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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.

Coronavirus disease secondary to infection by SARS-CoV-2 (COVID19 or C19) causes respiratory illness, as well as severe neurological symptoms that have not been fully characterized. In a previous study, we developed a computational pipeline for the automated, rapid, high-throughput and objective analysis of electroencephalography (EEG) rhythms. In this retrospective study, we used this pipeline to define the quantitative EEG changes in patients with a PCR-positive diagnosis of C19 (n = 31) in the intensive care unit (ICU) of Cleveland Clinic, compared to a group of age-matched PCR-negative (n = 38) control patients in the same ICU setting. Qualitative assessment of EEG by two independent teams of electroencephalographers confirmed prior reports with regards to the high prevalence of diffuse encephalopathy in C19 patients, although the diagnosis of encephalopathy was inconsistent between teams. Quantitative analysis of EEG showed distinct slowing of brain rhythms in C19 patients compared to control (enhanced delta power and attenuated alpha–beta power). Surprisingly, these C19-related changes in EEG power were more prominent in patients below age 70. Moreover, machine learning algorithms showed consistently higher accuracy in the binary classification of patients as C19 versus control using EEG power for subjects below age 70 compared to older ones, providing further evidence for the more severe impact of SARS-CoV-2 on brain rhythms in younger individuals irrespective of PCR diagnosis or symptomatology, and raising concerns over potential long-term effects of C19 on brain physiology in the adult population and the utility of EEG monitoring in C19 patients.

Background: Post-stroke depression poses an important challenge for patients and delays reintegration to societal roles. Earlier identification of patients at higher risk for depression based on clinical imaging would allow a tailored treatment approach. Methods: We conducted machine-learning based lesion-symptom mapping (LSM) using a retrospective cohort of 477 patients with first-ever acute ischemic stroke (AIS) presenting to a large cerebrovascular center from 2013-2019 with mild motor impairment defined by mRS 0-2. Patient Health Questionnaire (PHQ-9) depression scale was collected within 60 days of index stroke. The location and volume of AIS lesions on brain MRI were analyzed using a machine-learning based algorithm coupled with the FreeSurfer parcellation package. LSM after random field theory-based multiple comparison correction was conducted to examine the association of AIS location and volume with PHQ-9 scale, adjusting for patient age, sex and NIHSS. Results: AIS in the right temporal, parietal, occipital lobes and the right basal ganglia were associated with depressive symptoms (Figure A). Sensitivity analysis excluding those with significant sleep disturbance (n=24) demonstrated that strokes in the right frontal and parietal lobes were associated with severe depression measured by PHQ-9>10 (Figure B). Conclusions: This hypothesis generating study was suggestive of a neuroanatomic basis for the development of post-stroke depression. Further studies in a larger dataset are needed to confirm these associations. The methods will help to predict those patients at higher risk for post-stroke depression, allowing for earlier intervention and recovery.

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: To examine whether PT visit frequency is independently associated with functional improvement, discharge home, and both outcomes combined. RESEARCH DESIGN: Retrospective cohort study. SUBJECTS: Patients discharged from hospitals in one 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 visits/week, >2–4 visits/week, >4–7 visits/week, >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/week) to 40.5% (≤2 visits/week) and varied by subgroup. In the full sample, 36% of patients improved function, 64% 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 [CI]: 1.14–1.26 for >2–4 visits to aRR=1.78, 95% CI: 1.55–2.03 for >7 visits). For all patients and within subgroups, higher frequency was also associated with 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.

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.

Objective:We investigated the quality of life (QoL) of patients hospitalized with C. difficile infection (CDI).Design:Prospective survey study.Setting:US tertiary-care referral center, acute-care setting.Participants:Adults hospitalized with a diagnosis of CDI, defined as ≥3 episodes of unformed stool in 24 hours and a positive laboratory test for C. difficile.Methods:We surveyed patients from July 2019 to March 2020 using the disease-specific Cdiff32 questionnaire and the generic PROMIS GH survey. We compared differences in Cdiff32 scores among demographic and clinical subgroups (including CDI severity, CDI recurrence, and various comorbidities) using 2-sample t tests. We compared PROMIS GH scores to the general population T score of 50 using 1-sample t tests. We performed multivariable linear regression to identify predictors of Cdiff32 scores.Results:In total, 100 inpatients (mean age, 58.6 ±17.1 years; 53.0% male; 87.0% white) diagnosed with CDI completed QoL surveys. PROMIS GH physical health summary scores (T = 37.3; P < .001) and mental health summary scores (T = 43.4; P < .001) were significantly lower than those of the general population. In bivariate analysis, recurrent CDI, severe CDI, and number of stools were associated with lower Cdiff32 scores. In multivariable linear regression, recurrent CDI, severe CDI, and each additional stool in the previous 24 hours were associated with significantly decreased Cdiff32 scores.Conclusions:Patients hospitalized with CDI reported low scores on the Cdiff32 and PROMIS GH, demonstrating a negative impact of CDI on QoL in multiple health domains. The Cdiff32 questionnaire is particularly sensitive to QoL changes in patients with recurrent or severe disease.

