Do Atopic Dermatitis Patient-Reported Outcomes Correlate With Validated Investigator Global Assessment? Insights From TARGET-AD Registry.

BACKGROUND: Research examining associations between the clinician-reported validated Investigator Global Assessment for AD (vIGA-AD) and patient-reported disease burden is sparse. This study aims to evaluate the relationship between vIGA-AD with patient-reported disease severity and quality of life (QoL). METHODS: A cross-sectional analysis was conducted using a September 2021 data cut from the TARGET-DERM AD study, a real-world, longitudinal cohort of children, adolescents, and adults with AD enrolled at 44 academic and community dermatology and allergy sites in the US. Clinical AD severity was measured using vIGA-AD while disease severity and QoL were assessed by the Patient Oriented Eczema Measure (POEM) and (Children's) Dermatology Life Quality Index (C/DLQI), respectively. Patient characteristics, clinical- and patient reported-outcomes were assessed by stratified POEM and C/DLQI categories using descriptive statistics. Associations with vIGA-AD were evaluated using unadjusted and adjusted ordinal logistic regression and linear regression models. RESULTS: The analysis cohort (n=1,888) primarily consisted of adults (57%), females (56%), and patients with private insurance (63%). Unadjusted analyses suggest that clinical AD severity was associated with age, with more adolescents and adults having moderate/severe vIGA-AD than pediatric patients. Clinical AD severity was also associated with disease severity, with greater POEM scores observed at greater vIGA-AD severity levels (r = 0.496 and 0.45 for adults and pediatrics, respectively). Clinical AD severity and QoL were positively correlated, with greater CDLQI/DLQI scores at greater vIGA-AD severity levels (r = 0.458 and 0.334 for DLQI and CDLQI, respectively). After adjusting for demographics and other risk factors, vIGA-AD continued to show significant associations with POEM and DLQI/CDLQI. Compared to patients with clear/almost clear disease, adults and pediatrics with moderate-to-severe AD were 8.19 and 5.78 times as likely to be in a more severe POEM category, respectively. Similarly, compared to patients with clear/almost clear disease, adults and pediatrics with moderate/severe AD were 6.69 and 3.74 times as likely to be in a more severe DLQI/CDLQI category. Adjusted linear regression analyses of DLQI in adults showed significant differences by vIGA-AD level, with mild AD and moderate/severe AD associated with a 2.26-point and 5.42-point greater DLQI relative to clear/almost clear AD. CONCLUSIONS: In this real-world study of patients with AD, greater clinician-reported disease severity is positively correlated with higher patient-reported disease severity and lower QoL. J Drugs Dermatol. 2023;22(4): doi:10.36849/JDD.7473 Access Supplementary Material here Citation: Guttman-Yassky E, Bar J, Rothenberg Lausell C, et al. Do atopic dermatitis patient-reported outcomes correlate with validated investigator global assessment? Insights from TARGET-AD registry. J Drugs Dermatol. 2023;22(4):344-355. doi:10.36849/JDD.7473.

Epidemiology and clinical characteristics of interstitial lung disease in patients with rheumatoid arthritis from the JointMan database.

Interstitial lung disease (ILD) is a progressive fibrotic disease associated with rheumatoid arthritis (RA); real-world data for evaluating RA-associated ILD (RA-ILD) are limited. We evaluated prevalence, time to onset, clinical characteristics and prognostic factors in patients diagnosed with RA (n = 8963) in the Discus Analytics JointMan database (2009-2019) with and without ILD. ILD prevalence was 4.1% (95% confidence interval 3.7-4.5); > 90% had an ILD diagnosis after RA diagnosis (mean time to onset 3.3 years). At baseline, a higher proportion of patients with RA-ILD were older (> 65 years), male, with history of chronic obstructive pulmonary disease (COPD) compared with patients in the RA cohort. Patients in the RA-ILD cohort were likely to have more severe RA characteristics and joint evaluation compared with patients without ILD, at baseline and before/after ILD diagnosis. In this large, real-world database patients with (vs without) ILD had a higher burden of RA characteristics. Previously established risk factors for RA-ILD were confirmed (age, baseline COPD, anti-cyclic citrullinated peptide positivity, C-reactive protein, Clinical Disease Activity Index score); thus, recognition of these factors and tracking routine disease activity metrics may help identify patients at higher risk of RA complications and lead to improved diagnosis and earlier treatment.

