Prognoses Associated With Palliative Performance Scale Scores in Modern Palliative Care Practice.

Importance: The Palliative Performance Scale (PPS) is one of the most widely used prognostic tools for patients with serious illness. However, current prognostic estimates associated with PPS scores are based on data that are over a decade old. Objective: To generate updated prognostic estimates by PPS score, care setting, and illness category, and examine how well PPS predicts short- and longer-term survival. Design, Setting, and Participants: This prognostic study was conducted at a large academic medical center with robust inpatient and outpatient palliative care practices using electronic health record data linked with data from California Vital Records. Eligible participants included patients who received a palliative care consultation between January 1, 2018, and December 31, 2020. Data analysis was conducted from November 2022 to February 2024. Exposure: Palliative care consultation with a PPS score documented. Main Outcomes and Measures: The primary outcomes were predicted 1-, 6-, and 12-month mortality and median survival of patients by PPS score in the inpatient and outpatient settings, and performance of the PPS across a range of survival times. In subgroup analyses, mortality risk by PPS score was estimated in patients with cancer vs noncancer illnesses and those seen in-person vs by video telemedicine in the outpatient setting. Results: Overall, 4779 patients (mean [SD] age, 63.5 [14.8] years; 2437 female [51.0%] and 2342 male [49.0%]) had a palliative care consultation with a PPS score documented. Of these patients, 2276 were seen in the inpatient setting and 3080 were seen in the outpatient setting. In both the inpatient and outpatient settings, 1-, 6-, and 12-month mortality were higher and median survival was shorter for patients with lower PPS scores. Prognostic estimates associated with PPS scores were substantially longer (2.3- to 11.7-fold) than previous estimates commonly used by clinicians. The PPS had good ability to discriminate between patients who lived and those who died in the inpatient setting (integrated time-dependent area under the curve [iAUC], 0.74) but its discriminative ability was lower in the outpatient setting (iAUC, 0.67). The PPS better predicted 1-month survival than longer-term survival. Mortality rates were higher for patients with cancer than other serious illnesses at most PPS levels. Conclusions and Relevance: In this prognostic study, prognostic estimates associated with PPS scores were substantially longer than previous estimates commonly used by clinicians. Based on these findings, an online calculator was updated to assist clinicians in reaching prognostic estimates that are more consistent with modern palliative care practice and specific to the patient's setting and diagnosis group.

Comparative transcriptomics provides insight into molecular mechanisms of zinc tolerance in the ectomycorrhizal fungus Suillus luteus.

Zinc (Zn) is a major soil contaminant and high Zn levels can disrupt growth, survival, and reproduction of fungi. Some fungal species evolved Zn tolerance through cell processes mitigating Zn toxicity, though the genes and detailed mechanisms underlying mycorrhizal fungal Zn tolerance remain unexplored. To fill this gap in knowledge, we investigated the gene expression of Zn tolerance in the ectomycorrhizal fungus Suillus luteus. We found that Zn tolerance in this species is mainly a constitutive trait that can also be environmentally dependent. Zinc tolerance in S. luteus is associated with differences in expression of genes involved in metal exclusion and immobilization, as well as recognition and mitigation of metal-induced oxidative stress. Differentially expressed genes were predicted to be involved in transmembrane transport, metal chelation, oxidoreductase activity, and signal transduction. Some of these genes were previously reported as candidates for S. luteus Zn tolerance, while others are reported here for the first time. Our results contribute to understanding the mechanisms of fungal metal tolerance and pave the way for further research on the role of fungal metal tolerance in mycorrhizal associations.

Enhancing point-of-care ultrasound (POCUS) utilization in primary care: A thyroid POCUS training course for internal medicine residents.

