Health-Related Quality of Life for Patients with Post-Acute COVID-19 Syndrome: Identification of Symptom Clusters and Predictors of Long-Term Outcomes.

BACKGROUND: Following COVID-19 infection, as many as a third of patients have long-term symptoms, known as post-acute sequelae (PASC). The mechanisms contributing to PASC remain largely unknown and, due to the heterogeneity of symptoms, treating PASC provides unique challenges. OBJECTIVE: Our study sought to (1) identify clinical symptom profiles based on PROMIS Global Health (GH) items, (2) evaluate demographic and clinical differences across profiles, and (3) identify predictors of change in health-related quality of life (HRQL) over time. DESIGN: This was an observational cohort study of patients with PASC who completed PROMIS-GH between 2/11/21 and 12/3/21 as part of routine care, with data extracted from the electronic health record. PARTICIPANTS: There were 1407 adult patients (mean age 49.6 ± 13.7, 73% female, 81% White race) with PASC seen in the recovery clinic between 2/11/21 and 12/3/21, with 1129 (80.2%) completing PROMIS-GH as routine care. MAIN MEASURES: HRQL was measured with PROMIS-GH at initial visit and after 12 months. KEY RESULTS: Latent profile analysis identified symptom classes based on five PROMIS-GH items (mental health, ability to carry out physical activities, pain, fatigue, and emotional problems). Four latent profiles were identified: (1) "Poor HRQL" (n = 346), (2) "Mixed HRQL: good mental/poor physical" (n = 232), (3) "Mixed HRQL: poor mental/good physical" (n = 324), and (4) "Good HRQL" (n = 227). Demographics and comorbidities varied significantly across profile with patients with more severe COVID-19 infection more likely to be in profiles 1 and 2. Overall, patients improved 2 T-score points on PROMIS-GH after 12 months, with differences by profile. Predictors of improved HRQL included profile, lower body mass index, and fewer COVID symptoms. CONCLUSIONS: Patients with PASC have distinct HRQL symptom profiles which were able to differentiate across COVID-19 severity and symptoms. Improvement over 12 months differed by profile. These profiles may be used to better understand the mechanisms behind PASC. Future research should evaluate their ability to guide treatment decisions to improve HRQL.

An 8-week Forced-rate Aerobic Cycling Program Improves Cardiorespiratory Fitness in Persons With Chronic Stroke: A Randomized Controlled Trial.

OBJECTIVE: To examine the cardiorespiratory effects of a forced-rate aerobic exercise (FE) intervention among individuals with chronic stroke compared with an upper extremity repetitive task practice (UE RTP) control group. DESIGN: Secondary analysis of data from a randomized controlled trial. SETTING: Research laboratory. PARTICIPANTS: Individuals with chronic stroke (N=60). INTERVENTIONS: Participants completed 24 sessions of FE followed by RTP (FE+RTP, N=30) or time matched RTP alone (N=30). The FE+RTP group was prescribed exercise at 60%-80% of heart rate reserve on a motorized stationary cycle ergometer for 45 minutes followed by 45 minutes of RTP. The control group completed 90 minutes of RTP. MAIN OUTCOME MEASURES: Metabolic exercise stress tests on a cycle ergometer were conducted at baseline and post-intervention. Outcomes included peak oxygen consumption (peak V̇o2) and anaerobic threshold (AT). RESULTS: Fifty participants completed the study intervention and pre/post stress tests. The FE+RTP group demonstrated significantly greater improvements in peak V̇o2 from 16.4±5.7 to 18.3±6.4 mL/min/kg compared with the RTP group (17.0±5.6 to 17.2±5.6 mL/min/kg, P=.020) and significantly greater improvements in AT from 10.3±2.8 to 11.5±3.6 mL/min/kg compared with the RTP group (10.8±3.9 to 10.4±3.2 mL/min/kg, P=.020). In analyzing predictors of post-intervention peak V̇o2, the multivariable linear regression model did not reveal a significant effect of age, sex, body mass index, or beta blocker usage. Similarly, bivariate linear regression models for the FE group only did not find any exercise variables (aerobic intensity, power, or cycling cadence) to be significant predictors of peak V̇o2. CONCLUSIONS: While the aerobic exercise intervention was integrated into rehabilitation to improve UE motor recovery, it was also effective in eliciting significant and meaningful improvements in cardiorespiratory fitness. This novel rehabilitation model may be an effective approach to improve motor and cardiorespiratory function in persons recovering from stroke.

Validation of a Health-Related Quality of Life Questionnaire in Patients With Recurrent Clostridioides difficile Infection in ECOSPOR III, a Phase 3 Randomized Trial.

