Analytical and Clinical Validation of a Target-Enhanced Whole Genome Sequencing-Based Comprehensive Genomic Profiling Test.

Evaluation of the test performance of the Target enhanced whole-genome sequencing (TE-WGS) assay for comprehensive oncology genomic profiling. The analytical validation of the assay included sensitivity and specificity for single nucleotide variants (SNVs), insertions/deletions (indels), and structural variants (SVs), revealing a revealed a sensitivity of 99.8% for SNVs and 99.2% for indels. The positive predictive value (PPV) was 99.3% SNVs and 98.7% indels. Clinical validation was benchmarked against established orthogonal methods and demonstrated high concordance with reference methods. TE-WGS provides insights beyond targeted panels by comprehensive analysis of key biomarkers and the entire genome encompassing both germline and somatic findings.

Clinical Utility of Whole-Genome Analysis as One-for-All Test for Breast Cancer: A Case Series.

Introduction: Breast cancer exhibits vast genomic diversity, leading to varied clinical manifestations. Integrating molecular subtyping with in-depth genomic profiling is pivotal for informed treatment choices and prognostic insights. Whole-genome clinical analysis provides a holistic view of genome-wide variations, capturing structural changes and affirming tumor suppressor gene loss of heterozygosity. Case Presentation: Here we detail four unique breast cancer cases from Seoul St. Mary's Hospital, highlighting the actionable benefits and clinical value of whole-genome sequencing (WGS). As an all-in-one test, WGS demonstrates significant clinical utility in these cases, including: (1) detecting homologous recombination deficiency with underlying somatic causal variants (case 1), (2) distinguishing double primary cancer from metastasis (case 2), (3) uncovering microsatellite instability (case 3), and (4) identifying rare germline pathogenic variants in TP53 gene (case 4). Our observations underscore the enhanced clinical relevance of WGS-based testing beyond pinpointing a few driver mutations in conventional targeted panel sequencing platforms. Conclusion: With genomic advancements and decreasing sequencing costs, WGS stands out as a transformative tool in oncology, paving the way for personalized treatment plans rooted in individual genetic blueprints.

Barriers and Facilitators to End-of-Life Care Delivery in ICUs: A Qualitative Study.

OBJECTIVES: To understand frontline ICU clinician's perceptions of end-of-life care delivery in the ICU. DESIGN: Qualitative observational cross-sectional study. SETTING: Seven ICUs across three hospitals in an integrated academic health system. SUBJECTS: ICU clinicians (physicians [critical care, palliative care], advanced practice providers, nurses, social workers, chaplains). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In total, 27 semi-structured interviews were conducted, recorded, and transcribed. The research team reviewed all transcripts inductively to develop a codebook. Thematic analysis was conducted through coding, category formulation, and sorting for data reduction to identify central themes. Deductive reasoning facilitated data category formulation and thematic structuring anchored on the Systems Engineering Initiative for Patient Safety model identified that work systems (people, environment, tools, tasks) lead to processes and outcomes. Four themes were barriers or facilitators to end-of-life care. First, work system barriers delayed end-of-life care communication among clinicians as well as between clinicians and families. For example, over-reliance on palliative care people in handling end-of-life discussions prevented timely end-of-life care discussions with families. Second, clinician-level variability existed in end-of-life communication tasks. For example, end-of-life care discussions varied greatly in process and outcomes depending on the clinician leading the conversation. Third, clinician-family-patient priorities or treatment goals were misaligned. Conversely, regular discussion and joint decisions facilitated higher familial confidence in end-of-life care delivery process. These detailed discussions between care teams aligned priorities and led to fewer situations where patients/families received conflicting information. Fourth, clinician moral distress occurred from providing nonbeneficial care. Interviewees reported standardized end-of-life care discussion process incorporated by the people in the work system including patient, family, and clinicians were foundational to delivering end-of-life care that reduced both patient and family suffering, as well as clinician moral distress. CONCLUSIONS: Standardized work system communication tasks may improve end-of life discussion processes between clinicians and families.

Nomenclature in Palliative Surgery.

Surgical palliative care, palliative care interventions, and palliative surgery all reference a blend of these 2 sub-specialty fields. Despite prior published definitions, use of these phrases both clinically and in the literature is varied and can lead to confusion and misunderstanding. Herein, we proposed the adoption of standardized nomenclature to guide the consistent use of these phrases.

