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Although SARS-CoV-2 vaccines are very safe, we report 4 cases of the bifacial weakness with paresthesias variant of Guillain-Barre syndrome (GBS) occurring within 3 weeks of vaccination with the Oxford-AstraZeneca SARS-CoV-2 vaccine. This rare neurological syndrome has previously been reported in association with SARS-CoV-2 infection itself. Our cases were given either intravenous immunoglobulin, oral steroids, or no treatment. We suggest vigilance for cases of bifacial weakness with paresthesias variant GBS following vaccination for SARS-CoV-2 and that postvaccination surveillance programs ensure robust data capture of this outcome, to assess for causality. ANN NEUROL 2021;90:315-318.

Background: Advantages of digital clock drawing metrics for dementia subtype classification needs examination. Objective: To assess how well kinematic, time-based, and visuospatial features extracted from the digital Clock Drawing Test (dCDT) can classify a combined group of Alzheimer’s disease/Vascular Dementia patients versus healthy controls (HC), and classify dementia patients with Alzheimer’s disease (AD) versus vascular dementia (VaD). Methods: Healthy, community-dwelling control participants (n = 175), patients diagnosed clinically with Alzheimer’s disease (n = 29), and vascular dementia (n = 27) completed the dCDT to command and copy clock drawing conditions. Thirty-seven dCDT command and 37 copy dCDT features were extracted and used with Random Forest classification models. Results: When HC participants were compared to participants with dementia, optimal area under the curve was achieved using models that combined both command and copy dCDT features (AUC = 91.52%). Similarly, when AD versus VaD participants were compared, optimal area under the curve was, achieved with models that combined both command and copy features (AUC = 76.94%). Subsequent follow-up analyses of a corpus of 10 variables of interest determined using a Gini Index found that groups could be dissociated based on kinematic, time-based, and visuospatial features. Conclusion: The dCDT is able to operationally define graphomotor output that cannot be measured using traditional paper and pencil test administration in older health controls and participants with dementia. These data suggest that kinematic, time-based, and visuospatial behavior obtained using the dCDT may provide additional neurocognitive biomarkers that may be able to identify and tract dementia syndromes.

Background Delayed recognition of decompensation and failure-to-rescue on surgical wards are major sources of preventable harm. This review assimilates and critically evaluates available evidence and identifies opportunities to improve surgical ward safety. Data sources Fifty-eight articles from Cochrane Library, EMBASE, and PubMed databases were included. Conclusions Only 15–20% of patients suffering ward arrest survive. In most cases, subtle signs of instability often occur prior to critical illness and arrest, and underlying pathology is reversible. Coarse risk assessments lead to under-triage of high-risk patients to wards, where surveillance for complications depends on time-consuming manual review of health records, infrequent patient assessments, prediction models that lack accuracy and autonomy, and biased, error-prone decision-making. Streaming electronic heath record data, wearable continuous monitors, and recent advances in deep learning and reinforcement learning can promote efficient and accurate risk assessments, earlier recognition of instability, and better decisions regarding diagnosis and treatment of reversible underlying pathology.

Objective The relationship between preexisting osteoarthritic pain and subsequent post-total knee arthroplasty (TKA) pain is not well defined. This knowledge gap makes diagnosis of post-TKA pain and development of management plans difficult and may impair future investigations on personalized care. Therefore, a set of diagnostic criteria for identification of acute post-TKA pain would inform standardized management and facilitate future research. Methods The Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public–private partnership with the US Food and Drug Administration (FDA), the American Pain Society (APS), and the American Academy of Pain Medicine (AAPM) formed the ACTTION-APS-AAPM Pain Taxonomy (AAAPT) initiative to address this goal. A multidisciplinary work group of pain experts was invited to conceive diagnostic criteria and dimensions of acute post-TKA pain. Results The working group used contemporary literature combined with expert opinion to generate a five-dimensional taxonomical structure based upon the AAAPT framework (i.e., core diagnostic criteria, common features, modulating factors, impact/functional consequences, and putative mechanisms) that characterizes acute post-TKA pain. Conclusions The diagnostic criteria created are proposed to define the nature of acute pain observed in patients following TKA.

Objective Develop unifying definitions and paradigms for data-driven methods to augment postoperative resource intensity decisions. Summary background data Postoperative level-of-care assignments and frequency of vital sign and laboratory measurements (i.e., resource intensity) should align with patient acuity. Effective, data-driven decision-support platforms could improve value of care for millions of patients annually, but their development is hindered by the lack of salient definitions and paradigms. Methods Embase, PubMed, and Web of Science were searched for articles describing patient acuity and resource intensity after inpatient surgery. Study quality was assessed using validated tools. Thirty-five studies were included and assimilated according to PRISMA guidelines. Results Perioperative patient acuity is accurately represented by combinations of demographic, physiologic, and hospital-system variables as input features in models that capture complex, non-linear relationships. Intraoperative physiologic data enriches these representations. Triaging high-acuity patients to low-intensity care is associated with increased risk for mortality; triaging low-acuity patients to ICUs has low value and imparts harm when other, valid requests for ICU admission are denied due to resource limitations, increasing their risk for unrecognized decompensation and failure-to-rescue. Providing high-intensity care for low-acuity patients may also confer harm through unnecessary testing and subsequent treatment of incidental findings, but there is insufficient evidence to evaluate this hypothesis. Compared with data-driven models, clinicians exhibit volatile performance in predicting complications and making postoperative resource intensity decisions. Conclusions To optimize value, postoperative resource intensity decisions should align with precise, data-driven patient acuity assessments augmented by models that accurately represent complex, non-linear relationships among risk factors.

This cross-sectional study investigates the association of undertriage to hospital wards after surgical procedures with mortality, morbidity, and resource use., Key Points Question Is postoperative undertriage associated with increased mortality, morbidity, and resource use? Findings In this cross-sectional study of 14 890 postoperative admissions, undertriage to hospital wards was associated with increased mortality and morbidity compared with admissions that had similar risk profiles and were triaged to intensive care units. Postoperative undertriage was identifiable using automated preoperative and intraoperative data as features for real-time machine-learning models. Meaning These findings suggest that there is a rationale and framework for clinical decision support platforms to augment postoperative triage decisions., Importance Undertriaging patients who are at increased risk for postoperative complications after surgical procedures to low-acuity hospital wards (ie, floors) rather than highly vigilant intensive care units (ICUs) may be associated with risk of unrecognized decompensation and worse patient outcomes, but evidence for these associations is lacking. Objective To test the hypothesis that postoperative undertriage is associated with increased mortality and morbidity compared with risk-matched ICU admission. Design, Setting, and Participants This longitudinal cross-sectional study was conducted using data from the University of Florida Integrated Data Repository on admissions to a university hospital. Included patients were individuals aged 18 years or older who were admitted after a surgical procedure from June 1, 2014, to August 20, 2020. Data were analyzed from April through August 2021. Exposures Ward admissions were considered undertriaged if their estimated risk for hospital mortality or prolonged ICU stay (ie, ≥48 hours) was in the top quartile among all inpatient surgical procedures according to a validated machine-learning model using preoperative and intraoperative electronic health record features available at surgical procedure end time. A nearest neighbors algorithm was used to identify a risk-matched control group of ICU admissions. Main Outcomes and Measures The primary outcomes of hospital mortality and morbidity were compared among appropriately triaged ward admissions, undertriaged wards admissions, and a risk-matched control group of ICU admissions. Results Among 12 348 postoperative ward admissions, 11 042 admissions (89.4%) were appropriately triaged (5927 [53.7%] women; median [IQR] age, 59 [44-70] years) and 1306 admissions (10.6%) were undertriaged and matched with a control group of 2452 ICU admissions. The undertriaged group, compared with the control group, had increased median [IQR] age (64 [54-74] years vs 62 [50-73] years; P = .001) and increased proportions of women (649 [49.7%] women vs 1080 [44.0%] women; P

