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ObjectivesHealth systems are increasingly accountable for patients and require accurate electronic health record (EHR) vital status. We recently demonstrated that 19% of seriously ill primary care patients in one system were not marked dead in the EHR and 80% of these decedents had an encounter or appointment outstanding after death. Herein we describe the mechanism of identifying decedents whose death is not captured at the level of the EHR, characterize these decedents, and describe medications refilled after death.Materials and methodsDescription of multistep process to identify deceased patients not marked dead in the EHR among a cohort of seriously ill primary care patients including public death file matching, utilization analysis, and chart abstraction. We compared decedents not marked dead in the EHR to known decedents and described pharmacy requests and refills.ResultsNearly 90% of encounters and appointments occurred because the health system EHR did not record the death although 11% of these encounters contained condolences or death notifications. Decedents not marked dead in the EHR were older and lived in more vulnerable areas than those marked dead. Of 146 refill requests after death, 88 medications were authorized.Discussion and conclusionMatching with a limited public death file is an inadequate solution to inaccurate vital status. Better workflows are needed to capture deaths about which clinicians and staff are aware, but will identify only a fraction of the decedents inaccurately listed as alive. Efforts are needed to connect EHRs with more specific sources of linkable decedent information.

BackgroundEnd-of-life (EOL) care patterns may differ by physician age given differences in how physicians are trained or changes associated with aging. We sought to compare patterns of EOL care delivered to older Americans according to physician age.MethodsWe conducted a cross-sectional study of a 20% sample of Medicare fee-for-service beneficiaries aged ≥66 years who died in 2016-2019 (n = 487,293). We attributed beneficiaries to the physician who had >50% of primary care visits during the last 6 months of life. We compared beneficiary-level outcomes by physician age (

PURPOSE COVID-19 is a condition that can lead to other chronic conditions. These conditions are frequently diagnosed in the primary care setting. We used a novel primary care registry to quantify the burden of post-COVID conditions among adult patients with a COVID-19 diagnosis across the United States. METHODS We used the American Family Cohort, a national primary care registry, to identify study patients. After propensity score matching, we assessed the prevalence of 17 condition categories individually and cumulatively, comparing patients having COVID-19 in 2020-2021 with (1) historical control patients having influenza-like illness in 2018 and (2) contemporaneous control patients seen for wellness or preventive visits in 2020- 2021. RESULTS We identified 28,215 patients with a COVID-19 diagnosis and 235,953 historical control patients with influenza-like illness. The COVID-19 group had higher prevalences of breathing difficulties (4.2% vs 1.9%), type 2 diabetes (12.0% vs 10.2%), fatigue (3.9% vs 2.2%), and sleep disturbances (3.5% vs 2.4%). There were no differences, however, in the postdiagnosis monthly trend in cumulative morbidity between the COVID-19 patients (trend = 0.026; 95% CI, 0.025-0.027) and the patients with influenza- like illness (trend = 0.026; 95% CI, 0.023-0.027). Relative to contemporaneous wellness control patients, COVID-19 patients had higher prevalences of breathing difficulties and type 2 diabetes. CONCLUSIONS Our findings show a moderate burden of post-COVID conditions in primary care, including breathing difficulties, fatigue, and sleep disturbances. Based on clinical registry data, the prevalence of post-COVID conditions in primary care practices is lower than that reported in subspecialty and hospital settings. Key words: long COVID; post-COVID conditions; post-infectious disorders; primary health care; family practice; chronic illness; morbidity https://doi.org/10.1370/afm.3131, INTRODUCTION The direct and immediate impact of COVID-19 on the health of the US population has been of generational significance, and the secondary wave of persistent symptoms and new conditions [...]

