Loss to patient-reported outcome measure follow-up after hip arthroplasty and knee arthroplasty:patient satisfaction, associations with non-response, and maximizing returns

AIMS: The aim of this study was to determine satisfaction rates after hip and knee arthroplasty in patients who did not respond to postoperative patient-reported outcome measures (PROMs), characteristics of non-responders, and contact preferences to maximize response rates. METHODS: A prospective cohort study of patients planned to undergo hip arthroplasty (n = 713) and knee arthroplasty (n = 737) at a UK university teaching hospital who had completed preoperative PROMs questionnaires, including the EuroQol five-dimension health-related quality of life score, and Oxford Hip Score (OHS) and Oxford Knee Score (OKS). Follow-up questionnaires were sent by post at one year, including satisfaction scoring. Attempts were made to contact patients who did not initially respond. Univariate, logistic regression, and receiver operator curve analysis was performed. RESULTS: At one year, 667 hip patients (93.5%) and 685 knee patients (92.9%) had undergone surgery and were alive. No response was received from 151/667 hip patients (22.6%), 83 (55.0%) of whom were ultimately contacted); or from 108/685 knee patients (15.8%), 91 (84.3%) of whom were ultimately contacted. There was no difference in satisfaction after arthroplasty between initial non-responders and responders for hips (74/81 satisfied vs 476/516 satisfied; p = 0.847) or knees (81/93 satisfied vs 470/561 satisfied; p = 0.480). Initial non-response and persistent non-response was associated with younger age, higher BMIs, and worse preoperative PROMs for both hip and knee patients (p 66.4 years predicted a preference for contact by post (area under the curve 0.723 (95% confidence interval (CI) 0.647 to 0.799; p < 0.001, though this CI crosses the 0.7 limit considered reliable). CONCLUSION: The majority of initial non-responders were ultimately contactable with effort. Satisfaction rates were not inferior in patients who did not initially respond to PROMs. Cite this article: Bone Jt Open 2022;3(4):275–283

Dietary nitrate and diet quality: An examination of changing dietary intakes within a representative sample of Australian women

Dietary nitrate is increasingly linked to a variety of beneficial health outcomes. Our purpose was to estimate dietary nitrate consumption and identify key dietary changes which have occurred over time within a representative sample of Australian women. Women from the 1946–1951 cohort of the Australian Longitudinal Study on Women’s Health with complete food frequency questionnaire data for both 2001 and 2013 were included for analysis. Dietary nitrate intakes were calculated using key published nitrate databases. Diet quality scores including the Australian Recommended Food Score, the Mediterranean Diet Score and the Nutrient Rich Foods Index were calculated along with food group serves as per the Australian Dietary Guidelines. Wilcoxon matched pairs tests were used to test for change in dietary intakes and Spearman’s correlations were used to examine associations. In our sample of 8161 Australian women, dietary nitrate intakes were on average 65–70 mg/day, and we detected a significant increase in dietary nitrate consumption over time (+6.57 mg/day). Vegetables were the primary source of dietary nitrate (81–83%), in particular lettuce (26%), spinach (14–20%), beetroot (10–11%), and celery (7–8%) contributed primarily to vegetable nitrate intakes. Further, increased dietary nitrate intakes were associated with improved diet quality scores (r = 0.3, p \u3c 0.0001). Although there is emerging evidence indicating that higher habitual dietary nitrate intakes are associated with reduced morbidity and mortality, future work in this area should consider how dietary nitrate within the context of overall diet quality can facilitate health to ensure consistent public health messages are conveyed

A New Spontaneously Transformed Syngeneic Model of High-Grade Serous Ovarian Cancer with a Tumor-Initiating Cell Population

Improving screening and treatment options for patients with epithelial ovarian cancer has been a major challenge in cancer research. Development of novel diagnostic and therapeutic approaches, particularly for the most common subtype, high-grade serous ovarian cancer (HGSC), has been hampered by controversies over the origin of the disease and a lack of spontaneous HGSC models to resolve this controversy. Over long-term culture in our laboratory, an ovarian surface epithelial (OSE) cell line spontaneously transformed OSE (STOSE). The objective of this study was to determine if the STOSE cell line is a good model of HGSC. STOSE cells grow faster than early passage parental M0505 cells with a doubling time of 13 and 48 h, respectively. STOSE cells form colonies in soft agar, an activity for which M0505 cells have negligible capacity. Microarray analysis identified 1755 down-regulated genes and 1203 up-regulated genes in STOSE compared to M0505 cells, many associated with aberrant Wnt/β-catenin and Nf-κB signaling. Upregulation of Ccnd1 and loss of Cdkn2a in STOSE tumors is consistent with changes identified in human ovarian cancers by The Cancer Genome Atlas. Intraperitoneal injection of STOSE cells into severe combined immunodeficient and syngeneic FVB/N mice produced cytokeratin+, WT1+, inhibin−, and PAX8+ tumors, a histotype resembling human HGSC. Based on evidence that a SCA1+ stem cell-like population exists in M0505 cells, we examined a subpopulation of SCA1+ cells that is present in STOSE cells. Compared to SCA1− cells, SCA1+ STOSE cells have increased colony-forming capacity and form palpable tumors 8 days faster after intrabursal injection into FVB/N mice. This study has identified the STOSE cells as the first spontaneous murine model of HGSC and provides evidence for the OSE as a possible origin of HGSC. Furthermore, this model provides a novel opportunity to study how normal stem-like OSE cells may transform into tumor-initiating cells

RNA:DNA hybrids are a novel molecular pattern sensed by TLR9.