Aims: Reduced pre-operative cognitive functioning in older adults is a risk factor for postoperative complications, but it is unknown if preoperative digitally-acquired clock drawing test (CDT) cognitive screening variables, which allow for more nuanced examination of patient performance, may predict lengthier hospital stay and greater cost of hospital care. This issue is particularly relevant for older adults undergoing transcatheter aortic valve replacement (TAVR), as this surgical procedure is chosen for intermediate-risk older adults needing aortic replacement. This proof of concept research explored if specific latency and graphomotor variables indicative of planning from digitally-acquired command and copy clock drawing would predict post-TAVR duration and cost of hospitalization, over and above age, education, American Society of Anesthesiologists (ASA) physical status classification score, and frailty. Methods: Form January 2018 to December 2019, 162 out of 190 individuals electing TAVR completed digital clock drawing as part of a hospital wide cognitive screening program. Separate hierarchical regressions were computed for the command and copy conditions of the CDT and assessed how a-priori selected clock drawing metrics (total time to completion, ideal digit placement difference, and hour hand distance from center; included within the same block) incrementally predicted outcome, as measured by R2 change significance values. Results: Above and beyond age, education, ASA physical status classification score, and frailty, only digitally-acquired CDT copy performance explained significant variance for length of hospital stay (9.5%) and cost of care (8.9%). Conclusions: Digital variables from clock copy condition provided predictive value over common demographic and comorbidity variables. We hypothesize this is due to the sensitivity of the copy condition to executive dysfunction, as has been shown in previous studies for subtypes of cognitive impairment. Individuals undergoing TAVR procedures are often frail and executively compromised due to their cerebrovascular disease. We encourage additional research on the value of digitally-acquired clock drawing within different surgery types. Type of cognitive impairment and the value of digitally-acquired CDT command and copy parameters in other surgeries remain unknown.

Existing pain assessment methods in the intensive care unit rely on patient self-report or visual observation by nurses. Patient self-report is subjective and can suffer from poor recall. In the case of non-verbal patients, behavioral pain assessment methods provide limited granularity, are subjective, and put additional burden on already overworked staff. Previous studies have shown the feasibility of autonomous pain expression assessment by detecting Facial Action Units (AUs). However, previous approaches for detecting facial pain AUs are historically limited to controlled environments. In this study, for the first time, we collected and annotated a pain-related AU dataset, Pain-ICU, containing 55,085 images from critically ill adult patients. We evaluated the performance of OpenFace, an open-source facial behavior analysis tool, and the trained AU R-CNN model on our Pain-ICU dataset. Variables such as assisted breathing devices, environmental lighting, and patient orientation with respect to the camera make AU detection harder than with controlled settings. Although OpenFace has shown state-of-the-art results in general purpose AU detection tasks, it could not accurately detect AUs in our Pain-ICU dataset (F1-score 0.42). To address this problem, we trained the AU R-CNN model on our Pain-ICU dataset, resulting in a satisfactory average F1-score 0.77. In this study, we show the feasibility of detecting facial pain AUs in uncontrolled ICU settings.

In a preoperative anesthesia setting with integrated neuropsychology for individuals >64 years, we completed a pilot study examining the association between neurocognitive disorders with frequency of missed colonoscopies and quality of bowel preparation. Gastroenterologists completed the Boston Bowel Preparation Scale (BBPS) for each patient. Of 47 older adults seen in our service, 68% met criteria for neurocognitive disorders. All individuals failing to attend the colonoscopy procedure had met criteria for major neurocognitive disorder. Poor bowel preparation was also identified in 100% of individuals with major neurocognitive disorder and 28% of individuals with mild neurocognitive disorder. Our pilot data suggest that, in high-risk individuals, the presence of neurocognitive disorders are risk factors for missed appointments and inadequate bowel preparation. These pilot data provide reference statistics for future intervention protocols.

Background Clock drawing is a neurocognitive screening tool used in preoperative settings. This study examined hypothesized changes in clock drawing to command and copy test conditions 3 weeks and 3 months after total knee arthroplasty (TKA) with general anesthesia. Methods Participants included 67 surgery and 66 nonsurgery individuals >60 years who completed the digital clock drawing test before TKA (or a pseudosurgery date), and 3 weeks and 3 months postsurgery. Generalized linear mixed models assessed digital clock drawing test latency (ie, total time to completion, seconds between digit placement) and graphomotor output (ie, total number of strokes, clock size). Reliable change analyses examined the percent of participants showing change beyond differences found in nonsurgery peers. Results After adjusting for age, education, and baseline cognition, both digital clock drawing test latency measures were significantly different for surgery and nonsurgery groups, where the surgery group performed slower on both command and copy test conditions. Reliable change analyses 3 weeks after surgery found that total time to completion was slower among 25% of command and 21% of copy constructions in the surgery group. At 3 months, 18% of surgery participants were slower than nonsurgery peers. Neither graphomotor measure significantly changed over time. Conclusions Clock drawing construction slowed for nearly one-quarter of patients after TKA surgery, whereas nonsurgery peers showed the expected practice effect, ie, speed increased from baseline to follow-up time points. Future research should investigate the neurobiological basis for these changes after TKA.

Background In the 1990s, emergency medicine (EM) physicians were responsible for intubating about half of the patients requiring airway management in emergency rooms. Since then, no studies have characterized the airway management responsibilities in the emergency room. Methods A survey was sent via the Eastern Association for Surgery and Trauma and the Trauma Anesthesiology Society listservs, as well as by direct solicitation. Information was collected on trauma center level, geographical location, department responsible for intubation in the emergency room, department responsible for intubation in the trauma bay, whether these roles differed for pediatrics, whether an anesthesiologist was available "in-house" 24 hours a day, and whether there was a protocol for anesthesiologists to assist as backup during intubations. Responses were collected, reviewed, linked by city, and mapped using Python. Results The majority of the responses came from the Eastern Association for Surgery of Trauma (84.6%). Of the respondents, 72.6% were from level-1 trauma centers, and most were located in the eastern half of the United States. In the emergency room, EM physicians were primarily responsible for intubations at 81% of the surveyed institutions. In trauma bays, EM physicians were primarily responsible for 61.4% of intubations. There did not appear to be a geographical pattern for personnel responsible for managing the airway at the institutions surveyed. Conclusions The majority of institutions have EM physicians managing their airways in both emergency rooms and trauma bays. This may support the observations of an increased percentage of airway management in the emergency room and trauma bay setting by EM physicians compared to 20 years ago.

OBJECTIVES/HYPOTHESIS Head and neck cancer pain is a prevalent problem, and the current opioid crisis has highlighted concerns raised in chronic pain management. This study assessed the characteristics of opioid use in patients undergoing treatment for oropharynx cancer and identified risk factors associated with chronic opioid use. STUDY DESIGN Retrospective cohort study. METHODS A study was conducted of 198 eligible patients who underwent radiotherapy as part of their treatment for oropharynx cancer at a single institution from 2012 to 2017. p16/human papillomavirus (HPV) status was determined by pathology report review. Opioid use was recorded. Statistical analysis was performed to assess risk factors for chronic opioid use and effect on overall survival. RESULTS The average age was 62 years, and the mean follow-up was 38 months. Eighty-three percent of patients had stage III/IV disease, and 73% received chemoradiotherapy. Sixty-nine percent were HPV/p16 positive. Fifty-seven (29%) patients had preexisting chronic pain conditions. Chronic opioid use was observed in 53% of the patients. Age ≤ 62 years (P < .0001), history of depression (P = .0356), p16 negative status (P = .0097), opioid use at pretreatment visit (P = .0021), and presence of a preexisting chronic pain condition at time of diagnosis (P = .0181) were associated with chronic opioid use using univariate analysis. On multivariate analysis, T stage and anxiety/depression were associated with chronic opioid use. Overall survival was worse for patients who had chronic opioid use, but was not significant when recurrence was taken into consideration. CONCLUSIONS More than 50% of the patients treated for oropharynx squamous cell carcinoma in this cohort were chronic opioid users after treatment. Identifying patients at greatest risk for chronic opioid use prior to treatment may help with long-term pain management in this patient population. LEVEL OF EVIDENCE 4 Laryngoscope, 129:2087-2093, 2019.