Bipedalism is unique among mammals. Until modern times, a fall and resulting leg fracture could be fatal. Balance maintenance after a destabilizing event requires instantaneous decision making. The vestibular system plays an essential role in this process, initiating an emergency response. The afferent otolithic neural response is the first directionally oriented information to reach the cortex, and it can then be used to initiate an appropriate protective response. Some vestibular efferent axons feed directly into type I vestibular hair cells. This allows for rapid vestibular feedback via the striated organelle (STO), which has been largely ignored in most texts. We propose that this structure is essential in emergency fall prevention, and also that the system of sensory detection and resultant motor response works by having efferent movement information simultaneously transmitted to the maculae with the movement commands. This results in the otolithic membrane positioning itself precisely for the planned movement, and any error is due to an unexpected external cause. Error is fed back via the vestibular afferent system. The efferent system causes macular otolithic membrane movement through the STO, which occurs simultaneously with the initiating motor command. As a result, no vestibular afferent activity occurs unless an error must be dealt with.

BackgroundPatients experiencing systemic patterns of disadvantage, such as racial/ethnic minorities and those with limited English proficiency, are underrepresented in research. This is particularly true for large pragmatic trials of potentially sensitive research topics, such as advance care planning (ACP). It is unclear how phone outreach may affect research participation by underrepresented individuals.ObjectiveTo assess the effect of phone outreach, in addition to standard mail survey recruitment, in a population-based ACP pragmatic trial at three academic health systems in California.DesignRetrospective cohort study PATIENTS: Primary care patients with serious illness were mailed a survey in their preferred language. Patients who did not initially respond by mail received up to three reminder phone calls with the option of survey completion by phone.Main measuresEffect of phone outreach on survey response rate associated with respondent demographic characteristics (e.g., Social Vulnerability Index [SVI], range 0 (low) to 1 (high)).ResultsAcross the health systems, 5998 seriously ill patients were mailed surveys. We obtained completed surveys from 1215 patients (20% response rate); 787 (65%) responded after mail alone and 428 (35%) participated only after phone outreach. Patients recruited after phone outreach compared to mail alone were more socially vulnerable (SVI 0.41 v 0.35, P < 0.001), were more likely to report being a racial/ethnic minority (35% v 28%, P = 0.006), and non-English speaking (16% v 10%, P = 0.005). Age and gender did not differ significantly. The inclusion of phone outreach resulted in a sample that better represented the baseline population than mail alone in racial/ethnic minority (28% mail alone, 30% including phone outreach, 36% baseline population), non-English language preference (10%, 12%, 15%, respectively), and SVI (0.35, 0.37, 0.38, respectively).ConclusionsPhone outreach for a population-based survey in a pragmatic trial concerning a potentially sensitive topic significantly enhanced recruitment of underrepresented seriously ill patients.

In 1943, Salvador Luria, then at Indiana University, and Max Delbrück, then at Vanderbilt, published an analysis of mutations in Escherichia coli conferring resistance to infection by bacterial viruses, also referred to as bacteriophages [1]. Of note, Luria and Delbrück advanced our understanding of mutation prior to the publication by Oswald Avery, Colin MacLeod, and Maclyn McCarty in 1944, demonstrating that the so-called transforming principle, which was able to dramatically alter the surface and functional phenotypes of pneumococci, was composed of DNA [2]. The Avery et al paper is the focus of the initial Historical Highlight [3].

In this interview, Jonathan Yewdell talks with Pathogens and Immunity senior editor Neil Greenspan about the evolution of viral immunology, highlighting his work and the contributions of other influential scientists. He emphasizes the importance of passion and collaboration in scientific research, illustrating the potential for groundbreaking discoveries through networking. He provides advice on navigating a scientific career, stressing the significance of strong mentorship. And he shares his perspective on transforming the scientific publishing industry and research education.

