Measures Of Disease Severity Research Articles

Cough-Specific Quality of Life Predicts Disease Progression Among Patients With Interstitial Lung Disease: Data From the Pulmonary Fibrosis Foundation Patient Registry

Cough is a common symptom of interstitial lung disease (ILD) and negatively impacts health-related quality of life (QOL). Previous studies have shown that among patients with idiopathic pulmonary fibrosis, cough may predict progression of lung disease and perhaps even respiratory hospitalizations and mortality. Does cough-specific QOL predict disease progression, respiratory hospitalization, lung transplantation, and death among patients with ILD? We analyzed data from the Pulmonary Fibrosis Foundation Registry, which comprises a multicenter population of well-characterized patients with ILD. We first examined associations between patient factors and baseline scores on the Leicester Cough Questionnaire (LCQ), a cough-specific QOL tool, using a proportional odds model. Next, we examined associations between baseline LCQ scores and patient-centered clinical outcomes, as well as pulmonary function parameters, using a univariable and multivariable proportional hazards model that was adjusted for clinically relevant variables, including measures of disease severity. One thousand four hundred forty-seven patients with ILD were included in our study. In the multivariable proportional odds model, we found that the following patient factors were associated with worse cough-specific QOL: younger age, diagnosis of "other ILD," gastroesophageal reflux disease, and lower FVC %predicted. Multivariable Cox regression models, adjusting for several variables including baseline disease severity, showed that a 1-point decrease in LCQ score (indicating lower cough-specific QOL) was associated with a 6.5%higher risk of respiratory-related hospitalization (hazard ratio [HR], 1.065; 95%CI, 1.025-1.107), a 7.4%higher risk of death (HR, 1.074; 95%CI, 1.020-1.130), and an 8.7%higher risk of lung transplantation (HR, 1.087; 95%CI, 1.022-1.156). Among a large population of well-characterized patients with ILD, cough-specific QOL was associated independently with respiratory hospitalization, death, and lung transplantation.

Self-Reported Health Outcomes of Children and Youth with 10 Chronic Diseases

To identify pediatric patient-reported outcomes (PROs) that are associated with chronic conditions and to evaluate the effects of chronic disease activity on PROs. Participants (8-24years old) and their parents were enrolled into 14 studies that evaluated Patient-Reported Outcome Measurement Information SystemPROs across 10 chronic conditions-asthma, atopic dermatitis, cancer, cancer survivors, chronic kidney disease, Crohn's disease, juvenile idiopathic arthritis, lupus, sickle cell disease, and type 1 diabetes mellitus. PRO scores were contrasted with the US general population of children using nationally representative percentiles. PRO-specific coefficients of variation were computed to illustrate the degree of variation in scores within vs between conditions. Condition-specific measures of disease severity and Cohen d effect sizes were used to examine PRO scores by disease activity. Participants included 2975 child respondents and 2392 parent respondents who provided data for 3409 unique children: 52% were 5-12years old, 52% female, 25% African American/Black, and 14% Hispanic. Across all 10 chronic conditions, children reported more anxiety, fatigue, pain, and mobility restrictions than the general pediatric population. Variation in PRO scores within chronic disease cohorts was equivalent to variation within the general population, exceeding between-cohort variation by factors of 1.9 (mobility) to 5.7 (anxiety). Disease activity was consistently associated with poorer self-reported health, and these effects were weakest for peer relationships. Chronic conditions are associated with symptoms and functional status in children and adolescents across 10 different disorders. These findings highlight the need to complement conventional clinical evaluations with those obtained directly from patients themselves using PROs.

211 Deep Phenotyping Reveals Germline Determinants of Disease Severity in Neurofibromatosis Type 2

INTRODUCTION: Neurofibromatosis type 2 (NF2) is an autosomal dominant tumor predisposition syndrome with central and peripheral nervous system tumors and non-neoplastic manifestations including peripheral neuropathy. NF2 presents with a large variation in penetrance and severity. Although germline nonsense and frameshift NF2mutations are hypothesized to confer severe disease, the relationship between mutation type and manifestations of this disease is not completely understood. METHODS: Patients (n = 169) with NF2 (Manchester criteria) were enrolled in a Natural History protocol (NCTNCT00598351). Deep phenotypic profiles were created (serially for 5 years) including clinical evaluations, self-reported functional measures, lifetime interventions (surgical, radiation and drug treatments), and imaging (tumor number, type and volume using volumetric MRI of the neuroaxis). Validated germline mutation data (n = 68) was used to examine relationships between genotype and phenotype with attention to NF2 mutation type (indel/large deletion), genomic effect (missense/nonsense/frameshift), predicted protein effect (truncating/non-truncating) and location (exonic/intronic/splice-site). RESULTS: Tumor burden varied greatly between patients (tumor number range 1-165, median 25). We found that cranial meningiomas were a major determinant of total tumor burden. Total tumor burden (number and volume) was associated with worse KPS and decline in KPS over the study protocol (p < 0.001). We found that truncating mutations in exons 11-12 were associated with more severe disease in terms of tumor number on MRI (p = 0.0439). CONCLUSION: This is the first large scale study to deeply phenotype patients with NF2 including longitudinal analysis and demonstrates several previously unrecognized trends related to germline mutations type, imaging findings, and measures of disease severity.