BACKGROUND: Debilitating symptoms of recurrent Clostridioides difficile infection (rCDI) often lead to long-term effects on health-related quality-of-life (HRQOL). In ECOSPOR III, SER-109, an investigational oral microbiome therapeutic, was superior to placebo in reducing rCDI. We investigated the validity, reliability, and responsiveness of a 32-item, CDI-specific questionnaire-the Clostridium difficile Quality of Life Survey (Cdiff32)-across mental, physical, and social domains in patients with rCDI. METHODS: In this post hoc analysis of a phase 3 clinical trial, 182 outpatients with rCDI completed Cdiff32 and EQ-5D at baseline and at 1 and 8 weeks. Cdiff32 was evaluated for item performance, internal reliability, and convergent validity. To assess known-groups validity, Cdiff32 scores were compared by disease recurrence status at week 1; internal responsiveness was evaluated in the nonrecurrent disease group by 8 weeks by means of paired t test. RESULTS: All 182 patients (mean age [standard deviation], 65.5 [16.5] years; 59.9% female) completed baseline Cdiff32. Confirmatory factor analysis identified 3 domains (physical, mental, and social relationships) with good item fit. High internal reliability was demonstrated (Cronbach α = 0.94 with all subscales >0.80). Convergent validity was evidenced by significant correlations between Cdiff32 subscales and EQ-5D (r = 0.29-0.37; P < .001). Cdiff32 differentiated patients by disease recurrence status at week 1 (effect sizes, 0.38-0.42; P < .05 overall), with significant improvement from baseline through week 8 in patients with nonrecurrent disease at week 1 (effect sizes, 0.75-1.02; P < .001 overall). CONCLUSIONS: Cdiff32 is a valid, reliable, and responsive disease-specific HRQOL questionnaire that is fit for purpose for interventional treatment trials. The significant improvement in patients with nonrecurrent disease by 8 weeks demonstrates the negative impact of rCDI on HRQOL.

Emergency department utilization among patients who receive outpatient specialty care for headache: A retrospective cohort study analysis.

OBJECTIVES: To compare clinical characteristics among outpatient headache clinic patients who do and do not self-report visiting the emergency department for headache. BACKGROUND: Headache is the fourth most common reason for emergency department visits, compromising 1%-3% of visits. Limited data exist about patients who are seen in an outpatient headache clinic but still opt to frequent the emergency department. Clinical characteristics may differ between patients who self-report emergency department use and those who do not. Understanding these differences may help identify which patients are at greatest risk for emergency department overutilization. METHODS: This observational cohort study included adults treated at the Cleveland Clinic Headache Center between October 12, 2015 and September 11, 2019, who completed self-reported questionnaires. Associations between self-reported emergency department utilization and demographics, clinical characteristics, and patient-reported outcome measures (PROMs: Headache Impact Test [HIT-6], headache days per month, current headache/face pain, Patient Health Questionnaire-9 [PHQ-9], Patient-Reported Outcomes Measurement Information System [PROMIS] Global Health [GH]) were evaluated. RESULTS: Of the 10,073 patients (mean age 44.7 ± 14.9, 78.1% [7872/10,073] female, 80.3% [8087/10,073] White patients) included in the study, 34.5% (3478/10,073) reported visiting the emergency department at least once during the study period. Characteristics significantly associated with self-reported emergency department utilization included younger age (odds ratio = 0.81 [95% CI = 0.78-0.85] per decade), Black patients (vs. White patients) (1.47 [1.26-1.71]), Medicaid (vs. private insurance) (1.50 [1.29-1.74]), and worse area deprivation index (1.04 [1.02-1.07]). Additionally, worse PROMs were associated with greater odds of emergency department utilization: higher (worse) HIT-6 (1.35 [1.30-1.41] per 5-point increase), higher (worse) PHQ-9 (1.14 [1.09-1.20] per 5-point increase), and lower (worse) PROMIS-GH Physical Health T-scores (0.93 [0.88-0.97]) per 5-point increase. CONCLUSION: Our study identified several characteristics associated with self-reported emergency department utilization for headache. Worse PROM scores may be helpful in identifying which patients are at greater risk for utilizing the emergency department.

Clinical characteristics and patient-reported outcomes of chronic and episodic migraine patients at a US tertiary headache center: A retrospective observational study.

