Understanding Experiences of Youth with Long COVID: A Qualitative Approach.

There is limited information on the specific impacts of Long COVID in youth. Long COVID presents as persisting or new symptoms following initial COVID-19 infection. The aim of this study was to better understand how children and their families describe their experiences seeking diagnosis and support following the onset of symptoms of Long COVID. Six children and five caregivers located in the United States participated in this study. Study procedures included an online video interview with caregiver-child dyads. Interview transcriptions were then analyzed using a conventional approach to content analysis, with two independent coders generating themes. Eight themes emerged from this analysis including the severity of illness and symptomatology, difficulty surrounding the diagnostic process and not being believed, the impact on family and social connections, poor school functioning, positive coping, subsequent positive medical experiences, mental health, and knowledge of the medical field and healthcare experience. Themes revealed difficulty for youth and families in navigating the medical system and functioning in areas of daily life as well as areas of positive experiences related to coping and medical involvement. These findings also highlighted areas of needed improvement for the medical community and for research on Long COVID in youth.

Long-term outcomes of the pentaspline pulsed-field ablation catheter for the treatment of paroxysmal atrial fibrillation: results of the prospective, multicentre FARA-Freedom Study.

AIMS: Pulmonary vein isolation (PVI) is a well-established strategy for the treatment of paroxysmal atrial fibrillation (PAF). Despite randomized controlled trials and real-world data showing the promise of pulsed-field ablation (PFA) for this treatment, long-term efficacy and safety data demonstrating single-procedure outcomes off antiarrhythmic drugs remain limited. The aim of the FARA-Freedom Study was to evaluate the long-term efficacy and safety of PFA using the pentaspline catheter for PAF. METHODS AND RESULTS: FARA-Freedom, a prospective, non-randomized, multicentre study, enrolled patients with PAF undergoing de novo PVI with PFA, who were followed for 12 months with weekly transtelephonic monitoring and a 72-h Holter ECG at 6 and 12 months. The primary safety endpoint was a composite of device- or procedure-related serious adverse events out to 7 days post-ablation and PV stenosis or atrioesophageal (AE) fistula out to 12 months. Treatment success is a composite of acute PVI and chronic success, which includes freedom from any documented atrial tachyarrhythmia longer than 30 s, use of antiarrhythmic drugs or cardioversion after a 3-month blanking period, or use of amiodarone or repeat ablation at any time. The study enrolled 179 PAF patients (62 ± 10 years, 39% female) at 13 centres. At the index procedure, all PVs were successfully isolated with the pentaspline PFA catheter. Procedure and left atrial dwell times, with a 20-min waiting period, were 71.9 ± 17.6 and 41.0 ± 13.3 min, respectively. Fluoroscopy time was 11.5 ± 7.4 min. Notably, monitoring compliance was high, with 88.4 and 90.3% with weekly events and 72-h Holter monitors, respectively. Freedom from the composite primary effectiveness endpoint was 66.6%, and 41 patients had atrial tachyarrhythmia recurrence, mostly recurrent atrial fibrillation (31 patients). The composite safety endpoint occurred in two patients (1.1%), one tamponade and one transient ischaemic attack. There was no coronary spasm, PV stenosis, or AE fistula. There were four cases of transient phrenic nerve palsy, but all resolved during the index procedure. CONCLUSION: In this prospective, non-randomized, multicentre study, PVI using a pentaspline PFA catheter was effective in treating PAF patients despite rigourous endpoint definitions and high monitoring compliance and demonstrated favourable safety. REGISTRATION: Clinical Trials.gov Identifier: NCT05072964 (sponsor: Boston Scientific Corporation).

Who Cares? Unpaid Caregiving by Sexual Identity, Gender, and Partnership Status Among U.S. Adults.