The interleukin 1 receptor antagonist anakinra to reduce disease severity of palmoplantar pustulosis in adults: APRICOT RCT and PLUM mechanistic study

Background Palmoplantar pustulosis is a rare, debilitating, chronic skin disease involving the hands and feet, and there are limited treatment options. Mechanistic findings suggest that interleukin 1 may be a pathogenic driver. Objective To determine whether or not anakinra [Sobi (Swedish Orphan Biovitrum AB), Stockholm, Sweden], an interleukin 1 receptor antagonist, delivers therapeutic benefit in palmoplantar pustulosis. Design A Phase IV, randomised, double-blind, placebo-controlled study with two stages and an adaptive element (24 participants in stage 1, 64 participants in total) with an open-label extension. Setting Sixteen hospitals across England, Scotland and Wales. Participants Adults (aged ≥ 18 years) with a diagnosis of palmoplantar pustulosis and a disease duration of > 6 months and of sufficient impact and severity to require systemic therapy. Interventions Participants were randomised (1 : 1) to daily self-administered subcutaneous injection of either anakinra or a placebo for 8 weeks. Main outcome measures The primary outcome was the Palmoplantar Pustulosis Area and Severity Index score measured at 0, 1, 4, 8 and 12 weeks, with the primary end point at 8 weeks adjusted for baseline. Secondary outcomes included other investigator-assessed efficacy measures of disease severity, safety measures and participant-reported measures of efficacy and impact. Results A total of 64 participants (mean baseline Palmoplantar Pustulosis Area and Severity Index score of 17.8, standard deviation 10.5) received anakinra (n = 31) or the placebo (n = 33). In the primary intention-to-treat analysis, which estimated the effect of the treatment policy, the mean treatment group difference at 8 weeks after adjustment for baseline Palmoplantar Pustulosis Area and Severity Index score was –1.65 (95% confidence interval –4.77 to 1.47; p = 0.300), in favour of anakinra relative to placebo, but was not statistically significant. Similarly, secondary investigator-assessed outcomes did not show statistical superiority of anakinra: the baseline-adjusted mean difference in fresh pustule count (palms and soles) between the anakinra group and the placebo group was 2.94 (95% confidence interval –26.44 to 32.33), in favour of placebo, and the mean difference in total pustule count was –30.08 (95% confidence interval –83.20 to 23.05), in favour of anakinra. Participant-assessed outcomes were consistent with these objective findings: the baseline-adjusted mean difference in Dermatology Life Quality Index between the anakinra group and the placebo group was 0.52 (95% confidence interval –2.04 to 3.07), in favour of placebo, and the mean difference in Palmoplantar Quality-of-Life Index was 1.27 (95% confidence interval –3.04 to 5.57), in favour of placebo. However, the proportion of participants who strongly agreed that treatment was worthwhile was greater in the anakinra group (12/29, 41%) than in the placebo group (4/28, 14%), a difference in proportion of 27% (95% confidence interval 5% to 49%). In the complier-average causal effect analysis, the baseline-adjusted mean treatment group difference in the week 8 Palmoplantar Pustulosis Area and Severity Index score in individuals who received ≥ 50% of injections was –2.30 (95% confidence interval –6.54 to 1.93; p = 0.287) and in those who received ≥ 90% of injections was –3.80 (95% confidence interval –10.76 to 3.16; p = 0.285), in favour of anakinra. No serious infections, significant neutropenia or other serious adverse events occurred. Injection site reactions were more frequent for those receiving anakinra (19/31, 61%) than for those receiving placebo (1/33, 3%). Conclusions There was no evidence that anakinra was superior to placebo. For the treatment of palmoplantar pustulosis, interleukin 1 blockade is not a useful intervention. Limitations The sample size was calculated to detect a large effect size. Treatment adherence was lower than expected. It cannot be ruled out that there was some selection bias towards less severe or unstable participants entering the trial given that the trial was placebo controlled with a required washout period. Future work Palmoplantar pustulosis remains an area of high unmet need and further research is recommended to (1) identify new drug targets, (2) determine the contributory role of drug exposure (including pharmacokinetics and adherence) and (3) validate outcome measures in palmoplantar pustulosis. Trial registration This trial is registered as ISCRTN13127147 and EudraCT 2015-003600-23. Funding This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a MRC and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 9, No. 2. See the NIHR Journals Library for further project information.

