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Background: Australia's commitment to consumer and community participation in health and medical research has grown over the past decade. Participatory research models of engagement are the most empowering for consumers.Methods: As part of a project to develop a diagnostic instrument for fetal alcohol spectrum disorders (FASD) in Australia (FASD Project), the Australian FASD Collaboration (Collaboration), including a consumer advocate and two consumer representatives, was established. On completion of the FASD Project an on-line survey of Collaboration members was conducted to assess their views on consumer involvement. Women in the community were also invited to participate in Community Conversations to discuss real life situations regarding communications with health professionals about alcohol and pregnancy. Community Conversation feedback was analysed qualitatively and attendees were surveyed about their views of the Community Conversation process.Results: The on-line survey was completed by 12 members of the Collaboration (71%). Consumer and community participation was considered important and essential, worked well, and was integral to the success of the project. The 32 women attending the Community Conversations generated 500 statements that made reference to prevention, how information and messages are delivered, and appropriate support for women. Nearly all the attendees at the Community Conversations (93%) believed that they had an opportunity to put forward their ideas and 96% viewed the Community Conversations as a positive experience.Conclusions: The successful involvement of consumers and the community in the FASD Project can be attributed to active consumer and community participation, which included continued involvement throughout the project, funding of participation activities, and an understanding of the various contributions by the Collaboration members. [ABSTRACT FROM AUTHOR]

An abstract of the study "Nicotinamide Inhibits Neutrophil Infiltration of the Lungs in Ventilator-Induced Lung Injury but Does Not Improve Survival," by Heather Jones, Pierre Kyme and colleagues is presented.

Background: The United States has unacceptably high rates of maternal and infant mortality, especially among Black women and their infants. Prenatal and postpartum care help reduce maternal and infant morbidity and mortality; however, Black women are less likely to access and utilize peripartum care largely due to structural racism. Identifying factors that buffer against the systemic barriers disproportionately impacting this community is an important step in addressing racial health disparities. Using existing data from a randomized controlled trial (RCT) targeting maternal and infant health disparities, this study aims to (1) explore predictors of peripartum care attendance and (2) examine clinical trial sample representativeness. Methods: The analyses addressing the primary aim of the study included Black women at risk for low prenatal care (PNC) engagement who consented to RCT participation and had a documented live birth (n = 123). For the secondary study aim, comparisons between women who consented to the RCT (Consenters; n = 149) and those who did not (Non-consenters; n = 122) were made using chi-square and t-tests. Results: Hierarchical linear and logistic regression identified predictors of prenatal and postpartum care attendance, respectively. After controlling for multiple comparisons, no significant differences were identified between characteristics of Consenters and Non-consenters. Older age (p = 0.038), high-risk pregnancy (p < 0.001), and no past week substance use (p = 0.033) predicted better PNC attendance. PNC attendance predicted postpartum visit attendance (p < 0.001). Conclusions: This study provides benchmark data on predictors of peripartum care and sample representativeness in RCTs. Findings have important implications for health care system changes and development of culturally informed interventions. [ABSTRACT FROM AUTHOR]

Objectives: To validate a diagnostic assay for detecting CALR mutations in the clinical setting.Methods: Traditional polymerase chain reaction (PCR) was performed on DNA previously extracted from 60 specimens (30 bone marrow aspirates [BMAs] and 30 peripheral blood [PB] samples) from 55 patients. Nearly all reported CALR mutations are insertions or deletions in exon 9. Therefore, we performed amplicon sizing by capillary electrophoresis and fragment length analysis (FLA) to determine mutation status. Mutations were confirmed by Sanger sequencing.Results: Fourteen samples from 10 patients with JAK2 and MPL wild-type myeloproliferative neoplasms were positive for CALR mutation. Detected mutations included a 52-base pair (bp) deletion (n = 6), a 5-bp insertion (n = 2), a 31-bp deletion (n = 1), and a 61-bp deletion (n = 1). Sanger sequencing of 15 samples showed 100% concordance. Matched patient PB and BMA samples (n = 5) harbored identical mutations, and samples run multiple times (n = 8) showed 100% reproducibility.Conclusions: We conclude that CALR mutations may be quickly and accurately detected by FLA of PCR amplicons by capillary electrophoresis. These methods are routine procedures for most molecular laboratories and should allow for straightforward incorporation of the CALR assay into the clinical diagnostic testing menu. [ABSTRACT FROM AUTHOR]