Introduction While sleep disorders are implicated in atrial fibrillation (AF), the interplay and overlap of these disorders in AF risk remains unclear and a risk stratification challenge. Sleep-based clusters associated with AF can account for this complexity and translate to actionable approaches to identify at-risk patients. We hypothesized discrete phenotypes of symptoms and polysomnography (PSG)-based data differ in relation to incident AF. Methods Cleveland Clinic patients (age>18) who underwent PSG 11/27/2004-12/30/2015 were retrospectively examined. Clusters were identified using latent class analysis of 23 symptoms (e.g. related to sleep disordered breathing (SDB), sleepiness, REM intrusion, NREM parasomnias), Epworth Sleepiness Scale (ESS) score, and 24 measures of SDB and sleep architecture from PSG reports. Outcome was 5-year incident AF. Cox-proportional hazards models were adjusted for age, sex, race, body mass index, cardiovascular disease and risk factors, tobacco use, chronic obstructive pulmonary disease, anti-arrhythmic medication use, and positive airway pressure use. Results The sample included 43,433 patients: age 51.8±14.5, 51.9% (n=22,548) male, 74.4% (n=32,313) White, 7.3% (n=3,151) with baseline AF, and 4.3% (n=1,875) developed 5-year incident AF. Five clusters were identified and ranked by strength of AF association: 1) Hypoxemic (n=3,245): highest %time SaO2< 90% (T90), 2) Apneas+Arousals (n=4,592): most witnessed apneas, highest apnea hypopnea index (AHI), highest arousal index, least hypopneas, 3) Short sleep+NREM (n=6,126): shortest sleep time, longest REM latency, lowest %REM, 4) Hypopneas (n=2,661): most hypopneas, 5) Long sleep+REM (n=26,809): longest sleep time, shortest REM latency, highest %REM. Compared to ‘Long sleep+REM’, ‘Hypoxemic’ had 47% higher AF risk (HR=1.47,95%CI=1.27-1.69), and ‘Hypopneas’ did not differ (HR=1.05,95%CI=0.86-1.28). Conclusion Of five clusters identified, the ‘Hypoxemic’ subtype conferred the strongest AF risk with the highest degree of hypoxemia (highest T90, lowest minimum and mean SaO2), maximum end-tidal CO2, heart rate, and ESS score. Consistent with prior evidence of hypoxemia as an AF driver and cardiovascular risk of the sleepy phenotype, this constellation of symptoms and physiologic alterations illustrates risk in the clinical setting, providing potential value as a risk prediction tool. Future investigation should focus on external validation of these findings. Support (if any) Cleveland Clinic Neurological Institute Center for Outcomes Research & Evaluation Pilot Grant, Transformative Research Resource Development Award

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.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.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.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.

Despite declining physical function, individuals with ALS report relative preservation of overall health perception, or health-related quality of life (HRQoL). This paradoxical finding is attributed to psychological adaptation to deficits.The aim of this cross-sectional study was to examine reprioritization of factors that determine HRQoL with disease progression.As standard care, patients with ALS self-reported ALSFRS-R (measure of bulbar, motor, and respiratory function), PHQ-9 (measure of depression), and EQ-5D-3L (utility index that includes a visual analog scale asking about health perception [EQ-VAS]). ALS was staged by the FT9 method and classified into early (stages 0-2) and late (stages 3-4) disease. Multigroup structural equation modeling was used to evaluate weights of physical (PHY) and psychological well-being (PSY) for early and late disease, on EQ-VAS (as a measure of overall HRQoL).There were 578 patients (mean age 61.5 ± 11.9, 59% male) with ALS: 423 (73%) early and 155 (27%) late disease. A measurement model was established with good model fit (RMSEA = 0.076, CFI = 0.943, SRMR = 0.045). In adjusted models, standardized weights of PHY and PSY on HRQoL in early disease were 0.34 (standard error = 0.06) and 0.24 (0.06) respectively, whereas for late disease they were 0.39 (0.07) and 0.42 (0.07). Importantly, PHY and PSY were significantly correlated in early but not in late disease.Our study found health perception is more representative of psychological well-being and less representative of physical function across the disease progression. Greater allocation for psychological health would be the most effective strategy to maximize subjective health status as ALS advances.

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. 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. 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. 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.

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.

Objectives: To demonstrate that 1) models based on small numbers of tests can be statistically developed to identify neuropsychological impairment in a general adult neuropsychology clinic and 2) those models show strong predictive validity on replication in a slightly different sample. Method: Latent Class Analyses (LCA) were used to determine neuropsychological classification in 231 patients referred to general adult neuropsychology services. A clinical rating scale was also used to approximate clinical decision-making. Regression models were constructed in a training sample (n = 127) drawn from an adult neuropsychology clinic using test scores from seven different a priori test battery combinations to predict group membership or clinical rating. The utility of the seven models was assessed in a testing sample (n = 104) from another independent adult neuropsychology clinic. Results: The LCA yielded a two class solution characterized by impaired versus non-impaired performance on neuropsychological tests. A seven test battery provided the best balance of accuracy and length in predicting LCA group with a sensitivity of 84.4% and a specificity of 90%. Sensitivity and specificity were slightly attenuated using the clinical rating scale as the criterion, but the seven test battery still provided good accuracy (AUC=.906). Conclusions: Test protocols based on only five to eight test scores can accurately identify most patients with clinical impairment in a diverse adult neuropsychology clinic. Development of short protocols with adequate sensitivity and specificity will become increasingly important to address long waiting lists in light of the COVID pandemic against the general backdrop of increasing demand for neuropsychological services.

Objective The purpose of this study was to test the reliability of the Activity Measure for Post-Acute Care (AM-PAC) “6-Clicks” mobility and activity short forms between patients and therapist proxies. As a secondary aim, reliability was examined when patients completed their self-report before versus after the therapist evaluation. Methods Patients being seen for an initial physical therapist (N = 70) or occupational therapist (N = 71) evaluation in the acute care hospital completed the “6-Clicks” mobility short form (if a physical therapist evaluation) or activity short form (if an occupational therapist evaluation). Whether patients completed their self-assessment before or after the evaluation was randomized. Patient- and therapist-rated “6-Clicks” raw scores were converted to AM-PAC T-scores for comparison. Reliability was assessed with intraclass correlation coefficients (ICCs) and Bland–Altman plots, and agreement was assessed with weighted kappa values. Results The ICCs for the “6-Clicks” mobility and daily activity short forms were 0.57 (95% CI = 0.42–0.69) and 0.45 (95% CI = 0.28–0.59), respectively. For both short forms, reliability was higher when the patient completed the self-assessment after versus before the therapist evaluation (ICC = 0.67, 95% CI = 0.47–0.80 vs ICC = 0.50, 95% CI = 0.26–0.67 for the mobility short form; and ICC = 0.52, 95% CI = 0.29–0.70 vs ICC = 0.34, 95% CI = 0.06–0.56 for the activity short form). Conclusion Reliability of the “6-Clicks” total scores was moderate for both the mobility and activity short forms, though higher for the mobility short form and when patients’ self-report occurred after the therapist evaluation. Impact Reliability of the AM-PAC “6-Clicks” short forms is moderate when comparing scores from patients with those of therapists responding as proxies. The short forms are useful for measuring participants’ function in the acute care hospital; however, it is critical to recognize limitations in reliability between clinician- and patient-reported AM-PAC scores when evaluating longitudinal change and recovery.