Clinical Impact and Accuracy of Shave Biopsy for Initial Diagnosis of Cutaneous Melanoma.

INTRODUCTION: Effective treatment of malignant melanomas is dependent upon accurate histopathological staging of preoperative biopsy specimens. While narrow excision is the gold standard for melanoma diagnosis, superficial shave biopsies have become the preferred method by dermatologists but may transect the lesion and result in inaccurate Breslow thickness assessment. This is a retrospective cohort study evaluating an initial method of biopsy for diagnosis of cutaneous melanoma and indication for reoperation based on inaccurate initial T-staging. METHODS: We retrospectively analyzed consecutive patients referred to the Medical College of Wisconsin, a tertiary cancer center, with a diagnosis of primary cutaneous melanoma. Adult patients seen between 2015 and 2018 were included. Fisher's exact test was used to assess the association between method of initial biopsy and need for unplanned reoperation. RESULTS: Three hundred twenty three patients with cutaneous melanoma from the head and neck (H&N, n = 101, 31%), trunk (n = 90, 15%), upper extremity (n = 84, 26%), and lower extremity (n = 48, 28%) were analyzed. Median Breslow thickness was 0.54 mm (interquartile range = 0.65). Shave biopsy was the method of initial biopsy in 244 (76%), excision in 23 (7%), and punch biopsy in 56 (17%). Thirty nine (33%) shave biopsies had a positive deep margin, as did seven (23%) punch biopsies and 0 excisional biopsies. Residual melanoma at definitive excision was found in 131 (42.5%) of all surgical specimens: 95 (40.6%) shave biopsy patients, 32 (60.4%) punch biopsy patients, and four (19.0%) excision biopsy patients. Recommendations for excision margin or sentinel lymph node biopsy changed in 15 (6%) shave biopsy patients and five (9%) punch biopsy patients. CONCLUSIONS: Shave biopsy is the most frequent method of diagnosis of cutaneous melanoma in the modern era. While shave and punch biopsies may underestimate true T-stage, there was no difference in need for reoperation due to T-upstaging based on initial biopsy type, supporting current diagnostic practices. Partial biopsies can thus be used to guide appropriate treatment and definitive wide local excision when adjusting for understaging.

What Are the Priorities in Surgical Palliative Care Research?

In the 20 years since the American College of Surgeons outlined the first research agenda for surgical palliative care, there has been immense growth in the evidence. In this article, we briefly review the state of the science and priority research areas in surgical palliative care.

Medical students and mattering on the surgery clerkship rotation.

BACKGROUND: Mattering is a psychosocial construct that describes an individual's perception that they make a difference in the lives of others and that they are significant in the world. The purpose of this study was to explore the current perception of behaviors that impact mattering among third year medical students on their surgery clerkship with the goal of improving the clerkship experience. METHODS: A qualitative interview study was conducted during the 2019-2020 academic year. Medical students who had completed their surgery clerkship at a single institution volunteered to participate. Qualitative thematic analysis of students' comments during interviews were categorized to the three primary domains of mattering: awareness, importance, and reliance. RESULTS: Six medical student interviews were conducted and responses were coded for the three primary domains of mattering. Eight subthemes emerged highlighting positive observations that may influence student mattering on the surgery clerkship. Awareness behaviors included acknowledging the student's presence, maintaining eye contact, educators offering students their undivided attention, and getting to know the students as individuals. Importance behaviors included taking time to teach, setting expectations early, and providing timely feedback. Reliance behaviors involve developing trust to match autonomy with experience and depending on students to provide unique information about patient care to the team. CONCLUSIONS: These findings can help educators recognize the words, actions, and behaviors that make medical students feel they matter on their surgery clerkship. Interventions should continue focus on how to increase the sense of awareness, importance, and reliance for both the students and faculty.

Palliative Cytoreductive Surgery With or Without Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis: Is It Safe and Effective?

