumab monotherapy. Of 74 patients (median [range] age, 68.5 [33-87] years; 36 [48.7%] women; 53 [71.6%] White individuals) with median follow-up of 19.5 (95% CI, 13.4-27.8) months, 45 (60.8%) had an ECOG PS of 0 or 1, while 29 (39.2%) had an ECOG PS of at least 2. There were no significant differences in the baseline characteristics, except in age. Compared with patients with PS scores of 0 or 1, those with PS scores of at least 2 had significantly lower disease control rates (38 [88.4%] vs 15 [53.6%]; P = .002), shorter median PFS (7.9 [95% CI, 4.6-15.4] months vs 2.3 [95% CI, 1.8-4.8] months; P = .004), and shorter median OS (23.2 [14.0 vs 35.7] months vs 4.1 [95% CI, 2.1-6.9] months; P < .001). Among those potentially eligible for subsequent cancer-directed therapy beyond pembrolizumab monotherapy, patients in the group with PS scores of at least 2 were less likely to receive it than those with PS scores of 0 or 1 (2 [8.3%] vs 14 [45.2%]; P = .003). Multivariable adjustment for baseline characteristics confirmed ECOG PS of at least 2 as an independent risk factor for worse PFS (HR, 2.02; 95% CI, 1.09-3.74; P = .03) and worse OS (HR, 2.87; 95% CI, 1.40-5.89; P = .004). In this cohort study, having an ECOG PS score of at least 2 was associated with poorer prognosis for treatment of advanced NSCLC with palliative pembrolizumab monotherapy. Further prospective studies are needed to evaluate more objective and consistent measures of functional status to facilitate identification of patients with borderline performance status who may achieve durable clinical benefit from treatment with pembrolizumab monotherapy.