OBJECTIVE: To describe differences in clinical and demographic characteristics between patients with episodic migraine (EM) or chronic migraine (CM) and determine the effect of migraine subtype on patient-reported outcome measures (PROM). BACKGROUND: Prior studies have characterized migraine in the general population. While this provides a basis for our understanding of migraine, we have less insight into the characteristics, comorbidities, and outcomes of migraine patients who present to subspecialty headache clinics. These patients represent a subset of the population that bears the greatest burden of migraine disability and are more representative of migraine patients who seek medical care. Valuable insights can be gained from a better understanding of CM and EM in this population. METHODS: We conducted a retrospective observational cohort study of patients with CM or EM seen in the Cleveland Clinic Headache Center between January 2012 and June 2017. Demographics, clinical characteristics, and patient-reported outcome measures (3-Level European Quality of Life 5-Dimension [EQ-5D-3L], Headache Impact Test-6 [HIT-6], Patient Health Questionnaire-9 [PHQ-9]) were compared between groups. RESULTS: Eleven thousand thirty-seven patients who had 29,032 visits were included. More CM patients reported being on disability 517/3652 (14.2%) than EM patients 249/4881 (5.1%) and had significantly worse mean HIT-6 (67.3 ± 7.4 vs. 63.1 ± 7.4, p < 0.001) and median [interquartile range] EQ-5D-3L (0.77 [0.44-0.82] vs. 0.83 [0.77-1.00], p < 0.001), and PHQ-9 (10 [6-16] vs. 5 [2-10], p < 0.001). CONCLUSIONS: There are multiple differences in demographic characteristics and comorbid conditions between patients with CM and EM. After adjustment for these factors, CM patients had higher PHQ-9 scores, lower quality of life scores, greater disability, and greater work restrictions/unemployment.

Impact of acute symptomatic seizures and their management on patient-reported outcomes after stroke.

OBJECTIVE: Acute symptomatic seizures (ASyS) after stroke are not uncommon. However, the impact of ASyS and its management with anti-seizure medications (ASMs) on patient-reported outcome measures (PROMs) remains poorly investigated. The objective of our study is to evaluate the association between PROMs and ASyS and ASMs following stroke. METHODS: We performed a retrospective cohort study of all stroke patients who underwent inpatient continuous EEG (cEEG) monitoring performed due to suspected ASyS, including the ones with observed convulsive ASyS, from 04/01/2012 to 03/31/2018, who completed PROMs within 6 months of hospital discharge. Patient-reported outcome measures, including one Neuro-QoL and six PROMIS v1.0 domain scales, were completed by patients as the standard of care in ambulatory stroke clinics. Since ASMs are sometimes used without clearly diagnosed ASyS, we performed group comparisons based on ASM status at discharge, irrespective of their ASyS status. T-tests or Wilcoxon rank sum tests compared continuous variables across groups and chi-square tests or Fisher's exact tests were used for categorical variables. RESULTS: A total of 508 patients were included in the study [mean age 62.0 ± 14.1 years, 51.6% female; 244 (48.0%) ischemic stroke, 165 (32.5%) intracerebral hemorrhage, and 99 (19.5%) subarachnoid hemorrhage]. A total of 190 (37.4%) patients were discharged on ASMs. At the time of the first PROM, conducted a median of 47 (IQR = 33-78) days after the suspected ASyS, and 162 (31.9%) were on ASMs. ASM use was significantly higher in patients diagnosed with ASyS. Physical Function and Satisfaction with Social Roles and Activities were the most affected health domains. Patient-reported outcome measures were not significantly different between groups based on ASyS (electrographic and/or convulsive), ASM use at hospital discharge, or ASM status on the day of PROM completion. SIGNIFICANCE: There were no differences in multiple domain-specific PROMs in patients with recent stroke according to ASyS status or ASM use suggesting the possible lack of the former's sensitivity to detect their impact. Additional research is necessary to determine if there is a need for developing ASyS-specific PROMs.

PROMIS global health: potential utility as a screener to trigger construct-specific patient-reported outcome measures in clinical care.

PURPOSE: Patient-reported outcome measures (PROMs), including global health and construct-specific measures, are collected across healthcare systems. Efforts should be made to reduce data collection burden and individualize survey administration to patient needs. Our study evaluated the ability of utilizing items on a global health measure to identify patients who may require additional screening. METHODS: A cross-sectional study was conducted of patients who completed PROMIS Global Health (GH) as part of routine care, as well as additional construct-specific surveys, in a large healthcare system from 1/1/2016 to 12/31/2018. Receiver operating characteristic (ROC) analysis identified optimal thresholds for PROMIS GH items identifying clinically meaningful thresholds on construct-specific PROMs: PHQ-9 score ≥10, Neuro-QoL Cognitive Function, PROMIS Physical Function, and Satisfaction with Social Roles and Activities T-score ≤40, PROMIS Anxiety, Fatigue, Sleep Disturbance, and Pain Interference T-score ≥60. RESULTS: There were 206,685 patients who completed PROMIS GH and additional construct-specific surveys. Scores ≤3 on PROMIS GH item 10 (emotional problems) had 90.0% sensitivity (area under the curve (AUC) = 0.821) for identifying patients with moderate-severe depressive symptoms on PHQ-9. Similarly high sensitivities and AUCs were demonstrated for PROMIS GH items assessing mental and physical health, fatigue, and pain to identify poor scores on their corresponding construct-specific PROMs. CONCLUSIONS: Our study provides preliminary support for the ability of utilizing PROMIS GH items as screening tools to identify patients with poor scores on additional construct-specific PROMs. Through directing construct-specific PROMs to patients for whom they are most applicable, survey burden could be reduced for many patients, allowing a more efficient and targeted use of PROMs in healthcare decision-making.