BACKGROUND: POCUS is valuable in primary care, yet outpatient-specific point-of-care ultrasound (POCUS) curriculum integration into internal medicine (IM) residency is limited. We addressed this gap by developing a thyroid POCUS workshop for IM residents. AIM: Develop and implement an educational curriculum to integrate thyroid POCUS into an IM residency program and evaluate the impact on resident knowledge, perceived skills, and attitudes. SETTING: The study was conducted in a resident primary care clinic at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Residency Program in Internal Medicine at North Shore University Hospital and Long Island Jewish Medical Center. PARTICIPANTS: All 108 IM residents (PGY1-3) in one program participated in the study during their ambulatory clinic block. PROGRAM DESCRIPTION: Residents participated in a 1-hour workshop involving a didactic session and two breakout groups: one for hands-on practice and another for case-based discussions with image review. PROGRAM EVALUATION: Residents completed pre- and post-session surveys assessing knowledge, perceived skills, and attitudes toward thyroid POCUS. These data showed statistically significant increases in all assessed areas. DISCUSSION: Integrating thyroid POCUS into an IM residency curriculum significantly improved resident knowledge, attitudes, and perceived skills related to these exams. Residents valued this learning experience and expressed intentions to incorporate it into their future practice.

World Psychiatric Association-Asian Journal of Psychiatry Commission on Public Mental Health.

Although there is considerable evidence showing that the prevention of mental illnesses and adverse outcomes and mental health promotion can help people lead better and more functional lives, public mental health remains overlooked in the broader contexts of psychiatry and public health. Likewise, in undergraduate and postgraduate medical curricula, prevention and mental health promotion have often been ignored. However, there has been a recent increase in interest in public mental health, including an emphasis on the prevention of psychiatric disorders and improving individual and community wellbeing to support life trajectories, from childhood through to adulthood and into older age. These lifespan approaches have significant potential to reduce the onset of mental illnesses and the related burdens for the individual and communities, as well as mitigating social, economic, and political costs. Informed by principles of social justice and respect for human rights, this may be especially important for addressing salient problems in communities with distinct vulnerabilities, where prominent disadvantages and barriers for care delivery exist. Therefore, this Commission aims to address these topics, providing a narrative overview of relevant literature and suggesting ways forward. Additionally, proposals for improving mental health and preventing mental illnesses and adverse outcomes are presented, particularly amongst at-risk populations.

Exploring the scope and applications of anti-doping measures in ultramarathon: an analysis of the positions of ultramarathon race organizers.

Introduction: With ultramarathon attracting burgeoning interest, evidence has emerged about doping behaviors. However, currently, research into the anti-doping policy landscape and the adoption of testing and athlete surveillance is limited, including the applicability of rubric from the World Anti-Doping Agency (WADA) and National Anti-Doping Organizations (NADOs). Consequently, it remains unclear if anti-doping provisions have been developed and enforced in ultramarathon, which is a timely consideration given growth in the sport. Methods: This study gathered perspectives on anti-doping and testing procedures from ultramarathon race organizers (UMROs). To that end, a sample of n = 35 prominent competitions was compiled using web materials and community engagement, encompassing elite and amateur entrants, diverse course designs, and prize money opportunities. Data-gathering was conducted across two phases between November and December 2023, with an initial review of UMRO web resources. Subsequently, UMROs were contacted via email to validate or ascertain their anti-doping and testing policies. Insights from UMRO respondents were reviewed and coded. UMROs who did not reply were excluded from the analysis. Results: Based on this methodology, the positions of n = 17 UMROs were captured, covering 159 ultramarathon races and approximately 96,500 annual participants. Of these, n = 8 UMROs did not have a self-developed policy and their rubric was pursuant to external authorities like WADA and NADOs. n = 4 had created a specific proprietary policy, which often incorporated WADO or NADO materials. The remaining n = 5 UMROs reported no anti-doping controls were in place at the time of the study. There was also notable heterogeneity in testing and surveillance, ranging from rigorous procedures to an absence of protocols. Interestingly, none of the included UMROs explicitly reported that they had enacted anti-doping measures against athletes. Discussion: Various determinants could inform these regulatory inconsistencies across UMROs, such as financial constraints, infrastructural and logistical barriers, cultural factors, and the lack of a unifying international federation in ultramarathon. Given the disparate approaches identified in our results, greater cooperation and education may be necessary to enhance understanding about the implications of doping and advance cohesive frameworks. This should involve collaborations with WADA and NADOs to promote best-practices and evidence-based exchanges within the community.