BackgroundFederally Qualified Health Centers (FQHCs) are an essential place for historically underserved patients to access health care, including screening for colorectal cancer (CRC), one of the leading causes of cancer death in the United States. Novel interventions aimed at increasing CRC screening completion rates at FQHCs are crucial. ObjectiveThis study conducts user testing of a digital patient navigation tool, called eNav, designed to support FQHC patients in preparing for, requesting, and completing CRC screening tests. MethodsWe recruited English- and Spanish-speaking patients (N=20) at an FQHC in New York City to user-test the eNav website (2 user tests; n=10 participants per user test). In each user test, participants engaged in a “think aloud” exercise and a qualitative interview to summarize and review their feedback. They also completed a baseline questionnaire gathering data about demographics, technology and internet use, medical history, and health literacy, and completed surveys to assess the website’s acceptability and usability. Based on participant feedback from the first user test, we modified the eNav website for a second round of testing. Then, feedback from the second user test was used to modify and finalize the eNav website. ResultsSurvey results supported the overall usability and acceptability of the website. The average System Usability Scale score for our first user test was 75.25; for the second, it was 75.28. The average Acceptability E-scale score for our first user test was 28.3; for the second, it was 29.2. These scores meet suggested benchmarks for usability and acceptability. During qualitative think-aloud exercises, in both user tests, many participants favorably perceived the website as motivating, interesting, informative, and user-friendly. Respondents also gave suggestions on how to improve the website’s content, usability, accessibility, and appeal. We found that some participants did not have the digital devices or internet access needed to interact with the eNav website at home. ConclusionsBased on participant feedback on the eNav website and reported limitations to digital access across both user tests, we made modifications to the content and design of the website. We also designed alternative methods of engagement with eNav to increase the tool’s usability, accessibility, and impact for patients with diverse needs, including those with limited access to devices or the internet at home. Next, we will test the eNav intervention in a randomized controlled trial to evaluate the efficacy of the eNav website for improving CRC screening uptake among patients treated at FQHCs.

Introduction Successful organ transplantation in patients with end-stage organ failure improves long-term survival, improves quality of life and reduces costs to the NHS. Despite an increase in the number of deceased organ donors over the last decade, there remains a considerable shortfall of suitable organs available for transplantation. Over half of UK donors are certified dead by neurological criteria following brain stem compression, which leads to severe physiological stress in the donor, combined with a hyperinflammatory state. Brain stem death-related dysfunction is an important reason for poor organ function and hence utilisation. For example, more than 30% of donation after brain stem death cardiac transplant recipients need short-term mechanical cardiac support, reflecting donor heart dysfunction.A small, randomised study previously showed improved outcomes for cardiac transplant recipients if the donor was given simvastatin. SIGNET takes inspiration from that study and hypothesises a potential reduction in damage to the heart and other organs during the period after diagnosis of death and prior to organ retrieval in donors that receive simvastatin.Methods and analysis SIGNET is a multicentre, single-blind, prospective, group sequential, randomised controlled trial to evaluate the benefits of a single high dose of simvastatin given to potential organ donors diagnosed dead by neurological criteria on outcomes in all organ recipients. The trial will run across a minimum of 89 UK sites with a recruitment target of 2600 donors over 4 years.Ethics and dissemination SIGNET received a favourable opinion from the London, Queen Square Research Ethics Committee (Ref: 21/LO/0412) and following approval of substantial amendment 1 in January 2023, the current protocol is version 2 (7 December 2022). Substantial amendment 1 clarified consent procedures and added additional sites and prescribers. Findings from the study will be publicly available and disseminated locally and internationally through manuscript publications in peer-reviewed journals and conference presentations at national and international platforms.Trial registration number ISRCTN11440354

Background: High-quality doctor-patient communication is essential for patients with serious illnesses. The reliability and validity of Consumer Assessment of Healthcare Providers and Systems (CAHPS®) communication items among these patients are unknown. Methods: Five CAHPS communication items, a 4-item Advance Care Planning (ACP) engagement scale, 5-item confidence in others' knowledge of ACP medical wishes scale, and a question about confidence in filling out ACP-related medical forms were administered to 1100 patients (20% response rate) with serious illness receiving primary care at three University of California Health Systems. Results: Average age was 69 (range 22-102); 52% male, 18% Hispanic, 9% Asian, and 7% Black; 24% had high school or less education. Eigenvalues and internal consistency reliability (0.88) supported a 5-item communication scale. Item characteristic curves showed a monotonic relationship of response options with the communication score. Item thresholds indicated that most patients reported positive patient experiences (i.e., items were negatively skewed). Item slopes ranging from 2.52 to 5.10 confirmed that all items were strongly related to the communication score. Information (reliability) of the communication scale was higher for assessing patients with negative experiences of care than for the positive end of the spectrum. Communication was positively correlated with confidence in other's knowledge of ACP medical wishes (r = 0.32, p

