What is a star worth to Medicare beneficiaries? A discrete choice experiment of hospital quality ratings.

Hospital quality ratings are widely available to help Medicare beneficiaries make an informed choice about where to receive care. However, how beneficiaries' trade-off between different quality domains (clinical outcomes, patient experience, safety, efficiency) and other considerations (out-of-pocket cost, travel distance) is not well understood. We sought to study how beneficiaries make trade-offs when choosing a hypothetical hospital. We administered an online survey that included a discrete choice experiment to a nationally representative sample of 1025 Medicare beneficiaries. On average, beneficiaries were willing to pay $1698 more for a hospital with a 1-star higher rating on clinical outcomes. This was over twice the value of the patient experience ($691) and safety ($615) domains and nearly 8 times the value of the efficiency domain ($218). We also found that the value of a 1-star improvement depends not only on the quality domain but also the baseline level of performance of the hospital. Generally, it is more valuable for low-performing hospitals to achieve average performance than for average hospitals to achieve excellence.

Comparative Evolutionary Genomics in Insects.

Genome sequencing quality, in terms of both read length and accuracy, is constantly improving. By combining long-read sequencing technologies with various scaffolding techniques, chromosome-level genome assemblies are now achievable at an affordable price for non-model organisms. Insects represent an exciting taxon for studying the genomic underpinnings of evolutionary innovations, due to ancient origins, immense species-richness, and broad phenotypic diversity. Here we summarize some of the most important methods for carrying out a comparative genomics study on insects. We describe available tools and offer concrete tips on all stages of such an endeavor from DNA extraction through genome sequencing, annotation, and several evolutionary analyses. Along the way we describe important insect-specific aspects, such as DNA extraction difficulties or gene families that are particularly difficult to annotate, and offer solutions. We describe results from several examples of comparative genomics analyses on insects to illustrate the fascinating questions that can now be addressed in this new age of genomics research.

Major changes in domain arrangements are associated with the evolution of termites.

Domains as functional protein units and their rearrangements along the phylogeny can shed light on the functional changes of proteomes associated with the evolution of complex traits like eusociality. This complex trait is associated with sterile soldiers and workers, and long-lived, highly fecund reproductives. Unlike in Hymenotpera (ants, bees, and wasps), the evolution of eusociality within Blattodea, where termites evolved from within cockroaches, was accompanied by a reduction in proteome size, raising the question of whether functional novelty was achieved with existing rather than novel proteins. To address this, we investigated the role of domain rearrangements during the evolution of termite eusociality. Analysing domain rearrangements in the proteomes of three solitary cockroaches and five eusocial termites, we inferred more than 5000 rearrangements over the phylogeny of Blattodea. The 90 novel domain arrangements that emerged at the origin of termites were enriched for several functions related to longevity, such as protein homeostasis, DNA repair, mitochondrial activity, and nutrient sensing. Many domain rearrangements were related to changes in developmental pathways, important for the emergence of novel castes. Along with the elaboration of social complexity, including permanently sterile workers and larger, foraging colonies, we found 110 further domain arrangements with functions related to protein glycosylation and ion transport. We found an enrichment of caste-biased expression and splicing within rearranged genes, highlighting their importance for the evolution of castes. Furthermore, we found increased levels of DNA methylation among rearranged compared to non-rearranged genes suggesting fundamental differences in their regulation. Our findings indicate an importance of domain rearrangements in the generation of functional novelty necessary for termite eusociality to evolve.

Can prediction models for hospital readmission be improved by incorporating patient-reported outcome measures? A systematic review and narrative synthesis.