Introduction Concurrent use of prescription opioids with gabapentinoids may pose risks of serious drug interactions. Yet, little is known about the trends in and patient characteristics associated with concurrent opioid–gabapentinoid use among older Medicare opioid users with chronic noncancer pain. Methods A cross-sectional study was conducted among Medicare older beneficiaries (aged ≥65 years) with chronic noncancer pain who filled ≥1 opioid prescription within 3 months after a randomly selected chronic noncancer pain diagnosis (index date) in a calendar year between 2011 and 2018. Patient characteristics were measured in the 6-month baseline before the index date, and concurrent opioid–gabapentinoid use for ≥1 day was measured in the 3-month follow-up after the index date. Multivariable modified Poisson regression hwas used to assess the trends and characteristics of concurrent opioid–gabapentinoid use. Analyses were conducted from January to June 2021. Results Among 464,721 eligible older beneficiaries with chronic noncancer pain and prescription opioids, the prevalence of concurrent opioid–gabapentinoid use increased from 17.0% in 2011 to 23.5% in 2018 (adjusted prevalence ratio=1.48, 95% CI=1.45, 1.53). Concurrent users versus opioid-only users tended to be non-Black, low-income subsidy recipients, and Southern residents. The clinical factors associated with concurrent opioid–gabapentinoid use included having a diagnosis of neuropathic pain, polypharmacy, and risk factors for opioid-related adverse events. Conclusions Concurrent opioid–gabapentinoid use among older Medicare beneficiaries with chronic noncancer pain and prescription opioids has increased significantly between 2011 and 2018. Future studies are warranted to investigate the impact of concurrent use on outcomes in older patients. Interventions that reduce inappropriate concurrent use may target older patients with identified characteristics.

Objective: To understand ethnic differences in SARS-CoV-2 infection risk and symptoms in hospital healthcare workers (HCW). Methods: A Prospective longitudinal observational cohort study. 1364 HCW at five UK hospitals were studied with up to 16 weeks of symptom questionnaires and antibody testing (to both nucleocapsid and spike protein) during the first UK wave in five NHS hospitals. The main outcome measures were SARS-CoV-2 infection (seropositivity at any time-point) and symptoms. Results: 272 of 1364 HCW (mean age 40.7 years, 72% female, 74% white, ≥6 samples per participant) seroconverted, reporting predominantly mild or no symptoms. Seropositivity was lower in ITU workers (OR=0.43 95%CI 0.24, 0.76; p=0.0033). Seropositivity was higher in black (compared to white) participants, independent of age, sex, role and index of multiple deprivation (OR=2.61 95%CI 1.47-4.62 p=0.0009). No association was seen with other ethnic groups. Conclusions: In the UK first wave, black ethnicity (but not other ethnicities) more than doubled HCW infection risk, independent of age, sex, measured socio-economic factors and role. Trial Registration: NCT04318314 Funding Statement: Funding for the PANTHER study was from the UKRI/MRC (Cov-0331 - MR/V027883/1 ), with additional institutional support from the Nottingham NIHR BRC. Funding for COVIDsortium was donated by individuals, charitable Trusts, and corporations including Goldman Sachs, Citadel and Citadel Securities, The Guy Foundation, GW Pharmaceuticals, Kusuma Trust, and Jagclif Charitable Trust, and enabled by Barts Charity with support from UCLH Charity. Wider support is acknowledged on the COVIDsortium website. Institutional support from Barts Health NHS Trust and Royal Free NHS Foundation Trust facilitated study processes, in partnership with University College London and Queen Mary University London. Serology tests (anti-S1 and anti-NP) were funded by Public Health England. JCM, CMa and TAT are directly and indirectly supported by the University College London Hospitals (UCLH) and Barts NIHR Biomedical Research Centres and through the British Heart Foundation (BHF) Accelerator Award (AA/18/6/34223). TAT is funded by a BHF Intermediate Research Fellowship (FS/19/35/34374). MN is supported by the Wellcome Trust (207511/Z/17/Z) and by NIHR Biomedical Research Funding to UCL and UCLH. None of the aforementioned funding bodies have contributed to the design, collection, or analysis of the data. Declaration of Interests: None to declare. Ethics Approval Statement: The study was approved by a UK Research Ethics Committee (South Central - Oxford A Research Ethics Committee, reference 20/SC/0149).

Objective To assess the incidence of symptomatic and asymptomatic SARS-CoV-2 seropositivity in healthcare workers and subsequent transmission to their close contacts within their household. To assess changes in immunoglobulin (Ig) and neutralising antibodies (nAbs) in exposed participants. Setting Two acute National Health Service (NHS) hospitals within the East Midlands region of England. Background The UK has been one of the most severely affected countries during the COVID-19 pandemic. Transmission from healthcare workers to the wider community is a potential major vector for spread of SARS-CoV-2 which is not well described in the current literature. Methods Healthcare workers (HCW) were recruited from two Hospitals within the East Midlands of England and underwent serial blood sampling for anti-SARS-CoV-2 antibodies (both nucleocapsid and spike protein for IgG, IgM and IgA) between 20 April and 30 July 2020, with the presence of neutralising antibodies (nAbs) assessed for positive participants. Cohabitees of the volunteers were invited to attend testing in July -August 2020 and underwent identical serological testing as the HCWs. Results 633 healthcare professionals were recruited. 178 household contacts of 137 professionals volunteered for the study. 18% of healthcare professionals (115 out of 633) tested as seropositive during the study period, compared to an estimated seroprevalence of 7% within the general population. The rate of symptomatic COVID-19 was 27.5% compared to an asymptomatic rate of 15.1%. Rates of positivity declined across the study period for all immunoglobulins (overall positivity from 16.7% to 6.9%). 7.2% of the cohabitees tested as seropositive. 58 cohabitees lived with a serologically positive HCW; this group had a seropositive rate of 15.5%, compared to 2.5% of cohabitees without a seropositive HCW, a six-fold increase in risk (Odds ratio 7.16 95% CI 1.86 to 27.59), p = 0.0025). Given the observed decay rates and data from Public Health England, we estimate that the proportion of seropositive cohabitees living with a seropositive HCW at the height of the first wave could have been as high as 44%. 110 out of 115 (95.7%) HCWs and 12 out of 13 (92.3%) cohabitees who tested positive developed detectable nAbs. 56.5% (65 out of 115) of SARS-CoV-2 positive HCWs developed a neutralising titre with an IC50≥1/300; no cohabitee achieved this level.. Conclusions Transmission of SARS-CoV-2 between healthcare professionals and their home contacts appears to be a significant factor of viral transmission, but, even accounting for the decline in seropositivity over time, less than 44% of adult cohabitees of seropositive healthcare workers became seropositive. Routine screening and priority vaccination of both healthcare professionals and their close contacts should be implemented to reduce viral transmission from hospitals to the community. SUMMARY BOXES Section 1: What is already known on this topic Healthcare workers (HCWs) have increased rates of SARS-CoV-2 infection compared with the general population due, at least in part, to high levels of occupational exposure. IgA, IgM and IgG are detectable for most patients after 11 days post SARS-CoV-2 infection but all decline in the weeks following SAR-CoV-2 exposure. Rates of transmission to healthcare workers, and therefore subsequent transmission to their close contacts, may be reduced with effective PPE. Section 2: What this study adds The amount of neutralising antibodies formed may be dependent on IgG response as it is much lower among seropositive cohabitees than seropositive healthcare workers. NHS Healthcare workers had a far greater seroprevalence of SARS-CoV-2 infection compared to the general population. Cohabitees of positive healthcare workers have a 6-fold increased risk of developing serological evidence of SARS-CoV-2 infection compared to the general population. Despite this increased risk, transmission at home is less than 50% even from highly exposed healthcare workers, but remains an important potential vector of transmission from hospitals to the wider community. Research into context Evidence before this study We searched PubMed for articles published between January 1 2020 and January 27, 2021 with the terms “Covid-19”, “healthcare workers”, and “transmission” “home {NOT nursing} or household”. We did not restrict our search by language or type of publication. We identified 38 studies of which only one assessed the prevalence among HCW households using Canadian national databases. Our PubMed search yielded only one serological study within the German Healthcare system, which suggested very low transmission from healthcare workers to their close cohabitees. Added value of this study To our knowledge, this is the largest longitudinal serological cohort study assessing transmission of SARS-CoV-2 infection from the UK healthcare environment to the home (n = 633 healthcare workers, 178 cohabitees). Our findings showed that serological evidence within the HCW was high with 18% of healthcare professionals (115 out of 633) tested as seropositive during the study period, compared to an estimated seroprevalence of 7% within the general population. A cohabitee of a seropositive HCW had a six-fold increase of being seropositive themselves compared to a baseline rate of 2.5%. Despite this increased risk, transmission at home is less than 50% even from highly exposed healthcare workers, but remains an important potential vector of transmission from hospitals to the wider community. Rates of positivity declined across the study period for all immunoglobulins (overall positivity from 16.7% to 6.9%). Given the observed decay rates and data from Public Health England, we estimate that the proportion of seropositive cohabitees living with a seropositive HCW at the height of the first wave could have been as high as 44%. Implications of all available evidence Understanding the transmission during the first wave from the healthcare setting into the home and the extent of such transmissions is essential to understand containment strategies of novel SARS-CoV-2 variants or to understand viral transmission of future respiratory viruses. NHS workers appeared to be at an increased risk of contracting of SARS-CoV-2 infection compared to the HCWs of other nations; we hypothesise that this may be related to a scarcity of appropriate personal protective equipment during the initial wave of SARS-CoV-2. Healthcare workers (HCWs) have increased rates of SARS-CoV-2 infection compared with the general population. An infected HCW, whether symptomatic or not, appears to be a significant bridge for transmission of SARS-CoV-2 to their close home contacts.