Abstract Polygenic variation unrelated to disease contributes to interindividual variation in baseline white blood cell (WBC) counts, but its clinical significance is uncharacterized. We investigated the clinical consequences of a genetic predisposition toward lower WBC counts among 89,559 biobank participants from tertiary care centers using a polygenic score for WBC count (PGSWBC) comprising single nucleotide polymorphisms not associated with disease. A predisposition to lower WBC counts was associated with a decreased risk of identifying pathology on a bone marrow biopsy performed for a low WBC count (odds-ratio = 0.55 per standard deviation increase in PGSWBC [95%CI, 0.30−0.94], p = 0.04), an increased risk of leukopenia (a low WBC count) when treated with a chemotherapeutic (n = 1724, hazard ratio [HR] = 0.78 [0.69−0.88], p = 4.0 × 10−5) or immunosuppressant (n = 354, HR = 0.61 [0.38–0.99], p = 0.04). A predisposition to benign lower WBC counts was associated with an increased risk of discontinuing azathioprine treatment (n = 1,466, HR = 0.62 [0.44−0.87], p = 0.006). Collectively, these findings suggest that there are genetically predisposed individuals who are susceptible to escalations or alterations in clinical care that may be harmful or of little benefit.

Abstract Background Historically, in-person physical therapy serves as a foundational component of nonoperative treatment of adhesive capsulitis (AC). This study compares the effectiveness of an at-home high-intensity stretch (HIS) device to traditional physical therapy (PT) and to PT in combination with the HIS device. We hypothesize that the HIS device will be as effective as PT alone or as combination therapy in the first-line treatment of AC and use of the HIS device will exhibit improvement at higher rate. Methods Thirty-four patients with idiopathic adhesive capsulitis and a minimum of 12 months follow-up were included in this study. Patients were randomized into one of the three groups: HIS device, PT alone, or HIS device + PT. Passive range of motion (ROM), American Shoulder and Elbow Surgeons (ASES), and Simple Shoulder Test (SST) scores were measured. Additionally, patient satisfaction, compliance and complications were recorded. Paired t-test, ANOVA and Chi-squared tests were used in analysis. Results Final ROM in all planes improved for all groups compared to baseline (p 95% of contralateral ROM in all planes at final follow-up. Patients with PT alone were on average slowest to improve ROM from baseline, at 3 months, 6 months, and 1 year in all planes except internal rotation. ASES and SST scores improved for all groups when compared to baseline (p

Abstract Ethical animal use follows the 3R’s: Replacement, Reduction and Refinement. Here, we present the use of simultaneous jugular vein and cisterna magna catheterization via a port system in rats for repeated fluid sampling for 14 consecutive days without loss of catheter patency. This technique allows repeated intra-animal sampling without anesthesia and, if used with pooling samples from a cohort of animals, replaces the need for terminal collections for sufficient sample volumes.

Background 5.4 million people in the UK have asthma, with one third experiencing suboptimal control, leading to co-morbidities and increased healthcare use. A quarter of people with long-term conditions informally access peer support through online health communities (OHCs). However, integrating online peer support into primary care services to facilitate self-management is a new concept.Objectives To develop together with stakeholders the content, delivery, and recruitment strategy of a digital social intervention to promote use of online peer support amongst asthma patients in primary care.Methods Data was collected by qualitative, audio-recorded, one-to-one interviews with clinicians, and focus groups with patients with asthma from East London general practices. The topic guide was informed by patient and public involvement work. Data collected was iterative (i.e. new ideas were added to subsequent interviews and focus groups). Verbatim transcripts were uploaded to NVivo12 and thematically analysed.Results Twenty patients from several ethnicities participated across five focus groups, and three general practitioners and three practice nurses were interviewed. The study’s outputs included: the intervention’s face-to-face content; content of clinician training; patient-facing leaflets/material; and a survey to recruit eligible patients. An intervention consisting of a structured consultation with a primary care clinician followed by OHC engagement, was developed based on three generated themes: ‘introducing OHCs’, describing how clinicians should introduce OHCs; ‘OHC engagement’, describing factors influencing OHC engagement; and ‘clinician training’.Conclusion Findings will assist clinicians in consultations about supporting self-management of patients through OHCs. Future research should evaluate feasibility, effectiveness, and cost-effectiveness of such support.