To fully assess the resilience and recovery of life in response to the Cretaceous–Paleogene (K-Pg) boundary mass extinction ~ 66 million years ago, it is paramount to understand biodiversity prior to the Chicxulub impact event. The peak ring of the Chicxulub impact structure offshore the Yucatán Peninsula (México) was recently drilled and extracted a ~ 100 m thick impact-generated, melt-bearing, polymict breccia (crater suevite), which preserved carbonate clasts with common biogenic structures. We pieced this information to reproduce for the first time the macrobenthic tracemaker community and marine paleoenvironment prior to a large impact event at the crater area by combining paleoichnology with micropaleontology. A variable macrobenthic tracemaker community was present prior to the impact (Cenomanian–Maastrichtian), which included soft bodied organisms such as annelids, crustaceans and bivalves, mainly colonizing softgrounds in marine oxygenated, nutrient rich, conditions. Trace fossil assemblage from these upper Cretaceous core lithologies, with dominant Planolites and frequent Chondrites, corresponds well with that in the overlying post-impact Paleogene sediments. This reveals that the K-Pg impact event had no significant effects (i.e., extinction) on the composition of the macroinvertebrate tracemaker community in the Chicxulub region. [ABSTRACT FROM AUTHOR]

We previously identified a novel alternatively spliced isoform of human myeloid differentiation protein-2 (MD-2s) that competitively inhibits binding of MD-2 to TLR4 in vitro. In this study, we investigated the protective role of MD-2s in LPS-induced acute lung injury by delivering intratracheally an adenovirus construct that expressed MD-2s (Ad-MD-2s). After adenovirus-mediated gene transfer, MD-2s was strongly expressed in lung epithelial cells and readily detected in bronchoalveolar lavage fluid. Compared to adenovirus serotype 5 containing an empty vector lacking a transgene control mice, Ad-MD-2s delivery resulted in significantly less LPS-induced inflammation in the lungs, including less protein leakage, cell recruitment, and expression of proinflammatory cytokines and chemokines, such as IL-6, keratinocyte chemoattractant, and MIP-2. Bronchoalveolar lavage fluid front Ad-MD-2s mice transferred into lungs of naive mice before intratracheal LPS challenge diminished proinflammatory cytokine levels. As house dust mite (HDM) sensitization is dependent on TLR4 and HDM Der p 2, a structural homolog of MD-2, we also investigated the effect of MD-2s on HDM-induced allergic airway inflammation. Ad-MD-2s given before HDM sensitization significantly inhibited subsequent allergic airway inflammation after HDM challenge, including reductions in eosinophils, goblet cell hyperplasia, and IL-5 levels. Our study indicates that the alternatively spliced short isoform of human MD-2 could be a potential therapeutic candidate to treat human diseases induced or exacerbated by TLR4 signaling, such as Gram-negative bacterial endotoxin-induced lung injury and HDM-triggered allergic lung inflammation. [ABSTRACT FROM AUTHOR]

Background: Screening facilitates the early identification of fetal alcohol spectrum disorder (FASD) and prevalence estimation of FASD for timely prevention, diagnostic, and management planning. However, little is known about FASD screening tools.Aims: The aims of this systematic review are to identify FASD screening tools and examine their performance characteristics.Methods: Four electronic databases were searched for eligible studies that examined individuals with FASD or prenatal alcohol exposure and reported the sensitivity and specificity of FASD screening tools. The quality of the studies was assessed using the Quality Assessment of Diagnostic Studies-2 tool.Results: Sixteen studies were identified, comprising five fetal alcohol syndrome (FAS) and seven FASD screening tools. They varied in screening approach and performance characteristics and were linked to four different diagnostic criteria. FAS screening tools performed well in the identification of individuals at risk of FAS while the performance of FASD screening tools varied in the identification of individuals at risk of FASD.Conclusion and Implications: Results highlight the vast differences in the screening approaches performance characteristics, and diagnostic criteria linked to FASD screening tools. More research is needed to identify biomarkers unique to FASD to guide the development of accurate FASD screening tools. [ABSTRACT FROM AUTHOR]