Association of Physical Therapy Treatment Frequency in the Acute Care Hospital With Improving Functional Status and Discharging Home.

BACKGROUND: Physical therapists (PTs) are consulted to address functional deficits during hospitalization, but the effect of PT visit frequency on patients' outcomes is not clear. OBJECTIVE: The objective of this study was to examine whether PT visit frequency is independently associated with functional improvement, discharge home, and both outcomes combined. RESEARCH DESIGN: This was a retrospective cohort study. SUBJECTS: Patients discharged from hospitals in 1 health system between 2017 and 2020, stratified by diagnostic subgroup: cardiothoracic and vascular, general medical/surgical, neurological, oncology, and orthopedic. MEASURES: PT visit frequency was categorized as ≤2, >2-4, >4-7, >7 visits/week. Functional improvement was defined as ≥5-point improvement in Activity Measure for Post-Acute Care mobility score. Other outcomes were discharge home and both outcomes combined. RESULTS: There were 243,779 patients included. Proportions within frequency categories ranged from 11.0% (>7 visits/wk) to 40.5% (≤2 visits/wk) and varied by subgroup. In the full sample, 36% of patients improved function, 64% were discharged home, and 27% achieved both outcomes. In adjusted analyses, relative to ≤2 visits/week, the adjusted relative risk (aRR) for functional improvement increased incrementally with higher frequency (aRR=1.20, 95% confidence interval: 1.14-1.26 for >2-4 visits to aRR=1.78, 95% confidence interval: 1.55-2.03 for >7 visits). For all patients and within subgroups, the higher frequency was also associated with a greater likelihood of discharging home and achieving both outcomes. CONCLUSIONS: More frequent PT visits during hospitalization may facilitate functional improvement and discharge home. Most patients, however, receive infrequent visits. Further research is needed to determine the optimal delivery of PT services to meet individual patient needs.

Health-Related Quality of Life Mildly Affected Following COVID-19: a Retrospective Pre-post Cohort Study with a Propensity Score-Matched Control Group.

IMPORTANCE: Long-term health effects have been indicated following COVID-19; however, the impact of COVID-19 on health-related quality of life (HRQOL), including who may experience ongoing symptoms, is unknown. OBJECTIVE: To identify change in HRQOL following COVID-19 compared to pre-infection HRQOL and a matched control group, and identify predictors of patients who worsen. DESIGN: Retrospective pre-post cohort study with a matched control group. SETTING: Large healthcare system in northeast Ohio. PARTICIPANTS: A total of 3,690 adult patients diagnosed with COVID-19 who completed HRQOL surveys during routine care for ambulatory visits before and after infection. Propensity-score 1:1 match was utilized to identify controls without COVID who completed HRQOL at two time points. MAIN OUTCOMES: HRQOL was assessed with PROMIS Global Health: global mental and physical health summary scores. Pre- and post-COVID PROMIS Global Health was completed as part of routine care from 1/1/2019 to 2/29/2020 and 4/4/2020 to 11/1/2021, respectively, and extracted from the electronic health record. RESULTS: COVID-19 patients (mean age 53±15; 66% female) completed PROMIS Global Health in the year prior (median 11.1 months) and after diagnosis (median 7.8 months). Compared to before infection, COVID-19 patients had a significant reduction in global mental health and stable global physical health (-0.85 and 0.05 T-score points, respectively) with clinically meaningful reduction (≥5 T-score points) experienced by 27% and 23% of patients, respectively. Predictors of worsening global health included being female, having depression, being hospitalized for COVID-19, and better pre-COVID global health. Compared to the control group, there was significantly worse global mental and physical health decline following COVID-19 (-0.53 and -0.37 T-score points, respectively). CONCLUSIONS AND RELEVANCE: A quarter of patients with COVID-19 experienced meaningful reductions in HRQOL. Reductions in global mental and physical health were modest, although significantly worse than a control group. Additionally, identified predictors of patients who worsen may assist clinicians when counseling patients of their risk of worse HRQOL following COVID-19.

Early initiation of riluzole may improve absolute survival in amyotrophic lateral sclerosis.