BackgroundThe end-of-life (EOL) experience in the intensive care unit (ICU) is emotionally challenging, and there are opportunities for improvement. The 3 Wishes Program (3WP) promotes the dignity of dying patients and their families by eliciting and implementing wishes at the EOL.AimTo assess whether the 3WP is associated with improved ratings of EOL care.Program descriptionIn the 3WP, clinicians elicit and fulfill simple wishes for dying patients and their families.Setting2-hospital academic healthcare system.ParticipantsDying patients in the ICU and their families.Program evaluationA modified Bereaved Family Survey (BFS), a validated tool for measuring EOL care quality, was completed by families of ICU decedents approximately 3 months after death. We compared patients whose care involved the 3WP to those who did not using three BFS-derived measures: Respectful Care and Communication (5 questions), Emotional and Spiritual Support (3 questions), and the BFS-Performance Measure (BFS-PM, a single-item global measure of care).ResultsOf 314 completed surveys, 117 were for patients whose care included the 3WP. Bereaved families of 3WP patients rated the Emotional and Spiritual Support factor significantly higher (7.5 vs. 6.0, p = 0.003, adjusted p = 0.001) than those who did not receive the 3WP. The Respectful Care and Communication factor and BFS-PM were no different between groups.DiscussionThe 3WP is a low-cost intervention that may be a feasible strategy for improving the EOL experience.

Summary: As therapies, oncolytic viruses regress tumors and have the potential to induce antitumor immune responses that clear hard-to-treat and late-stage cancers. Despite this promise, clearance from the blood prevents treatment of internal solid tumors. To address this issue, we developed virus-delivering Salmonella (VDS) to carry oncolytic viruses into cancer cells. The VDS strain contains the PsseJ-lysE delivery circuit and has deletions in four homologous recombination genes (ΔrecB, ΔsbcB, ΔsbcCD, and ΔrecF) to preserve essential hairpins in the viral genome required for replication and infectivity. VDS delivered the genome for minute virus of mice (MVMp) to multiple cancers, including breast, pancreatic, and osteosarcoma. Viral delivery produced functional viral particles that are cytotoxic and infective to neighboring cells. The release of mature virions initiated new rounds of infection and amplified the infection. Using Salmonella for delivery will circumvent the limitations of oncolytic viruses and will provide a new therapy for many cancers.

Background: The natural transmission cycle of tick-borne encephalitis (TBE) virus is enhanced by complex interactions between ticks and key hosts strongly connected to habitat characteristics. The diversity of wildlife host species and their relative abundance is known to affect transmission of tick-borne diseases. Therefore, in the current context of global biodiversity loss, we explored the relationship between habitat richness and the pattern of human TBE cases in Europe to assess biodiversity's role in disease risk mitigation. Methods: We assessed human TBE case distribution across 879 European regions using official epidemiological data reported to The European Surveillance System (TESSy) between 2017 and 2021 from 15 countries. We explored the relationship between TBE presence and the habitat richness index (HRI1) by means of binomial regression. We validated our findings at local scale using data collected between 2017 and 2021 in 227 municipalities located in Trento and Belluno provinces, two known TBE foci in northern Italy. Findings: Our results showed a significant parabolic effect of HRI on the probability of presence of human TBE cases in the European regions included in our dataset, and a significant, negative effect of HRI on the local presence of TBE in northern Italy. At both spatial scales, TBE risk decreases in areas with higher values of HRI. Interpretation: To our knowledge, no efforts have yet been made to explore the relationship between biodiversity and TBE risk, probably due to the scarcity of high-resolution, large-scale data about the abundance or density of critical host species. Hence, in this study we considered habitat richness as proxy for vertebrate host diversity. The results suggest that in highly diverse habitats TBE risk decreases. Hence, biodiversity loss could enhance TBE risk for both humans and wildlife. This association is relevant to support the hypothesis that the maintenance of highly diverse ecosystems mitigates disease risk.