Recent scholarship indicates that sexual minority adults have higher caregiving rates than heterosexuals and that women are more likely to be caregivers than men. However, little research has addressed how gender and sexuality intersect in shaping caregiving status. This study uses data from the Behavioral Risk Factor Surveillance System and aggregates a probability-based sample of adults living in 36 U.S. states between 2015 and 2021. We examine who provides care among adult heterosexual, lesbian, gay, and bisexual men and women. Results reveal that women are more likely to be caregivers than men, but only among heterosexuals. We find little variation in caregiving by sexuality among women, but bisexual men are more likely than heterosexual men to be caregivers; the latter result appears to be driven by unpartnered, bisexual men. Lastly, we contextualize caregivers' experiences and reveal selected descriptive differences in patterns of care recipient-caregiver relationships across gender and sexual identity groups. Our findings advance understanding of caregiving and changing family ties in an era of population aging and increasing diversity in sexual identities.

Contextual Influences on Nonresponse to Health Survey Questions About Sexual Orientation and Gender Identity.

Purpose: We examined the relationship between state context and survey nonresponse to sexual orientation (SO) and gender identity (GI) questions. Methods: We obtained data from the 2014-2020 Behavioral Risk Factor Surveillance System (BRFSS) surveys. Item nonresponse was defined as selecting "don't know/not sure" or "refused" for each of two questions about SO and GI. Nonresponse patterns included responding to both SO and GI questions; responding only to the SO question (nonresponse to GI); responding only to the GI question (nonresponse to SO); and responding to neither question. State-level contextual measures included legal protections for lesbian, gay, bisexual, transgender, or other sexual or gender minority (LGBT+) people, LGBT+ social movement strength, and public opinion regarding LGBT+ issues. Results: The analysis included 1,459,525 respondents from 44 states (190 state-years). On weighted analysis, 96.5% of adults answered both SO/GI questions, 2.4% responded only to GI, 0.4% responded only to SO, and 0.7% responded to neither. The demographic profile of individuals with GI-only nonresponse differed markedly from the profile of adults with SO-only nonresponse. An increasingly favorable legal climate for LGBT+ people was associated with greater rates of response to SO and GI questions. However, a more LGBT+ friendly state climate measured by social movement strength or public opinion was not consistently associated with reduced SO and GI question nonresponse. Conclusion: Contextual factors have mixed association with nonresponse to SO and GI question on BRFSS surveys. Our results warrant continued development of health survey questionnaires to elicit accurate information on respondents' SO and GI.

Pediatric Post-Acute Sequelae of SARS-CoV-2 Infection.

Aim: Youth who have not recovered from COVID-19 have been referred to as having Post-Acute Sequelae of SARS-CoV-2 Infection (PASC). The goal of this study was to better understand which symptoms persisted since onset of infection and how these symptoms compare to symptoms experienced by those with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Method: A sample of 19 parents who had a child with PASC were recruited using social media to fill out a questionnaire detailing symptoms at two time points. The first time point included their child's current symptoms and the second captured symptoms at initial infection. These participants were compared to a sample of 19 youth with ME/CFS. Results: Findings indicated significant decreases among several immune, neuroendocrine, pain, post-exertional malaise (PEM), and COVID-19 Centers for Disease Control and Prevention (CDC) domain symptoms from time of acute infection to time of current reporting. Fatigue remained at a high level as did several symptoms within the sleep and PEM domains. Participants with ME/CFS had overall worse symptomatology when compared to participants with PASC, especially in the neurocognitive domain. Conclusion: Most symptoms of those with PASC decline over time, but several remain at high levels, including fatigue. These findings are helpful in better understanding common symptom presentation profiles for youth with PASC and can be used to more adequately tailor diagnostic criteria and treatment strategies for youth.

A thalamo-parietal cortex circuit is critical for place-action coordination.