PURPOSE: To investigate the roles, challenges, and implications of using patient-reported outcome measures (PROMs) in predicting the risk of hospital readmissions. METHODS: We systematically searched four bibliometric databases for peer-reviewed studies published in English between 1 January 2000 and 15 June 2023 and used validated PROMs to predict readmission risks for adult populations. Reported studies were analysed and narratively synthesised in accordance with the CHARMS and PRISMA guidelines. RESULTS: Of the 2858 abstracts reviewed, 23 studies met predefined eligibility criteria, representing diverse geographic regions and medical specialties. Among those, 19 identified the positive contributions of PROMs in predicting readmission risks. Seven studies utilised generic PROMs exclusively, eleven used generic and condition-specific PROMs, while 5 focussed solely on condition-specific PROMs. Logistic regression was the most used modelling approach, with 13 studies aiming at predicting 30-day all-cause readmission risks. The c-statistic, ranging from 0.54 to 0.84, was reported in 22/23 studies as a measure of model discrimination. Nine studies reported model calibration in addition to c-statistic. Thirteen studies detailed their approaches to dealing with missing data. CONCLUSION: Our study highlights the potential of PROMs to enhance predictive accuracy in readmission models, while acknowledging the diversity in data collection methods, readmission definitions, and model evaluation approaches. Recognizing that PROMs serve various purposes beyond readmission reduction, our study supports routine data collection and strategic integration of PROMs in healthcare practices to improve patient outcomes. To facilitate comparative analysis and broaden the use of PROMs in the prediction framework, it is imperative to consider the methodological aspects involved.

Impacts of fire and prospects for recovery in a tropical peat forest ecosystem.

Uncontrolled fires place considerable burdens on forest ecosystems, compromising our ability to meet conservation and restoration goals. A poor understanding of the impacts of fire on ecosystems and their biodiversity exacerbates this challenge, particularly in tropical regions where few studies have applied consistent analytical techniques to examine a broad range of ecological impacts over multiyear time frames. We compiled 16 y of data on ecosystem properties (17 variables) and biodiversity (21 variables) from a tropical peatland in Indonesia to assess fire impacts and infer the potential for recovery. Burned forest experienced altered structural and microclimatic conditions, resulting in a proliferation of nonforest vegetation and erosion of forest ecosystem properties and biodiversity. Compared to unburned forest, habitat structure, tree density, and canopy cover deteriorated by 58 to 98%, while declines in species diversity and abundance were most pronounced for trees, damselflies, and butterflies, particularly for forest specialist species. Tracking ecosystem property and biodiversity datasets over time revealed most to be sensitive to recurrent high-intensity fires within the wider landscape. These megafires immediately compromised water quality and tree reproductive phenology, crashing commercially valuable fish populations within 3 mo and driving a gradual decline in threatened vertebrates over 9 mo. Burned forest remained structurally compromised long after a burn event, but vegetation showed some signs of recovery over a 12-y period. Our findings demonstrate that, if left uncontrolled, fire may be a pervasive threat to the ecological functioning of tropical forests, underscoring the importance of fire prevention and long-term restoration efforts, as exemplified in Indonesia.

The Impact of reference pricing on prescribing patterns, costs, and health services utilization of proton pump inhibitors: A quasi-experimental study in British Columbia, Canada.

INTRODUCTION: The Reference Drug Program (RDP) was established to steer patients toward equally safe and cost-effective medication under British Columbia's public drug coverage. Each RDP class covers at least one reference drug, and non-reference drugs are reimbursed up to the cost of the reference drug. In 2016, the RDP updated to include proton pump inhibitors (PPIs). This study evaluated the impact on drug expenditures, prescription patterns, and health services utilization. METHODS: We identified a cohort of individuals covered by Fair Pharmacare who used PPIs, and a control group of H2 Blockers users. We used interrupted time series analysis on administrative data from June 2014 to December 2019 on the following outcomes: new users, day supply, expenditures, drug costs, reference drug use, and physician visits and costs. RESULTS: The RDP had little impact on overall PPI use patterns. We did not observe any changes in reference drug uptake, new users, physician visits, cost-savings, or significant changes to days supplied post-policy. Cost expenditure results were likely biased due to co-occurring changes to drug prices. CONCLUSION: Inclusion of PPIs to the RDP saw no cost-savings for the provincial drug program and had little impact on prescribing patterns. Overall, our findings are consistent with existing evidence that the RDP is safe for similar therapeutic alternatives, but the impact on PPI costs remains unclear.

A scoping review of triage approaches for the referral of patients with suspected inflammatory arthritis, from primary to rheumatology care.