Associations of genetically predicted vitamin D status and deficiency with the risk of carotid artery plaque: a Mendelian randomization study.

Low concentrations of circulating 25-hydroxy-vitamin D are observationally associated with an increased risk of subclinical atherosclerosis and cardiovascular disease. However, randomized controlled trials have not reported the beneficial effects of vitamin D supplementation on atherosclerotic cardiovascular disease (ASCVD) outcomes. Whether genetically predicted vitamin D status confers protection against the development of carotid artery plaque, a powerful predictor of subclinical atherosclerosis, remains unknown. We conducted a two-sample Mendelian randomization (MR) study to explore the association of genetically predicted vitamin D status and deficiency with the risk of developing carotid artery plaque. We leveraged three genome-wide association studies (GWAS) of vitamin D status and one GWAS of vitamin D deficiency. We used the inverse-variance weighted (IVW) approach as our main method, and MR-Egger, weighted-median, and radialMR as MR sensitivity analyses. We also conducted sensitivity analyses using biologically plausible genetic instruments located within genes encoding for vitamin D metabolism (GC, CYP2R1, DHCR7, CYP24A1). We did not find significant associations between genetically predicted vitamin D status (Odds ratio (OR) = 0.99, P = 0.91) and deficiency (OR = 1.00, P = 0.97) with the risk of carotid artery plaque. We additionally explored the potential causal effect of vitamin D status on coronary artery calcification (CAC) and carotid intima-media thickness (cIMT), two additional markers of subclinical atherosclerosis, and we did not find any significant association (ßCAC = - 0.14, P = 0.23; ßcIMT = 0.005, P = 0.19). These findings did not support the causal effects of vitamin D status and deficiency on the risk of developing subclinical atherosclerosis.

Psychosocial distress among spouses of persons with dementia before and after their partner's death.

BACKGROUND: Spouses of persons living with dementia may face heightened psychosocial distress in the years immediately before and after their partner's death. We compared the psychosocial needs of spouses of partners with dementia with spouses of partners with non-impaired cognition nearing and after the end of life, focusing on loneliness, depression, life satisfaction, and social isolation. METHODS: We used nationally representative Health and Retirement Study married couples data (2006-2018), restricting to spouses 50+ years old. We included 2098 spouses with data on loneliness and depressive symptoms 2 years before and after the partner's death. We additionally examined a subset of spouses (N = 1113) with available data on life satisfaction and social isolation 2 years before their partner's death. Cognitive status of partners was classified as non-impaired cognition, cognitive impairment not dementia (cognitive impairment), and dementia. We used multivariable logistic regression to determine: 1) the change in loneliness and depression for spouses pre- and post-partner's death, and 2) life satisfaction and social isolation 2 years before the partner's death. RESULTS: Spouses were on average 73 years old (SD: 10), 66% women, 7% Black, 7% Hispanic non-White, 24% married to persons with cognitive impairment, and 19% married to partners with dementia. Before their partner's death, spouses married to partners with dementia experienced more loneliness (non-impaired cognition: 8%, cognitive impairment: 16%, dementia: 21%, p-value = 0.002) and depressive symptoms (non-impaired cognition: 20%, cognitive impairment: 27%, dementia: 31%, p-value < 0.001), and after death a similar prevalence of loneliness and depression across cognitive status. Before their partner's death, spouses of partners with dementia reported less life satisfaction (non-impaired cognition: 74%, cognitive impairment: 68%; dementia: 64%, p-value = 0.02) but were not more socially isolated. CONCLUSION: Results emphasize a need for clinical and policy approaches to expand support for the psychosocial needs of spouses of partners with dementia in the years before their partner's death rather than only bereavement.