INTRODUCTION/AIMS: Riluzole improves survival in amyotrophic lateral sclerosis (ALS), but optimal time and duration of treatment are unknown. The aim of this study was to examine if timing of riluzole initiation and duration of treatment modified its effect on survival. METHODS: Patients from the PRO-ACT dataset with information on ALS Functional Rating Scale, time from onset to enrollment (TFOE), and riluzole use were selected for analysis. Survival from enrollment was the outcome. Multivariable Cox proportional hazard models were examined for interactions between riluzole and TFOE. Inverse probability of treatment weighting (IPTW) was used to assess average treatment effect. RESULTS: Of 4778 patients, 3446 (72.1%) had received riluzole. In unadjusted analyses, riluzole improved median survival significantly (22.6 vs. 20.2 months, log-rank p < 0.001). In multivariable analyses, no significant interaction between TFOE and riluzole was found. Riluzole effect was uniform during follow-up. By IPTW, estimated riluzole hazard ratio was 0.798 (95% confidence interval 0.686-0.927). Delaying riluzole initiation by 1 y (6 to 18 months from onset) may translate to reducing median survival from onset by 1.9 months (40.1 to 38.2 months). DISCUSSION: Riluzole appears to reduce risk of death uniformly, regardless of time from onset to treatment, and duration of treatment. Earlier treatment with riluzole may be associated with greater absolute survival gain from onset. Early diagnosis of ALS will facilitate early treatment and is expected to improve survival.

Development and validation of the Value of Uterus instrument and visual analog scale to measure patients' valuation of their uterus.

BACKGROUND: Currently, there are no clear frameworks or tools to objectively or subjectively evaluate patient attitudes toward uterine preservation and how they influence the decision to proceed with hysterectomy vs uterine preservation when undergoing prolapse surgery. OBJECTIVE: This study aimed to develop a reliable and valid instrument to measure patients' valuation of their uterus. STUDY DESIGN: The Value of Uterus instrument was developed on the basis of existing literature and created with structured patient-reported outcome measurement development methodology. An initial 14-question instrument was administered to 152 patients, and the instrument was revised on the basis of an analysis of internal consistency. The resulting Value of Uterus instrument has 6 items and includes a visual analog scale for the question "How important is it to you to keep your uterus when you have a gynecologic condition?" To validate the instrument, we recruited 51 patients aged >45 years with uterovaginal prolapse who presented to the urogynecology department and were scheduled to undergo vaginal surgery with or without hysterectomy. Internal reliability of the instrument was measured with Cronbach alpha. For known-groups validity, Value of Uterus summary scores were compared between women who underwent hysteropexy and those who underwent hysterectomy using the t test. Intraclass correlation coefficient was used to assess test-retest reliability with Value of Uterus administered to women twice. Lastly, a receiver-operating characteristic curve analysis was conducted to identify a cutoff Value of Uterus and visual analog scale score for predicting whether a woman would undergo hysteropexy (vs hysterectomy). RESULTS: A total of 51 patients were recruited (26 patients in the hysterectomy and 25 in the hysteropexy group), with a mean age of 64±10 years; 87.8% of patients self-identified as White. There were no differences in demographics between the groups. Cronbach's alpha was 0.94, suggesting excellent internal consistency of the items in the Value of Uterus instrument. The Value of Uterus instrument was highly correlated with the visual analog scale question, with r=0.82 (95% confidence interval, 0.69-0.89; P<.001). Patients in the hysteropexy group had significantly higher Value of Uterus scores (indicating greater value placed on the uterus) than women who underwent hysterectomy (20.8 vs 12.2; P<.001). Receiver-operating characteristic curve analysis identified a Value of Uterus cutoff score ≥14, with good accuracy for predicting hysteropexy (area under the curve, 0.87; sensitivity, 92.0%; specificity, 68%). CONCLUSION: Value of Uterus is a reliable and valid 6-item instrument that measures patients' valuation of the uterus and preferences for uterine preservation when undergoing surgery for pelvic organ prolapse. Value of Uterus and visual analog scale were shown to reliably predict whether a patient undergoes uterine-preserving prolapse surgery. The Value of Uterus instrument and visual analog scale tool can be useful tools to ensure that the patient's preferences are included in the medical decision-making. Value of Uterus may be useful for future research in other gynecologic conditions where uterine preservation is an option.

Quality of life following concurrent temozolomide-based chemoradiation therapy or observation in low-grade glioma.