We aimed to (1) identify existing triage approaches for referral of patients with suspected inflammatory arthritis (IA) from primary care physicians (PCP) to rheumatologists, (2) describe their characteristics and methodologies for clinical use, and (3) report their level of validation for use in a publicly funded healthcare system. The comprehensive search strategy of multiple databases up to October 2023 identified relevant literature and focussed on approaches applied at the PCP-Rheumatologist referral stage. Primary, quantitative studies, reported in English were included. Triage approaches were grouped into patient conditions as defined by the authors of the reports, including IA, its subtypes and combinations. 13952 records were identified, 425 full text reviewed and 55 reports of 53 unique studies were included. Heterogeneity in disease nomenclature and study sample pretest probability was found. The number of published studies rapidly increased after 2012. Studies were mostly from Europe and North America, in IA and Axial Spondyloarthritis (AxSpa). We found tools ranging the continuum of development with those best performing, indicated by the area under the receiver operating curve (AUC) >0.8), requiring only patient-reported questions. There were AUCs for some tools reported from multiple studies, these were in the outstanding to excellent range for the Early IA Questionnaire (EIAQ) (0.88 to 0.92), acceptable for the Case Finding AxSpa (CaFaSpa) (0.70 to 0.75), and poor to outstanding for the Psoriasis Epidemiology Screening Tool (PEST) (0.61 to 0.91). Given the clinical urgency to improve rheumatology referrals and considering the good.

3-Year Post-Transcatheter Aortic Valve Replacement (TAVR) Restenosis: A Rare Complication.

The pathophysiology of aortic valve stenosis is degenerative and calcific. It may be exacerbated by atherosclerotic processes characterized by lipid accumulation and inflammation. When the stenosis gets hemodynamically severe, the valves would need to be replaced. They could be replaced using mechanical or bioprosthetic heart valves. Balloon-expandable (BE) transcatheter heart valves (THVs) were compared to the self-expanding (SE) THVs and it was found that the rate of bioprosthetic valve failure was low over a five-year period. We present the case of a 70-year-old female who presented with worsening shortness of breath three years after transcatheter aortic valve replacement and was found to have early valve degeneration.

Cardiogenic Shock in a Patient With 4G/4G PAI Polymorphism and MTHFR A1298C Mutation.

Myocardial infarction (MI) remains a common cause of morbidity and mortality. Although many well-known risk factors exist, the association between inherited thrombophilia disorders and acute MI is not well described. Here, we present a case of a 75-year-old male with known 4G/4G PAI-1 polymorphism, methylenetetrahydrofolate reductase (MTHFR) mutation, and peripheral artery disease (PAD) post stent placement who presented with cardiogenic shock in the setting of acute MI with no prior significant cardiac history.

Effect of a Billing Code to Reimburse Nurse-Supported Rheumatology Care on Health Care Costs and Access: An Interrupted Time Series Analysis.

OBJECTIVE: This study was undertaken to evaluate the impact of a Multidisciplinary Care Assessment (MCA) billing code on health system costs and access to care in British Columbia (BC). METHODS: Data on all people treated by rheumatologists in BC were obtained from five linked health administrative databases held by Population Data BC from April 1, 2006, to March 31, 2020. Rheumatologists were allocated to either the intervention (ever-billers) or control groups (never-billers). For the intervention group, the index date was the month of the first MCA code billing. For the control group the index dates were imputed from intervention index dates. Our analysis focused on a 48-month period (24 months before and after the index date). We evaluated the impact on two cost (costs related to rheumatoid arthritis [RA]; total health care costs) and access outcomes (rheumatology-related visits per rheumatologist; days between rheumatology visits for patients with RA) using an interrupted time series analysis. RESULTS: A total of 46 rheumatologists (31 intervention and 15 control) met our inclusion criteria. Introduction of the MCA was associated with a small but significant increase in RA-related costs that, at 2 years, translates to a net absolute change of $9.66 per patient per month, but no statistically significant changes in total health care costs. There was no statistically significant change in the number of rheumatology-related visits, but at 2 years there was a net absolute reduction in the median days between rheumatologist visits for patients with RA (6.3 days). CONCLUSION: The introduction of the MCA code was associated with a negligible increase in the RA-related costs and an improvement in access to ongoing care for patients.

Disentangling specific and unspecific components of innate immune memory in a copepod-tapeworm system.