INTRODUCTION: Palliation is a controversial indication for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Patients with peritoneal carcinomatosis (PC) are living longer, and the roles of palliative CRS and HIPEC are increasingly challenged. The purpose of this study is to evaluate indications, morbidity, and symptom improvement from CRS/HIPEC in advanced PC. METHODS: A retrospective review of patients undergoing CRS and/or HIPEC with a palliative intent at a single institution from February 2008 to February 2018 was performed. Main end points included symptom improvement, symptom-free interval, and overall survival. RESULTS: Two hundred and seventy seven patients were referred for CRS/HIPEC during the study period and 17 underwent 20 palliative procedures. Appendiceal (n = 6) and colorectal cancers (n = 6) were the most common malignancies. Ascites (n = 8) and bowel obstruction (n = 8) were the most common indications for intervention. The postoperative complication rate was 50% and major complication rate was 20%. Partial symptom improvement or resolution of symptoms was achieved in 18 (90%) cases. A durable symptom control at 90 d was achieved in 13 (65%) cases. The median time to symptom recurrence was 5.1 mo (interquartile range: 2-11.4), and the median overall survival was 11.6 mo (interquartile range: 3.8-28.5). CONCLUSIONS: Palliative CRS and/or HIPEC achieve symptom improvement in patients with advanced PC. Risk assessment and expected time to recovery from surgery remain paramount for patient selection.

Improvement in clinical disease activity index when treatment selection is informed by the tumor necrosis factor-ɑ inhibitor molecular signature response classifier: analysis from the study to accelerate information of molecular signatures in rheumatoid arthritis.

BACKGROUND: A blood-based molecular signature response classifier (MSRC) predicts non-response to tumor necrosis factor-ɑ inhibitors (TNFi) in rheumatoid arthritis (RA). RESEARCH DESIGN AND METHODS: This is an interim analysis of data collected in the Study to Accelerate Information of Molecular Signatures (AIMS) in RA from patients who received the MSRC test between September 2020 and November 2021. Absolute changes in clinical disease activity index (CDAI) scores from baseline were evaluated at 12 weeks (n = 470) and 24 weeks (n = 274). RESULTS: Predicted TNFi non-responders who received a biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) with an alternative mechanism of action (altMOA) experienced up to 1.8-fold greater improvements in CDAI scores than those treated with a TNFi (12 weeks: 12.2 vs 8.0; p-value = 0.083; 24 weeks: 14.2 vs 7.8 p-value = 0.009). In patients with a molecular signature of non-response to TNFi in high disease activity at baseline, this corresponded to 43.2% relative improvement in achieving a lower CDAI disease activity level when likely TNFi non-responders were treated with a non-TNFi therapy (38.9% vs 55.7%). Commensurate improvements in efficiency of spend are expected when TNFi are avoided in favor of altMOA. CONCLUSIONS: RA treatment selection informed by MSRC test results improves clinical outcomes in real-world care and offers improvements in efficiency of healthcare spending.

Nursing implications of an early warning system implemented to reduce adverse events: a qualitative study.

BACKGROUND: Unrecognised changes in a hospitalised patient's clinical course may lead to a preventable adverse event. Early warning systems (EWS) use patient data, such as vital signs, nursing assessments and laboratory values, to aid in the detection of early clinical deterioration. In 2018, an EWS programme was deployed at an academic hospital that consisted of a commercially available EWS algorithm and a centralised virtual nurse team to monitor alerts. Our objective was to understand the nursing perspective on the use of an EWS programme with centralised monitoring. METHODS: We conducted and audio-recorded semistructured focus groups during nurse staff meetings on six inpatient units, stratified by alert frequency (high: >100 alerts/month; medium: 50-100 alerts/month; low: <50 alerts/month). Discussion topics included EWS programme experiences, perception of EWS programme utility and EWS programme implementation. Investigators analysed the focus group transcripts using a grounded theory approach. RESULTS: We conducted 28 focus groups with 227 bedside nurses across all shifts. We identified six principal themes: (1) Alert timeliness, nurses reported being aware of the patient's deterioration before the EWS alert, (2) Lack of accuracy, nurses perceived most alerts as false positives, (3) Workflow interruptions caused by EWS alerts, (4) Questions of actionability of alerts, nurses were often uncertain about next steps, (5) Concerns around an underappreciation of core nursing skills via reliance on the EWS programme and (6) The opportunity cost of deploying the EWS programme. CONCLUSION: This qualitative study of nurses demonstrates the importance of earning user trust, ensuring timeliness and outlining actionable next steps when implementing an EWS. Careful attention to user workflow is required to maximise EWS impact on improving hospital quality and patient safety.

Clinical utility of therapy selection informed by predicted nonresponse to tumor necrosis factor-ɑ inhibitors: an analysis from the Study to Accelerate Information of Molecular Signatures (AIMS) in rheumatoid arthritis.