Caregiver assessment of quality of life in individuals with genetic developmental and epileptic encephalopathies.

To summarize quality of life (QoL) and its determinants, including disease severity, in individuals with developmental and epileptic encephalopathies (DEEs) through a tailored questionnaire. A questionnaire containing 89 items addressing demographic characteristics, genetic diagnosis, clinical features, and QoL was distributed to primary caregivers of individuals with DEEs through patient advocacy organizations. Composite scores were generated from the mean values of QoL items, grouped into domain scores. Out of 176 received responses, the most common genetic diagnoses reported were SCN2A (n=42/173, 24%), SLC6A1 (n=28/173, 16%), SCN1A (n=22/173, 13%), and KCNQ2 (n=21/173, 12%). Composite QoL scores centered around a mean score of 61.67 of 100 (SD 17.10). QoL scores were strongly associated with the number of days minimally disrupted by seizures, medication side effects, genetic diagnosis, and community type. The mean QoL scores for individuals with DEEs was significantly lower than for individuals with Rett syndrome, cerebral palsy, autism spectrum disorder, and Down syndrome. QoL in DEEs can be assessed through a standardized instrument. QoL only partially overlaps with objective measurements of disease severity and may represent an independent outcome measure in precision medicine trials.

Emerging Drugs for Generalized Myasthenia Gravis


 Horizon Scan reports provide brief summaries of information regarding new and emerging health technologies. These technologies are identified through the CADTH Horizon Scanning Service as topics of potential interest to health care decision-makers in Canada. This Horizon Scan summarizes the available information regarding emerging targeted therapies for the treatment of generalized myasthenia gravis (MG).
 MG is a rare and chronic autoimmune disease in which autoantibodies attack specific proteins in the neuromuscular junction, resulting in muscle weakness. Many patients develop generalized MG resulting in severe fatigable muscle weakness with difficulties in facial expression, speech, swallowing, and mobility.
 Current treatments for MG include anticholinesterase inhibitors, systemic corticosteroids, and nonsteroidal immunosuppressive drugs. IV immunoglobulins or therapeutic plasma exchange are the current treatment options for patients with severe or acutely worsening generalized MG. Thymectomy is also considered a treatment option for patients with generalized MG who fail to respond to immunotherapy or have intolerable side effects.
 In this scan, we have reviewed 6 new treatment strategies that target specific areas of the immune system involved in the pathogenesis of MG: efgartigimod, rozanolixizumab, zilucoplan, ravulizumab, batoclimab, and nipocalimab. Phase II and III clinical trials have shown that these drugs may potentially benefit patients with generalized MG based on improvements in measures of disease severity and functional disability.
 The information presented is limited in that most of the available evidence comes from phase II trials that were designed to primarily investigate safety and tolerability based on small sample sizes, short trial duration, and narrow inclusion criteria. Therefore, findings do not reflect current standard of practice for maintenance therapy for generalized MG in the real-world setting.
 Considerations for future use include identifying the population that will most likely benefit from therapy and evaluating these drugs for rare and serious adverse events. Factors such as ease of administration, dosing schedule, and cost are all important factors that will help determine uptake and place in therapy for these emerging targeted therapies.

Filtration-histogram based texture analysis and CALIPER based pattern analysis as quantitative CT techniques in idiopathic pulmonary fibrosis: head-to-head comparison.

To assess the prognostic performance of two quantitative CT (qCT) techniques in idiopathic pulmonary fibrosis (IPF) compared to established clinical measures of disease severity (GAP index). Retrospective analysis of high-resolution CT scans for 59 patients (age 70.5 ± 8.8 years) with two qCT methods. Computer-aided lung informatics for pathology evaluation and ratings based analysis classified the lung parenchyma into six different patterns: normal, ground glass, reticulation, hyperlucent, honeycombing and pulmonary vessels. Filtration histogram-based texture analysis extracted texture features: mean intensity, standard deviation (SD), entropy, mean of positive pixels (MPPs), skewness and kurtosis at different spatial scale filters. Univariate Kaplan-Meier survival analysis assessed the different qCT parameters' performance to predict patient outcome and refine the standard GAP staging system. Multivariate cox regression analysis assessed the independence of the significant univariate predictors of patient outcome. The predominant parenchymal lung pattern was reticulation (16.6% ± 13.9), with pulmonary vessel percentage being the most predictive of worse patient outcome (p = 0.009). Higher SD, entropy and MPP, in addition to lower skewness and kurtosis at fine texture scale (SSF2), were the most significant predictors of worse outcome (p < 0.001). Multivariate cox regression analysis demonstrated that SD (SSF2) was the only independent predictor of survival (p < 0.001). Better patient outcome prediction was achieved after adding total vessel percentage and SD (SSF2) to the GAP staging system (p = 0.006). Filtration-histogram texture analysis can be an independent predictor of patient mortality in IPF patients. qCT analysis can help in risk stratifying IPF patients in addition to clinical markers.