Background: Midwives are an influential profession and a key group in informing women about alcohol consumption in pregnancy and its consequences. There are no current quantitative Australian data on midwives' knowledge, attitudes and practice in relation to alcohol consumption during pregnancy and Fetal Alcohol Spectrum Disorder. We aimed to reduce this knowledge gap by understanding midwives' perceptions of their practice in addressing alcohol consumption during pregnancy. Methods: This cross-sectional study was conducted at 19 maternity sites across the seven health regions of country Western Australia. A questionnaire was designed following review of the literature and other relevant surveys. Midwifery managers of the maternity sites distributed questionnaires to all midwives working in their line of management. A total of 334 midwives were invited to participate in the research and (n = 245, 73.4%) of these were eligible. Results: The response fraction was (n = 166, 67.8%). Nearly all (n = 151, 93.2%) midwives asked pregnant women about their alcohol consumption during pregnancy and (n = 164, 99.4%) offered advice about alcohol consumption in accordance with the Australian Alcohol Guideline, which states "For women who are pregnant or planning a pregnancy, not drinking is the safest option". Nearly two thirds (n = 104, 64.2%) of the midwives informed pregnant women about the effects of alcohol consumption in pregnancy, they did not always use the recommended AUDIT screening tool (n = 66, 47.5%) to assess alcohol consumption during pregnancy, nor conduct brief intervention when indicated (n = 107, 70.4%). Most midwives endorsed professional development about screening tools (n = 145, 93.5%), brief intervention (n = 144, 92.9%), and alcohol consumption during pregnancy and FASD (n = 144, 92.9%). Conclusion: Nearly all midwives in this study asked and advised about alcohol consumption in pregnancy and around two thirds provided information about the effects of alcohol in pregnancy. Our findings support the need for further professional development for midwives on screening and brief intervention. Policy should support midwives' practice to screen for alcohol consumption in pregnancy and offer brief intervention when indicated. [ABSTRACT FROM AUTHOR]

The effects of social stimulation on ethanol drinking in humans may depend on the gender of the drinker, the gender of the social stimulus, and the availability of ethanol provided to the social stimulus. The present study employed the Proximal Cagemate Drinking (PCD) Procedures to evaluate the effects of the gender of the social stimulus Cagemate mouse and the effects of providing ethanol to the Cagemate mouse on the drinking of ethanol and water by the male or female CD-1 Drinker mouse. Twelve groups of subjects were arranged in a 322 factorial design with 3 levels of Cagemate Gender (Male vs. Female vs. None), 2 levels of Drinker Gender (Male vs. Female), and 2 levels of Cagemate Ethanol (Ethanol vs. No Ethanol). In the 8 groups assigned to social housing conditions, each Drinker mouse was housed with a Cagemate mouse on opposite sides of a clear plastic shoebox cage equipped with a clear plastic barrier that divided the cage lengthwise into 2 equal compartments. Six groups of Drinkers and 4 groups of Cagemates were provided with continuous access to 2 bottles (ethanol vs. water), while the 4 groups of Cagemates in the No Ethanol condition were provided with 2 bottles containing water. Results revealed that providing the Cagemate with ethanol elevated ethanol intake and ethanol preference but reduced water intake in Drinkers in Other-Gender Pairings (Male Drinker-Female Cagemate or Female Drinker-Male Cagemate) relative to Drinkers in Same-Gender Pairings (Male Drinker-Male Cagemate or Female Drinker-Female Cagemate). In contrast, when the Cagemate was not provided with access to ethanol, the opposite effects were observed. These novel PCD procedures reveal that the gender of the Cagemate and the Cagemate's access to ethanol influenced ethanol drinking in proximal-housed CD-1 Drinker mice. [ABSTRACT FROM AUTHOR]