Evidence that the innate immune system can respond with forms of memory upon reinfection has been accumulating over the past few years. These phenomena of "immune priming" in invertebrates, and "trained immunity" in vertebrates, are contrary to previous belief that immune memory and specificity are restricted to the adaptive immune system. However, while trained immunity is usually a response with rather low specificity, immune priming has shown highly specific responses in certain species. To date, it is largely unknown how specificity in innate immune memory can be achieved in response to different parasite types. Here, we revisited a system where an exceptionally high degree of innate immune specificity had been demonstrated for the first time, consisting of the copepod Macrocyclops albidus and its natural parasite, the tapeworm Schistocephalus solidus. Using homologous (same family) vs. heterologous (different family) priming-challenge experiments, we first confirm that copepods exposed to the same parasite family benefit from reduced secondary infections. We further focused on exposed-but-not-infected copepods in primary exposure to employ a transcriptomic approach, distinguishing between immunity that was either specific or unspecific regarding the discrimination between tapeworm types. A weighted gene co-expression network (WGCN) revealed differences between specific and unspecific immunity; while both involved histone modification regulation, specific immunity involved gene-splicing factors, whereas unspecific immunity was primarily involved in metabolic shift. We found a functional enrichment in spliceosome in specific immunity, whereas oxidative phosphorylation and carbon metabolism were enriched in unspecific immunity. Our findings allow discrimination of specific and unspecific components of an innate immune memory, based on gene expression networks, and deepen our understanding of basic aspects of immune systems.

Reporting of determinants of health inequities and participant characteristics in randomized controlled trials of systemic lupus erythematosus in Canada: A scoping review.

OBJECTIVE: To report participant characteristics relevant to identifying health inequities in systemic lupus erythematosus (SLE) randomized controlled trials conducted in Canada. METHODS: We conducted a scoping review by searching MEDLINE (Ovid) and Embase (1990 to June 2023), and CENTRAL (inception to June 2023). Eligible studies: used an RCT design; evaluated interventions (pharmacologic and non-pharmacologic) among SLE patients aged ≥18 years; and were conducted in Canada. Data extraction was guided by the Campbell and Cochrane Equity Methods Group's PROGRESS-Plus framework on 11 factors leading to health inequities (Place of residence; Race, culture, ethnicity, and language; Occupation; Gender and sex; Religion; Education; Socioeconomic status; Social capital; Plus: Personal characteristics associated with discrimination; Features of relationships; and Time-dependent relationships). RESULTS: Of 1901 unique records, 6 met the inclusion criteria. Sex and age were the only PROGRESS factors that were reported in all studies. The majority of participants were female (84.4% to 100%), and mean ages of participants ranged from 42 to 52.3 years. Place of residence, race, education, and social capital were reported in three studies. Socioeconomic status was reported in two studies, and occupation was reported in one study. Religion, features of relationships, and time-dependent relationships were not reported in any included studies. CONCLUSION: Limited reporting of determinants of health inequities in RCTs for SLE in Canada suggests the need for reporting standards to support equity, diversity, and inclusion practices in research.

AI assisted reader evaluation in acute CT head interpretation (AI-REACT): protocol for a multireader multicase study.

INTRODUCTION: A non-contrast CT head scan (NCCTH) is the most common cross-sectional imaging investigation requested in the emergency department. Advances in computer vision have led to development of several artificial intelligence (AI) tools to detect abnormalities on NCCTH. These tools are intended to provide clinical decision support for clinicians, rather than stand-alone diagnostic devices. However, validation studies mostly compare AI performance against radiologists, and there is relative paucity of evidence on the impact of AI assistance on other healthcare staff who review NCCTH in their daily clinical practice. METHODS AND ANALYSIS: A retrospective data set of 150 NCCTH will be compiled, to include 60 control cases and 90 cases with intracranial haemorrhage, hypodensities suggestive of infarct, midline shift, mass effect or skull fracture. The intracranial haemorrhage cases will be subclassified into extradural, subdural, subarachnoid, intraparenchymal and intraventricular. 30 readers will be recruited across four National Health Service (NHS) trusts including 10 general radiologists, 15 emergency medicine clinicians and 5 CT radiographers of varying experience. Readers will interpret each scan first without, then with, the assistance of the qER EU 2.0 AI tool, with an intervening 2-week washout period. Using a panel of neuroradiologists as ground truth, the stand-alone performance of qER will be assessed, and its impact on the readers' performance will be analysed as change in accuracy (area under the curve), median review time per scan and self-reported diagnostic confidence. Subgroup analyses will be performed by reader professional group, reader seniority, pathological finding, and neuroradiologist-rated difficulty. ETHICS AND DISSEMINATION: The study has been approved by the UK Healthcare Research Authority (IRAS 310995, approved 13 December 2022). The use of anonymised retrospective NCCTH has been authorised by Oxford University Hospitals. The results will be presented at relevant conferences and published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT06018545.