A master regulator of opioid reward in the ventral prefrontal cortex.

In addition to their intrinsic rewarding properties, opioids can also evoke aversive reactions that protect against misuse. Cellular mechanisms that govern the interplay between opioid reward and aversion are poorly understood. We used whole-brain activity mapping in mice to show that neurons in the dorsal peduncular nucleus (DPn) are highly responsive to the opioid oxycodone. Connectomic profiling revealed that DPn neurons innervate the parabrachial nucleus (PBn). Spatial and single-nuclei transcriptomics resolved a population of PBn-projecting pyramidal neurons in the DPn that express µ-opioid receptors (µORs). Disrupting µOR signaling in the DPn switched oxycodone from rewarding to aversive and exacerbated the severity of opioid withdrawal. These findings identify the DPn as a key substrate for the abuse liability of opioids.

Postoperative Hypotension After Cardiac Surgery Is Associated With Acute Kidney Injury.

OBJECTIVES: To describe the incidence of postoperative hypotension in patients undergoing cardiac surgery during the first 12 hours in the intensive care unit (ICU) and any relationship between hypotension and the development of acute kidney injury (AKI). DESIGN: This was a retrospective, observational cohort study. SETTING: The study took place in a single-center tertiary teaching hospital in London, UK. PARTICIPANTS: Adult patients (n = 100) who underwent elective cardiac surgery requiring intraoperative cardiopulmonary bypass between May and November 2021 were enrolled. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A hypotensive event was defined as mean arterial pressure <65 mmHg lasting at least 1 minute. Invasive blood pressure data was analyzed for the first 12 hours after surgery, and any association between postoperative hypotension and AKI was assessed. A total of 91% of patients experienced hypotension in the first 12 hours postprocedure. On average, patients experienced 9 hypotensive events, with events lasting an average of 5 minutes. A total of 16 patients (16%) developed at least stage 1 AKI. The average duration of hypotension was significantly higher in the AKI group (4.6 min [IQR 3.3, 8.0] v 8.1 min [IQR 5.2, 14.2], p = 0.029). Those suffering AKI had longer ICU and hospital stays. CONCLUSIONS: This study demonstrated that hypotension in the first 12 hours following cardiac surgery is common and prolonged hypotensive events are associated with developing AKI. This emphasizes the importance of treating hypotension aggressively and highlights a target for further research and intervention.

Mental health and the ballot box: A correlational analysis of Google searches for mental health and national election periods in the United States and the United Kingdom from 2008 to 2020.

BACKGROUND: In electoral contexts, mental health topics have recently attracted sociopolitical relevance, influenced by policy developments, election-related psychopathology and popular discourse about individual candidates. Yet, whether this reflects generalised trends or is contingent on election-specific and contextual factors remains difficult to ascertain. AIMS: This study sought to examine correlations between Google Trends (GT) data on mental health and four national elections in the US and the UK from 2008 to 2020. This was intended to yield preliminary insights into the relevance of mental health topics amongst voters and the potential impact of electoral cycles on patterns of online engagement with these issues. METHODS: Monthly and daily Search Volume Indexes (SVI) were gathered from the 'Mental Health' category on GT in the US and UK from 2008 to 2023. SVI were evaluated around the past four national ballots, comparing election-year intervals and baseline data from the preceding year. Statistical tests were conducted to assess SVI and short- and long-term dynamics. FINDINGS: The results showed heterogeneous SVI patterns related to mental health during elections in the US and the UK. In the US, there were statistically significant SVI increases proximal to the majority of elections as compared to data in the same calendar year, but these did not typically exceed baseline SVI. However, interestingly, divisive US contests showed correlations with several elevated SVI measures in the same and previous years. Conversely, there was a lack of consistent longitudinal trends in UK elections, perhaps informed by its disparate sociopolitical landscape. CONCLUSIONS: These findings underline the composite relationship between electoral politics and popular engagement with mental health topics around national votes, suggesting that this is driven more by situational factors rather than a recurrent electoral effect or signs of burgeoning engagement. Detailed research is required to understand the nuances and causality behind these dynamics and their wider implications.