A166 CANNABIS USE IN CANADIAN INDIVIDUALS WITH INFLAMMATORY BOWEL DISEASE FOLLOWING LEGALIZATION OF CANNABIS

Abstract Background Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are characterized by remitting and relapsing symptoms of abdominal pain, diarrhea, nausea, fatigue, and poor sleep. Most patients with IBD require chronic immunosuppressive therapy to maintain their disease in remission. Due to their disease chronicity, individuals often seek additional complementary or alternative medicines such as cannabis to treat their symptoms. Reports from the US show cannabis use in 12% of UC and 16% of CD patients. However, these numbers are likely underestimates given that cannabis remains illegal in many states. Aims The aim of our study is to evaluate the use of cannabis in a cohort of patients with IBD and to assess its association with IBD disease severity. Methods We conducted a prospective cohort survey of adult patients with IBD seen in tertiary care in London Health Sciences Centre. A 40-question online survey was completed by consenting patients and collected data on demographics, IBD disease history, cannabis use, and included the Short Inflammatory Bowel Disease Questionnaire (SIBDQ) as a measure of disease severity. The study was approved by the Western University Ethics Committee. Statistical analyses was performed using a Chi squared test for categorical data, and a two-tailed t-test for continuous data. Results Completed surveys were obtained from 210 individuals (135 individuals with CD and 75 with UC) and demographics were similar between the CD and UC cohort. Fifty-six percent of participants reported cannabis use at least once in their lifetime, with 38% of participants reporting cannabis use in the preceding 6 months. Interestingly, 46 percent of life-time cannabis users did not divulge their cannabis use to their physicians. In patients with UC, those who actively used cannabis were less likely to be on 5-ASA therapy (9 active users vs 22 non-users, p&amp;lt;0.05). Medical therapy was otherwise similar between cannabis users and non-users. Surgical rates were similar between cannabis users and non-users amongst both IBD subtypes. With respect to the burden of disease, patients with CD reported higher rates of abdominal pain if they were active users, however, overall SIBDQ scores were not altered by cannabis use (21 user vs 20 non-user). Similarly, SIBDQ scores were similar amongst patients with UC who were cannabis users and non-users (20 user vs 16 non-user). Conclusions Cannabis use in patients with IBD is very common and much higher than previously reported prior to the legalization in Canada, but its use is not associated with lower disease severity based on patient reported outcomes. Our study also reveals that patients often do not report this use to their doctors so physicians must be aware of its prevalence amongst their IBD patient population. Funding Agencies None

Electromyographic measures of asymmetric muscle control of swallowing in Parkinson's disease.

During the early stages, Parkinson's disease (PD) is well recognized as an asymmetric disease with unilateral onset of resting tremor with varying degrees of rigidity, and bradykinesia. However, it remains unknown if other impairments, such as swallowing impairment (i.e., dysphagia), also present asymmetrically. The primary aim of this study was to examine muscle activity associated with swallow on the most affected side (MAS) and least affected side (LAS) in persons with PD. A secondary aim was to explore the relationship between differences in muscle activity associated with swallow and subjective reports of swallowing impairment and disease severity. Function of muscles associated with swallowing was assessed using surface electromyography placed over the right and left submental and laryngeal regions during three swallows for a THIN and THICK condition. The Swallowing Quality of Life (SWAL-QOL) questionnaire and the Unified Parkinson's Disease Rating Scale (UPDRS) were collected as measures of subjective swallow impairment and disease severity, respectively. Thirty-five participants diagnosed with idiopathic PD and on a stable antiparkinsonian medication regimen completed this study. Results revealed no significant mean difference in muscle activity during swallow between the more and less affected side. For the laryngeal muscle region, a significant difference in coefficient of variation between the MAS and LAS was revealed for peak amplitude for the THIN swallow condition. For the laryngeal muscle region, a significant association was revealed between muscle activity and disease severity but not subjective reports of swallowing impairment. Superficially it appears that swallowing impairment present symmetrical during the early stages of PD, however, our variability data indicates otherwise. These results will be used to inform future studies in specific types of swallowing impairment (i.e., oral dysphagia, pharyngeal dysphagia, and esophageal dysphagia), disease progression, and overall asymmetry.