The sensing of nucleic acids by receptors of the innate immune system is a key component of antimicrobial immunity. RNA:DNA hybrids, as essential intracellular replication intermediates generated during infection, could therefore represent a class of previously uncharacterised pathogen-associated molecular patterns sensed by pattern recognition receptors. Here we establish that RNA:DNA hybrids containing viral-derived sequences efficiently induce pro-inflammatory cytokine and antiviral type I interferon production in dendritic cells. We demonstrate that MyD88-dependent signalling is essential for this cytokine response and identify TLR9 as a specific sensor of RNA:DNA hybrids. Hybrids therefore represent a novel molecular pattern sensed by the innate immune system and so could play an important role in host response to viruses and the pathogenesis of autoimmune disease

Lived Experience-Led Research Agenda to Address Early Death in People With a Diagnosis of a Serious Mental Illness: A Consensus Statement

Importance People with serious mental illness (SMI), defined as a diagnosis of schizophrenia spectrum disorder, bipolar disorder, or disabling major depressive disorder) die approximately 10 to 25 years earlier than the general population. Objective To develop the first-ever lived experience–led research agenda to address early mortality in people with SMI. Evidence Review A virtual 2-day roundtable comprising 40 individuals convened on May 24 and May 26, 2022, and used a virtual Delphi method to arrive at expert group consensus. Participants responded to 6 rounds of virtual Delphi discussion via email that prioritized research topics and agreement on recommendations. The roundtable was composed of individuals with lived experience of mental health and/or substance misuse, peer support specialists, recovery coaches, parents and caregivers of people with SMI, researchers and clinician-scientists with and without lived experience, policy makers, and patient-led organizations. Twenty-two of 28 (78.6%) of the authors who provided data represented people with lived experiences. Roundtable members were selected by reviewing the peer-reviewed and gray literature on early mortality and SMI, direct email, and snowball sampling. Findings The following recommendations are presented in order of priority as identified by the roundtable participants: (1) improve the empirical understanding of the direct and indirect social and biological contributions of trauma on morbidity and early mortality; (2) advance the role of family, extended families, and informal supporters; (3) recognize the importance of co-occurring disorders and early mortality; (4) redefine clinical education to reduce stigma and support clinicians through technological advancements to improve diagnostic accuracy; (5) examine outcomes meaningful to people with an SMI diagnosis, such as loneliness and sense of belonging, and stigma and their complex relationship with early mortality; (6) advance the science of pharmaceuticals, drug discovery, and choice in medication use; (7) use precision medicine to inform treatment; and (8) redefine the terms system literacy and health literacy. Conclusions and Relevance The recommendations of this roundtable are a starting point for changing practice and highlighting lived experience–led research priorities as an option to move the field forward.publishedVersio

Expression of Transient Receptor Potential Ankyrin 1 (TRPA1) and Its Role in Insulin Release from Rat Pancreatic Beta Cells

<div><h3>Objective</h3><p>Several transient receptor potential (TRP) channels are expressed in pancreatic beta cells and have been proposed to be involved in insulin secretion. However, the endogenous ligands for these channels are far from clear. Here, we demonstrate the expression of the transient receptor potential ankyrin 1 (TRPA1) ion channel in the pancreatic beta cells and its role in insulin release. TRPA1 is an attractive candidate for inducing insulin release because it is calcium permeable and is activated by molecules that are produced during oxidative glycolysis.</p> <h3>Methods</h3><p>Immunohistochemistry, RT-PCR, and Western blot techniques were used to determine the expression of TRPA1 channel. Ca²⁺ fluorescence imaging and electrophysiology (voltage- and current-clamp) techniques were used to study the channel properties. TRPA1-mediated insulin release was determined using ELISA.</p> <h3>Results</h3><p>TRPA1 is abundantly expressed in a rat pancreatic beta cell line and freshly isolated rat pancreatic beta cells, but not in pancreatic alpha cells. Activation of TRPA1 by allyl isothiocyanate (AITC), hydrogen peroxide (H₂O₂), 4-hydroxynonenal (4-HNE), and cyclopentenone prostaglandins (PGJ₂) and a novel agonist methylglyoxal (MG) induces membrane current, depolarization, and Ca²⁺ influx leading to generation of action potentials in a pancreatic beta cell line and primary cultured pancreatic beta cells. Activation of TRPA1 by agonists stimulates insulin release in pancreatic beta cells that can be inhibited by TRPA1 antagonists such as HC030031 or AP-18 and by RNA interference. TRPA1-mediated insulin release is also observed in conditions of voltage-gated Na⁺ and Ca²⁺ channel blockade as well as ATP sensitive potassium (K_ATP) channel activation.</p> <h3>Conclusions</h3><p>We propose that endogenous and exogenous ligands of TRPA1 cause Ca²⁺ influx and induce basal insulin release and that TRPA1-mediated depolarization acts synergistically with K_ATP channel blockade to facilitate insulin release.</p> </div