Background: A large portion of COVID-19 cases and deaths in the United States have occurred in nursing homes; however, current literature including the frontline perspective of staff working in nursing homes is limited. The objective of this qualitative assessment was to better understand what individual and facility level factors may have contributed to the impact of COVID-19 on Certified Nursing Assistants (CNAs) and Environmental Services (EVS) staff working in nursing homes. Methods: Based on a simple random sample from the National Healthcare Safety Network (NHSN), 7,520 facilities were emailed invitations requesting one CNA and/or one EVS staff member for participation in a voluntary focus group over Zoom. Facility characteristics were obtained via NHSN and publicly available sources; participant demographics were collected via SurveyMonkey during registration and polling during focus groups. Qualitative information was coded using NVIVO and Excel. Results: Throughout April 2021, 23 focus groups including 110 participants from 84 facilities were conducted homogenous by participant role. Staffing problems were a recurring theme reported. Participants often cited the toll the pandemic took on their emotional well-being, describing increased stress, responsibilities, and time needed to complete their jobs. The lack of consistent and systematic guidance resulting in frequently changing infection prevention protocols was also reported across focus groups. Conclusions: Addressing concerns of low wages and lack of financial incentives may have the potential to attract and retain employees to help alleviate nursing home staff shortages. Additionally, access to mental health resources could help nursing home staff cope with the emotional burden of the COVID-19 pandemic. These frontline staff members provided invaluable insight and should be included in improvement efforts to support nursing homes recovering from the impact of COVID-19 as well as future pandemic planning. [ABSTRACT FROM AUTHOR]

Abstract: The room temperature crystal structures of six A 2 MMoO6 and A 2 MWO6 ordered double perovskites were determined from X-ray and neutron powder diffraction data. Ba2MgWO6 and Ba2CaMoO6 both adopt cubic symmetry (space group Fm3̄m, tilt system a 0 a 0 a 0). Ba2CaWO6 has nearly the same tolerance factor (t=0.972) as Ba2CaMoO6 (t=0.974), yet it surprisingly crystallizes with I4/m symmetry indicative of out-of-phase rotations of the MO6 octahedra about the c-axis (a 0 a 0 c −). Sr2ZnMoO6 (t=0.979) also adopts I4/m symmetry; whereas, Sr2ZnWO6 (t=0.976) crystallizes with monoclinic symmetry (P21/n) with out-of-phase octahedral tilting distortions about the a- and b-axes, and in-phase tilting about the c-axis (a − a − c +). Ca2CaWO6 (t=0.867) also has P21/n symmetry with large tilting distortions about all three crystallographic axes and distorted CaO6 octahedra. Analysis of 93 double perovskites and their crystal structures showed that while the type and magnitude of the octahedral tilting distortions are controlled primarily by the tolerance factor, the identity of the A-cation acts as the secondary structure directing factor. When A=Ba2+ the boundary between cubic and tetragonal symmetries falls near t=0.97, whereas when A=Sr2+ this boundary falls somewhere between t=1.018 and t=0.992. [Copyright &y& Elsevier]

In the current study, we examined how caregiver prompting of tobacco products (e.g., asking a child to empty an ashtray), caregiver monitoring, and caregiver-adolescent communication were associated with adolescents' tobacco use, intentions to use, and efficacy to refuse using tobacco. Caregiver-adolescent dyads were recruited from a southeastern city in the United States. Approximately 48% of the population in this city is Black. Participants included 101 Black caregivers who smoke and their adolescents (Mage = 14.4 years). Multiple regression analyses (R2 ranged from 0.10 to 0.44 across models) indicated that higher levels of adolescent-reported caregiver prompting were associated with a higher likelihood of adolescent-reported use and intentions to smoke tobacco products in their lifetime. Caregiver monitoring was associated with lower levels of adolescent tobacco use and intentions to use tobacco, and higher levels of tobacco refusal self-efficacy. General caregiver-adolescent communication was associated with greater tobacco refusal self-efficacy. Differences among caregiver prompting behavior by reporter highlight the importance of obtaining both adolescent and caregiver perceptions. These findings illustrate that caregivers may play a critical role in shaping their adolescents' tobacco-related outcomes through adolescent perceptions of their prompting of tobacco products, as well as their overall knowledge or monitoring of adolescent activities. Highlights: Black caregivers who smoke and their adolescent were both assessed. Prompting behavior from caregivers is associated with adolescent smoking. Caregivers that smoke tobacco products may shape their adolescents smoking behavior. [ABSTRACT FROM AUTHOR]