As opportunities for artificial intelligence to augment surgical care expand, the accompanying surge in published literature has generated both substantial enthusiasm and grave concern regarding the safety and efficacy of artificial intelligence in surgery. For surgeons and surgical data scientists, it is increasingly important to understand the state-of-the-art, recognize knowledge and technology gaps, and critically evaluate the deluge of literature accordingly. This article summarizes the experiences and perspectives of a global, multi-disciplinary group of experts who have faced development and implementation challenges, overcome them, and produced incipient evidence thereof. Collectively, evidence suggests that artificial intelligence has the potential to augment surgeons via decision-support, technical skill assessment, and the semi-autonomous performance of tasks ranging from resource allocation to patching foregut defects. Most applications remain in pre-clinical phases. As technologies and their implementations improve and positive evidence accumulates, surgeons will face professional imperatives to lead the safe, effective clinical implementation of artificial intelligence in surgery. Substantial challenges remain; recent progress in using artificial intelligence to achieve performance advantages in surgery suggests that remaining challenges can and will be overcome.

We aimed to explore student and staff perceptions and experiences of a pilot COVID-19 asymptomatic testing service (P-ATS) in a UK university campus setting. This was a mixed-method study comprised of an online survey, and thematic analysis of qualitative data from interviews and focus groups conducted at the end of the 12-week P-ATS programme. Ninety-nine students (84.8% female, 70% first year; 93.9% P-ATS participants) completed an online survey, 41 individuals attended interviews or focus groups, including 31 students (21 first year; 10 final year) and 10 staff. All types of testing and logistics were highly acceptable (virus: swab, saliva; antibody: finger prick) and 94.9% would participate again. Reported adherence to weekly virus testing was high (92.4% completed ≥6 tests; 70.8% submitted all 10 swabs; 89.2% completed ≥1 saliva sample) and 76.9% submitted ≥3 blood samples. Students tested to ‘keep campus safe’, ‘contribute to national efforts to control COVID-19’, and ‘protect others’. 31.3% had high anxiety as measured by the Generalized Anxiety Disorder scale (GAD-7) (27.1% of first year). Students with lower levels of anxiety and greater satisfaction with university communications around P-ATS were more likely to adhere to virus and antibody tests. Increased adherence to testing was associated with higher perceived risk of COVID-19 to self (virus) and others (antibody). Qualitative findings revealed 5 themes and 13 sub-themes: ‘emotional responses to COVID-19’, ‘university life during COVID-19’, ‘influences on testing participation’, ‘testing physical and logistical factors’ and ‘testing effects on mental wellbeing’. Asymptomatic COVID-19 testing (virus/antibodies) is highly acceptable to students and staff in a university campus setting. Clear communications and support for mental wellbeing is likely to be important for testing uptake and adherence. Strategies are needed to facilitate social connections and mitigate the mental health impacts of COVID-19 and self-isolation.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. \ud \ud \ud METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. \ud \ud \ud FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. \ud \ud \ud INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. \ud \ud \ud FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca.

Pain and physical function are both essential indices of recovery in critically ill patients in the Intensive Care Units (ICU). Simultaneous monitoring of pain intensity and patient activity can be important for determining which analgesic interventions can optimize mobility and function, while minimizing opioid harm. Nonetheless, so far, our knowledge of the relation between pain and activity has been limited to manual and sporadic activity assessments. In recent years, wearable devices equipped with 3-axis accelerometers have been used in many domains to provide a continuous and automated measure of mobility and physical activity. In this study, we collected activity intensity data from 57 ICU patients, using the Actigraph GT3X device. We also collected relevant clinical information, including nurse assessments of pain intensity, recorded every 1-4 hours. Our results show the joint distribution and state transition of joint activity and pain states in critically ill patients., Comment: Accepted for Publication in EMBC 2020

OBJECTIVE: Acute postoperative pain intensity is associated with persistent postsurgical pain risk. However, it remains unclear whether acute postoperative pain intensity mediates the relationship between clinical factors and persistent pain. METHODS: Subjects from a mixed surgical population completed the Brief Pain Inventory and pain catastrophizing scale before surgery, and the Brief Pain Inventory daily after surgery for 7 days and at 30 and 90 days after surgery. We considered mediation models using the mean of the worst pain intensities collected daily on each of postoperative days (PODs) 1 to 7 against outcomes of worst pain intensity at the surgical site endpoints reflecting persistent postsurgical pain (POD 90) and subacute pain (POD 30). RESULTS: The analyzed cohort included 284 subjects for the POD 90 outcome. For every unit increase of maximum acute postoperative pain intensity through PODs 1 to 7, there was a statistically significant increase of mean POD 90 pain intensity by 0.287 after controlling for confounding effects. The effects of female vs. male sex (m=0.212, P=0.034), pancreatic/biliary vs. colorectal surgery (m=0.459, P=0.012), thoracic cardiovascular vs. colorectal surgery (m=0.31, P=0.038), every minute increase of anesthesia time (m=0.001, P=0.038), every unit increase of preoperative average pain score (m=0.012, P=0.015), and every unit increase of catastrophizing (m=0.044, P=0.042) on POD 90 pain intensity were mediated through acute PODs 1 to 7 postoperative pain intensity. DISCUSSION: Our results suggest the mediating relationship of acute postoperative pain on persistent postsurgical pain may be predicated on select patient and surgical factors.

Critical care patients experience varying levels of pain during their stay in the intensive care unit, often requiring administration of analgesics and sedation. Such medications generally exacerbate the already sedentary physical activity profiles of critical care patients, contributing to delayed recovery. Thus, it is important not only to minimize pain levels, but also to optimize analgesic strategies in order to maximize mobility and activity of ICU patients. Currently, we lack an understanding of the relation between pain and physical activity on a granular level. In this study, we examined the relationship between nurse assessed pain scores and physical activity as measured using a wearable accelerometer device. We found that average, standard deviation, and maximum physical activity counts are significantly higher before high pain reports compared to before low pain reports during both daytime and nighttime, while percentage of time spent immobile was not significantly different between the two pain report groups. Clusters detected among patients using extracted physical activity features were significant in adjusted logistic regression analysis for prediction of pain report group., 4 pages, 3 figures, 6 tables. Accepted for presentation at IEEE EMBC 2020

Post-weaning social isolation of rats produces neuroanatomical, neurochemical and behavioral alterations resembling some core features of schizophrenia. This study examined the ability of the 5-HT6 receptor antagonist SB-399885 to reverse isolation-induced cognitive deficits, then investigated alterations in hippocampal cell proliferation and hippocampal and frontal cortical expression of selected intracellular signaling molecules and cytokines. Male Lister hooded rats (weaned on post-natal days 21–24 and housed individually or in groups of 3–4) received six i.p. injections of vehicle (1% Tween 80, 1 mL/kg) or SB-399885 (5 or 10 mg/kg) over a 2-week period starting 40 days post-weaning, on the days that locomotor activity, novel object discrimination (NOD), pre-pulse inhibition of acoustic startle and acquisition, retention and extinction of a conditioned freezing response (CFR) were assessed. Tissue was collected 24 h after the final injection for immunohistochemistry, reverse-phase protein microarray and western blotting. Isolation rearing impaired NOD and cue-mediated CFR, decreased cell proliferation within the dentate gyrus, and elevated hippocampal TNFα levels and Cdc42 expression. SB-399885 reversed the NOD deficit and partially normalized CFR and cell proliferation. These effects were accompanied by altered expression of several members of the c-Jun N-terminal Kinase (JNK) and p38 MAPK signaling pathways (including TAK1, MKK4 and STAT3). Although JNK and p38 themselves were unaltered at this time point hippocampal TAK1 expression and phosphorylation correlated with visual recognition memory in the NOD task. Continued use of this neurodevelopmental model could further elucidate the neurobiology of schizophrenia and aid assessment of novel therapies for drug-resistant cognitive symptoms.