The anterior and lateral thalamus (ALT) contains head direction cells that signal the directional orientation of an individual within the environment. ALT has direct and indirect connections with the parietal cortex (PC), an area hypothesized to play a role in coordinating viewer-dependent and viewer-independent spatial reference frames. This coordination between reference frames would allow an individual to translate movements toward a desired location from memory. Thus, ALT-PC functional connectivity would be critical for moving toward remembered allocentric locations. This hypothesis was tested in rats with a place-action task that requires associating an appropriate action (left or right turn) with a spatial location. There are four arms, each offset by 90°, positioned around a central starting point. A trial begins in the central starting point. After exiting a pseudorandomly selected arm, the rat had to displace the correct object covering one of two (left versus right) feeding stations to receive a reward. For a pair of arms facing opposite directions, the reward was located on the left, and for the other pair, the reward was located on the right. Thus, each reward location had a different combination of allocentric location and egocentric action. Removal of an object was scored as correct or incorrect. Trials in which the rat did not displace any objects were scored as "no selection" trials. After an object was removed, the rat returned to the center starting position and the maze was reset for the next trial. To investigate the role of the ALT-PC network, muscimol inactivation infusions targeted bilateral PC, bilateral ALT, or the ALT-PC network. Muscimol sessions were counterbalanced and compared to saline sessions within the same animal. All inactivations resulted in decreased accuracy, but only bilateral PC inactivations resulted in increased non selecting, increased errors, and longer latency responses on the remaining trials. Thus, the ALT-PC circuit is critical for linking an action with a spatial location for successful navigation.

Lon degrades stable substrates slowly but with enhanced processivity, redefining the attributes of a successful AAA+ protease.

Lon is a widely distributed AAA+ (ATPases associated with diverse cellular activities) protease known for degrading poorly folded and damaged proteins and is often classified as a weak protein unfoldase. Here, using a Lon-degron pair from Mesoplasma florum (MfLon and MfssrA, respectively), we perform ensemble and single-molecule experiments to elucidate the molecular mechanisms underpinning MfLon function. Notably, we find that MfLon unfolds and degrades stably folded substrates and that translocation of these unfolded polypeptides occurs with a ∼6-amino-acid step size. Moreover, the time required to hydrolyze one ATP corresponds to the dwell time between steps, indicating that one step occurs per ATP-hydrolysis-fueled "power stroke." Comparison of MfLon to related AAA+ enzymes now provides strong evidence that HCLR-clade enzymes function using a shared power-stroke mechanism and, surprisingly, that MfLon is more processive than ClpXP and ClpAP. We propose that ample unfoldase strength and substantial processivity are features that contribute to the Lon family's evolutionary success.

Visual Misrepresentations: The Lack of Skin Tone and Sex Equity in General Surgical Textbooks.

OBJECTIVE: Lack of racial and ethnic diversity in educational material contributes to health disparities. This study sought to determine if images of skin color and sex in general surgery textbooks were reflective of the U.S. DESIGN: All human figures with discernable sex characteristics and/or skin tone were evaluated independently by 4 coders. Each image was categorized as male or female. Skin tone in each image was categorized using the Massey- Martin skin color scale. This data was compared to 2020 U.S. Census Data. SETTING: U.S. Medical School. PARTICIPANTS: Not applicable. RESULTS: A total of 1179 images were evaluated for skin tone alone; 293 images for sex alone. 650 images depicted characteristics of both sex and skin tone. Interrater reliability was 0.78 for skin tone and 0.91 for sex. While the U.S. population is 59.3% white, 29.5% non-black persons of color and 13.6% black, in surgical textbooks, 90.7% of images were white, 6.5% were non-black persons of color, and 2.8% were black. Distribution of skin tone for all textbooks were significantly different. (p < 0.001) compared to the U.S. POPULATION: The U.S. population is 49.5% male and 50.5% female. When images of sex specific genitalia and breasts are excluded, surgical textbook images are 62.9% male and 37.1% female. Only 1 textbook had a distribution of sex that was similar to the U.S. CONCLUSIONS: Despite increasing diversity in the U.S. population there is a lack of skin tone and sex diversity in traditional surgical textbooks.

Adults with ME/CFS report surprisingly high rates of youth symptoms: A qualitative analysis of patient blog commentary.

BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic illness that impacts pediatric populations. OBJECTIVE: The current study aimed to better understand adult perceptions of their experiences leading up to their diagnosis of ME/CFS. METHOD: Patients provided data regarding symptoms of ME/CFS they may have experienced during childhood through a popular community blog forum, with participants interacting via blog comments in real-time and across various geographical locations. RESULTS: Descriptive analyses indicated that roughly 43% of adult survey participants reported having developed ME/CFS prior to age 18. A standard content analysis of patient blog commentary revealed several themes, such as poor mental health, family pattern/history, healthy childhood preceding sick adulthood, feeling misunderstood, lack of clarity until adulthood, sharing of resources, poor school functioning, isolation/poor social supports, and coping mechanisms. CONCLUSION: There are unique benefits and insights that can be used by investigators who collaborate with patient organizations as a means of better understanding ME/CFS illness severity, presentation, and lived experiences.