We sought to evaluate the effects of concurrent temozolomide-based chemoradiation therapy on neurocognitive function in patients with low-grade glioma (LGG).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.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).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.

The aim of this study was to conduct item reduction of the Memory Assessment Clinics Self-Rating Scale (MAC-S) to create a briefer measure that can be used to quickly evaluate subjective memory com...

Patient-reported outcomes (PROs) refer to patient perceived and reported health-related quality of life (HRQOL), functional status, and symptom burden. PROs have become an important measure in oncologic care to identify the impact of the disease and its treatment on a patient's health status. Hematopoietic cell transplantation (HCT) is an aggressive and potentially curative therapy for patients with high-risk hematologic malignancies. A common complication of HCT is graft-versus-host disease (GVHD), which can be a significant contributor to morbidity and mortality, as well as a wide spectrum of physical and psychosocial effects. Quality of life and symptom burden have been shown to be important measures in the study of posttransplant complications, including chronic GVHD. We review the need for a novel tool in acute GVHD to capture disease symptoms and HRQOL to better understand patient symptoms, disease trajectory and outcome.

STUDY DESIGN Retrospective cohort study. OBJECTIVE To (1) confirm validity of Patient-Reported Outcomes Measurement Information System (PROMIS) physical function and pain interference computer-adaptive tests (CATs) and (2) assess the validity of PROMIS Global Health (GH) and five additional PROMIS CATs: social role satisfaction, fatigue, anxiety, depression, and sleep disturbance in a population of patients with chronic low back pain (cLBP) who completed a 3-month Interdisciplinary Pain Program (IPP). SUMMARY OF BACKGROUND DATA Recent recommendations for assessing outcomes in patients with cLBP have included PROMIS scales; however, there is a need for further evaluation, and PROMIS GH has not been studied in this population. METHODS The study cohort included patients with cLBP who completed the entirety of a 3-month IPP between August 2016 and December 2018. Patient-reported outcome measures (PROMs) were analyzed before the start of the IPP and at graduation. Convergent and discriminant validity were evaluated using Pearson correlation coefficients. Known groups' validity assessed the change in PROMIS scores stratified by improvement on the Modified LBP Disability Questionnaire. Responsiveness was evaluated with standardized response means based on global impression of change. RESULTS IPP was completed by 217 patients (67.7% women, age 53.8 ± 12.8). Convergent validity was supported (P

Coronavirus disease secondary to infection by SARS-CoV-2 (COVID19 or C19) causes respiratory illness, as well as severe neurological symptoms that have not been fully characterized. In a previous study, we developed a computational pipeline for the automated, rapid, high-throughput and objective analysis of brain encephalography (EEG) rhythms. In this retrospective study, we used this pipeline to define the quantitative EEG changes in patients with a PCR-positive diagnosis of C19 (n=31) in the intensive care unit (ICU) of Cleveland Clinic, compared to a group of age-matched PCR-negative (n=38) control patients in the same ICU setting. Qualitative assessment of EEG by two independent teams of electroencephalographers confirmed prior reports with regards to the high prevalence of diffuse encephalopathy in C19 patients, although the diagnosis of encephalopathy was inconsistent between teams. Quantitative analysis of EEG showed distinct slowing of brain rhythms in C19 patients compared to control (enhanced delta power and attenuated alpha-beta power). Surprisingly, these C19-related changes in EEG power were more prominent in patients below age 70. Moreover, machine learning algorithms showed consistently higher accuracy in the binary classification of patients as C19 versus control using EEG power for subjects below age 70 compared to older ones, providing further evidence for the more severe impact of SARS-CoV-2 on brain rhythms in younger individuals irrespective of PCR diagnosis or symptomatology, and raising concerns over potential long-term effects of C19 on brain physiology in the adult population and the utility of EEG monitoring in C19 patients.

ImportanceRecurrent Clostridioides difficile infection (CDI) is a debilitating disease leading to poor health-related quality of life (HRQOL), loss of productivity, anxiety, and depression. The potential association of treatment with HRQOL has not been well evaluated.ObjectivesTo explore the association of SER-109 compared with placebo on HRQOL in patients with recurrent CDI up to week 8.Design, Setting, and ParticipantsThis study was a secondary analysis of a randomized, double-blind, placebo-controlled trial that took place at 56 sites in the US and Canada from July 2017 to April 2020 and included 182 patients randomized to SER-109 or placebo groups.InterventionsSER-109 or placebo (4 capsules once daily for 3 days) following antibiotics for CDI.Main Outcomes and MeasuresExploratory analysis of HRQOL using the disease specific Clostridioides difficile Quality of Life Survey (Cdiff32) assessed at baseline, week 1, and week 8.ResultsIn this study, 182 patients (109 [59.9%] female; mean age, 65.5 [16.5] years) were randomized to SER-109 (89 [48.9%]) or placebo (93 [51.1%]) groups and were included in the primary and exploratory analyses. Baseline Cdiff32 scores were similar between patients in the SER-109 and placebo groups (52.0 [18.3] vs 52.8 [18.7], respectively). The proportion of patients with overall improvement from baseline in the Cdiff32 total score was higher in the SER-109 arm than placebo at week 1 (49.4% vs 26.9%; P = .012) and week 8 (66.3% vs 48.4%; P = .001).Greater improvements in total and physical domain and subdomain scores were observed in patients in the SER-109 group compared with placebo as early as week 1, with continued improvements observed at week 8. Among patients in the placebo group, improvements in HRQOL were primarily observed in patients with nonrecurrent CDI while patients in the SER-109 group reported improvements in HRQOL, regardless of clinical outcome.Conclusions and RelevanceIn this secondary analysis of a phase 3 clinical trial, SER-109, an investigational microbiome therapeutic was associated with rapid and steady improvement in HRQOL compared with placebo through 8 weeks, an important patient-reported outcome.Trial RegistrationClinicalTrials.gov Identifier: NCT03183128