Quality of Life Outcomes after Iliac Vein Stenting for Chronic Deep Venous Obstruction: A Tertiary Centre Experience Using The VEINES-QoL/Sym

Chronic venous disease has a debilitating impact on quality of life with significant psychological and economic burden. The VEINES-QoL/SYM is an extensively validated venous-disease specific quality of life assessment, which has been used in the outpatient clinic at St Thomas' since 2016 to measure disease severity before and after stenting. We measured the change in venous disease-specific quality of life after iliac vein stenting for chronic deep venous obstruction. We also identifies factors associated with improvement in quality of life after stenting.

Assessment of Virological Contributions to COVID-19 Outcomes in a Longitudinal Cohort of Hospitalized Adults.

BackgroundWhile several demographic and clinical correlates of coronavirus disease 2019 (COVID-19) outcome have been identified, their relationship to virological and immunological parameters remains poorly defined.MethodsTo address this, we performed longitudinal collection of nasopharyngeal swabs and blood samples from a cohort of 58 hospitalized adults with COVID-19. Samples were assessed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load, viral genotype, viral diversity, and antibody titer. Demographic and clinical information, including patient blood tests and several composite measures of disease severity, was extracted from electronic health records.ResultsSeveral factors, including male sex, higher age, higher body mass index, higher 4C Mortality score, and elevated lactate dehydrogenase levels, were associated with intensive care unit admission. Of all measured parameters, only the retrospectively calculated median Deterioration Index score was significantly associated with death. While quantitative polymerase chain reaction cycle threshold (Ct) values and genotype of SARS-CoV-2 were not significantly associated with outcome, Ct value did correlate positively with C-reactive protein levels and negatively with D-dimer, lymphocyte count, and antibody titer. Intrahost viral genetic diversity remained constant through the disease course and resulted in changes in viral genotype in some participants.ConclusionsUltimately, these results suggest that worse outcomes are driven by immune dysfunction rather than by viral load and that SARS-CoV-2 evolution in hospital settings is relatively constant over time.

A mask R-CNN based automatic assessment system for nail psoriasis severity

Nail psoriasis significantly impacts the quality of life in patients with psoriasis, which affects approximately 2–3% of the population worldwide. Disease severity measures are essential in guiding treatment and evaluation of therapeutic efficacy. However, due to subsidy, convenience and low costs of health care in Taiwan, doctor usually needs to manage nearly hundreds of patients in single outpatient clinic, leading to difficulty in performing complex assessment tools. For instance, Nail Psoriasis Severity index (NAPSI) is used by dermatologists to measure the severity of nail psoriasis in clinical trials, but its calculation is quite time-consuming, which hampers its application in daily clinical practice. Therefore, we developed a simple, fast and automatic system for the assessment of nail psoriasis severity by constructing a standard photography capturing system combined with utilizing one of the deep learning architectures, mask R-CNN. This system not only assist doctors in capturing signs of disease and normal skin, but also able to extract features without pre-processing of image data. Expectantly, the system could help dermatologists make accurate diagnosis, assessment as well as provide precise treatment decision more efficiently.

Measuring plant disease severity in R: introducing and evaluating the pliman package

Image analysis based on color thresholding is the reference method for measuring severity as percent area affected. It is deemed to produce accurate results, usually considered the “true” severity value. More than a dozen applications have been used for the task in phytopathometry studies, but none was coded in R language. Here we introduced and evaluated pliman, a suite for the analysis of plant images. In particular, we show functions for computing percent severity based on RGB information contained in image palettes prepared by the user. Six image collections, totaling 249 images, from different diseases (wheat tan spot, soybean rust, olive leaf spot, rice brown spot, bean angular spot, and Xyllela fastidiosa on tobacco) exhibiting a range of symptomatic patterns and severity were used to evaluate the agreement of pliman predictions with measures by three other software: APS Assess, LeafDoctor, and ImageJ. Three users independently prepared three image palettes (each representing leaf background, symptomatic, or healthy leaf tissue) by manually inspecting and subsetting these target areas of the images. Pliman predictions by a joint palette (by joining images by the three users into one) were highly concordant (ρc > 0.98) with measures by the other software for all but Xylella fastidiosa on tobacco (ρc = 0.49). The error for the latter may be due to the low contrast between symptomatic and healthy tobacco tissues. Users showed to be a source of variation in the overall concordance depending on the disease. Reduction in the image resolution (< 1 megapixel) did not impact the results. Combined with parallel processing, the use of low image resolution (1078 × 680) decreased processing time, resulting in pliman being ~ 150 to ~ 700 times faster than existing tools for disease quantification. Pliman showed great potential to produce accurate measures and accelerate studies involving plant disease severity measurements, especially for the batch processing of large sets of image collections.