Vaccine Attitudes Mediate Relationships Between Caregiver Political Ideology and Likelihood of Child Vaccination for COVID-19.

INTRODUCTION: The COVID-19 vaccine has become available to children ages 5-12, yet vaccine uptake is suboptimal. Political ideology is a correlate of COVID-related beliefs and vaccine likelihood among US adults. However, since political ideology is not easily modifiable, attention to modifiable mechanisms that may explain links between political ideology and vaccine hesitancy is important in addressing this public health crisis. Caregiver attitudes around vaccine safety and efficacy have been related to vaccine uptake in other populations and warrant additional study in the context of COVID-19. The current study examined whether caregiver's attitudes regarding the safety and efficacy of the COVID-19 vaccine mediated the relationship between caregiver political ideology and likelihood of having their child vaccinated. METHODS: 144 US caregivers of children (6-12 years) completed an online survey in summer 2021 to assess political ideology, vaccine-related beliefs, and likelihood of having their child vaccinated against COVID-19. RESULTS: Caregivers with more liberal political views reported higher likelihood of eventual child vaccination compared to caregivers who reported a more conservative views (t(81) = 6.08, BCa CI [2.97, 5.67]). Moreover, parallel mediation models indicated caregiver?s perceptions of risks (BCa CI [-.98, -.10]) and efficacy (BCa CI [-3.16, -2.15]) of the vaccine each mediated the aforementioned relationship, with perceived efficacy explaining significantly more variance than risks. CONCLUSIONS: Findings extend knowledge by identifying social cognitive factors that impact caregiver vaccine hesitancy. Interventions to address caregiver's hesitancy to have their child vaccinated through modifying caregiver's inaccurate beliefs regarding vaccines or enhancing perceptions of vaccine efficacy is warranted.

Transgender Adults Have Higher Rates Of Disability Than Their Cisgender Counterparts.

In the US population, the burden of disability among transgender adults compared with their cisgender peers is largely unknown. This study used seven years of pooled cross-sectional data from the Behavioral Risk Factor Surveillance System to examine how disability varies by gender across age groups. I present a series of nested logistic regression models to show the adjusted probability of disability among adults. Transgender adults have a higher probability of reporting a disability compared with cisgender men and women. After confounders are controlled for, transgender adults have a 27 percent chance of having at least one disability at age twenty and a 39 percent chance at age fifty-five, which is nearly twice the rate of their cisgender counterparts at both ages. The findings show the importance of considering disability from a life-course perspective, the effect of intersectional identities on disability risk, and the urgency of targeted health interventions for transgender people in the US.

Single-molecule investigations of single-chain cellulose biosynthesis.

Cellulose biosynthesis in sessile bacterial colonies originates in the membrane-integrated bacterial cellulose synthase (Bcs) AB complex. We utilize optical tweezers to measure single-strand cellulose biosynthesis by BcsAB from Rhodobacter sphaeroides. Synthesis depends on uridine diphosphate glucose, Mg2+, and cyclic diguanosine monophosphate, with the last displaying a retention time of ∼80 min. Below a stall force of 12.7 pN, biosynthesis is relatively insensitive to force and proceeds at a rate of one glucose addition every 2.5 s at room temperature, increasing to two additions per second at 37°. At low forces, conformational hopping is observed. Single-strand cellulose stretching unveiled a persistence length of 6.2 nm, an axial stiffness of 40.7 pN, and an ability for complexes to maintain a tight grip, with forces nearing 100 pN. Stretching experiments exhibited hysteresis, suggesting that cellulose microstructure underpinning robust biofilms begins to form during synthesis. Cellohexaose spontaneously binds to nascent single cellulose strands, impacting polymer mechanical properties and increasing BcsAB activity.