Intermittent cytomegalovirus infection alters neurobiological metabolism and induces cognitive deficits in mice.

Risk factors contributing to dementia are multifactorial. Accumulating evidence suggests a role for pathogens as risk factors, but data is largely correlative with few causal relationships. Here, we demonstrate that intermittent murine cytomegalovirus (MCMV) infection of mice, alters blood brain barrier (BBB) permeability and metabolic pathways. Increased basal mitochondrial function is observed in brain microvessels cells (BMV) exposed to intermittent MCMV infection and is accompanied by elevated levels of superoxide. Further, mice score lower in cognitive assays compared to age-matched controls who were never administered MCMV. Our data show that repeated systemic infection with MCMV, increases markers of neuroinflammation, alters mitochondrial function, increases markers of oxidative stress and impacts cognition. Together, this suggests that viral burden may be a risk factor for dementia. These observations provide possible mechanistic insights through which pathogens may contribute to the progression or exacerbation of dementia.

Understanding general practitioners' prescribing choices to patients with chronic low back pain: a discrete choice experiment.

BACKGROUND: Although NSAIDs are recommended as a first line analgesic treatment, opioids are very commonly prescribed to patients with low back pain (LBP) despite risks of harms. AIM: This study aimed to determine factors contributing to general practitioners' (GPs') prescribing choices to patients with chronic LBP in a primary care setting. METHOD: This discrete choice experiment (DCE) presented 210 GPs with hypothetical scenarios of a patient with chronic LBP. Participants chose their preferred treatment for each choice set, either the opioid, NSAID or neither. The scenarios varied by two patient attributes; non-specific LBP or LBP with referred leg pain (sciatica) and number of comorbidities. The three treatment attributes also varied, being: the type of opioid or NSAID, degree of pain reduction and number of adverse events. The significance of each attribute in influencing clinical decisions was the primary outcome and the degree to which GPs preferred the alternative based on the number of adverse events or the amount of pain reduction was the secondary outcome. RESULTS: Overall, GPs preferred NSAIDs (45.2%, 95% CI 38.7-51.7%) over opioids (28.8%, 95% CI 23.0-34.7%), however there was no difference between the type of NSAID or opioid preferred. Additionally, the attributes of pain reduction and adverse events did not influence a GP's choice between NSAIDs or opioids for patients with chronic LBP. CONCLUSION: GPs prefer prescribing NSAIDs over opioids for a patient with chronic low back pain regardless of patient factors of comorbidities or the presence of leg pain (i.e. sciatica).

Genomic signatures of eusocial evolution in insects.

The genomes of eusocial insects allow the production and regulation of highly distinct phenotypes, largely independent of genotype. Although rare, eusociality has evolved convergently in at least three insect orders (Hymenoptera, Blattodea and Coleoptera). Despite such disparate origins, eusocial phenotypes show remarkable similarity, exhibiting long-lived reproductives and short-lived sterile workers and soldiers. In this article, we review current knowledge on genomic signatures of eusocial evolution. We confirm that especially an increased regulatory complexity and the adaptive evolution of chemical communication are common to several origins of eusociality. Furthermore, colony life itself can shape genomes of divergent taxa in a similar manner. Future research should be geared towards generating more high-quality genomic resources, especially in hitherto understudied clades, such as ambrosia beetles and termites. The application of more sophisticated tools such as machine learning techniques may allow the detection of more subtle convergent genomic footprints of eusociality.

The Association of Rheumatologist Supply and Multidisciplinary Care With Timely Patient Access to Rheumatologists: Evidence From British Columbia, Canada.