Associations between the Composite Response Index in Diffuse Cutaneous Systemic Sclerosis (CRISS), survival and other disease measures

ObjectiveDiffuse cutaneous systemic sclerosis (dcSSc) is a multifaceted disease for which the Composite Response Index in dcSSc (CRISS) was developed as a global outcome measure. We aimed to further validate the CRISS by examining its association with other disease measures, patient reported quality of life (QoL), and mortality. MethodsDcSSc patients with ≤5 year disease duration were recruited from multinational registries. CRISS improvers (score ≥0.6) and non-improvers (score <0.6) were identified after one year. Median changes in European Scleroderma Group Activity Index (EScSG-AI), Medsger Disease Severity Scale (DSS), Scleroderma Clinical Trials Consortium Damage Index (SCTC-DI), and Short Form 36 physical component score (SF-36 PCS) after one year was compared between CRISS groups. Kaplan Meier and adjusted Cox analyses compared SCTC-DI damage accrual and mortality between CRISS groups. ResultsOf 212 patients, 68 (32.1%) were CRISS improvers. CRISS improvers had improved median EScSG-AI (-1.1 points [IQR -2.6, -0.3] vs. 0 [-1.1, 1.0], p<0.001), DSS (-1 [-3, 1] vs. 0 [-2, 2], p = 0.015), and SF-36 PCS (+3.6 [-1.0, 8.9] vs. -0.3 [-5.9, 4.5], p<0.001) compared to non-improvers. CRISS improvers were less likely to accumulate damage on the SCTC-DI (hazard ratio [95% confidence interval] 0.68 [0.47, 0.96]) adjusting for age, sex, disease duration, and immunosuppression use. CRISS improvers had a trend towards better survival. ConclusionCRISS improvers had more favourable changes in measures of disease activity, disease severity, and QoL compared to non-improvers. These findings support the construct validity of a CRISS outcome after one year in early dcSSc.

Multiple Sclerosis Disease Activity and Disability Following Discontinuation of Natalizumab for Pregnancy

The magnitude of risk of pregnancy-related multiple sclerosis relapses, particularly severe relapses, following natalizumab cessation is unclear, as is whether this risk is reduced by pregnancy or other modifiable factors. To determine the association of early natalizumab withdrawal before or during pregnancy with risk of severe relapses and relapse-related disability. This prospective cohort study used data from the German Multiple Sclerosis and Pregnancy Registry, which enrolled participants between November 2006 and February 2018. Data were collected through structured telephone-administered questionnaires and review of neurologists' notes. Registry patients who stopped natalizumab treatment within the 2 years before or in the first trimester of pregnancy were included in this analysis. Data were analyzed between January and November 2021. Cessation of natalizumab before pregnancy or until the first trimester. Severe and significant relapse-related disability was defined as at least a 2.0-point increase on the expanded disability status scale or new or worsening relapse-related ambulatory impairment. Multivariable models accounting for measures of disease severity and repeated events were used. The cohort comprised 255 women with 274 pregnancies (mean [SD] age at pregnancy onset, 31.25 [4.27] years) who stopped natalizumab before pregnancy (n = 85; median time before last menstrual period, 14.29 weeks [IQR, 3.14-42.43 weeks]) or in the first trimester (n = 189). During pregnancy and the postpartum year, relapses were reported in 183 pregnancies (66.78%), severe relapses in 44 pregnancies (16.05%), and potentially life-threatening relapses in 3 pregnancies (1.10%). One year post partum, significant relapse-related disability was accrued in 29 pregnancies (10.58%). Relapses during pregnancy (n = 109; 39.78%) and in the postpartum period (n = 135; 49.27%) were common. Pregnancy (as a time-dependent covariate) was not associated with a reduced relapse risk (adjusted HR, 0.90; 95% CI, 0.64-1.27). Neither exclusive breastfeeding (adjusted HR, 1.34; 95% CI, 0.86-2.10) nor restarting natalizumab within 4 weeks post partum (adjusted HR, 1.06; 95% CI, 0.48-2.36) were associated with a reduced risk of early postpartum relapses 6 months after delivery. However, the relapse rate ratio during 12 months post partum was lower (0.49; 95% CI, 0.28-0.86) when natalizumab was restarted in the first 4 weeks after birth. This cohort study's finding suggest that 10% of women may retain clinically meaningful disability from pregnancy-related natalizumab cessation relapses 1 year post partum. This information should be shared with women on natalizumab who desire pregnancy to weigh the high risk of pregnancy-related relapses and disability to the partly uncertain risks of continuing natalizumab throughout pregnancy or switching to depleting agents before conception.