PURPOSE: Low-grade glioma (LGG) exhibits longer median survival than high-grade brain tumors, and thus impact of our therapies on patient quality of life remains a crucial consideration. This study evaluated the effects of concurrent temozolomide-based chemoradiation (RT + TMZ) or observation on quality of life (QOL) in patients with low-grade glioma. METHODS: We completed a retrospective cross-sectional study of adults with LGG who underwent surgery with known molecular classification from 1980 to 2018. Postoperatively, patients were either observed or received adjuvant concurrent temozolomide-based chemoradiation. EQ-5D and PHQ-9 depression screen were completed before outpatient visits every 2-3 months. Baseline score was defined as ± 30 days within initial operation. RESULTS: Of the 63 patients (mean age 44 ± 17 years, 51% female) with baseline EQ-5D or PHQ-9 depression screen data and at least one follow-up measure, 30 (48%) were observed and 33 (52%) received RT + TMZ. No significant decline was seen in EQ-5D or PHQ-9 scores at 3, 6, 9, 12, and 24 months compared to baseline scores for all patients. At each time point, there was no significant difference between those who were observed or received adjuvant therapy. The linear mixed model estimating PHQ-9 value or EQ-5D index demonstrated that there was no significant difference in PHQ-9 or EQ-5D index between treatment groups (p = 0.42 and p = 0.54, respectively) or time points (p = 0.24 and p = 0.99, respectively). CONCLUSION: Our study found no significant decline in patient QOL or depression scores as assessed by patient- reported outcome measures for patients with low-grade glioma up to 2 years following surgery. We found no difference between RT + TMZ compared to observation during this time frame. Additional follow-up can help identify the longer-term impact of treatment strategy on patient experience.

Cognitive function after concurrent temozolomide-based chemoradiation therapy in low-grade gliomas.

PURPOSE: We sought to evaluate the effects of concurrent temozolomide-based chemoradiation therapy on neurocognitive function in patients with low-grade glioma (LGG). MATERIALS/METHODS: We included adult patients with LGG who were treated postoperatively with radiotherapy (RT) with concurrent and adjuvant temozolomide (TMZ). Patients were evaluated with comprehensive psychometric tests at baseline (prior to RT + TMZ) and at various time intervals following RT + TMZ. Baseline cognitive performance was analyzed by sex, age, education history, history of seizures, IDH mutation status, and 1p/19q codeletion status. Changes in neurocognitive performance were evaluated over time. RESULTS: Thirty-seven LGG patients (mean age 43.6, 59.5% male) had baseline neurocognitive evaluation. Patients with an age > 40 years old at diagnosis and those with an education > 16 years demonstrated superior baseline verbal memory as assessed by HVLT. No other cognitive domains showed differences when stratified by the variables mentioned above. A total of 22 LGG patients had baseline and post RT + TMZ neurocognitive evaluation. Overall, patients showed no statistical difference between group mean test scores prior to and following RT + TMZ on all psychometric measures (with the exception of HVLT Discrimination). CONCLUSION: Cognitive function remained stable following RT + TMZ in LGG patients evaluated prospectively up to 2 years. The anticipated analysis of RTOG 0424 will provide valuable neurocognitive outcomes specifically for high risk LGG patients treated with RT + TMZ.

Mapping PROMIS physical function and pain interference to the modified low back pain disability questionnaire.

PURPOSE: The Modified Low Back Pain Disability Questionnaire (MDQ) is a commonly used tool to assess functioning of patients with low back pain (LBP). Recently, the Patient-Reported Outcomes Measurement Information System (PROMIS) was suggested as an alternative platform to assess LBP patient-reported health. We sought to map between the MDQ and PROMIS Physical Function (PROMIS-PF) and Pain Interference (PROMIS-PI) scales using multiple methods. METHODS: In a retrospective analysis of LBP patients seen at Cleveland Clinic 11/14/18-12/11/19, T-scores from each PROMIS scale were mapped to MDQ total score individually and together. MDQ item and total scores were mapped to each PROMIS scale. Linear regression as well as linear and equipercentile equating were used. Split sample internal validation using root mean squared error (RMSE), mean absolute error (MAE), and correlations were used to assess accuracy of mapping equations. RESULTS: 13585 patients completed the three scales. In the derivation cohort, average age was 59.0 (SD = 15.8); 53.3% female and 82.9% white. Average MDQ total, PROMIS-PF, and PROMIS-PI T-scores were 40.3 (SD = 19.0), 37.2 (SD = 7.6), and 62.9 (SD = 7.2), respectively. For estimating MDQ total scores, methods that used both PROMIS-PF and PROMIS-PI had closest estimated means, lowest RMSE and MAE, and highest correlations. For estimating each of PROMIS-PF and PROMIS-PI T-scores, the best performing method was equipercentile equating using the MDQ items. CONCLUSIONS: We created and internally validated maps between MDQ and PROMIS-PF and PROMIS-PI using linear regression, linear and equipercentile equating. Our equations can be used by researchers wishing to translate scores between these scales.

Somatic symptoms have negligible impact on Patient Health Questionnaire-9 depression scale scores in neurological patients.