Phase 1/2 AAV5-hRKp.RPGR (Botaretigene Sparoparvovec) Gene Therapy: Safety and Efficacy in RPGR-associated X-linked Retinitis Pigmentosa.

PURPOSE: To assess the safety and efficacy of AAV5-hRKp.RPGR in participants with retinitis pigmentosa GTPase regulator (RPGR)-associated X-linked retinitis pigmentosa (XLRP). DESIGN: Open-label, phase 1/2 dose escalation/expansion study (NCT03252847). METHODS: Males (≥5 years old) with XLRP-RPGR were evaluated. In the dose escalation phase, subretinal AAV5-hRKp.RPGR (low: 1.0×1011 vg/ml; intermediate: 2.0×1011 vg/ml; high: 4.0×1011 vg/ml) was administered to the poorer-seeing eye (n = 10). Dose confirmation (intermediate dose) was carried out in 3 pediatric participants. In the dose expansion phase, 36 participants were randomized 1:1:1 to immediate (low or intermediate dose) or deferred (control) treatment. The primary outcome was safety. Secondary efficacy outcomes included static perimetry, microperimetry, vision-guided mobility, best corrected visual acuity, and contrast sensitivity. Safety and efficacy outcomes were assessed for 52 weeks for immediate treatment participants and 26 weeks for control participants. RESULTS: AAV5-hRKp.RPGR was safe and well tolerated, with no reported dose-limiting events. Most adverse events (AEs) were transient and related to the surgical procedure, resolving without intervention. Two serious AEs were reported with immediate treatment (retinal detachment, uveitis). A third serious AE (increased intraocular pressure) was reported outside the reporting period. All ocular inflammation-related AEs responded to corticosteroids. Treatment with AAV5-hRKp.RPGR resulted in improvements in retinal sensitivity and functional vision compared with the deferred group at Week 26; similar trends were observed at Week 52. CONCLUSIONS: AAV5-hRKp.RPGR demonstrated an anticipated and manageable AE profile through 52 weeks. Safety and efficacy findings support investigation in a phase 3 trial.

Resilience, Survival and Functional Independence in Older Adults Facing Critical Illness.

BACKGROUND: Older adults surviving critical illness often experience new or worsening functional impairments. Modifiable positive psychological constructs, like resilience, may mitigate post-intensive care morbidity. RESEARCH QUESTION: Is pre-ICU resilience associated with: (1) post-ICU survival; (2) the drop in post-ICU functional independence; and (3) a lesser decline of independence before versus after the ICU? STUDY DESIGN AND METHODS: We performed a retrospective cohort study using Medicare-linked Health and Retirement Study surveys from 2006-2018. We included Older adults ≥65 years admitted to an ICU. We calculated resilience before ICU admission. The resilience measure was defined from the Simplified Resilience Score which was previously adapted and validated for the Health and Retirement Study. Resilience was scored using the leave-behind survey normalized to 0 (lowest resilience) to 12 (highest resilience) point scale. Outcomes were survival and probability of functional independence. We modeled survival using Gompertz models and independence using joint survival models adjusting for sociodemographic and clinical variables. We estimated average marginal effects to determine independence probabilities. RESULTS: Across 3,409 patients ≥65 years old admitted to ICUs, pre-existing frailty (30.5%) and cognitive impairment (24.3%) were common. Most patients were previously independent (82.7%). Mechanical ventilation occurred in 14.8% and sepsis in 43.2%. Highest versus lowest resilience had lower risk of post-ICU mortality (aHR 0.81 95% CI [0.70, 0.94]). Higher resilience was associated with greater likelihood in post-ICU independence (estimated probability of independence 5 years post-ICU in highest-to-lowest resilience: 0.53 CI 95% [0.33, 0.74], 0.47 [0.26, 0.68], 0.49 [0.28, 0.70], 0.36 [0.17, 0.55] p<0.01). Resilience was not associated with a difference in the drop of independence across resilience groups, nor a difference in declines of independence post-ICU. INTERPRETATION: ICU survivors with higher resilience had increased rates of survival and functional independence, though the slope of functional decline did not differ by resilience group pre- to post-ICU.