As newer pharmacologic and procedural interventions, technology, and data on outcomes in pain management are becoming available, effective acute pain management will require a dedicated Acute Pain Service (APS) to help determine the most optimal pain management plan for the patients. Goals for pain management must take into consideration the side effect profile of drugs and potential complications of procedural interventions. Multiple objective optimization is the combination of multiple different objectives for acute pain management. Simple use of opioids, for example, can reduce all pain to minimal levels, but at what cost to the patient, the medical system, and to public health as a whole? Many models for APS exist based on personnel's skills, knowledge and experience, but effective use of an APS will also require allocation of time, space, financial, and personnel resources with clear objectives and a feedback mechanism to guide changes to acute pain medicine practices to meet the constantly evolving medical field. Physician-based practices have the advantage of developing protocols for the management of low-variability, high-occurrence scenarios in addition to tailoring care to individual patients with high-variability, low-occurrence scenarios. Frequent feedback and data collection/assessment on patient outcomes is essential in evaluating the efficacy of the Acute Pain Service's intervention in improving patient outcomes in the acute and perioperative setting.

Objective With the increasing societal awareness of the prevalence and impact of acute pain, there is a need to develop an acute pain classification system that both reflects contemporary mechanistic insights and helps guide future research and treatment. Existing classifications of acute pain conditions are limiting, with a predominant focus on the sensory experience (e.g., pain intensity) and pharmacologic consumption. Consequently, there is a need to more broadly characterize and classify the multidimensional experience of acute pain. Setting Consensus report following expert panel involving the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION), American Pain Society (APS), and American Academy of Pain Medicine (AAPM). Methods As a complement to a taxonomy recently developed for chronic pain, the ACTTION public-private partnership with the US Food and Drug Administration, the APS, and the AAPM convened a consensus meeting of experts to develop an acute pain taxonomy using prevailing evidence. Key issues pertaining to the distinct nature of acute pain are presented followed by the agreed-upon taxonomy. The ACTTION-APS-AAPM Acute Pain Taxonomy will include the following dimensions: 1) core criteria, 2) common features, 3) modulating factors, 4) impact/functional consequences, and 5) putative pathophysiologic pain mechanisms. Future efforts will consist of working groups utilizing this taxonomy to develop diagnostic criteria for a comprehensive set of acute pain conditions. Perspective The ACTTION-APS-AAPM Acute Pain Taxonomy (AAAPT) is a multidimensional acute pain classification system designed to classify acute pain along the following dimensions: 1) core criteria, 2) common features, 3) modulating factors, 4) impact/functional consequences, and 5) putative pathophysiologic pain mechanisms. Conclusions Significant numbers of patients still suffer from significant acute pain, despite the advent of modern multimodal analgesic strategies. Mismanaged acute pain has a broad societal impact as significant numbers of patients may progress to suffer from chronic pain. An acute pain taxonomy provides a much-needed standardization of clinical diagnostic criteria, which benefits clinical care, research, education, and public policy. For the purposes of the present taxonomy, acute pain is considered to last up to seven days, with prolongation to 30 days being common. The current understanding of acute pain mechanisms poorly differentiates between acute and chronic pain and is often insufficient to distinguish among many types of acute pain conditions. Given the usefulness of the AAPT multidimensional framework, the AAAPT undertook a similar approach to organizing various acute pain conditions.

OBJECTIVE: With the increasing societal awareness of the prevalence and impact of acute pain, there is a need to develop an acute pain classification system that both reflects contemporary mechanistic insights and helps guide future research and treatment. Existing classifications of acute pain conditions are limiting, with a predominant focus on the sensory experience (eg, pain intensity) and pharmacologic consumption. Consequently, there is a need to more broadly characterize and classify the multidimensional experience of acute pain.SETTING: Consensus report following expert panel involving the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION), American Pain Society (APS), and American Academy of Pain Medicine (AAPM).METHODS: As a complement to a taxonomy recently developed for chronic pain, the ACTTION public-private partnership with the US Food and Drug Administration, the APS, and the AAPM convened a consensus meeting of experts to develop an acute pain taxonomy using prevailing evidence. Key issues pertaining to the distinct nature of acute pain are presented followed by the agreed-upon taxonomy. The ACTTION-APS-AAPM Acute Pain Taxonomy will include the following dimensions: 1) core criteria, 2) common features, 3) modulating factors, 4) impact/functional consequences, and 5) putative pathophysiologic pain mechanisms. Future efforts will consist of working groups utilizing this taxonomy to develop diagnostic criteria for a comprehensive set of acute pain conditions.PERSPECTIVE: The ACTTION-APS-AAPM Acute Pain Taxonomy (AAAPT) is a multidimensional acute pain classification system designed to classify acute pain along the following dimensions: 1) core criteria, 2) common features, 3) modulating factors, 4) impact/functional consequences, and 5) putative pathophysiologic pain mechanisms.CONCLUSIONS: Significant numbers of patients still suffer from significant acute pain, despite the advent of modern multimodal analgesic strategies. Mismanaged acute pain has a broad societal impact as significant numbers of patients may progress to suffer from chronic pain. An acute pain taxonomy provides a much-needed standardization of clinical diagnostic criteria, which benefits clinical care, research, education, and public policy. For the purposes of the present taxonomy, acute pain is considered to last up to seven days, with prolongation to 30 days being common. The current understanding of acute pain mechanisms poorly differentiates between acute and chronic pain and is often insufficient to distinguish among many types of acute pain conditions. Given the usefulness of the AAPT multidimensional framework, the AAAPT undertook a similar approach to organizing various acute pain conditions.

Objective Inappropriate opioid prescribing after surgery contributes to opioid use disorder and risk of opioid overdose. In this cross-sectional analysis of orthopedic surgical patients, we examined the role of patient location on postoperative pain intensity and opioids prescribed on hospital discharge. Methods We used geospatial analyses to characterize spatial patterns of mean pain intensity on the day of discharge (PiDoD) and opioid units prescribed on the day of discharge (OuPoD), as well as the effect of regional social deprivation on these outcomes. Results At a 500-km radius from the surgery site, the Global Moran’s I for PiDoD (2.71 × 10−3, variance = 1.67 × 10−6, P = 0.012) and OuPoD (2.19 × 10−3, SD = 1.87, variance = 1.66 × 10−6, P = 0.03) suggested significant spatial autocorrelation within each outcome. Local indicators of spatial autocorrelation, including local Moran’s I, Local Indicator of Spatial Autocorrelation cluster maps, and Getis-Ord Gi* statistics, further demonstrated significant, specific regions of clustering both OuPoD and PiDoD. These spatial patterns were associated with spatial regions of area deprivation. Conclusions Our results suggest that the outcomes of pain intensity and opioid doses prescribed exhibit varying degrees of clustering of patient locations of residence, at both global and local levels. This indicates that a given patient’s pain intensity on discharge is related to the pain intensity of nearby individuals. Similar interpretations exist for OuPoD, although the relative locations of hot spots of opioids dispensed in a geographic area appear to differ from those of hot spots of pain intensity on discharge.

