Search

Introduction Patients with central nervous system malignancies have limited representation in studies evaluating DOACs for VTE treatment. This study evaluated the safety and efficacy of DOACs in comparison with LMWH for cancer-associated VTE in patients with primary brain tumors or secondary brain metastases. Materials & methods In this multicenter, retrospective cohort study, adult patients with a diagnosis of primary brain tumor or secondary brain metastases who received either a DOAC or LMWH for treatment of cancer-associated VTE were evaluated. The primary outcome was the cumulative incidence of any intracranial hemorrhage within a 6-month period following the initiation of anticoagulation. Secondary outcomes included the cumulative incidence of any bleeding event, and recurrent VTE events. Results Between January 1, 2012 and October 9, 2019, one-hundred eleven patients met inclusion criteria. The 6-month cumulative incidence of intracranial hemorrhage was 4.3% (95% CI, 0.74–13.2%) in the DOAC group, compared to 5.9% (95% CI, 1.5–14.9%) in the LMWH group (p = 0.61). The 6-month cumulative incidence of bleeding events was 14.3% (95% CI, 6.2–25.8%) in the DOAC group, compared to 27.8% (95% CI, 15.5–41.6%) in the LMWH group (p = 0.10). The 6-month cumulative incidence of recurrent VTE events was 5.6% in the DOAC group (95% CI, 1.5–14.2%), compared to 6.6% in the LMWH group (95% CI, 1.7–16.5%) (p = 0.96). No differences were found with respect to other secondary outcomes. Conclusion There were no significant differences in bleeding or recurrent VTE events between DOACs and LMWH. These findings suggest DOACs may be safe and effective for VTE treatment in this patient population.

Objective Given incarcerated women's lack of access to contraception prior to, during, and post-incarceration and concerns of potential reproductive coercion in correctional settings, the objective was to explore incarcerated women's perspective of making provider-controlled methods of long-acting reversible contraception (LARC) available in an U.S. urban jail. Study design Using a concurrent mixed-methods approach, we explored contraceptive use and method choice prior to and after incarceration among women detained in a U.S. urban jail. Focus group discussions primarily focused on incarcerated women's perceptions of LARC. Results In the 30 days prior to arrest, 28 of 116 women (24%) were using a non-barrier contraceptive method. Methods of LARC were used the least, and the majority (n = 74, 64%) were not interested in initiating LARC in jail. Concern about the potential side effects of LARC was the main reason for disinterest followed by distrust in correctional health care staffs’ qualifications. Study participants did not reference coercion as a concern. Conclusions Apprehension about the training of health care providers and cleanliness of the detention facility outweighed participants’ concerns regarding autonomy restrictions associated with provider-controlled methods of LARC. Despite limited interest in initiating LARC use while incarcerated, participants supported making all forms of contraception more accessible in jail settings. Implications Understanding incarcerated women's reproductive and contraceptive desires, including their perceptions of LARC, will help improve the provision of equitable reproductive health care in correctional settings. Our findings highlight the importance of contextual factors in determining women's willingness to access contraceptive care in carceral settings, if available.

Autosomal recessive osteopetrosis has a variable presentation, most commonly including failure to thrive, hypocalcemia, seizures, hepatosplenomegaly, hydrocephalus, vision or hearing loss, and cytopenias. Multiple symptoms are usually seen at presentation. The variability of presentation often delays diagnosis and subsequent treatment. Here, we present a case of an infant with this condition who initially presented with triventricular hydrocephalus with Chiari I malformation. This alone is not a common presentation of this disease, and we present this case to highlight autosomal recessive osteopetrosis as a potential diagnosis in infants presenting with hydrocephalus and discuss the other associated symptoms, management, and prognosis of this condition. The patient was a full-term infant with a routine newborn period. At 6 months, the infant had macrocephaly and frontal bossing with a bulging fontanelle. She was found to have hydrocephalus with moderate ventriculomegaly involving the third and lateral ventricles with an associated Chiari 1 malformation. The infant was asymptomatic at the time. The infant was promptly referred to neurosurgery and underwent an uncomplicated ventriculoperitoneal shunt placement. Post-operative X-rays showed increased density of the skull with other bone changes suggestive of autosomal recessive osteopetrosis. Subsequent lab work and imaging studies were consistent with this condition. The diagnosis was confirmed by genetic testing, and the patient has undergone treatment with hematopoietic stem cell transplant. Hydrocephalus is a common feature of this condition, typically seen in conjunction with other systemic symptoms and laboratory findings. Our patient had a limited initial presentation of triventricular hydrocephalus with Chiari I malformation and was otherwise clinically asymptomatic. There is limited literature of such a presentation, and we highlight this case to increase awareness, as timely diagnosis of these patients is critical for treatment and future outcomes.