BACKGROUND: The molecular signature response classifier (MSRC) is a blood-based precision medicine test that predicts nonresponders to tumor necrosis factor-ɑ inhibitors (TNFi) in rheumatoid arthritis (RA) so that patients with a molecular signature of non-response to TNFi can be directed to a treatment with an alternative mechanism of action. RESEARCH DESIGN AND METHODS: This study evaluated decision choice and treatment outcomes resulting from MSRC-informed treatment selection within a real-world cohort. RESULTS: Therapy selection by providers was informed by MSRC results for 73.5% (277/377) of patients. When MSRC results were not incorporated into decision-making, 62.0% (62/100) of providers reported deviating from test recommendations due to insurance-related restrictions. The 24-week ACR50 responses in patients prescribed a therapy in alignment with MSRC results were 39.6%. Patients with a molecular signature of non-response had significantly improved responses to non-TNFi therapies compared with TNFi therapies (ACR50 34.8% vs 10.3%, p-value = 0.05). This indicates that predicted non-responders to TNFi therapies are not nonresponders to other classes of RA targeted therapy. Significant changes were also observed for CDAI, ACR20, ACR70, and for responses at 12 weeks. CONCLUSIONS: Adoption of the MSRC into patient care could fundamentally shift treatment paradigms in RA, resulting in substantial improvements in real-world treatment outcomes.

Guided therapy selection in rheumatoid arthritis using a molecular signature response classifier: an assessment of budget impact and clinical utility.

BACKGROUND: Patients with moderate to severe rheumatoid arthritis (RA) can be treated with a range of targeted therapies following inadequate response to conventional synthetic disease-modifying antirheumatic drugs such as methotrexate. Whereas clinical practice guidelines provide no formal recommendations for initial targeted therapies, the tumor necrosis factor alpha inhibitor (TNFi) class is the prevalent first-line selection based on clinician experience, its safety profile, and/or formulary requirements, while also being the costliest. Most patients do not achieve adequate clinical response with a first-line TNFi, however. A molecular signature response classifier (MSRC) test that assesses RA-related biomarkers can identify patients who are unlikely to achieve adequate response to TNFi-class therapies. OBJECTIVE: To model cost-effectiveness of MSRC-guided, first-line targeted therapy selection compared with current standard care. METHODS: This budget impact analysis used data sourced from August to September 2020. The prevalence of each first-line targeted therapy was obtained using market intelligence from Datamonitor/Informa PLC Rheumatology Dashboard Forecast 2020, and the average first-year cost of treatment for each class was calculated using wholesale acquisition costs from IBM Micromedex RED BOOK Online. Average effectiveness for each class was based on manufacturer-reported ACR50 response rates (American College of Rheumatology adequate response criteria of 50% improvement at 6 months after therapy initiation). The impact of MSRC testing on first therapy selection was predicted based on a third party-generated decision-impact study that analyzed potential alterations in rheumatologist prescribing patterns after receiving MSRC test reports. Sensitivity analysis evaluated potential impacts of variation in first-year medication cost, adherence to MSRC report, and test price on the first-year cost of treatment. Cost for response (first-year therapy cost therapy divided by probability of achieving ACR50) was compared between standard care and MSRC-guided care. RESULTS: The estimated cost for first-year, standard-care treatment was $65,117, with 80% of patients initiating treatment with a TNFi. Cost for achieving ACR50 response was $177,046. After applying MSRC-guided patient stratification and therapy selection, the first-year cost was $56,543, net of test price, with 49.0% of patients initiating with a TNFi. First-year MSRC-guided care cost, including test price, was estimated at $117,103, a 33.9% improvement over standard care. Sensitivity analysis showed a net cost improvement for guided care vs standard care across all scenarios. Patients predicted to be inadequate TNFi responders, when modeled with lower-priced alternatives, were predicted to show increased ACR50 response rates. Those with MSRC test results indicating a first-line TNFi were predicted to show an ACR50 response rate superior to that for any other class. In this model, if implemented clinically, MSRC-guided care might save the US health care system more than $850 million annually and improve ACR50 by up to 31.3%. CONCLUSIONS: Precision medicine using MSRC-guided patient stratification and therapy selection may both decrease cost and improve efficacy of targeted RA therapies. DISCLOSURES: This work was funded in full by Scipher Medicine Corporation, which participated in data analysis and interpretation and drafting, reviewing, and approving the publication. All authors contributed to data analysis and interpretation and publication preparation, maintaining control over the final content. Arnell, Withers, and Connolly-Strong are employees of and have stock ownership in Scipher Medicine Corporation. Bergman has received consulting fees from AbbVie, Gilead, GlaxoSmithKline, Novartis, Pfizer, Regeneron, Sanofi, and Scipher Medicine and owns stock or stock options in Johnson & Johnson. Kenney, Logan, and Lim-Harashima are consultants for Scipher Medicine Corporation. Basu has nothing to disclose.