BACKGROUND AND PURPOSE: There is concern that the Patient Health Questionnaire-9 (PHQ-9) depression scale may be impacted by the presence of somatic symptoms (differential item functioning [DIF]) in patients with neurological conditions. We evaluated the PHQ-9 for the presence and impact of DIF in large clinical samples of neurological patients. METHODS: We conducted a cross-sectional study of patients seen at the Cleveland Clinic Cerebrovascular, Headache, Movement Disorder, and Neuromuscular clinics who completed the PHQ-9 and patient-reported disease severity measures as part of standard care between 29 July 2008 and 21 February 2013. We evaluated PHQ-9 items for DIF with respect to disease-specific severity for each condition. Salient DIF impact was characterized as a difference between DIF-adjusted and unadjusted PHQ-9 scores. RESULTS: Included in the study were 2112 patients with stroke, 8221 with migraine, 440 with amyotrophic lateral sclerosis (ALS), and 5022 with Parkinson disease (PD). Several PHQ-9 items demonstrated DIF with respect to disease-specific severity, although salient DIF was present in very few patients (stroke, n = 0; migraine, n = 1; ALS, n = 13; PD, n = 1). CONCLUSIONS: PHQ-9 items function consistently across disease severity, with salient levels of DIF impact found only for a very small proportion of people. These results suggest that the PHQ-9 provides a consistent measure of depression severity among people with neurological conditions associated with somatic symptoms that overlap with depression.

Evidence of Stability in Patient-Reported Global Health During the COVID-19 Pandemic.

OBJECTIVES: Measures of health-related quality of life (HRQOL) are collected throughout healthcare systems and used in clinical, economic, and outcomes studies to direct patient-centered care and inform health policy. Studies have demonstrated increases in stressors unique to the COVID-19 pandemic, however, their effect on HRQOL is unknown. Our study aimed to assess the change in self-reported global health during the pandemic for patients receiving care in a large healthcare system compared with 1 year earlier. METHODS: An observational cross-sectional study of 2 periods was conducted including adult patients who had a healthcare appointment and completed the Patient-Reported Outcomes Measurement Information System Global Health (PROMIS GH) as standard care during the COVID-19 pandemic and a year earlier. The effect of time on PROMIS global mental health (GMH) and global physical health (GPH) was evaluated through multiple statistical methods. RESULTS: There were 38 037 patients (mean age 56.1 ± 16.6 years; 61% female; 87% white) who completed the PROMIS GH during the pandemic (August 2020) and 33 080 (age 56.7 ± 16.5 years; 61% female; 86% white) who had completed it 1 year earlier (August 2019). GMH was significantly worse, whereas GPH was similar during the pandemic compared with a year earlier (adjusted estimate [standard error]: -1.21 (0.08) and 0.11 (0.08) T-score points, respectively). CONCLUSIONS: Our study found modest, nonclinically meaningful decreases in GMH and similar GPH during the COVID-19 pandemic compared with a year earlier in patients cared for in a large healthcare system. Nevertheless, healthcare systems are likely seeing a biased sample of patients during these times. Findings from our study have implications for the interpretation of HRQOL during this pandemic.

The validity of proxy responses on patient-reported outcome measures: Are proxies a reliable alternative to stroke patients' self-report?

PURPOSE: Caregivers, or proxies, often complete patient-reported outcome measures (PROMs) on behalf of patients with stroke. The objective of our study was to assess the validity and responsiveness of proxy-responses compared to patient-responses across multiple domains of health. METHODS: Stroke patients and their proxies were recruited to complete PROMs between 7/2018-11/2019. PROMs included Neuro-QoL cognitive function, PROMIS physical function, satisfaction with social roles, anxiety, fatigue, pain interference, sleep disturbance, Global Health, and PHQ-9. Internal consistency and convergent validity were compared between patient- and proxy-reported measures. Known-groups validity was assessed across levels of stroke disability. Internal responsiveness was evaluated using paired t-tests for a subset of patients who attended rehabilitation following stroke. Analyses were stratified by patients ≤ 3 vs > 3 months from stroke. RESULTS: This cross-sectional study included 200 stroke patients (age 62.2 ± 13.3, 41.5% female) and their proxies (age 56.5 ± 13.9, 70% female, 72% spouses). PROMs had high internal consistency and were significantly correlated for patients and proxies. Patient- and proxy-reported measures worsened with increasing stroke disability. For 34 (17%) patients who attended rehabilitation, patients self-reported improvement on 5 domains whereas proxies reported no improvement. Compared to patient self-reports, validity was worse for proxy-reports on patients ≤ 3 months but better > 3 months from stroke. CONCLUSIONS: Both patient- and proxy-reported PROMs demonstrated strong validity. Only patient-reported PROMs were responsive to change, and proxies had worse validity for patients ≤ 3 months from stroke but better validity for patients > 3 months from stroke. These findings justify the utilization of proxy responses in stroke patients > 3 months from stroke.

Patient-reported experience with patient-reported outcome measures in adult patients seen in rheumatology clinics.