Patient profiles, treatment patterns, and outcomes among persistent, recurrent, or metastatic cervical cancer patients under routine care in the United States.

OBJECTIVE: Patients with persistent, recurrent, or metastatic cervical cancer have poor prognosis. While recent advances have expanded treatment options, real-world data on treatment patterns and outcomes in this population are lacking. METHODS: This retrospective study identified adult females with persistent, recurrent, or metastatic cervical cancer from the ConcertAI Oncology Dataset who received systemic therapy on or after August 15, 2014. Patients were followed from persistent, recurrent, or metastatic diagnosis through third-line (3 L) therapy, death, end of record, or study end (June 2021). Data collection included patient characteristics, treatment patterns, and clinical outcomes. Kaplan-Meier methods were used for the three most common first-line (1 L) regimens to analyze real-world time on treatment (rwToT), real-world progression-free survival (rwPFS), and real-world overall survival (rwOS). Analyses were stratified by bevacizumab receipt by treatment line. RESULTS: 307 patients were included (mean [standard deviation] age 51.5 [13.2] years, 70.7% White). 91.2% of patients had metastatic disease, 8.5% had persistent disease, and <1% had recurrent disease. The most common 1 L regimen was carboplatin+paclitaxel+bevacizumab (40.7%) with median (95% confidence interval [CI]) rwToT of 3.5 (2.9-4.4) months. 57.0% of patients proceeded to second line (2 L), and 25.7% went to 3 L. Median (95% CI) rwPFS was 7.2 (6.4-8.1) months, and median (95% CI) rwOS was 16.5 (14.2-19.9) months, from initiation of 1 L. CONCLUSIONS: 1 L regimens received in patients with persistent, recurrent, or metastatic cervical cancer generally followed clinical guidelines, and the rwOS agrees with clinical trials. This study highlights the burden of disease and unmet need for specific treatments in these patients.

Treatment Patterns, Disease Burden, and Outcomes in Patients with Giant Cell Arteritis and Polymyalgia Rheumatica: A Real-World, Electronic Health Record-Based Study of Patients in Clinical Practice.

INTRODUCTION: Because of the chronic nature of giant cell arteritis (GCA) and/or polymyalgia rheumatica (PMR), patients may require continued glucocorticoid treatment to achieve treatment targets or prevent disease relapse, resulting in high cumulative doses. This study evaluated patterns of glucocorticoid use and outcomes in patients with GCA, PMR, or both. METHODS: This retrospective study used electronic medical records from a US rheumatology clinic utilizing the JointMan® (Discus Analytics, LLC) rheumatology software. Patients aged ≥ 50 years with a diagnosis of GCA or PMR and ≥ 1 entry for a glucocorticoid prescription after diagnosis were included. Outcomes at 2 years after glucocorticoid initiation included the proportion of patients discontinuing glucocorticoids for ≥ 6 months, proportion of patients discontinuing glucocorticoids for ≥ 6 months and remaining off glucocorticoids at 2 years, time to discontinuation of glucocorticoids for ≥ 6 months, and prednisone dose and were compared between patients with GCA only, PMR only, or GCA and PMR. RESULTS: At 2 years after the initiation of glucocorticoids, 32% of patients (26/91) with GCA, 32% (248/779) with PMR, and 27% (26/97) with GCA and PMR discontinued glucocorticoids for ≥ 6 months; 17, 23, and 18% discontinued glucocorticoids for ≥ 6 months and remained off glucocorticoids at 2 years, respectively. Median (range) time to discontinuation of glucocorticoids for ≥ 6 months was 202.5 (0-635) days and shorter in patients with both GCA and PMR vs. GCA or PMR only. The majority of patients required daily prednisone at 2 years, with similar doses observed between groups. CONCLUSIONS: Fewer than one-third of patients with GCA and/or PMR discontinued glucocorticoids for ≥ 6 months; the majority of patients required prednisone therapy for ≥ 2 years after its initiation. These data highlight the need for the use of more efficacious and glucocorticoid-sparing therapies in patients with GCA and/or PMR.

An evaluation of contemporary hidden Markov model genefinders with a predicted exon taxonomy.