Describes the dependency of the trafficking of the calcium-activated potassium channel, hIK1, with a C-terminal leucine zipper. Results of the C-terminal truncation of hIK1; Measurement of surface expression and channel function by immunofluorescence, cell surface immunoprecipitation and whole-cell patch clamp techniques; Demonstration of the importance of the C-terminal leucine zipper.

Discusses a study which investigated adenosine triphosphate (ATP) release during Enteropathogenic Escherichia coli-mediated killing of human cell lines and whether released adenine nucleotides function as secretory mediators. Cause of diarrhea in children in developing countries; Use of cacterial strains in the research; Comparison of ATP accumulation in the presence and absence of various inhibitor-regenerator combinations.

Within the literature, there is overlap in the histopathological features described in eosinophilic folliculitis associated with chronic lymphocytic leukemia (CLL), eosinophilic dermatosis of hematologic malignancy, and acneiform follicular mucinosis. These disorders are described with varying degrees of superficial and deep lymphocytic and eosinophilic inflammation demonstrating perivascular, perifollicular, and folliculocentric involvement with or without follicular mucin deposition. Given significant histopathological overlap, these diagnoses may represent a continuum on a spectrum of dermatoses. Here, we present two cases with histopathological elements that reflect components of this clinicopathological spectrum and compare our findings with previously reported cases to compare and contrast reported features. Our first case is a 71‐year‐old African American man with long‐standing CLL who developed a pruritic erythematous papular eruption on the face and chest with biopsy revealing a dense folliculotropic lymphocytic infiltrate with conspicuous eosinophils and follicular mucinosis. Our second case is a 70‐year‐old Caucasian man recently diagnosed with CLL/small lymphocytic lymphoma who developed an erythematous papular rash on the neck and face with biopsy revealing superficial and deep perivascular and periadnexal lymphocytic inflammation with scattered eosinophils. Characterization of our two cases and comparison with available literature suggest that these disorders may represent a continuum of dermatoses. [ABSTRACT FROM AUTHOR]

Previous ichnological analysis at the Chicxulub impact crater, Yucatán Peninsula, México (International Ocean Discovery Program [IODP]/International Continental Scientific Drilling Program [ICDP] Site M0077), showed a surprisingly rapid initial tracemaker community recovery after the end-Cretaceous (Cretaceous-Paleogene [K-Pg]) mass extinction event. Here, we found that full recovery was also rapid, with the establishment of a well-developed tiered community within -700 k.y. Several stages of recovery were observed, with distinct phases of stabilization and diversification, ending in the development of a trace fossil assemblage mainly consisting of abundant Zoophycos, Chondrites, and Planolites, assigned to the Zoophycos ichnofacies. The increase in diversity is associated with higher abundance, larger forms, and a deeper and more complex tiering structure. Such rapid recovery suggests that favorable paleoenvironmental conditions were quickly reestablished within the impact basin, enabling colonization of the substrate. Comparison with the end-Permian extinction reveals similarities during recovery, yet postextinction recovery was significantly faster after the K-Pg event. The rapid recovery has significant implications for the evolution of macrobenthic biota after the K-Pg event. Our results have relevance in understanding how communities recovered after the K-Pg impact and how this event differed from other mass extinction events. [ABSTRACT FROM AUTHOR]