Risk factors for suicide in chronic fatigue syndrome.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) includes symptoms such as post-exertional malaise, unrefreshing sleep, and cognitive impairments. Several studies suggest these patients have an increased risk of suicidal ideation and early mortality, although few have published in this area. This study explores risk factors for suicide among 64 individuals with ME/CFS using archival data, 17 of which died from suicide. Results indicated an increased risk of suicide for those for those utilizing the label CFS, for those with limited overall functioning, and for those without comorbid illnesses. Findings suggest that stigma and functional impairments limit access to care and social supports.

The bitter end: T2R bitter receptor agonists elevate nuclear calcium and induce apoptosis in non-ciliated airway epithelial cells.

Bitter taste receptors (T2Rs) localize to airway motile cilia and initiate innate immune responses in retaliation to bacterial quorum sensing molecules. Activation of cilia T2Rs leads to calcium-driven NO production that increases cilia beating and directly kills bacteria. Several diseases, including chronic rhinosinusitis, COPD, and cystic fibrosis, are characterized by loss of motile cilia and/or squamous metaplasia. To understand T2R function within the altered landscape of airway disease, we studied T2Rs in non-ciliated airway cell lines and primary cells. Several T2Rs localize to the nucleus in de-differentiated cells that typically localize to cilia in differentiated cells. As cilia and nuclear import utilize shared proteins, some T2Rs may target to the nucleus in the absence of motile cilia. T2R agonists selectively elevated nuclear and mitochondrial calcium through a G-protein-coupled receptor phospholipase C mechanism. Additionally, T2R agonists decreased nuclear cAMP, increased nitric oxide, and increased cGMP, consistent with T2R signaling. Furthermore, exposure to T2R agonists led to nuclear calcium-induced mitochondrial depolarization and caspase activation. T2R agonists induced apoptosis in primary bronchial and nasal cells differentiated at air-liquid interface but then induced to a squamous phenotype by apical submersion. Air-exposed well-differentiated cells did not die. This may be a last-resort defense against bacterial infection. However, it may also increase susceptibility of de-differentiated or remodeled epithelia to damage by bacterial metabolites. Moreover, the T2R-activated apoptosis pathway occurs in airway cancer cells. T2Rs may thus contribute to microbiome-tumor cell crosstalk in airway cancers. Targeting T2Rs may be useful for activating cancer cell apoptosis while sparing surrounding tissue.

Targeting Co-Sleeping in Children With Anxiety Disorders Using a Modified Bedtime Pass Intervention: A Case Series Using a Changing Criterion Design.

Children with anxiety disorders experience high rates of sleep-related problems, with co-sleeping and resistance to sleeping independently being among the more frequent problems reported. Although extinction-based behavioral sleep interventions have repeatedly been shown to be highly effective for treating bedtime resistance, the primary obstacle to their implementation is parent discomfort with these procedures. The bedtime pass intervention was developed to minimize extinction bursts when implementing extinction procedures for childhood sleep problems. Several studies have found this intervention to be effective for treating bedtime resistance behaviors, but not co-sleeping specifically, in nonclinical samples of children. The current paper describes the use of a modified bedtime pass procedure to target problematic co-sleeping and related bedtime resistance behaviors in two children with anxiety disorders who presented for treatment at an outpatient pediatric anxiety specialty clinic. A changing criterion, single subject methodology was used to evaluate the effectiveness of this procedure. Data indicate that both children were able to transition from co-sleeping with parents every night, to sleeping independently, with relatively limited need for contact with parents at night during the intervention. These findings extend the data for the bedtime pass procedure to both co-sleeping and children with anxiety disorders. Clinical implications of these findings are discussed given the limited guidance for treating comorbid sleep problems in anxious children. Strengths and limitations of the data being drawn from a clinical treatment setting are also discussed.

Molecular origins of reduced activity and binding commitment of processive cellulases and associated carbohydrate-binding proteins to cellulose III.