This is an observational cohort study.The aim of this study was to compare the effectiveness of PT to an interdisciplinary treatment approach in patients with chronic low back pain (CLBP).CLBP is a costly and potentially disabling condition. Physical therapy (PT), cognitive behavioral therapy, and interdisciplinary pain programs (IPPs) are superior to usual care. Empirical evidence is lacking to clearly support one treatment approach over another in patients with CLBP.One hundred seventeen adult patients who completed an IPP for individuals with ≥3 months of back pain were compared to 214 adult patients with similar characteristics who completed PT. The Modified Low Back Pain Disability Questionnaire was the primary outcome measure. Additional measures included: PROMIS physical function, global health, social role satisfaction, pain interference, anxiety, fatigue, sleep disturbance, and Patient Health Questionnaire. Patients who completed the IPP were matched by propensity score to a historical control group of patients who completed a course of PT. Change in functional disability was compared between IPP patients and matched controls. Patient-reported outcome measures were assessed pre to post participation in the IPP using paired t test and by calculating the proportion with clinically meaningful improvement.Propensity score matching generated 81 IPP and 81 PT patients. Patients enrolled in the IPP had significantly greater improvement in MDQ scores upon completion compared to patients in PT (15.8 vs. 7.1, P 0.001). The majority of IPP patients reached the threshold for clinically meaningful change of ≥10 point reduction (60.5%) compared to 34.6% of PT patients, P 0.01. Patients in the IPP also showed statistically and clinically significant improvement in social role satisfaction, fatigue, and sleep disturbance.CLBP patients in an IPP demonstrated greater functional improvements compared to similar patients participating in PT.3.

Patients treated in interdisciplinary chronic pain rehabilitation programs show long-term improvements in symptoms; however, outcomes may vary across heterogenous patient subpopulations. This longitudinal retrospective study characterizes the influence of opioids, mood, patient characteristics, and baseline symptoms on pain and functional impairment (FI) in 1,681 patients 6-months to 12-months post-treatment in an interdisciplinary chronic pain rehabilitation program incorporating opioid weaning. Linear mixed models showed immediate and durable treatment benefits with nonuniform worsening at follow up which slowed over time. Latent class growth analysis identified three post-treatment trajectories of pain and FI: mild symptoms and durable benefits, moderate symptoms and durable benefits, and intractable symptoms. A fourth pain trajectory showed immediate post-treatment improvement and worsening at follow up. Whether a patient was weaned from opioids was not predictive of treatment trajectory. Racial ethnic minority status, higher levels of post-treatment depression, and lower perceived treatment response were associated with less resolution (moderate symptoms) or intractable symptoms. Not having a college education was predictive of intractable or worsening pain and a moderate course of FI. Older age and male gender was associated with intractable FI. Treatment outcomes may be improved by the development of targeted interventions for patients at risk of poor recovery and/or deteriorating long-term course. PERSPECTIVE: This study examined predictors of treatment response in 1,681 patients treated in an interdisciplinary chronic pain rehabilitation program incorporating opioid weaning. Opioid weaning did not predict outcome. Higher levels of symptoms, lower levels of education, and being a racial-ethnic minority were associated with a less salubrious long-term treatment response.

Rates of perceived fatigue, anxiety, depression, sleepiness and mitochondrial disease severity were assessed prospectively in 2017-2018 using established validated questionnaires in 48 adult patients with genetically confirmed primary mitochondrial disease. Fatigue was found to be very common among patients with primary mitochondrial disease, with 34 to 48 (71-100%) patients reporting fatigue depending on the measure used, and the severity of fatigue correlating with the severity of disease. Moderate-to-severe depression (10/48; 20.8%) anxiety (28/48; 58.3%) and sleep problems (16/48; 33.3%) were frequent in our patients with fatigue and these conditions were even more prevalent in those with severe fatigue. In conclusion, perceived fatigue was common in patients with primary mitochondrial disease and appeared to correlate with disease severity. Depression, anxiety and sleep disorders were more common in the cohort than those with other chronic diseases but with rates similar to that seen in multiple sclerosis. The severity of perceived fatigue correlated with an increased risk of these comorbid conditions. The Fatigue Severity Scale may more selectively measure non-anxiety/sleep-related fatigue in primary mitochondrial disease and additional testing is planned.

Improving prognostic stratification for patients with low back pain (LBP) outside of a primary care setting has been identified as an important area for further research.Our study aimed to identify clinical symptom classes of patients presenting to a spine clinic based on 4 Patient Reported Outcome Measurement Information System (PROMIS) domains and evaluate demographic and clinical differences across classes.An observational cross-sectional study of patients seen in spine centers at a large health system.Adult patients with LBP seen in a spine center between November 14, 2018 and May 14, 2019 who completed patient-reported outcomes as part of routine care.PROMIS physical function, pain interference, satisfaction with social roles and activities, and fatigue.Latent class analysis identified symptom classes based on PROMIS domain scores ≥1 standard deviation worse (meaningfully worse) than the general population. A multivariable multinomial logistic regression model was constructed to evaluate differences in symptom classes based on demographics and socioeconomic characteristics. Lastly, the ability of the profiles to discriminate across levels of disability, based on the modified Oswestry Disability Questionnaire (ODI), was evaluated.There were 7,144 adult patients included in the study who visited spine clinics for a primary complaint of LBP and completed all 4 PROMIS domains (age 58.7±15.9, 54% female). Three distinct classes were identified. Class 1 ("Significant Symptoms," n=3238) had PROMIS scores that were meaningfully worse than the population average for all domains. Class 2 ("Mixed Symptoms," n=1366) had meaningfully worse scores on physical function and pain interference but average scores on other domains. Class 3 ("Mild Symptoms," n=2540) had average scores across all domains. Compared to patients in Class 3, those in Class 2 were more likely older, and those in Classes 1 and 2 were more likely to be divorced, have lower household income, and no employment. Level of disability was significantly different across each class (average (SD) ODI for Classes 1-3: 53.4 (14.3), 39.9 (12.5), 22.9 (12.1), p.01).Patients presenting to specialty clinics for LBP demonstrate distinct clinical symptom classes which could be utilized to inform specific symptom-based treatment. Future research should evaluate the ability of these classes to predict long-term disability.