The recent opioid prescribing guideline cautions about the concomitant prescribing of opioids and skeletal muscle relaxants (SMRs) given the additive central nervous system depressant effect. However, the clinical relevance remains unclear. In this retrospective cohort study, we compared the risk of opioid overdose associated with concomitant use of opioids and SMRs vs. opioid use alone. Adjusted hazard ratios were 1.09 (95% confidence interval (CI), 0.74-1.62) and 1.26 (95% CI, 1.00-1.58) in the incident and prevalent opioid user cohorts, respectively, generating a combined estimate of 1.21 (95% CI, 1.00-1.48). This risk seemed to increase with treatment duration (≤ 14 days: 0.91 and 95% CI, 0.67-1.22; 15-60 days: 1.37 and 95% CI, 0.81-2.37; >60 days: 1.80 and 95% CI, 1.30-2.48) and for baclofen (1.83 and 95% CI, 1.11-3.04) and carisoprodol (1.84 and 95% CI, 1.34-2.54). Concomitant users with daily opioid dose ≥50 mg (1.50 and 95% CI, 1.18-1.92) and benzodiazepine use (1.39 and 95% CI, 1.08-1.79) also had elevated risk. Clinicians should be cautious about these potentially unsafe practices to optimize pain care and improve patient safety.

BACKGROUND: Advanced age, frailty, low education level, and impaired cognition are generally reported to be associated with postoperative cognitive complications. To translate research findings into hospital-wide preoperative assessment clinical practice, we examined the feasibility of implementing a preoperative frailty and cognitive assessment for all older adults electing surgical procedures in a tertiary medical center. We examined associations among age, education, frailty, and comorbidity with the clock and 3-word memory scores, estimated the prevalence of mild to major cognitive impairment in the presurgical sample, and examined factors related to hospital length of stay. METHODS: Medical staff screened adults ≥65 years of age for frailty, general cognition (via the clock-drawing test command and copy, 3-word memory test), and obtained years of education. Feasibility was studied in 2 phases: (1) a pilot phase involving 4 advanced nurse practitioners and (2) a 2-month implementation phase involving all preoperative staff. We tracked sources of missing data, investigated associations of study variables with measures of cognition, and used 2 approaches to estimate the likelihood of dementia in our sample (ie, using extant data and logistic regression modeling and using Mini-Cog cut scores). We explored which protocol variables related to hospital length of stay. RESULTS: The final implementation phase sample included 678 patients. Clock and 3-word memory scores were significantly associated with age, frailty, and education. Education, clock scores, and 3-word scores were not significantly different by surgery type. Likelihood of preoperative cognitive impairment was approximately 20%, with no difference by surgery type. Length of stay was significantly associated with preoperative comorbidity and performance on the clock copy condition. CONCLUSIONS: Frailty and cognitive screening protocols are feasible and provide information for perioperative care planning. Challenges to clinical adaptation include staff training, missing data, and additional administration time. These challenges appear minimal relative to the benefits of identifying frailty and cognitive impairment in a group at risk for negative postoperative cognitive outcome.

The Clock Drawing Test is a cognitive screening tool gaining popularity in the perioperative setting. We compared 3 common scoring systems: (1) the Montreal Cognitive Assessment; (2) the Mini-Cog; and (3) the Libon scale. Three novice raters acquired interrater and intrarater reliability for each scoring system and then scored 738 preoperative clock drawings with each scoring system. Final scores correlated with each other but with notable discrepancies, indicating the need to attend to interrater and intrarater reliability when implementing any scoring approach in a clinical setting.

The aim of the study was to determine the long-term cardiovascular-specific mortality in patients with acute kidney injury (AKI) or chronic kidney disease (CKD) after major surgery.In surgical patients, pre-existing CKD and postoperative AKI are associated with increases in all-cause mortality.In a single-center cohort of 51,457 adult surgical patients undergoing major inpatient surgery, long-term cardiovascular-specific mortality was modeled using a multivariable subdistributional hazards model while treating any other cause of death as a competing risk and accounting for the progression to end-stage renal disease (ESRD) after discharge. Pre-existing CKD and ESRD, and postoperative AKI were the main independent predictors.Before the admission, 4% and 8% of the cohort had pre-existing ESRD and CKD not requiring renal replacement therapy, respectively. During hospitalization, 39% developed AKI. At 10-year follow-up, adjusted cardiovascular-specific mortality estimates were 6%, 11%, 12%, 19%, and 27% for patients with no kidney disease, AKI with no CKD, CKD with no AKI, AKI with CKD, and ESRD, respectively (P0.001). This association remained after excluding 916 patients who progressed to ESRD after discharge, although it was significantly amplified among them. Compared with patients having no kidney disease, adjusted hazard ratios for cardiovascular mortality were significantly higher among patients with kidney disease, ranging from 1.95 (95% confidence interval, 1.80-2.11) for patients with de novo AKI to 5.70 (95% confidence interval, 5.00-6.49) for patients with pre-existing ESRD.Both AKI and CKD were associated with higher long-term cardiovascular-specific mortality compared with patients having no kidney disease.

Signal transducer and activator of transcription (STAT) transcription factors family are involved in diverse cellular biological functions. Reports regarding the prognostic impact of STAT3 expression in breast cancer (BC) are variable whether being a factor of poor or good prognosis. Immunohistochemical expression of phospho-STAT3 (pSTAT3) was studied in large series of invasive BC (n = 1270). pSTAT3 and STAT3 were quantified using reverse phase protein array (RPPA) on proteins extracted from macro-dissected FFPE tissues (n = 49 cases). STAT3 gene expression in the METABRIC cohort was also investigated. STAT3 gene expression prognostic impact was externally validated using the online BC gene expression data (n = 26 datasets, 4.177 patients). pSTAT3 was expressed in the nuclei and cytoplasm of invasive BC cells. Nuclear pSTAT3 overexpression was positively associated with smaller tumour size, lower grade, good NPI, negative lymphovascular invasion (LVI), ER+, PgR+, p53−, HER2−, and low Ki67LI and an improved breast cancer-specific survival (BCSS), independently of other factors. On RPPA, the mean pSTAT3 and STAT3 expressions were higher in ER+, PgR+, and smaller size tumours. Higher STAT3 transcripts in the METABRIC cohort were observed in cases with favourable prognostic criteria and as well as improved BCSS within the whole cohort, ER+ cohort with and without hormonal therapy, and ER− cohort including those who did not receive adjuvant chemotherapy. Pooled STAT3 gene expression data in the external validation cohort showed an association with improved patients’ outcome (P

We aimed to explore student and staff perceptions and experiences of a pilot SARS-CoV-2 asymptomatic testing service (P-ATS) in a UK university campus setting. This was a mixed-method study comprised of an online survey, and thematic analysis of qualitative data from interviews and focus groups conducted at the mid-point and end of the 12-week P-ATS programme. Ninety-nine students (84.8% female, 70% first year, 93.9% P-ATS participants) completed an online survey, 41 individuals attended interviews or focus groups, including 31 students (21 first year, 10 final year) and 10 staff. All types of testing and logistics were highly acceptable (virus: swab, saliva, antibody: finger prick) and 94.9% would participate again. Reported adherence to weekly virus testing was high (92.4% completed &ge, 6 tests, 70.8% submitted all 10 swabs, 89.2% completed &ge, 1 saliva sample) and 76.9% submitted &ge, 3 blood samples. Students tested to &ldquo, keep campus safe&rdquo, &ldquo, contribute to national efforts to control COVID-19&rdquo, and &ldquo, protect others&rdquo, In total, 31.3% had high anxiety as measured by the Generalized Anxiety Disorder scale (GAD-7) (27.1% of first year). Students with lower levels of anxiety and greater satisfaction with university communications around P-ATS were more likely to adhere to virus and antibody tests. Increased adherence to testing was associated with higher perceived risk of COVID-19 to self and others. Qualitative findings revealed 5 themes and 13 sub-themes: &ldquo, emotional responses to COVID-19&rdquo, university life during COVID-19&rdquo, influences on testing participation&rdquo, testing physical and logistical factors&rdquo, testing effects on mental wellbeing&rdquo, Asymptomatic COVID-19 testing (SARS-CoV-2 virus/antibodies) is highly acceptable to students and staff in a university campus setting. Clear communications and strategies to reduce anxiety are likely to be important for testing uptake and adherence. Strategies are needed to facilitate social connections and mitigate the mental health impacts of COVID-19 and self-isolation.