OBJECTIVE: The objective was to understand how the expansion of rheumatology supply and the introduction of multidisciplinary care was associated with access to rheumatology services. METHODS: We accessed Population Data BC, a longitudinal database with de-identified individual-level health data on all residents of British Columbia, Canada, to analyze physician visits and prescribing from 2010-2011 to 2019-2020. We calculated access as the time from referral to first rheumatologist visit and, for people with rheumatoid arthritis (RA), time to first disease-modifying antirheumatic drug (DMARD). Associations between lag time, patient characteristics, and system variables were explored using quantile regression. RESULTS: Over the study period, there were 149,902 new rheumatologist visits, with 31% more visits in 2019-2020 than in 2010-2011. The proportion of first visits for patients with inflammatory arthritis increased from 28% to 51%. The median time from referral to first visit decreased by 22 days (35%) from 63 days (interquartile range 21-120 days) in 2010-2011. For people with RA, time from referral to DMARD decreased by 4 days (6%) to 62 days. Male sex, living in metropolitan areas, and having a rheumatologist who used a multidisciplinary care assessment code were associated with shorter times from referral to first DMARD. CONCLUSION: Access to rheumatology care improved, and the increased proportion of patients with IA in the first visits case-mix indicates that rheumatologist supply and incentives for multidisciplinary care may have improved referral patterns. However, time to DMARDs for people with RA remained long, and we found signals of unequal access for female patients and people living outside of metropolitan areas.

Reporting of determinants of health inequities and participant characteristics in randomized controlled trials of juvenile idiopathic arthritis in Canada: a scoping review.

BACKGROUND: Juvenile Idiopathic Arthritis (JIA) is the most common form of childhood inflammatory arthritis. The disease burden of JIA is substantial as patients require specialized medical practitioners for diagnosis and chronic treatments that are both costly and time intensive. Discrepancies in access to care due to health inequities such as socioeconomic status or geographic location may lead to vastly different health outcomes. As research informs advances in care, is important to consider inclusion and diversity in JIA research. METHODS: We reviewed and synthesized randomized controlled trials for juvenile idiopathic arthritis, the most common type of arthritis among children and adolescents, in Canada with the aim of characterizing participants and identifying how determinants of health inequities are reported. To do so, we searched Medline (1990 to July 2022), Embase (1990 to July 2022), and CENTRAL (inception to July 2022) for articles meeting all of the following criteria: Canadian randomized controlled trials evaluating pharmacological or non-pharmacological interventions on juvenile idiopathic arthritis populations. Data extraction was guided by the Campbell and Cochrane Equity Methods Group's PROGRESS-Plus framework on determinants that lead to health inequities (e.g., Place of residence; Race; Occupation; Gender/Sex; Religion; Education; Socioeconomic status; and Social capital). RESULTS: Of 4,074 unique records, 5 were deemed eligible for inclusion. From these determinants of health inequities, Gender/Sex and Age were the only that were reported in all studies with most participants being female and 12.6 years old on average. In addition, Race, Socioeconomic status, Education and Features of relationships were each reported once in three different studies. Lastly, Place of residence, Occupation, Religion, Social Capital and Time-dependent relationships were not reported at all. CONCLUSIONS: This scoping review suggests limited reporting on determinants of health inequities in randomized controlled trials for JIA in Canada and a need for a reporting framework that reflects typical characteristics of juvenile patient populations.

Live-bearing cockroach genome reveals convergent evolutionary mechanisms linked to viviparity in insects and beyond.

Live birth (viviparity) has arisen repeatedly and independently among animals. We sequenced the genome and transcriptome of the viviparous Pacific beetle-mimic cockroach and performed comparative analyses with two other viviparous insect lineages, tsetse flies and aphids, to unravel the basis underlying the transition to viviparity in insects. We identified pathways undergoing adaptive evolution for insects, involved in urogenital remodeling, tracheal system, heart development, and nutrient metabolism. Transcriptomic analysis of cockroach and tsetse flies revealed that uterine remodeling and nutrient production are increased and the immune response is altered during pregnancy, facilitating structural and physiological changes to accommodate and nourish the progeny. These patterns of convergent evolution of viviparity among insects, together with similar adaptive mechanisms identified among vertebrates, highlight that the transition to viviparity requires changes in urogenital remodeling, enhanced tracheal and heart development (corresponding to angiogenesis in vertebrates), altered nutrient metabolism, and shifted immunity in animal systems.