Background: Caregivers, or proxies, often complete patient-reported outcomes (PROs) on behalf of patients; yet, research has demonstrated proxies rate patient outcomes worse than patients rate their own outcomes. To improve interpretability of PROs in group-level analyses, our study aimed to identify optimal approaches for reducing proxy-introduced bias in the analysis of PROs. Methods: Data were simulated based on 200 patients with stroke and their proxies who both completed 9 PROMIS domains as part of a cross-sectional study. The sample size was varied as 50, 100, 200, and 500, and the proportion of patients with proxy-respondents was varied as 10%, 20%, and 50%. Six methods for handling proxy-completions were investigated: (1) complete case analysis; (2) proxy substitution; (3) Method 2 plus proxy adjustment; (4) Method 3 including inverse-probability of treatment weighting; (5) multiple imputation; (6) linear equating. These methods were evaluated by comparing average bias in PROMIS T -scores (estimated versus observed patient-only responses), as well as by comparing estimated regression coefficients to models using patient-only responses. Results: Overall mean T -score differences ranged from 0 to 1.75. The range of mean differences varied by the 6 methods with methods 1 and 5 providing estimates closest to the observed mean. In regression models, all but inverse-probability of treatment weighting resulted in low bias when proxy-completions were 10% to 20%. With 50% proxy-completions, method 5 resulted in less accurate estimations while methods 1 to 3 provided less proxy-introduced bias. Bias remained low across domain and varying sample sizes but increased with larger percentages of proxy-respondents. Conclusions: Our study found modest proxy-introduced bias when estimating PRO scores or regression estimates across multiple domains of health. This bias remained low, even when sample size was 50 and there were large proportions of proxy-completions. While many of these methods can be chosen for including proxies in stroke PRO research with

ObjectiveTo evaluate the interplay between seizures, quality of life (QoL), and neuropsychiatric outcomes in patients with leucine-rich glioma-inactived 1 antibody encephalitis (LGI1-Ab-E).BackgroundPatients with LGI1-Ab-E experience varied seizure semiologies, but their potential differing impact on long-term outcomes remains under-explored.Design/MethodsWe conducted a single-center retrospective cohort study of patients with antibody-confirmed LGI1-Ab-E with seizures. Patients were categorized as having faciobrachial dystonic seizures (FBDS) or non-faciobrachial dystonic seizures (non-FBDS). Patient Health Questionnaire-9 (PHQ-9), Neuro-QoL, Patient Reported Outcomes Measurement Information System (PROMIS), and modified Rankin Scale (mRS) were abstracted. Outcomes were compared using two-tailed independent sample t-tests for continuous variables and chi-square and Fisher's exact test for categorical variables. Change over time was evaluated using Wilcoxon signed-rank test.Results21 patients (33% female, median 65 years) were included, 10 (47.6%) with FBDS and 11 (53.4%) with non-FBDS. Levetiracetam (66%), lacosamide (42.9%), and valproate (19.0%) were the most common anti-seizure medications; 19 (90.5%) underwent immunotherapy. In patients with at least one year of follow-up, all patients with FBDS (n = 7) and 75% with non-FBDS (n = 6) achieved seizure freedom (p = 0.48). From 8 months to 30 months post-diagnosis, PHQ-9 improved in the FBDS cohort (median 6, IQR 5.5—9.5 to median 2.5, IQR 2.0—4.5, p = 0.06), but remained stable in the non-FBDS cohort (median 5.5, IQR 2.3—9.3 to median 5, IQR 3.0 to 8.0, p = 0.75). Both groups had similar mRS baselines (median mRS 1 for both, p = 0.91) and experienced similar significant mRS worsening at median 23 months post-symptoms onset (median increase 1, p < 0.001 over time). Neuro-QoL and PROMIS scores were similar between groups (for all, p > .05).ConclusionsPatients with LGI1-Ab-E who experience exclusively non-FBDS may be at higher risk of sustained depressive symptoms than those with FBDS. Regardless of seizure type, patients with LGI1-Ab-E are at risk for significantly worsening disability despite treatment and seizure freedom.

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.This study aimed to develop a reliable and valid instrument to measure patients' valuation of their uterus.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 aged45 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).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%).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.

Patient-reported outcome measures (PROMs) are often used in clinical research, but little is known about their performance as longitudinal outcomes.We used data from ASCEND, a large SPMS trial (PROM scores changed little over the 2 years of follow-up. In contrast to physical disability measures, there was no consistent trend in PROM change: significant worsening occurred about as often as improvement. Using a 6-month confirmation reduced the number of both worsening and improvement events without altering their relative balance. There was no clear difference in worsening events in groups based on population characteristics, nor was there a noticeable effect using different thresholds for clinically significant change.We found little consistent change in MSIS-29 and SF-36 over 2 years of follow-up in people with SPMS. Our findings show a disconnect between disability worsening and PROM change in this population. Our findings raise caution about the use of these PROMs as primary outcome measures in SPMS trials and call for a critical reappraisal of the longitudinal use of these measures in SPMS trials.

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.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.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).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.