A Molecular Signature Response Classifier to Predict Inadequate Response to Tumor Necrosis Factor-α Inhibitors: The NETWORK-004 Prospective Observational Study.

INTRODUCTION: Timely matching of patients to beneficial targeted therapy is an unmet need in rheumatoid arthritis (RA). A molecular signature response classifier (MSRC) that predicts which patients with RA are unlikely to respond to tumor necrosis factor-α inhibitor (TNFi) therapy would have wide clinical utility. METHODS: The protein-protein interaction map specific to the rheumatoid arthritis pathophysiology and gene expression data in blood patient samples was used to discover a molecular signature of non-response to TNFi therapy. Inadequate response predictions were validated in blood samples from the CERTAIN cohort and a multicenter blinded prospective observational clinical study (NETWORK-004) among 391 targeted therapy-naïve and 113 TNFi-exposed patient samples. The primary endpoint evaluated the ability of the MSRC to identify patients who inadequately responded to TNFi therapy at 6 months according to ACR50. Additional endpoints evaluated the prediction of inadequate response at 3 and 6 months by ACR70, DAS28-CRP, and CDAI. RESULTS: The 23-feature molecular signature considers pathways upstream and downstream of TNFα involvement in RA pathophysiology. Predictive performance was consistent between the CERTAIN cohort and NETWORK-004 study. The NETWORK-004 study met primary and secondary endpoints. A molecular signature of non-response was detected in 45% of targeted therapy-naïve patients. The MSRC had an area under the curve (AUC) of 0.64 and patients were unlikely to adequately respond to TNFi therapy according to ACR50 at 6 months with an odds ratio of 4.1 (95% confidence interval 2.0-8.3, p value 0.0001). Odds ratios (3.4-8.8) were significant (p value < 0.01) for additional endpoints at 3 and 6 months, with AUC values up to 0.74. Among TNFi-exposed patients, the MSRC had an AUC of up to 0.83 and was associated with significant odds ratios of 3.3-26.6 by ACR, DAS28-CRP, and CDAI metrics. CONCLUSION: The MSRC stratifies patients according to likelihood of inadequate response to TNFi therapy and provides patient-specific data to guide therapy choice in RA for targeted therapy-naïve and TNFi-exposed patients.

A blood-based molecular signature response classifier (MSRC) integrating next-generation RNA sequencing data with clinical features predicts the likelihood that a patient with rheumatoid arthritis will have an inadequate response to TNFi therapy. Treatment selection guided by test results, with likely inadequate responders appropriately redirected to a different therapy, could improve response rates to TNFi therapies, generate healthcare cost savings, and increase rheumatologists' confidence in prescribing decisions and altered treatment choices. The MSRC described in this study predicts the likelihood of inadequate response to TNFi therapies among targeted therapy-naïve and TNFi-exposed patients in a multicenter, 24-week blinded prospective clinical study: NETWORK-004. Patients with a molecular signature of non-response are less likely to have an adequate response to TNFi therapies than those patients lacking the signature according to ACR50, ACR70, CDAI, and DAS28-CRP with significant odds ratios of 3.4­8.8 for targeted therapy-naïve patients and 3.3­26.6 for TNFi-exposed patients. This MSRC provides a solution to the long-standing need for precision medicine tools to predict drug response in rheumatoid arthritis­a heterogeneous and progressive disease with an abundance of therapeutic options. These data validate the performance of the MSRC in a blinded prospective clinical study of targeted therapy-naïve and TNFi therapy-exposed patients.

The ALPHA Project: Establishing consensus and prioritisation of global community recommendations to address major challenges in lupus diagnosis, care, treatment and research.