Currently, many critical care indices are not captured automatically at a granular level, rather are repetitively assessed by overburdened nurses. In this pilot study, we examined the feasibility of using pervasive sensing technology and artificial intelligence for autonomous and granular monitoring in the Intensive Care Unit (ICU). As an exemplary prevalent condition, we characterized delirious patients and their environment. We used wearable sensors, light and sound sensors, and a camera to collect data on patients and their environment. We analyzed collected data to detect and recognize patient’s face, their postures, facial action units and expressions, head pose variation, extremity movements, sound pressure levels, light intensity level, and visitation frequency. We found that facial expressions, functional status entailing extremity movement and postures, and environmental factors including the visitation frequency, light and sound pressure levels at night were significantly different between the delirious and non-delirious patients. Our results showed that granular and autonomous monitoring of critically ill patients and their environment is feasible using a noninvasive system, and we demonstrated its potential for characterizing critical care patients and environmental factors.

Acute pain medicine services influence many different aspects of postoperative recovery and function. Here, we discuss the various stakeholders of an acute pain medicine service, review the direct and indirect impact on said stakeholders, review the shared and competing interests between acute pain medicine programs and various payer systems, and discuss how APM services can help service lines align with the interests of the recent CMS Innovations Comprehensive Care for Joint Replacement Model.

Older adults are at an increased risk to develop frequent and prolonged pain. Emerging evidence proposes a link between immune changes and pain, which is consistent with the inflammation theory of aging and the increased incidence of age-related diseases. This study tested the hypothesis that older adults show greater immune responses to experimental pain compared to younger individuals. Study subjects (8 younger and 9 older healthy adults) underwent 3 experimental sessions using well-validated human experimental pain models: the cold pressor task (CPT), focal heat pain (FHP), and a non-painful thermal control. Blood was collected through an indwelling catheter at baseline and 3, 15, 30, 45, 60, and 90 minutes post-stimuli administration. Pro-inflammatory cytokines (TNF-α IL-6 and IL-8) peaked at the same time points for both groups, with greater elevations among older subjects for TNF-α and IL-8 in both pain models and elevations in IL-6 only for CPT. Antiinflammatory cytokines (IL-4, IL-5, and IL-10) generally peaked later for the older subjects, with increased elevations for FHP but not the CPT. These data is consistent with the assertion that agerelated immune system dysregulation may account for the increased prevalence of pain in older adults.

Background Consensus indicates that a comprehensive, multimodal, holistic approach is foundational to the practice of acute pain medicine (APM), but lack of uniform, evidence-based clinical pathways leads to undesirable variability throughout U. S. healthcare systems. Acute pain studies are inconsistently synthesized to guide educational programs. Advanced practice techniques involving regional anesthesia assume the presence of a physician-led, multidisciplinary acute pain service, which is often unavailable or inconsistently applied. This heterogeneity of educational and organizational standards may result in unnecessary patient pain and escalation of healthcare costs. Methods A multidisciplinary panel was nominated through the APM Shared Interest Group of the American Academy of Pain Medicine. The panel met in Chicago, IL, in July 2014, to identify gaps and set priorities in APM research and education. Results The panel identified three areas of critical need: 1) an open-source acute pain data registry and clinical support tool to inform clinical decision making and resource allocation and to enhance research efforts; 2) a strong professional APM identity as an accredited subspecialty; and 3) educational goals targeted toward third-party payers, hospital administrators, and other key stakeholders to convey the importance of APM. Conclusion This report is the first step in a 3-year initiative aimed at creating conditions and incentives for the optimal provision of APM services to facilitate and enhance the quality of patient recovery after surgery, illness, or trauma. The ultimate goal is to reduce the conversion of acute pain to the debilitating disease of chronic pain.

TNF receptor associated periodic syndrome (TRAPS) is an autoinflammatory disease involving recurrent episodes of fever and inflammation. It is associated with autosomal dominant mutations in TNF receptor superfamily 1A gene localised to exons encoding the ectodomain of the p55 TNF receptor, TNF receptor-1 (TNFR1). The aim of this study was to investigate the role of cell surface TNFR1 in TRAPS, and the contribution of TNF-dependent and TNF-independent mechanisms to the production of cytokines. HEK-293 and SK-HEP-1 cell lines were stably transfected with WT or TRAPS-associated variants of human TNF receptor superfamily 1A gene. An anti-TNFR1 single domain antibody (dAb), and an anti-TNFR1 mAb, bound to cell surface WT and variant TNFR1s. In HEK-293 cells transfected with death domain-inactivated (R347A) TNFR1, and in SK-HEP-1 cells transfected with normal (full-length) TNFR1, cytokine production stimulated in the absence of exogenous TNF by the presence of certain TNFR1 variants was not inhibited by the anti-TNFR1 dAb. In SK-Hep-1 cells, specific TRAPS mutations increased the level of cytokine response to TNF, compared to WT, and this augmented cytokine production was suppressed by the anti-TNFR1 dAb. Thus, TRAPS-associated variants of TNFR1 enhance cytokine production by a TNF-independent mechanism and by sensitising cells to a TNF-dependent stimulation. The TNF-dependent mechanism requires cell surface expression of TNFR1, as this is blocked by TNFR1-specific dAb.

This study tested the hypothesis that older adults would have a stronger response for substance P (facilitatory) but weaker response to β-endorphin (inhibitory), in magnitude as well as time course. Eight younger and 9 older adults underwent 3 experimental sessions using well validated laboratory pain models: cold pressor task, contact heat pain, and a nonpainful control. Blood was collected through an indwelling catheter at baseline and 3, 15, 30, 45, and 60 minutes after stimuli administration. Older adults had higher baseline levels of both neuropeptides suggesting increased peripheral activity compared with younger adults. After the cold pressor task, older adults demonstrated a quick and strong release of substance P with dramatic recovery, whereas young adults maintained a constant low-grade response. Unlike substance P, β-endorphin increased between 3 and 15 minutes for both groups with the upsurge substantially higher for older adults. After heat pain, younger adults had an immediate surge in circulating substance P and β-endorphin that was more pronounced than among older adults. However, levels of substance P for younger adults slowly tapered whereas they continued to climb for the older adults through 30 minutes. β-endorphin peaked at 30 minutes for both groups and returned to baseline. No changes were observed during the nonpainful control session. Perspective Older adults had higher baseline levels of substance P and β-endorphin suggesting increased peripheral activity compared with younger adults. After pain evocation, older adults demonstrated a more intense early response for both neuropeptides suggesting peripheral mechanisms involved in the response to pain may change with age.

Previous investigations on acute postoperative pain dynamicity have focused on daily pain assessments, and so were unable to examine intraday variations in acute pain intensity. We analyzed 476,108 postoperative acute pain intensity ratings, which were clinically documented on postoperative days 1 to 7 from 8346 surgical patients using Markov chain modeling to describe how patients are likely to transition from one pain state to another in a probabilistic fashion. The Markov chain was found to be irreducible and positive recurrent, with no absorbing states. Transition probabilities ranged from 0.0031, for the transition from state 10 to state 1, to 0.69 for the transition from state 0 to state 0. The greatest density of transitions was noted in the diagonal region of the transition matrix, suggesting that patients were generally most likely to transition to the same pain state as their current state. There were also slightly increased probability densities in transitioning to a state of asleep or 0 from the current state. An examination of the number of steps required to traverse from a particular first pain score to a target state suggested that overall, fewer steps were required to reach a state of 0 (range 6.1-8.8 steps) or asleep (range 9.1-11) than were required to reach a mild pain intensity state. Our results suggest that using Markov chains is a feasible method for describing probabilistic postoperative pain trajectories, pointing toward the possibility of using Markov decision processes to model sequential interactions between pain intensity ratings, and postoperative analgesic interventions.