We investigated the quality of life (QoL) of patients hospitalized withProspective survey study.US tertiary-care referral center, acute-care setting.Adults hospitalized with a diagnosis of CDI, defined as ≥3 episodes of unformed stool in 24 hours and a positive laboratory test forWe surveyed patients from July 2019 to March 2020 using the disease-specific Cdiff32 questionnaire and the generic PROMIS GH survey. We compared differences in Cdiff32 scores among demographic and clinical subgroups (including CDI severity, CDI recurrence, and various comorbidities) using 2-sampleIn total, 100 inpatients (mean age, 58.6 ±17.1 years; 53.0% male; 87.0% white) diagnosed with CDI completed QoL surveys. PROMIS GH physical health summary scores (T = 37.3;Patients hospitalized with CDI reported low scores on the Cdiff32 and PROMIS GH, demonstrating a negative impact of CDI on QoL in multiple health domains. The Cdiff32 questionnaire is particularly sensitive to QoL changes in patients with recurrent or severe disease.

Objectives Research has indicated proxies overestimate symptoms on patients’ behalves, however it is unclear whether patients and proxies agree on meaningful change across domains over time. The objective of this study is to assess patient-proxy agreement over time, as well as agreement on identification of meaningful change, across 10 health domains in patients who underwent acute rehabilitation following stroke. Methods Stroke patients were recruited from an ambulatory clinic or inpatient rehabilitation unit, and were included in the study if they were undergoing rehabilitation. At baseline and again after 30 days, patients and their proxies completed PROMIS Global Health and eight domain-specific PROMIS short forms. Reliability of patient-proxy assessments at baseline, follow-up, and the change in T-score was evaluated for each domain using intra-class correlation coefficients (ICC(2,1)). Agreement on meaningful improvement or worsening, defined as 5+ T-score points, was compared using percent exact agreement. Results Forty-one patient-proxy dyads were included in the study. Proxies generally reported worse symptoms and functioning compared to patients at both baseline and follow-up, and reported less change than patients. ICCs for baseline and change were primarily poor to moderate (range: 0.06 (for depression change) to 0.67 (for physical function baseline)), and were better at follow-up (range: 0.42 (for anxiety) to 0.84 (for physical function)). Percent exact agreement between indicating meaningful improvement versus no improvement ranged from 58.5–75.6%. Only a small proportion indicated meaningful worsening. Conclusions Patient-proxy agreement across 10 domains of health was better following completion of rehabilitation compared to baseline or change. Overall change was minimal but the majority of patient-proxy dyads agreed on meaningful change. Our study provides important insight for clinicians and researchers when interpreting change scores over time for questionnaires completed by both patients and proxies.

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.

Background: Variable rate of cognitive decline among individuals with Alzheimer’s disease (AD) is an important consideration for disease management, but risk factors for rapid cognitive decline (RCD) are without consensus. Objective: To investigate demographic, clinical, and pathological differences between RCD and normal rates of cognitive decline (NCD) in AD. Methods: Neuropsychology test and autopsy data was pulled from the National Alzheimer’s Coordinating Center database from individuals with a clinical diagnosis of AD. Individuals with average decline of 3 or more points on the Mini-Mental Status Examination (MMSE) per year over 3 years were labeled RCD; all others were NCD. Results: Sixty individuals identified as RCD; 230 as NCD. These neuropsychology tests differed at baseline (RCD versus NCD): WMS-LM Immediate Recall (4.35[3.39] versus 6.31[3.97], p

ObjectiveWe sought to examine prevalence and predictors of noninvasive ventilation (NIV) in a composite cohort of patients with amyotrophic lateral sclerosis (ALS) followed in a clinical trials setting (Pooled Resource Open-Access ALS Clinical Trials database).MethodsNIV initiation and status were ascertained from response to question 12 of the revised ALS Functional Rating Scale (ALSFRS-R). Factors affecting NIV use in patients with forced vital capacity (FVC) ≤50% of predicted were examined. Predictors of NIV were evaluated by Cox proportional hazard models and generalized linear mixed models.ResultsAmong 1,784 patients with 8,417 simultaneous ALSFRS-R and FVC% measures, NIV was used by 604 (33.9%). Of 918 encounters when FVC% ≤50%, NIV was reported in 482 (52.5%). Independent predictors of NIV initiation were lower FVC% (hazard ratio [HR] 1.27, 95% confidence interval [CI] 1.17–1.37 for 10% drop), dyspnea (HR 2.62, 95% CI 1.87–3.69), orthopnea (HR 4.09, 95% CI 3.02–5.55), lower bulbar and gross motor subscores of ALSFRS-R (HRs 1.09 [95% CI 1.03–1.14] and 1.13 [95% CI 1.07–1.20], respectively, per point), and male sex (HR 1.73, 95% CI 1.31–2.28). Adjusted for other variables, bulbar onset did not significantly influence time to NIV (HR 0.72, 95% CI 0.47–1.08). Considerable unexplained variability in NIV use was found.ConclusionNIV use was lower than expected in this ALS cohort that was likely to be optimally managed. Absence of respiratory symptoms and female sex may be barriers to NIV use. Prospective exploration of factors affecting adoption of NIV may help bridge this gap and improve care in ALS.

Assessment of outcomes from a proxy is often substituted for the patient’s self-report when the patient is unable or unwilling to report their status. Research has indicated that proxies over-report symptoms on the patient’s behalf. This study aimed to quantify the extent of proxy-introduced bias on the Patient-Reported Outcomes Measurement Information System Global Health (PROMIS GH) scale for mental (GMH) and physical (GPH) scores. This retrospective cohort study included incident stroke patients seen in a cerebrovascular clinic who completed PROMIS GH between 10/12/15 and 6/6/18. Differential item functioning (DIF) evaluated measurement invariance of patient versus proxy responses. DIF impact was assessed by comparing the initial score to the DIF-adjusted score. Subgroup analyses evaluated DIF within strata of stroke severity, measured by modified Rankin Scale (≤ 1, 2, 3+), and time since stroke (≤ 30, 31–90, > 90 days). Of 1351 stroke patients (age 60.5 ± 14.9, 45.1% female), proxy help completing PROMIS GH was required by 406 patients (30.1%). Proxies indicated significantly worse response to all items. No items for GMH or GPH were identified as having meaningful DIF. In subgroup analyses, no DIF was found by severity or 31–90 days post-stroke. In patients within 30 and > 90 days of stroke, DIF was detected for 2 items. Accounting for DIF had negligible effects on scores. Our findings revealed the overestimation of symptoms by proxies is a real difference and not the result of measurement non-invariance. PROMIS GH items do not perform differently or have spuriously inflated severity estimates when administered to proxies instead of patients.