OBJECTIVES: Patient-reported outcome measures (PROMs) are increasingly utilized in the evaluation of patients with rheumatic diseases. The aim of our study was to assess the patient experience with completing PROMs within rheumatology clinics, and identify patient characteristics associated with a more positive experience. METHODS: We conducted a retrospective cross-sectional study of adult patients seen in rheumatology clinics between 1/1/2017 and 6/30/2017. Patients were included in the study if they completed at least one patient-reported experience question following completion of PROMs. Patient characteristics associated with more positive experiences were identified through multivariable proportional odds models. RESULTS: 12,597 adult patients (mean age 59 ± 15; 76% female; 84% white) completed PROMs, as well as questions on their experience completing PROMs. Patients agreed/strongly agreed that PROM questions were easy to understand (97%), useful (84%), helped their physician understand their health (78%), improved communication with their provider (78%) and improved control over their own care (70%). Predictors of better experience with PROMs included being younger, non-white, having lower income, and being a new patient. Worse self-reported health also predicted better experience with PROMs. CONCLUSION: Our study found a positive patient experience with PROMs, which is a crucial component of their successful implementation and utilization. Findings from this study suggest PROMs may be particularly beneficial in new patients, minorities, those with lower income, and worse self-reported quality of life. Collecting PROMs could provide opportunities to improve patient-provider communication and enhance control over care for rheumatology patients who could most benefit.

Magnitude and Variability of Stroke Patient-Proxy Disagreement Across Multiple Health Domains.

OBJECTIVES: To quantify the extent and variability of bias introduced when caregivers, or proxies, complete patient-reported outcome measures (PROM) on behalf of stroke patients. DESIGN: Cross-sectional survey study conducted between July 2018 and November 2019. SETTING: Ambulatory clinic of a cerebrovascular center or rehabilitation unit. PARTICIPANTS: A consecutive sample of stroke patients (N=200) and their proxies who were able and willing to complete PROMs. Proxies completed PROMs as they believed the patient would answer. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: PROMs included Neuro-QoL cognitive function, PROMIS physical function, social role satisfaction, anxiety, fatigue, pain interference, sleep disturbance, Patient Health Questionnaire-9 translated to PROMIS Depression, and PROMIS Global Health. RESULTS: The study included 200 stroke patients (age, 62.2±13.3; 41.5% women) and their proxies (age 56.5±13.9; 70% women, 72% spouses). Proxies reported worse functioning and more symptoms across all PROM domains compared with patients (average difference, 0.3-3.0 T score points). Reliability between dyad responses was moderate across all domains (intraclass correlation coefficients (2,1), 0.49-0.76) and effect sizes were small (d=0.04-0.35). Cognitive function, anxiety, and depression had the lowest agreement, whereas physical function, pain, and sleep had the highest agreement based on the Bland-Altman method. At the individual level, a large proportion of dyads had meaningfully different scores across domains (range, 40%-57%; dyads differed >5 T score points). Few predictors of disagreement were identified through multinomial regression models. CONCLUSIONS: At the aggregate level, small differences were detected between stroke patient-proxy pairs, with lower agreement on more subjective domains. At the individual level, a large proportion of dyads reported meaningfully different scores on all domains, affecting the interpretability of proxy responses on PROMs in a clinical setting.

A Cost-Effectiveness Framework for Amyotrophic Lateral Sclerosis, Applied to Riluzole.

OBJECTIVES: Reexamine cost-effectiveness of riluzole in the treatment of amyotrophic lateral sclerosis (ALS) in light of recent advances in disease staging and understanding of stage-specific drug effect. METHODS: ALS was staged according to the "fine'til 9" (FT9) staging method. Stage-specific health utilities (EQ-5D, US valuation) were estimated from an institutional cohort, whereas literature informed costs and transition probabilities. Costs at 2018 prices were disaggregated into recurring costs (RCs) and "one-off" transition/"tollgate" costs (TCs). Five- and 10-year horizons starting in stage 1 disease were examined from healthcare sector and societal perspectives using Markov models to evaluate riluzole use, at a threshold of $100 000/quality-adjusted life year (QALY). Probabilistic and deterministic sensitivity analyses were conducted. RESULTS: Mean EQ-5D utilities for stages 0 to 4 were 0.79, 0.74, 0.63, 0.54, and 0.46, respectively. From the healthcare sector perspective at the 5-year horizon, riluzole use contributed to 0.182 QALY gained at the cost difference of $12 348 ($5403 riluzole cost, $8870 RC and -$1925 TC differences), translating to an incremental cost-effectiveness ratio (ICER) of $67 658/QALY. Transition probability variation contributed considerably to ICER uncertainty (-30.2% to +90.0%). ICER was sensitive to drug price and RCs, whereas higher TCs modestly reduced ICER due to delayed tollgates. CONCLUSION: This study provides a framework for health economic studies of ALS treatments using FT9 staging. Prospective stage-specific and disaggregated cost measurement is warranted for accurate future cost-effectiveness analyses. Appropriate separation of TCs from RCs substantially mitigates the high burden of background cost of care on the ICER.