Intraoperative vital signals convey a wealth of complex temporal information that can provide significant insights into a patient's physiological status during the surgery, as well as outcomes after the surgery. Our study involves the use of a deep recurrent neural network architecture to predict patient's outcomes after the surgery, as well as to predict the immediate changes in the intraoperative signals during the surgery. More specifically, we will use a Long Short-Term Memory (LSTM) model which is a gated deep recurrent neural network architecture. We have performed two experiments on a large intraoperative dataset of 12,036 surgeries containing information on 7 intraoperative signals including body temperature, respiratory rate, heart rate, diastolic blood pressure, systolic blood pressure, fraction of inspired O 2 and end-tidal CO 2 . We first evaluated the capability of LSTM in predicting the immediate changes in intraoperative signals, and then we evaluated its performance on predicting each patient's length of stay outcome. Our experiments show the effectiveness of LSTM with promising results on both tasks compared to the traditional models.

The primary aim was to characterize the temporal dynamics of postoperative pain intensity using symbolic aggregate approximation (SAX). The secondary aim was to explore the effects of sociodemographic and clinical factors on the SAX representations of postoperative pain intensity.We applied SAX to a large-scale time series database of 226,808 acute postoperative pain intensity ratings. Pain scores were stratified by patient age, sex, type of surgery, home opioid use, and postoperative day (POD), and costratified by age and sex. Cosine similarity, a metric that measures distance using vector angle, was applied to these motif data to compare pain behavior similarities across strata.Across age groups, SAX clusters revealed a shift from low-to-low pain score transitions in older patients to high-to-high pain score transitions in younger patients, whereas analyses stratified by sex showed that males had a greater focus of pain score transitions among lower-intensity pain scores compared with females. Surgical stratification, using cardiovascular surgery as a reference, demonstrated that pulmonary surgery had the highest cosine similarity at 0.855. With POD stratification, POD 7 carried the greatest cosine similarity to POD 0 (0.611) after POD 1 (0.765), with POD 3 (0.419) and POD 4 (0.441) carrying the lowest cosine similarities with POD 0.SAX offers a feasible and effective framework for characterizing large-scale postoperative pain within the time domain. Stratification of SAX representations demonstrate unique temporal dynamic profiles on the basis of age group, sex, type of surgery, preoperative opioid use, and across PODs 1 to 7.

Epithelial mesenchymal transition (EMT), as defined by loss of epithelial characteristics and gain of a mesenchymal phenotype, has been reported in vivo although the occurrence of events remains unclear. This study aims at exploration of EMT portraits of breast cancer (BC) with relevance to different molecular pathways, especially potential EMT triggers and BC molecular subtypes. Immunohistochemical (IHC) expression of markers/triggers of EMT was studied on a well-defined cohort of invasive non-lobular BC (n = 1,035), prepared as tissue microarrays. IHC panel of biomarkers included cadherins (cad; E-cad and N-cad), TGFβ1, PIK3CA, pAkt, and others. Reverse phase protein array (RPPA) was performed for quantitative analysis of proteins extracted from formalin fixed paraffin embedded tissues of a subset of cases from this cohort. Four combinatorial phenotypic groups representing cadherin switch were defined, including E-cad(+)/N-cad(-), E-cad(-)/N-cad(-), E-cad(+)/N-cad(+), and E-cad(-)/N-cad(+). Statistically significant association was noticed between these phenotypes and histological tumour grade, tumour type and size and NPI staging classes. The E-cad/N-cad switch occurred more frequently in the triple negative molecular class, both basal and non-basal, and in the HER2(+) subtype than in luminal BC. Significant outcome differences were observed between cadherin switch combinatorial groups regarding BCSS and DMFS (p 0.001). Results of RPPA confirm those observed using IHC regarding differential expressions of EMT markers/triggers. EMT/cadherin switch programs in BC appear to occur in synergy with TGFβ1 and PIK3/Akt pathways activation. These data explain, at translational proteomic level, the molecular heterogeneity and in turn the varied clinical behaviour of BC molecular subtypes. RPPA is a promising high-throughput technique in monitoring subtle quantitative changes in protein expression in archival material.

Increasing gabapentinoid use has raised concerns of misuse and abuse in the United States (US). Little is known about the characteristics of gabapentinoid use in general clinical practice over time. This cross-sectional study used data from the National Ambulatory Medical Care Survey. We examined the trends of patient and prescriber characteristics and the diagnoses associated with US ambulatory care visits involving gabapentinoids for adult visits from 2003 to 2016. Using multivariable logistic regression, we estimated the adjusted proportion of gabapentinoid-involved visits among all visits and tested for trend significance. Among the weighted estimate of 260.1 million gabapentinoid-involved visits (aged 18−64 years: 61.8%; female: 61.9%; white: 85.5%), the adjusted annual proportion of gabapentinoid-involved visits nearly quadrupled from 2003 to 2016 (9.1 to 34.9 per 1000 visits; Ptrend < 0.0001), driven mainly by gabapentin. Nearly half had concurrent use with opioids (32.9%) or benzodiazepines (15.3%). Primary care physicians (45.8%), neurologists (8.2%), surgeons (6.2%), and psychiatrists (4.8%) prescribed two-thirds of the gabapentinoids. Most (96.6%) of the gabapentinoid visits did not have an approved indication for gabapentinoids among the first three diagnoses. Among US ambulatory care visits from 2003 to 2016, gabapentinoid use increased substantially, commonly prescribed by primary care physicians.

Objective The goal of this project was to explore the association between post-anesthesia care unit (PACU) pain scores recorded within the first and second hour of the end of surgery with maximum and median pain scores recorded on postoperative days (PODs) 1 through 5. Design This study was a retrospective cohort study of clinically documented pain scores in a mixed surgical population. Setting This study was set in a single tertiary-care teaching hospital over a 1-year time period. Patients All patients were adult patients undergoing a single, non-ambulatory, non-obstetric surgical procedure. Measures Pain scores, measured using the numerical rating scale, from PODs 0 through 5 were obtained from an integrated data repository. Kendall's Tau-b correlations were then calculated between maximum pain scores occurring within each of the two PACU time periods and maximum and median pain scores in each of the five ensuing PODs. Results A total of 349,797 pain scores from 8,332 patients were reviewed. Correlations between maximum pain score by time period demonstrated a significant and high correlation at Tau-b = 0.86, between 1-hour PACU pain scores and 2-hour PACU pain scores. However, the correlation of maximum pain scores recorded in the PACU with those recorded on PODs 1 through 5 was significantly lower, ranging from 0.19 to 0.27. The correlation of maximum PACU pain score with median pain scores recorded on PODs 1 through 5 ranged from 0.22 to 0.29. The correlation structures of the PODs 1 through 5 median pain scores may be consistent with an autoregressive pattern. Conclusions Maximum scores measured within the PACU likely reflect a set of circumstances distinct from those experienced on PODs 1 through 5.

Supplemental Digital Content is Available in the Text. A patient's experience of pain for the first 48 hours of an admission can be visualized with graphical pain score trajectories, providing clinically useful information., Pain care for hospitalized patients is often suboptimal. Representing pain scores as a graphical trajectory may provide insights into the understanding and treatment of pain. We describe a 1-year, retrospective, observational study to characterize pain trajectories of hospitalized adults during the first 48 hours after admission at an urban academic medical center. Using a subgroup of patients who presented with significant pain (pain score >4; n = 7762 encounters), we characterized pain trajectories and measured area under the curve, slope of the trajectory for the first 2 hours after admission, and pain intensity at plateau. We used mixed-effects regression to assess the association between pain score and sociodemographics (age, race, and gender), pain medication orders (opioids, nonopioids, and no medications), and medical service (obstetrics, psychiatry, surgery, sickle cell, intensive care unit, and medicine). K-means clustering was used to identify patient subgroups with similar trajectories. Trajectories showed differences based on race, gender, service, and initial pain score. Patients presumed to have dissimilar pain experiences (eg, sickle vs obstetrical) had markedly different pain trajectories. Patients with higher initial pain had a more rapid reduction during their first 2 hours of treatment. Pain reduction achieved in the 48 hours after admission was approximately 50% of the initial pain, regardless of the initial pain. Most patients' pain failed to fully resolve, plateauing at a pain score of 4 or greater. Visualizing pain scores as graphical trajectories illustrates the dynamic variability in pain, highlighting pain responses over a period of observation, and may yield new insights for quality improvement and research.