Objective To determine whether statin intake affects nephrolithiasis risk, and whether higher lipid levels correlate with stone risk. Dyslipidemia is a known independent risk factor for urolithiasis, and emerging evidence suggests common biological pathways. Previous work has suggested that statins protect against new stone formation, but these findings have not been verified by other investigators. Methods We queried our Institution's Electronic Data Warehouse for all patients who were newly diagnosed with hyperlipidemia between 2009 and 2011, and had never taken a statin drug. These patients' clinical outcomes were followed until 2015, to assess whether they had been newly prescribed statins and whether they had developed symptomatic urolithiasis. Patient demographics, stone risk factors, prescription data, and serum lipid values were collected. Results A total of 101,259 patients met inclusion criteria, 47.8% of whom received a statin prescription during the study period. Patients prescribed statins were significantly older, had a greater likelihood of osteoporosis, hemiplegia, immobility, and more likely to take a thiazide diuretic. Patients without a history of urolithiasis who were started on statin therapy were significantly less likely to develop new stones than patients not taking statins. This protective effect was even greater in patients with a history of stone disease. Lipid parameters (low-density lipoprotein, triglyceride, cholesterol) were lower in the statin-treated group, suggesting overall compliance with these medications. Conclusion Our data confirm previous work that statins protect against urinary stone formation; however, the underlying mechanism seems to be distinct from statins' lipid-lowering effect.

Introduction Sleep difficulties and fatigue are highly prevalent, pervasive symptoms reported in patients with Post-Acute Sequelae of COVID-19 (PASC). As little is known of the predictors and severity of PASC-related sleep disturbance and intersection with fatigue, we leverage systematic data collected from the Cleveland Clinic ReCOVer Clinic for further elucidation Methods Analysis of data collected from Cleveland Clinic ReCOVer Clinic patients (February-November 2021) who completed the Patient-Reported Outcomes Measurement (PROMIS) Sleep Disturbance and PROMIS Fatigue questionnaires was performed. Data were extracted from the Cleveland Clinic COVID-19 registry and the electronic health record.PROMIS scores are standardized to the general U.S. adult population on a T-scale with mean 50±10. PROMIS sleep disturbance and fatigue T-scores ≥60 indicates at least moderate disturbance and ≥70 indicate severe disturbance. T-test and Chi-square tests were used to examine cross-group differences. Multivariable logistic regression adjusted for age, race, sex, and body mass index(kg/m2) was performed to investigate factors associated with sleep disturbance severity. Results Out of 1321, 682 patients completed the PROMIS Sleep Disturbance questionnaire with age 49.8±13.6, 75.2% female and 12.3% black race. Average T-scores were 57.7±8.3, 281 (41.2%) patients reported at least moderate sleep disturbance and 50 (7.3%) reported severe sleep disturbances. Average PROMIS Fatigue T-score was 63.0±9.2; 68.6% patients reported at least moderate fatigue, 22.6% reported severe fatigue. Patients with moderate-severe compared to normal-to-mild sleep disturbances respectively had higher BMI (32.3±8.7 vs 30.9±7.5, p=0.049), were more likely of black race (40.0±10.0 vs 41.0±15.7,p=0.010), had worse eneral Anxiety Disorder (GAD)-2 questionnaires scores (2.8±2.1 vs 1.6±1.7,p Conclusion The prevalence of moderate to severe sleep disturbances reported by patients presenting for PASC was very high i.e.>40% and associated with obesity, black race and mood symptoms. Notably, after adjustment for demographics, black race conferred a 3-fold higher odds of moderate-severe sleep disturbance emphasizing the need to characterize race-specific determinants and disparities in COVID-19 survivors. Support (If Any)

As the implementation of Patient-Reported Outcomes Measurement Information System (PROMIS) scales has increased, so has the number of studies linking legacy scale scores to PROMIS scale scores. Variability in linked scores for a given PROMIS score can be considerable, leading to potential bias. An alternative method is imputation using a bridge study. We sought to compare linking to this alternative novel method in group-level analyses using linked legacy scores. Adult patients who completed PROMIS Depression and Patient Health Questionnaire (PHQ-9) were included. We randomly allocated data samples to be missing either PROMIS Depression or PHQ-9. We estimated PROMIS T scores using six methods: Linking methods by Choi et al. (2014), linking in our internal data, imputation using bridge study data from external data and from our internal data, each with and without patient demographics. Estimated mean PROMIS T scores using the linking and imputation methods were compared to actual PROMIS T scores across varying proportions of missingness and sample size. We also compared regression coefficients for the six estimation methods to a model using actual PROMIS T scores. Mean estimated versus actual PROMIS T scores varied between 1 and 4 points for the linking methods and within 0.4 points for the imputation method using internal data with patient demographics. The imputation methods had estimated regression coefficients closer to that of the model using actual scores as compared to the linking methods. For group-level analyses, imputation using a bridge study may be a feasible alternative to using linked scores or can be used as a sensitivity analysis. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Autoimmune (AI) diseases can affect many organs; however, the prostate has not been considered to be a primary target of these systemic inflammatory processes. Here, we utilize medical record data, patient samples, and in vivo models to evaluate the impact of inflammation, as seen in AI diseases, on prostate tissue. Human and mouse tissues are used to examine whether systemic targeting of inflammation limits prostatic inflammation and hyperplasia. Evaluation of 112,152 medical records indicates that benign prostatic hyperplasia (BPH) prevalence is significantly higher among patients with AI diseases. Furthermore, treating these patients with tumor necrosis factor (TNF)-antagonists significantly decreases BPH incidence. Single-cell RNA-seq and in vitro assays suggest that macrophage-derived TNF stimulates BPH-derived fibroblast proliferation. TNF blockade significantly reduces epithelial hyperplasia, NFκB activation, and macrophage-mediated inflammation within prostate tissues. Together, these studies show that patients with AI diseases have a heightened susceptibility to BPH and that reducing inflammation with a therapeutic agent can suppress BPH.