Efficient enzymatic saccharification of cellulosic biomass into fermentable sugars can enable production of bioproducts like ethanol. Native crystalline cellulose, or cellulose I, is inefficiently processed via enzymatic hydrolysis but can be converted into the structurally distinct cellulose III allomorph that is processed via cellulase cocktails derived from Trichoderma reesei up to 20-fold faster. However, characterization of individual cellulases from T. reesei, like the processive exocellulase Cel7A, shows reduced binding and activity at low enzyme loadings toward cellulose III. To clarify this discrepancy, we monitored the single-molecule initial binding commitment and subsequent processive motility of Cel7A enzymes and associated carbohydrate-binding modules (CBMs) on cellulose using optical tweezers force spectroscopy. We confirmed a 48% lower initial binding commitment and 32% slower processive motility of Cel7A on cellulose III, which we hypothesized derives from reduced binding affinity of the Cel7A binding domain CBM1. Classical CBM-cellulose pull-down assays, depending on the adsorption model fitted, predicted between 1.2- and 7-fold reduction in CBM1 binding affinity for cellulose III. Force spectroscopy measurements of CBM1-cellulose interactions, along with molecular dynamics simulations, indicated that previous interpretations of classical binding assay results using multisite adsorption models may have complicated analysis, and instead suggest simpler single-site models should be used. These findings were corroborated by binding analysis of other type-A CBMs (CBM2a, CBM3a, CBM5, CBM10, and CBM64) on both cellulose allomorphs. Finally, we discuss how complementary analytical tools are critical to gain insight into the complex mechanisms of insoluble polysaccharides hydrolysis by cellulolytic enzymes and associated carbohydrate-binding proteins.

How Is Surgical Risk Best Assessed? A Cohort Comparison of Measures in Total Joint Arthroplasty.

BACKGROUND: We designed this study to determine whether a Frailty Deficit Index (FI) confers added risk stratification beyond more traditional methods. The associations of preoperative scores on FI, American Society of Anesthesiologists (ASA) physical status, and Charlson Comorbidity Index (CCI) with complications after total joint arthroplasty (TJA) were compared. METHODS: Using a single institution cohort of adult patients ≥50 years undergoing primary or revision TJA from 2005 to 2016, we assessed how well the FI, CCI, and ASA scores predicted risk of mortality, infection, and reoperation. We performed 7 models for each outcome: FI, ASA, and CCI alone, FI + ASA, FI + CCI, ASA + CCI, and FI + ASA + CCI. Cox proportional hazards regression methods were used to calculate the concordance (C-) statistic, a measure of discrimination. RESULTS: Of 18,397 TJAs included, 98.9% were alive 1 year postoperatively. For mortality, all models had concordance between 0.76 and 0.79, with the FI + ASA + CCI model performing highest (C-statistic 0.79; 95% confidence interval [CI] 0.76-0.82). Unadjusted, FI had the strongest concordance (C-statistic 0.77). In FI + ASA + CCI, each increase in 1 comorbidity (of 32 total comorbidities) in the FI was significantly associated with a 12% increase in the rate of mortality (hazard ratio [HR] 1.12, 95% CI 1.07-1.17, P < .001), 10% increase in infection (HR 1.10, 95% CI 1.06-1.14; P < .001), and 6% increase in reoperation (HR 1.06, 95% CI 1.05-1.08, P < .001). CONCLUSION: Identifying at-risk patients preoperatively is crucial and may result in adjustment of postoperative care. FI was independently associated with risk of adverse outcomes following TJA even after taking into account other predictive measures.

Risk of major bleeding associated with aspirin use in non-surgical critically ill patients receiving therapeutic anticoagulation.