Disparities in Lung Transplant among Patients with Idiopathic Pulmonary Fibrosis: An Analysis of the IPF-PRO Registry.

RationaleLung transplant offers the potential to extend life for patients with idiopathic pulmonary fibrosis (IPF); yet, this therapeutic modality is only available to a small proportion of patients.ObjectivesTo identify clinical characteristics and social determinants of health that differentially associate with lung transplant compared with death in patients with IPF.MethodsWe evaluated data from the Idiopathic Pulmonary Fibrosis Prospective Outcomes (IPF-PRO) Registry, a multicenter U.S. registry of patients with IPF that was diagnosed or confirmed at the enrolling center in the previous 6 months. Patients were enrolled between June 2014 and October 2018. Patients who were listed for lung transplant were not eligible to enroll in the registry, but patients could be listed for transplant after enrollment. We performed a multivariable time-to-event analysis incorporating competing risks methodology to examine differential associations between prespecified covariates and the risk of lung transplant versus death. Covariates included factors related to lung transplant eligibility, clinical characteristics of IPF, and social determinants of health. Covariates were modeled as time independent or time dependent as appropriate.ResultsAmong 955 patients with IPF, event rates of lung transplant and death were 7.4% and 16.3%, respectively, at 2 years. Covariates with the strongest differential association were age, median zip code income, and enrollment at a center with a lung transplant program. Lung transplant was less likely (hazard ratio [HR], 0.13 [95% confidence interval (CI), 0.06–0.28] per 5-yr increase) and death more likely (HR, 1.41 [95% CI, 1.22–1.64] per 5-yr increase) among those older than 70 years of age. Higher median zip code income was associated with lung transplant (HR, 1.22 [95% CI, 1.13–1.31] per $10,000 increase) but not death (HR, 0.99 [95% CI, 0.94–1.04] per $10,000 increase). Enrollment at a center with a lung transplant program was associated with lung transplant (HR, 4.31 [95% CI, 1.76–10.54]) but not death (HR, 0.99 [95% CI, 0.69–1.43]). Oxygen use with activity was associated with both lung transplant and death, but more strongly with lung transplant. A higher number of comorbidities was associated with an increased likelihood of death but not lung transplant.ConclusionsFor patients in the Idiopathic Pulmonary Fibrosis Prospective Outcomes Registry, median zip code income and access to a lung transplant center differentially impact the risk of lung transplant compared with death, regardless of disease severity measures or other transplant eligibility factors. Interventions are needed to mitigate inequalities in lung transplantation based on socioeconomic status.Clinical trial registered with www.clinicaltrials.gov (NCT01915511).

DOP65 Development and validation of the TUMMY-UC, a patient-reported outcome in pediatric Ulcerative Colitis: A multicenter prospective study

Abstract Background In developing a patient-reported outcome (PRO) for pediatric ulcerative colitis (UC) with guidance from FDA and EMA, 8 items were previously selected based on 79 concept elicitation interviews. An observer RO (ObsRO) was determined to be required for children younger than 8 years. Here, we aimed to finalize the included items and to validate the TUMMY-UC for its psychometric properties. Methods The structure and exact wording of the PRO and the ObsRO versions were determined by cognitive debriefing interviews with children and their caregivers. Weights were assigned to each item based on ranking of importance. Then, in a prospective multicenter study, children with UC between 2–18 years who either underwent colonoscopy or provided stool for calprotectin completed the TUMMY-UC during 4 consecutive days, as well as 7 and 21 days thereafter for evaluating reliability and responsiveness. Construct and discriminative validity were assessed by different measures of disease severity and quality of life (QOL). Results In an iterative process of 129 cognitive interviews, the exact wording of the TUMMY-UC was determined. The PRO and ObsRO were formatted with identical structure to ensure conceptual equivalence for incorporating into one score. 71 children were included in the validation study (39 with colonoscopy and 32 with calprotectin; age 12.3±4.1 years, 26 (36%) in remission, 20 (29%) with moderate-severe disease). There was excellent reliability in the repeated day assessments (ICC 0.93 (0.88–0.96); p&amp;lt;0.001) and after 1 week in those judged as unchanged (0.90 (0.81–0.95); p&amp;lt;0.001). The TUMMY-UC total score had moderate to strong correlations with all constructs of disease severity: r=0.64 with UC Endoscopic Index of Severity (UCEIS, Figure 1), r=0.66 with IMPACT QOL questionnaire, r=0.43 with calprotectin, r=0.82 with the PUCAI, r=0.76 with patient/caregiver global assessment, r=0.5 with CRP, and r=-0.36 with albumin (all p&amp;lt;0.015). There was a slight superiority to combining TUMMY-UC scores of two consecutive days. The index had excellent discrimination of disease activity categories (figure 2) with a score&amp;lt;9 defining remission (Sen=93%, Spec=84%, AUROC=0.95 (95%CI 0.89–0.99). Showing high responsiveness, the DTUMMY-UC differentiated well between children who improved, worsened or remained unchanged after 3 weeks (Figure 3). The best cutoff of the TUMMY-UC to define response was a change of ≥10 points (AUROC 0.93 (95%CI 0.86–0.99)). Conclusion The TUMMY-UC, constructed from a PRO and ObsRO versions for children 8–18 and 2–7 years, respectively, is a reliable, valid and responsive index which can be now used in clinical practice and as an outcome measure in clinical trials.