Objective: This article positions the special issue on telepsychology amidst the COVID‐19 pandemic, which has dramatically accelerated the adoption and dissemination of telepsychology. Method: The article makes general observations about the themes emerging in the special issue with considerations for application, training, theory‐driven research, and policy. It then presents as a case example the rapid deployment during the pandemic of telepsychology doctoral training and services at the Virginia Commonwealth University (VCU) Primary Care Psychology Collaborative. Results: Facilitators to VCU telepsychology deployment included trainee and supervisor resources, strong telepsychology training, and prior experience. Barriers to overcome included limited clinic capacity, scheduling, technology, and accessibility and diversity issues. Lessons learned involved presenting clinical issues, supervision, and working with children and adolescents. Conclusions: Telepsychology is crucial for psychological service provision, during the COVID‐19 pandemic more than ever, and that is unlikely to change as psychologists and patients increasingly continue to appreciate its value. [ABSTRACT FROM AUTHOR]

Purpose: To improve patient safety and reduce drug waste through implementation of automated parenteral chemotherapy dose-banding within an electronic health record. Methods: Parenteral chemotherapy dose-rounding practices were transitioned from a manual, pharmacist-driven workflow to an automated process within the electronic health record. Initial medications transitioned included bevacizumab, rituximab, and trastuzumab. Dose-banding tables were built to standardize rounding within a 10% parameter and then subsequently incorporated into the electronic health record after receiving multidisciplinary approval. Following implementation, a retrospective chart review was performed to compare drug and associated cost savings with manual dose-rounding and automated dose-banding. Medication safety improvements were measured by comparing the change in the number of clicks needed for pharmacist verification as well as by evaluation of submissions to our event reporting system. Results: After implementing automated parenteral chemotherapy dose-banding, reported medication errors associated with the parenteral chemotherapy rounding process decreased. The number of event submissions related to incorrect rounding decreased from four submissions in the pre-implementation period to zero in the post-implementation period. Automation saved pharmacists at least 9,297 additional clicks and 11,363 additional keystrokes and also led to notable increases in total drug savings as well as drug cost savings. Conclusion: Overall safety of our parenteral chemotherapy ordering processes within our electronic health record was improved after the implementation of automated dose-banding. By standardizing the administered doses for three chemotherapy agents, we were also able to increase total drug savings and associated drug cost savings. [ABSTRACT FROM AUTHOR]

The goal of this narrative review was to summarize immunogenicity data of biosimilars or biosimilar candidates for rheumatic diseases, plaque psoriasis, or inflammatory bowel disease (IBD), available in peer-reviewed publications or regulatory documents. PubMed records and regulatory documents were searched for immunogenicity data of TNFα or CD20 inhibitor biosimilars or biosimilar candidates. Data collected included the proportion of patients positive for anti-drug antibodies (ADAbs), proportion with neutralizing antibodies (nAbs) among ADAb-positive patients, ADAb/nAb assay characteristics, cross-reactivity, and the effects of ADAbs on pharmacokinetics, pharmacodynamics, efficacy, and safety. We identified eight biosimilars or biosimilar candidates for adalimumab (BI 695501, SB5, ABP 501, GP2017, PF-06410293, MSB-11022, FKB-327, ZRC-3197) four for etanercept (SB4, GP2015, CHS-0214, LBEC0101), and three each for infliximab (SB2, CT-P13, GP1111) and rituximab (CT-P10, GP2013, PF-05280586) with immunogenicity data. Randomized, head-to-head trials with reference products varied in design and methodology of ADAb/nAb detection. The lowest proportions of ADAb-positive (0–13%) and nAb-positive patients (0–3%) were observed in the trials of etanercept and its biosimilars, and the highest with adalimumab, infliximab, and their biosimilars (ADAbs: ≤ 64%; nAbs: ≤ 100%). The most common method of ADAb detection was electrochemiluminescence, and ADAb positivity was associated with nominally inferior efficacy and safety. Overall, there were no significant immunogenicity differences between biosimilars and reference products. However, there are many discrepancies in assessing and reporting clinical immunogenicity. In conclusion, immunogenicity data of biosimilars or biosimilar candidates for TNFα or CD20 inhibitors were collected in trials that varied in design and procedures for ADAb/nAb detection. In general, immunogenicity parameters of biosimilars are similar to those of their reference products. [ABSTRACT FROM AUTHOR]