The Addressing Lupus Pillars for Health Advancement (ALPHA) Project is a global consensus effort to identify, prioritise and address top barriers in lupus impacting diagnosis, care, treatment and research. To conduct this process, the ALPHA Project convened a multistakeholder Global Advisory Committee (GAC) of lupus experts and collected input from global audiences, including patients. In phase I, the ALPHA Project used expert interviews and a global survey of lupus experts to identify and categorise barriers into three overarching pillars: drug development, clinical care and access to care. In phase II, reported here, the GAC developed recommended actionable solutions to address these previously identified barriers through an in-person stakeholder meeting, followed by a two-round scoring process. Recommendations were assessed for feasibility, impact and timeline for implementation (FIT), where potential FIT component values were between 1 and 3 and total scores were between 3 and 9. Higher scores represented higher achievability based on the composite of the three criteria. Simplifying and standardising outcomes measures, including steroid sparing as an outcome (drug development) and defining the lupus spectrum (clinical care) ranked as the highest two priority solutions during the GAC meeting and received high FIT scores (7.67 and 7.44, respectively). Leveraging social media (access to care) received the highest FIT score across all pillars (7.86). Cross-cutting themes of many solutions include leveraging digital technology and applying specific considerations for special populations, including paediatrics. Implementing the recommendations to address key barriers to drug development, clinical care and access to care is essential to improving the quality of life of adults and children with lupus. Multistakeholder collaboration and guidance across existing efforts globally is warranted.

High neutrophil-lymphocyte ratio is not independently associated with worse survival or recurrence in patients with extremity soft tissue sarcoma.

BACKGROUND: Soft tissue sarcomas are a heterogenous group of neoplasms without well-validated biomarkers. Cancer-related inflammation is a known driver of tumor growth and progression. Recent studies have implicated a high circulating neutrophil-lymphocyte ratio as a surrogate marker for the inflammatory tumor microenvironment and a poor prognosticator in multiple solid tumors, including colorectal and pancreatic cancers. The impact of circulating neutrophil-lymphocyte ratio in soft tissue sarcomas has yet to be elucidated. METHODS: We performed a retrospective analysis of patients undergoing curative resection for primary or recurrent extremity soft tissue sarcomas at academic centers within the US Sarcoma Collaborative. Neutrophil-lymphocyte ratio was calculated retrospectively in treatment-naïve patients using blood counts at or near diagnosis. RESULTS: A high neutrophil-lymphocyte ratio (≥4.5) was associated with worse survival on univariable analysis in patients with extremity soft tissue sarcomas (hazard ratio 2.07; 95% confidence interval, 1.54-2.8; P < .001). On multivariable analysis, increasing age (hazard ratio 1.03; 95% confidence interval, 1.02-1.04; P < .001), American Joint Committee on Cancer T3 (hazard ratio 1.89; 95% confidence interval, 1.16-3.09; P = .011), American Joint Committee on Cancer T4 (hazard ratio 2.36; 95% confidence interval, 1.42-3.92; P = .001), high tumor grade (hazard ratio 4.56; 95% confidence interval, 2.2-9.45; P < .001), and radiotherapy (hazard ratio 0.58; 95% confidence interval, 0.41-0.82; P = .002) were independently predictive of overall survival, but a high neutrophil-lymphocyte ratio was not predictive of survival (hazard ratio 1.26; 95% confidence interval, 0.87-1.82; P = .22). CONCLUSION: Tumor inflammation as measured by high pretreatment neutrophil-lymphocyte ratio was not independently associated with overall survival in patients undergoing resection for extremity soft tissue sarcomas.

Patient-reported flare frequency is associated with diminished quality of life and family role functioning in systemic lupus erythematosus.

PURPOSE: To understand the influence of the systemic lupus erythematosus (SLE)-related flares on patient's health-related quality of life (HRQoL). METHODS: An online survey included individuals with self-reported physician's diagnosis of SLE or lupus nephritis (LN). Lupus impact tracker (LIT) assessed lupus symptoms and HRQoL, SLE-Family questionnaire measured family role functioning, and Healthy Days Core Module (HDCM) measured overall mental and physical health. Chi-square and analysis of variance evaluated differences by flare frequency. Multivariable linear regression and generalized linear models evaluated the independent relationships of flare frequency to HRQoL. RESULTS: 1066 respondents with SLE or LN completed the survey. Mean (SD) duration of illness was 12.4 (10.1) years. 93.4% (n = 996) were women, 82.3% (n = 830) were White, and 49.7% (n = 530) were employed or students. More frequent flares were associated with significantly worse scores on all HRQoL measures: LIT (adjusted means: 0 flares, 31.8; 1-3 flares, 47.0; 4-6 flares, 56.1; ≥ 7 flares, 63.6; P < 0.001); SLE-Family (adjusted means: 0 flares, 3.1; 1-3 flares 3.8; 4-6 flares, 4.3; ≥ 7 flares, 4.6, P < 0.001); HDCM unhealthy days (0 flares, 8.7; 1-3 flares, 17.4; 4-6 flares, 21.5; ≥ 7 flares, 26.2 days, P < 0.001). CONCLUSION: Lupus flares contributed to impaired functional and psychological well-being, family functioning, and number of monthly healthy days. Better understanding of the burden of flare activity from the patient's perspective will support a holistic approach to lupus management.