We present an independent evaluation of six recent hidden Markov model (HMM) genefinders. Each was tested on the new dataset (FSH298), the results of which showed no dramatic improvement over the genefinders tested five years ago. In addition, we introduce a comprehensive taxonomy of predicted exons and classify each resulting exon accordingly. These results are useful in measuring (with finer granularity) the effects of changes in a genefinder. We present an analysis of these results and identify four patterns of inaccuracy common in all HMM-based results.

POEM, A 3-dimensional exon taxonomy and patterns in untranslated exons.

BACKGROUND: The existence of exons and introns has been known for thirty years. Despite this knowledge, there is a lack of formal research into the categorization of exons. Exon taxonomies used by researchers tend to be selected ad hoc or based on an information poor de-facto standard. Exons have been shown to have specific properties and functions based on among other things their location and order. These factors should play a role in the naming to increase specificity about which exon type(s) are in question. RESULTS: POEM (Protein Oriented Exon Monikers) is a new taxonomy focused on protein proximal exons. It integrates three dimensions of information (Global Position, Regional Position and Region), thus its exon categories are based on known statistical exon features. POEM is applied to two congruent untranslated exon datasets resulting in the following statistical properties. Using the POEM taxonomy previous wide ranging estimates of initial 5' untranslated region exons are resolved. According to our datasets, 29-36% of genes have wholly untranslated first exons. Untranslated exon containing sequences are shown to have consistently up to 6 times more 5' untranslated exons than 3' untranslated exons. Finally, three exon patterns are determined which account for 70% of untranslated exon genes. CONCLUSION: We describe a thorough three-dimensional exon taxonomy called POEM, which is biologically and statistically relevant. No previous taxonomy provides such fine grained information and yet still includes all valid information dimensions. The use of POEM will improve the accuracy of genefinder comparisons and analysis by means of a common taxonomy. It will also facilitate unambiguous communication due to its fine granularity.

Treatment Persistence and Clinical Outcomes of Tumor Necrosis Factor Inhibitor Cycling or Switching to a New Mechanism of Action Therapy: Real-world Observational Study of Rheumatoid Arthritis Patients in the United States with Prior Tumor Necrosis Factor Inhibitor Therapy.

INTRODUCTION: To examine treatment persistence and clinical outcomes associated with switching from a tumor necrosis factor inhibitor (TNFi) to a medication with a new mechanism of action (MOA) (abatacept, anakinra, rituximab, tocilizumab, or tofacitinib) versus cycling to another TNFi (adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab) among patients with rheumatoid arthritis. METHODS: This retrospective, longitudinal study included patients with rheumatoid arthritis in the JointMan® US clinical database who received a TNFi in April 2010 or later and either cycled to a TNFi or switched to a new MOA therapy by March 2015. Cox proportional hazards models were used for time to non-persistence (switching or discontinuing). An ordinary least squares regression model compared 1-year reduction from baseline for the Clinical Disease Activity Index (CDAI). RESULTS: There were 332 (54.2%) TNFi cyclers and 281 (45.8%) new MOA switchers. During a median follow-up of 29.9 months, treatment persistence was 36.7% overall. Compared with new MOA switchers, TNFi cyclers were 51% more likely to be non-persistent (adjusted hazard ratio, 1.511; 95% CI 1.196, 1.908), driven by a higher likelihood of switching again (adjusted hazard ratio, 2.016; 95% CI 1.428, 2.847). Clinical outcomes were evaluable for 239 (53.3%) TNFi cyclers and 209 (46.7%) new MOA switchers. One-year mean reduction in CDAI from baseline to end of follow-up was significantly higher for new MOA switchers than TNFi cyclers (-7.54 vs. -4.81; P = 0.037), but the difference was not statistically significant after adjustment for baseline CDAI (-6.39 vs. -5.83; P = 0.607). CONCLUSION: In this study, TNFi cycling was common in clinical practice, but switching to a new MOA DMARD was associated with significantly better treatment persistence and a trend toward greater CDAI reduction that was not significant after adjustment for baseline disease activity. FUNDING: Sanofi and Regeneron Pharmaceuticals.

Eliciting Goals of Care in a nursing home.