Background: We assessed the external validity of composite indices Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Assessment in SpondyloArthritis international Society (ASAS) 40 response (ASAS40) by evaluating the correlations between the changes in some patient reported outcomes (PROs) for patients with non-radiographic axial spondyloarthritis (nr-axSpA) and the changes in the scores of the composite indices.Methods: This was a post-hoc analysis of data from the EMBARK study in patients with nr-axSpA treated with etanercept. PROs were grouped according to ASDAS status (inactive [< 1.3], low [≥ 1.3 to < 2.1], high [≥ 2.1 to ≤3.5], and very high [> 3.5]), patient achievement of > 50% improvement in BASDAI (BASDAI50 responders), and > 40% improvement in ASAS (ASAS40 responders) at 104 weeks. Analyses were conducted on observed cases available at Week 104. Changes in PROs from Baseline to Week 104 were assessed using analysis of covariance with adjustment for baseline with linear contrast.Results: Higher ASDAS disease activity at 104 weeks was associated with lower long-term improvement from baseline in PROs (e.g., total back pain [visual analog scale, cm (95% confidence interval): - 4.58 (- 4.95, - 4.21), - 3.86 (- 4.28, - 3.43), - 2.15 (- 2.68, - 1.61), and 1.30 (- 0.51, 3.12) for inactive, low, high, and very high ASDAS disease activity, respectively; Multidimensional Fatigue Inventory (MFI) general fatigue: - 4.77 (- 5.70, - 3.84), - 2.96 (- 4.04, - 1.87), - 1.00 (- 2.32, 0.31), and 2.14 (- 2.10, 6.38); all p < 0.001)]. BASDAI50 non-responders had less improvement in PROs from Baseline to Week 104 vs. responders (e.g., total back pain: - 1.61 (- 2.05, - 1.18) vs. -4.43 (- 4.69, - 4.18); MFI general fatigue: - 0.01 (- 1.12, 1.09) vs. -4.30 (- 4.98, - 3.62); all p < 0.001). ASAS40 non-responders also had less improvement in PROs from Baseline to Week 104 vs. responders (e.g., total back pain: - 1.91 (- 2.30, - 1.52) vs. -4.75 (- 5.05, - 4.46); MFI general fatigue: - 0.63 (- 1.56, 0.30) vs. -4.64 (- 5.37, - 3.91); all p < 0.001).Conclusion: Composite indices are valid for monitoring treatment response and adequately reflect treatment-related changes experienced by patients with nr-axSpA.Trial Registration: ClinicalTrials.gov identifier: NCT01258738. Registered 9 December 2010. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to use real-world data to evaluate potential interactions between age, treatment, and the risk of developing four adverse events (AEs) common in the elderly: congestive heart failure, serious infections, non-melanoma skin cancer, and interstitial lung disease. These AEs were identified as important in a prior age-based analysis (≤ 65 vs > 65 years) of etanercept- or placebo-treated patients with rheumatoid arthritis (RA) in controlled clinical trials. Methods: Real-world data (1 January 2013 to 31 January 2018) were obtained from the IBM Watson Health MarketScan® Database. Patients were included if aged ≥ 18 years, enrolled for ≥ 1 year prior to RA diagnosis, and without any of the four AEs of interest prior to RA diagnosis or between RA diagnosis and first etanercept exposure. Logistic regression analysis was applied following propensity matching of patients receiving or not receiving etanercept based on age at diagnosis, age status at the beginning of observation (> 65 years or not), sex, geographic region, and follow-up duration. Results: The overall cohort comprised 403,689 patients. The absolute risk of each of the four AEs increased with age. In propensity-matched cohorts, etanercept was associated with significantly higher odds of developing each of the four AEs (p < 0.001 for all). However, the relative risk of experiencing the four AEs in patients who received etanercept versus those who did not was similar between patients ≤ 65 years of age and those > 65 years of age. Conclusions: In patients with RA, the relative increase in etanercept-associated risk of experiencing congestive heart failure, serious infection, non-melanoma skin cancer, or interstitial lung disease was similar between elderly and non-elderly. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether initiation of etanercept therapy among patients with rheumatoid arthritis (RA) impacts use of co-therapy with methotrexate or prednisone, and to describe etanercept dosing dynamics compared to product monograph in the Canadian real-world setting. Methods: A retrospective cohort study was conducted using claims-level data from IQVIA Private Drug Plan database, Ontario Public Drug Plan database and Régie de l'assurance maladie du Québec database. Bio-naïve RA patients initiating etanercept between July 2014 and June 2015 were identified and their claims for methotrexate or prednisone were analyzed. Utilization of methotrexate or prednisone was calculated as average weekly dose in milligrams, and compared in the 6 months pre-initiation versus 12 months post-initiation of etanercept. Weekly etanercept dosing of each patient was calculated and analyzed to determine whether patients had at least 20% higher or lower average dose than monograph recommended dose (50 mg/week), and were then flagged as above-monograph or below-monograph, respectively. Results: A total of 2876 patients with RA (66% female, 76% aged 18-65) were included; 62% (n = 1,140) used methotrexate and 27% used prednisone (n = 498) both pre- and post-initiation of etanercept. In methotrexate patients, the average weekly dose dispensed was 25.4 mg in the 6 months pre-etanercept, and 25.0 mg in the 12 months post-etanercept initiation (p = .5282). In prednisone patients, the average weekly dose dispensed reduced from 122.6 mg pre-etanercept to 107.1 mg post-etanercept initiation (p = .2173). Among patients who were already on methotrexate or prednisone, after initiating on etanercept 16% (n = 213) and 34% (n = 254) of patients stopped methotrexate and prednisone, respectively. When compared to the recommended dose, 12% (n = 168) of patients were below-monograph and 7.1% of patients were above-monograph during their first year of etanercept therapy. Average etanercept dosing was consistently lower than product monograph during the follow-up year. Conclusions: Patients had a modest but not statistically significant decrease in prescribed doses of co-therapy with methotrexate and prednisone when etanercept was added to patients' therapy. In addition, 12-14% of patients stopped their co-therapy with methotrexate or prednisone. Further study is needed to understand the impact on patient outcomes and safety. [ABSTRACT FROM AUTHOR]