A Systematic Review to Summarise and Appraise the Reporting of Surgical Innovation: a Case Study in Robotic Roux-en-Y Gastric Bypass.

Robotic Roux-en-Y gastric bypass (RRYGB) is an innovative alternative to traditional laparoscopic approaches. Literature has been published investigating its safety/efficacy; however, the quality of reporting is uncertain. This systematic review used the Idea, Development, Exploration, Assessment and Long-term follow-up (IDEAL) framework to assess the reporting quality of available literature. A narrative summary was formulated, assessing how comprehensively governance/ethics, patient selection, demographics, surgeon expertise/training, technique description and outcomes were reported. Forty-seven studies published between 2005 and 2024 were included. There was incomplete/inconsistent reporting of governance/ethics, patient selection, surgeon expertise/training and technique description, with heterogenous outcome reporting. RRYGB reporting was poor and did not align with IDEAL guidance. Robust prospective studies reporting findings using IDEAL/other guidance are required to facilitate safe widespread adoption of RRYGB and other surgical innovations.

Lost diagnoses? A multi-year trajectory of patients with childhood ADHD in the criminal justice system in Switzerland.

Background: Attention-deficit/hyperactivity disorder (ADHD) is prevalent amongst offenders, increasing risks for aggressive and delinquent behaviors. Since ADHD and its symptoms can persist into adulthood, accurately diagnosing and maintaining diagnoses in offenders is crucial to ensure appropriate treatment and reduce recidivism. Methods: This study employed a retrospective longitudinal design to investigate ADHD amongst adult offenders with a confirmed diagnosis of ADHD during childhood or adolescence at a Swiss forensic outpatient clinic between 2008 and 2021. N = 181 patient files were reviewed, including forensic expert witness assessments and treatment reports. We charted the adulthood trajectory of patients with a confirmed childhood/adolescence ADHD diagnosis, examining the course of their diagnoses. Results: Of 181 patients, evidence indicated that 12 (7%) had an ADHD diagnosis in childhood/adolescence. In 1 (8%) of these 12 cases, the diagnosis was maintained throughout the observation period. For 4 patients (33%), a diagnosis was given in the first forensic psychiatric expert witness assessment in adulthood but subsequently dropped. In another 4 cases (33%), the diagnosis was dropped in adulthood but later re-assigned, whereas in 3 cases (25%), the diagnosis was discontinued throughout the observation period. In 50% of cases with a diagnostic change, the discontinuation of an adult ADHD diagnosis coincided with a newly diagnosed personality disorder (or vice versa). Conclusions: Our findings highlighted considerable inconsistencies in the assignment of adult ADHD diagnoses amongst offenders. Whilst ADHD remission in adulthood occurs, the diagnostic variability in our results warrants detailed scrutiny. One possibility is that ADHD has similar fluctuations to conditions like depression, as argued elsewhere. Equally, diagnoses may become "lost", meaning they are not given even when applicable and replaced by other diagnoses. Additionally, residual symptoms may remain but beyond the diagnostic threshold. This is significant because untreated ADHD can increase re-offending risks and adverse health outcomes.

Prevalence and Sociodemographic Correlates of Chronic Pain Among a Nationally Representative Sample of Older Adults in the United States.