Treatment Patterns and Health Care Costs of Lupus Nephritis in a United States Payer Population.

OBJECTIVE: To describe the characteristics, treatment patterns, health care resource utilization (HCRU), and cost of care for members of a large United States (US) health insurance plan with lupus nephritis (LN). METHODS: A retrospective observational study was conducted using a health insurance plan database to identify adult members with a diagnosis of LN. Medical and pharmacy claims were used to describe demographics, comorbidities, HCRU, and cost patterns over a 12-month follow-up period for each patient, between January 1, 2014, and December 31, 2016. All study variables were examined descriptively. RESULTS: A total of 1039 patients were available for analysis (median age, 47 years; 83% female). The median Charlson Comorbidity Index (CCI) was 3.3. Less than half (41%) of patients received immunosuppressive therapies commonly used to treat LN. Evidence indicated that 58% of the study population were prescribed corticosteroid therapy, in most cases (73%) for more than 60 days. Adverse events known to be associated with corticosteroid therapy were recorded in 58% of patients. Guideline-recommended preventive therapy with hydroxychloroquine was prescribed for 54% of members with LN. Nearly half (47%) of members with LN did not see a nephrologist and more than one-third (36%) did not see a rheumatologist over 1 year of follow-up. Rates of all-cause hospitalization and emergency department (ED) use were 25% and 35%, respectively. The mean all-cause per-member-per-month (PMPM) medical cost for the study population was $2801, with LN-specific costs accounting for $1147 PMPM. CONCLUSION: Patients with LN who are insured through a large US health plan appeared to underutilize outpatient specialist services and guideline-recommended hydroxychloroquine therapy. Corticosteroid use and adverse events known to be associated with corticosteroids were common in this cohort.

Acthar Gel (repository corticotropin injection) for persistently active SLE: study design and baseline characteristics from a multicentre, randomised, double-blind, placebo-controlled trial.

Objective: SLE is a chronic inflammatory autoimmune disease characterised by the excessive production of autoantibodies, immune complexes and proinflammatory cytokines. Repository corticotropin injection (RCI) is a naturally sourced complex mixture of adrenocorticotropic hormone analogues and other pituitary peptides. RCI is approved by the US Food and Drug Administration for use during an exacerbation or as maintenance therapy in select cases of SLE. This paper discusses the design and baseline characteristics of a multicentre, double-blind, randomised, placebo-controlled, 24-week clinical trial evaluating the effect of RCI in reducing disease activity for patients with persistently active SLE despite moderate-dose corticosteroid use. Methods: Efficacy will be evaluated using the SLE Responder Index-4 (SRI-4), SLE Disease Activity Index-2000 (SLEDAI-2K), British Isles Lupus Assessment Group-2004 (BILAG-2004) and Physician's Global Assessment (PGA). The primary efficacy endpoint will be the proportion of SRI-4 responders at week 16. Secondary and exploratory endpoints will include changes in disease activity scores over time, prednisone dose and biomarkers of inflammation and bone turnover. The safety and tolerability profile of RCI will also be evaluated through adverse event profiles, physical examination, clinical laboratory tests and serum cortisol levels. Results: Target enrolment for this global study is 270 patients, and as of 15 November 2019, the modified intent-to-treat population included 169 patients. The study cohort had 91.7% women, had a mean age of 39.7 years, mean SLEDAI-2K total score of 9.9, mean BILAG-2004 total score of 18.1, mean PGA of 59.7 and mean prednisone or equivalent daily dose of 11.1 mg. A total of 79.3% and 64.5% of patients were receiving concomitant antimalarial or immunosuppressive therapy, respectively. Conclusions: Data from this study will provide valuable insights into the therapeutic role of RCI in refractory SLE, as well as important information regarding its safety profile.