Regional Variation in DLQI 0/1 within the CorEvitas Psoriasis Registry 6-months following Biologic Initiation

Background: Patients with psoriasis frequently experience anxiety, depression, and increased psychological distress in association with their disease. Previous work has shown that Dermatology Life Quality Index (DLQI) scores directly associate with measures of disease severity and parallel treatment response.&#x0D; Methods: Participants included new biologic initiations in 2018 in the CorEvitas Psoriasis registry with baseline and 6-month follow-up visits available. Logistic regressions resulted in adjusted odd ratios (OR) and 95% CIs for achievement of DLQI 0/1 for 7 US geographic regions. &#x0D; Results: There were 737 new biologic initiations included in the study. Of these, 644 had DLQI &gt; 0 at baseline. Baseline mean DLQI scores did not vary significantly among geographic regions. Overall, 42.7% of patients achieved DLQI 0/1 at 6-months. The Pacific region reported the smallest proportion achieving this target (26.9%) followed by the East South Central (ESC) (34.3%) and West South Central (WSC) (40.9%) with a range of 26.9-51.1% across all regions. In logistic regression models adjusted for age, sex, race, and BMI, the Pacific had 61% lower odds of achieving DLQI 0/1 compared to the Northeast.&#x0D; Conclusions: Improvement of DLQI scores at 6-months of treatment for psoriasis is not geographically uniform across the United States. Regions that had the lowest proportions of achieving PASI75 also had the lowest proportions of patients achieving DLQI 0/1; yet when fully adjusted only patients in the Pacific were less likely to achieve DLQI 0/1, suggesting factors beyond treatment response impact patient quality of life.

Psychometric Validation of the German Translation of the Quality of Life Questionnaire-Bronchiectasis (QOL-B)-Data from the German Bronchiectasis Registry PROGNOSIS.

Patients with bronchiectasis feature considerable symptom burden and reduced health-related quality of life (QOL). We provide the psychometric validation of the German translation of the disease-specific Quality of Life Questionnaire-Bronchiectasis (QOL-B), version 3.1, using baseline data of adults consecutively enrolled into the prospective German bronchiectasis registry PROGNOSIS. Overall, 904 patients with evaluable QOL-B scores were included. We observed no relevant floor or ceiling effects. Internal consistency was good to excellent (Cronbach’s α ≥0.73 for each scale). QOL-B scales discriminated between patients based on prior pulmonary exacerbations and hospitalizations, breathlessness, bronchiectasis severity index, lung function, sputum volume, Pseudomonas aeruginosa status and the need for regular pharmacotherapy, except for Social Functioning, Vitality and Emotional Functioning scales. We observed moderate to strong convergence between several measures of disease severity and QOL-B scales, except for Social and Emotional Functioning. Two-week test-retest reliability was good, with intraclass correlation coefficients ≥0.84 for each scale. Minimal clinical important difference ranged between 8.5 for the Respiratory Symptoms and 14.1 points for the Social Functioning scale. Overall, the German translation of the QOL-B, version 3.1, has good validity and test-retest reliability among a nationally representative adult bronchiectasis cohort. However, responsiveness of QOL-B scales require further investigation during registry follow-up.

Development of novel clinical examination scales for the measurement of disease severity in Creutzfeldt-Jakob disease

ObjectiveTo use a robust statistical methodology to develop and validate clinical rating scales quantifying longitudinal motor and cognitive dysfunction in sporadic Creutzfeldt-Jakob disease (sCJD) at the bedside.MethodsRasch analysis was used...