Subgroup analyses conducted among U.S. national survey data have estimated that 27 to 34% of adults aged ≥65 years have chronic pain. However, none of these studies focused specifically on older adults or examined disparities in chronic pain in those aged ≥65 years. To obtain current information on the prevalence and sociodemographic correlates of chronic pain in U.S. older adults, a cross-sectional analysis was conducted of data collected from 3,505 older adults recruited from the AmeriSpeak Panel. Chronic pain was defined as pain on most or every day in the last 3 months. Nationally representative chronic pain prevalence estimates were computed by incorporating study-specific survey design weights. Logistic regression analyses evaluated differences in chronic pain status as a function of sociodemographic characteristics (eg, gender, race/ethnicity, and socioeconomic status). The results indicated that 37.8% of older adults reported chronic pain. Compared with White older adults, Black (odds ratio [OR] = .6, 95% CI: .4-.8) and Asian (OR = .2, 95% CI: .1-.8) older adults were less likely to report chronic pain. The prevalence of chronic pain was also lower among those who reported the highest (vs lowest) household income (OR = .6, 95% CI: .4-.8). Those who were not working due to disability (vs working as a paid employee) were more likely to report chronic pain (OR = 3.2, 95% CI: 2.1-5.0). This study was the first to recruit a large, representative sample of older adults to estimate the prevalence of chronic pain and extends prior work by identifying subgroups of older adults that are disproportionately affected. PERSPECTIVE: This study was the first to estimate the prevalence and sociodemographic correlates of chronic pain among a large, representative sample of U.S. older adults. The findings underscore the high prevalence of chronic pain and highlight disparities in chronic pain prevalence rates among this historically understudied population.

Ligandability Assessment of IL-1ß by Integrated Hit Identification Approaches.

Human interleukin-1ß (IL-1ß) is a pro-inflammatory cytokine that plays a critical role in the regulation of the immune response and the development of various inflammatory diseases. In this publication, we disclose our efforts toward the discovery of IL-1ß binders that interfere with IL-1ß signaling. To this end, several technologies were used in parallel, including fragment-based screening (FBS), DNA-encoded library (DEL) technology, peptide discovery platform (PDP), and virtual screening. The utilization of distinct technologies resulted in the identification of new chemical entities exploiting three different sites on IL-1ß, all of them also inhibiting the interaction with the IL-1R1 receptor. Moreover, we identified lysine 103 of IL-1ß as a target residue suitable for the development of covalent, low-molecular-weight IL-1ß antagonists.

Comparing natural language processing representations of coded disease sequences for prediction in electronic health records.

OBJECTIVE: Natural language processing (NLP) algorithms are increasingly being applied to obtain unsupervised representations of electronic health record (EHR) data, but their comparative performance at predicting clinical endpoints remains unclear. Our objective was to compare the performance of unsupervised representations of sequences of disease codes generated by bag-of-words versus sequence-based NLP algorithms at predicting clinically relevant outcomes. MATERIALS AND METHODS: This cohort study used primary care EHRs from 6 286 233 people with Multiple Long-Term Conditions in England. For each patient, an unsupervised vector representation of their time-ordered sequences of diseases was generated using 2 input strategies (212 disease categories versus 9462 diagnostic codes) and different NLP algorithms (Latent Dirichlet Allocation, doc2vec, and 2 transformer models designed for EHRs). We also developed a transformer architecture, named EHR-BERT, incorporating sociodemographic information. We compared the performance of each of these representations (without fine-tuning) as inputs into a logistic classifier to predict 1-year mortality, healthcare use, and new disease diagnosis. RESULTS: Patient representations generated by sequence-based algorithms performed consistently better than bag-of-words methods in predicting clinical endpoints, with the highest performance for EHR-BERT across all tasks, although the absolute improvement was small. Representations generated using disease categories perform similarly to those using diagnostic codes as inputs, suggesting models can equally manage smaller or larger vocabularies for prediction of these outcomes. DISCUSSION AND CONCLUSION: Patient representations produced by sequence-based NLP algorithms from sequences of disease codes demonstrate improved predictive content for patient outcomes compared with representations generated by co-occurrence-based algorithms. This suggests transformer models may be useful for generating multi-purpose representations, even without fine-tuning.