BACKGROUND: We aimed to evaluate the risk of major bleeding in non-surgical critically ill patients who received aspirin in conjunction with therapeutic anticoagulation (concomitant therapy) compared to those who received therapeutic anticoagulation alone. METHODS: This is a retrospective cohort study of critically ill patients initiated on therapeutic anticoagulation at a large academic medical center from 2007 to 2016. The exposure of interest was aspirin therapy during anticoagulation. The primary outcome was the incidence of major bleeding during hospitalization. Secondary outcomes included in-hospital mortality, hospital free days, and new myocardial infarction or stroke. RESULTS: 5507 (73.2%) patients received anticoagulation alone and 2014 (26.8%) received concomitant therapy; major bleeding occurred in 19.0% and 22.2%, respectively. There was no increased risk of major bleeding [OR 1.10 (95% CI: 0.93-1.30); p = .27] or mortality [OR 0.93 (95% CI: 0.77-1.11); p = .43] with concomitant therapy. Patients receiving concomitant therapy had fewer hospital-free days (mean decrease of 0.73 [1.36, 0.09]; p = .03) and were more likely to experience new myocardial infarction or stroke [OR 2.61 (95% CI: 1.72-3.98); p < .001]. CONCLUSIONS: In non-surgical critically ill patients receiving therapeutic anticoagulation, concomitant use of aspirin was not associated with an increased risk of bleeding or in-hospital mortality.

Concomitant Aspirin and Anticoagulation Is Associated With Increased Risk for Major Bleeding in Surgical Patients Requiring Postoperative Intensive Care.

OBJECTIVES: Critically ill surgical patients may receive concomitant aspirin and therapeutic anticoagulation postoperatively, yet the safety of this practice remains unknown. We evaluated the risk of major bleeding with concomitant therapy compared with anticoagulation alone. DESIGN: Observational cohort study. Inverse probability of treatment weighting was used to assess the association between concomitant therapy and a primary outcome of major bleeding. SETTING: Postoperative ICUs at an academic medical center. PATIENTS: Adults (≥ 18 yr old) receiving anticoagulation during postoperative ICU admission between 2007 and 2016. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Nine thousand five hundred eighteen anticoagulated patients were included, including 3,237 (34%) receiving aspirin. A total of 1,874 unique patients (19.7%) experienced a major bleeding event. In inverse probability of treatment weighting analyses, concomitant therapy was associated with increased odds for major bleeding (odds ratio, 1.20; 95% CI, 1.05-1.36; p = 0.006) compared with anticoagulation alone. An interaction test suggested a differential relationship between aspirin use and major bleeding based on aspirin use in the 7 days prior to anticoagulation, such that a strong association between aspirin and major bleeding was observed for recent initiators of aspirin (1.40; 1.13-1.72;p = 0.002) but not for those continuing prior aspirin use. Aspirin use prior to anticoagulation did not modify the relationship between concomitant therapy and new myocardial infarction or stroke (i.e., rates were not increased with aspirin discontinuation prior to anticoagulation). CONCLUSIONS: Concomitant aspirin and anticoagulation in critically ill surgical patients was associated with an increased rate of major bleeding. Future investigations are warranted to further define optimal management of antiplatelet therapy during anticoagulation in surgical patients.

Serious games for serious crises: reflections from an infectious disease outbreak matrix game.

BACKGROUND: While there is widespread recognition of global health failures when it comes to infectious disease outbreaks, there is little discussion on how policy-makers and global health organizations can learn to better prepare and respond. Serious games provide an underutilized tool to promote learning and innovation around global health crises. In order to explore the potential of Serious Games as a policy learning tool, Global Affairs Canada, in collaboration with the Department of National Defense and academic partners, developed and implemented a matrix game aimed at prompting critical reflection and gender-based analysis on infectious disease outbreak preparedness and response. This commentary, written by the core development team, reflects on the process and outcomes of the gaming exercise, which we believe will be of interest to others hoping to promote innovative thinking and learning around global health policy and crisis response, as well as the application of serious games more broadly. MAIN BODY: Participants reported, through discussions and a post-game survey, that they felt the game was reflective of real-world decision-making and priority-setting challenges during a crisis. They reflected on the challenges that emerge around global health co-operation and outbreak preparedness, particularly noting the importance of learning to work with private actors. While participants only sporadically applied gender-based analysis or considered the social determinants of health during the game, post-game discussions led to reflection on the ways in which equity concerns are put aside during a crisis scenario and on why this happens, offering critical learning opportunities. CONCLUSION: Matrix games provide opportunities for policy-makers and health professionals to experience the challenges of global health co-operation, test ideas and explore how biases, such as those around gender, influence policy-making and implementation. Due to their flexibility, adaptability and accessibility, serious games offer a potentially powerful learning tool for global health policy-makers and practitioners.