Background Identification of stroke patients at increased risk of emergency department (ED) visits or hospital admissions allows implementation of mitigation strategies. We evaluated the ability of the Patient‐Reported Outcomes Information Measurement System (PROMIS) patient‐reported outcomes (PROs) collected as part of routine care to predict 1‐year emergency department (ED) visits and admissions when added to other readily available clinical variables. Methods and Results This was a cohort study of 1696 patients with ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, or transient ischemic attack seen in a cerebrovascular clinic from February 17, 2015, to June 11, 2018, who completed the following PROs at the visit: Patient Health Questionnaire‐9, Quality of Life in Neurological Disorders cognitive function, PROMIS Global Health, sleep disturbance, fatigue, anxiety, social role satisfaction, physical function, and pain interference. A series of logistic regression models was constructed to determine the ability of models that include PRO scores to predict 1‐year ED visits and all‐cause and unplanned admissions. In the 1 year following the PRO encounter date, 1046 ED visits occurred in 548 patients; 751 admissions occurred in 453 patients. All PROs were significantly associated with future ED visits and admissions except PROMIS sleep. Models predicting unplanned admissions had highest optimism‐corrected area under the curve (range, 0.684–0.724), followed by ED visits (range, 0.674–0.691) and then all‐cause admissions (range, 0.628–0.671). PROs measuring domains of mental health had stronger associations with ED visits; PROs measuring domains of physical health had stronger associations with admissions. Conclusions PROMIS scales improve the ability to predict ED visits and admissions in patients with stroke. The differences in model performance and the most influential PROs in the prediction models suggest differences in factors influencing future hospital admissions and ED visits.

Benign prostatic hyperplasia (BPH) is ostensibly linked to autoimmune (AI) diseases, but whether the prostate is a target of systemic inflammation associated with AI conditions is unknown. Prostatic inflammation is linked to fibrosis, hyperplasia, and reduced responses to BPH-related medical therapies. This study was conducted to determine if AI disease correlates with BPH diagnosis and whether systemic targeting of an inflammatory mediator limits prostatic inflammation and hyperplasia. Patient medical records (n=112,152) were evaluated to determine BPH prevalence among different AI diseases. Inflammatory cells from human BPH tissues were analyzed by single-cell (sc)RNA-seq and the tumor necrosis factor (TNF)α-antagonist etanercept was tested in two murine models of prostatic enlargement. BPH prevalence was significantly higher among patients with AI disease compared to unaffected individuals. However, AI patients treated with TNFα-antagonists had a significantly reduced incidence of BPH. Data from scRNA- seq identified macrophages as a dominant source of TNFα and in vitro assays confirmed that TNFα stimulates BPH-derived fibroblast proliferation. In the AI patient cohort and murine models, systemic treatment with TNFα-antagonists decreased prostatic epithelial proliferation, macrophage infiltration, and epithelial NFκB activation compared to control tissues. These studies are the first to show that patients with AI diseases have a heightened susceptibility to BPH and that the TNFα-signaling axis is important for BPH pathogenesis. Macrophage-secreted TNFα may mechanistically drive BPH via chronic activation of the signaling axis and NFκB. TNFα blockade appears to be a promising new pharmacological approach to target inflammation and suppress BPH.One sentence summaryPatient data and mouse models suggest that repurposing tumor necrosis factor alpha blockade reduces inflammation-mediated prostatic hyperplasia.

Background: Self-efficacy is the belief that one is able to respond to demands of a stressful situation and it has both direct and indirect effects on health. The study objective is to investigate the amount of variance in patient-reported physical function (PF) that is explained by self-efficacy compared to clinician-reported disability and other patient-reported domains of health, and evaluate whether self-efficacy mediates the relationship between PF and other domains of health. Methods: Observational cohort study of 248 patients who were seen in a cerebrovascular clinic 3/18/20 - 7/7/20 and completed the following patient-reported outcome measures (PROMs) as part of the routine office visit: PROMIS PF, general self-efficacy, fatigue, and pain interference. Linear regression models were constructed to determine the amount of variance (adjusted R 2 ) in PROMIS PF score explained by the modified Rankin Scale (mRS) and additional PROM scores. The mRS and individual PROMs were added separately to a base model adjusted for demographic characteristics. Mediation analysis was conducted to determine the extent to which self-efficacy mediated the relationship between PF and other PROMs. Results: Mean age of study cohort was 61.5 (SD=13.5) years and 48.4% were female. The base model explained 4.5% of the variance of PF. Adding PROMIS fatigue resulted in the largest increase in the proportion of variance explained (adj R 2 = 47.7%), followed by PROMIS self-efficacy (40.7%), PROMIS pain interference (38.7%), and mRS (26.6%). Self-efficacy significantly mediated the relationship between fatigue and PF (standardized indirect effect: 0.11 (bias-corrected 95% CI: 0.05-0.18), 20.9% of total effect) and pain interference and PF (standardized indirect effect 0.10 (95% CI: 0.06-0.17), 27.1% of total effect). Conclusion: PROMIS self-efficacy explains more variance in stroke patients’ perceived physical function than their disability. This suggests that interventions to improve self-efficacy could have a significant effect on patient’s perceived health. Patients’ fatigue, despite being partially mediated by self-efficacy, was a large contributor to self-reported PF and should be included as part of an evaluation of patient’s physical health.