OBJECTIVES: To identify enablers and barriers facing providers and staff in initiating Goals of Care (GOC) discussions with patients in the nursing home. DESIGN: Qualitative methods, one-on-one interviews. The interviews began with eliciting the participant's definition of GOC. The open-ended questions were designed to assess recent experience and satisfaction with the participant's role in the GOC discussion. SETTING: Nursing home. PARTICIPANTS: We interviewed 23 nursing home staff and providers. MEASUREMENTS: Transcripts were qualitatively analyzed. RESULTS: Five themes emerged that were identified as barriers to discussing GOC: (1) Fear of legal ramifications; (2) Not enough education on how to have a GOC discussion; (3) Family not involved on a regular basis; (4) Time pressure; (5) Interdisciplinary team not involved. Five themes also emerged that were identified as enablers to the GOC discussion: (1) Education/experience with the GOC discussion; (2) Interdisciplinary team involved in the discussion; (3) Established trusting relationship with the patient/family/other staff; (4) Terminal diagnosis/hospice involvement; (5) Discussion occurs in-person. CONCLUSION: A major finding of these interviews is the lack of systematic attention to GOC in the nursing home setting. Since education and experience were identified as crucial to understanding GOC, more formal education and observed practice discussing GOC is needed for all staff. The outcomes of GOC discussions should be documented in the patient record and be accessible to all staff and communicated systematically to all staff. Addressing these barriers and facilitating these enablers to the GOC discussion will improve the care of nursing home patients.

Eliciting goals of care in a nursing home.

OBJECTIVES: To identify enablers and barriers facing providers and staff in initiating Goals of Care (GOC) discussions with patients in the nursing home. DESIGN: Qualitative methods, one-on-one interviews. The interviews began with eliciting the participant's definition of GOC. The open-ended questions were designed to assess recent experience and satisfaction with the participant's role in the GOC discussion. SETTING: Nursing home. PARTICIPANTS: We interviewed 23 nursing home staff and providers. MEASUREMENTS: Transcripts were qualitatively analyzed. RESULTS: Five themes emerged that were identified as barriers to discussing GOC: (1) Fear of legal ramifications; (2) Not enough education on how to have a GOC discussion; (3) Family not involved on a regular basis; (4) Time pressure; (5) Interdisciplinary team not involved. Five themes also emerged that were identified as enablers to the GOC discussion: (1) Education/experience with the GOC discussion; (2) Interdisciplinary team involved in the discussion; (3) Established trusting relationship with the patient/family/other staff; (4) Terminal diagnosis/hospice involvement; (5) Discussion occurs in-person. CONCLUSION: A major finding of these interviews is the lack of systematic attention to GOC in the nursing home setting. Since education and experience were identified as crucial to understanding GOC, more formal education and observed practice discussing GOC is needed for all staff. The outcomes of GOC discussions should be documented in the patient record and be accessible to all staff and communicated systematically to all staff. Addressing these barriers and facilitating these enablers to the GOC discussion will improve the care of nursing home patients.

Water transfers, agriculture, and groundwater management: a dynamic economic analysis.

Water transfers from agricultural to urban and environmental uses will likely become increasingly common worldwide. Many agricultural areas rely heavily on underlying groundwater aquifers. Out-of-basin surface water transfers will increase aquifer withdrawals while reducing recharge, thereby altering the evolution of the agricultural production/groundwater aquifer system over time. An empirical analysis is conducted for a representative region in California. Transfers via involuntary surface water cutbacks tilt the extraction schedule and lower water table levels and net benefits over time. The effects are large for the water table but more modest for the other variables. Break-even prices are calculated for voluntary quantity contract transfers at the district level. These prices differ considerably from what might be calculated under a static analysis which ignores water table dynamics. Canal-lining implies that districts may gain in the short-run but lose over time if all the reduction in conveyance losses is transferred outside the district. Water markets imply an evolving quantity of exported flows over time and a reduction in basin net benefits under common property usage. Most aquifers underlying major agricultural regions are currently unregulated. Out-of-basin surface water transfers increase stress on the aquifer and management benefits can increase substantially in percentage terms but overall continue to remain small. Conversely, we find that economically efficient management can mitigate some of the adverse consequences of transfers, but not in many circumstances or by much. Management significantly reduced the water table impacts of cutbacks but not annual net benefit impacts. Neither the break-even prices nor the canal-lining impacts were altered by much. The most significant difference is that regional water users gain from water markets under efficient management.