Background: Elderly individuals are disproportionately affected by rheumatoid arthritis (RA), but few studies have addressed the efficacy and safety of treatments in this population. Objective: Our objective was to assess the efficacy and safety of etanercept in elderly patients (aged ≥ 65 years) with RA. Methods: The efficacy analysis was a post hoc analysis of data from the open-label period of three phase IV clinical trials of etanercept for RA. Least squares (LS) change from baseline (cfb) in 28-joint Disease Activity Score (DAS28), Health Assessment Questionnaire Disability Index (HAQ-DI), and modified Total Sharp Scores (mTSS) were analyzed by age (< 65 vs. ≥ 65 years) for each study. The safety analyses were of data pooled from the double-blind, placebo-controlled periods of 19 phase I–IV randomized studies of etanercept in patients with RA. The percentage occurrence of adverse events (AEs) in placebo- and etanercept-treated patients was analyzed by age (< 65 vs. ≥ 65 years). Results: There were no significant differences in LS mean cfb in DAS28 or mTSS between the two age groups. LS mean cfb in HAQ-DI scores was consistently lower in elderly than in non-elderly patients, although significant differences were not observed in all trials. Overall, AE occurrence was higher in elderly than non-elderly patients, regardless of treatment. In etanercept-treated patients, there were small yet statistically significant increases in the occurrence of congestive heart failure, serious infections, and non-melanoma skin cancers in elderly versus non-elderly patients. For most AEs, occurrence did not significantly differ between elderly and non-elderly patients. Conclusion: Overall, there were no substantial differences in the efficacy or safety of etanercept between elderly and non-elderly patients with RA. [ABSTRACT FROM AUTHOR]