BACKGROUND Hyperkalemia is a rare life-threatening complication of red blood cell (RBC) transfusion. Stored RBCs leak intracellular potassium (K+) into the supernatant; irradiation potentiates the K+ leak. As the characteristics of patients and implicated RBCs have not been studied systematically, a multicenter study of transfusion-associated hyperkalemia (TAH) in the pediatric population was conducted through the AABB Pediatric Transfusion Medicine Subsection. STUDY DESIGN The medical records of patients

Introduction CVT-301 (Inbrija®) is a levodopa inhalation powder for on-demand treatment of OFF episodes in Parkinson's disease patients treated with carbidopa/levodopa. Safety and efficacy results of a 12-month, dose-level blinded extension study of a phase 3 trial (SPAN℠-PD) of CVT-301 are presented. Methods Patients were receiving oral carbidopa/levodopa and adjunctive CVT-301 treatment, blinded to dose (60 mg or 84 mg, N = 325). Study visits occurred every 3 months. Pulmonary function was assessed by spirometry. Other safety assessments included dyskinesia and adverse events (AEs). Secondary objectives of the study included maintenance of improvement assessments for occurrence of an ON state during the 60-min post-dose period, change in total daily OFF time, and Patient Global Impression of Change (PGIC). Results Most frequent AEs (≥5%) were cough (15.4%), fall (13.1%), upper respiratory tract infection (7.1%), and dyskinesia (5.1%). Severe AEs (>1 event) were cough (1.9%) and dyskinesia (0.6%). Twelve-month mean changes from baseline for FEV1, FVC, and DLCO were −0.092 L, −0.097 L, and −0.922 mL/min/mmHg, respectively. At 12 months, 73.0% of patients on 84 mg achieved an ON state within 60 min. Total daily OFF time was reduced by 0.55 h (month 1) and 0.88 h (month 12) for the 84 mg dose. Percentage of patients self-reported as improved by PGIC was 65.5–91.9% over 12 months. Conclusion CVT-301 was generally well-tolerated. Twelve-month decline in pulmonary function was consistent with a prior PD control group. Exploratory efficacy results showed CVT-301 maintained improvement at achieving ON states in patients experiencing OFF episodes, decreasing daily OFF time, and maintaining improvement in PGIC.

Background: Arteriovenous fistulas and grafts are preferred access for hemodialysis. Outflow stenosis is a common complication that can be managed with angioplasty and stenting. Stent placement can be complicated by thrombosis, limited area of cannulation, fracture, and migration. Objective: This case reports a rare complication of endovascular stents, namely stent migration to the pulmonary artery in the setting of renal transplantation. Methods: A 55-year-old woman with end stage renal disease secondary to diabetes mellitus on hemodialysis via a left arm basilic vein transposition. She subsequently developed outflow stenosis that was treated with a stent placement. She was admitted for deceased donor kidney transplantation and preoperative x-ray showed migration of the stent into a segmental pulmonary artery. After a pre-operative, multidisciplinary discussion between interventional radiology, cardiothoracic surgery, transplant nephrology and transplant surgery, the decision was made to proceed with rental transplantation followed by stent removal. Interventional radiology removed the stent on postoperative day two without complication. She has not experienced any complications in the year following her transplantation. Conclusion: Postoperative stent removal by interventional radiology is a feasible management option in lieu of lifelong anticoagulation.

Objective: Pilot data was collected to examine providers’ beliefs, knowledge, self-efficacy, barriers, and practices related to perinatal depression and how they may differ across provider types. Background: High prevalence and detrimental impact of depression during pregnancy and the first year postpartum (i.e. perinatal period) on maternal and child health outcomes highlights the need for improving diagnosis and treatment during this critical period. Healthcare providers play a significant role in helping to identify and manage perinatal depression. Methods: Ninety-nine providers (e.g. physicians, nurses, mental health workers, public health practitioners) who provide care to pregnant women in Colorado completed a 64-item online survey. Results: Although 94% of providers reported it was their responsibility to recognize perinatal depression, variations across specialties with regards to responsibility to treat were found. Most providers (91%) reported use of a screening tool for depression, 60% of providers provide counseling on perinatal depression, and 80% of providers refer patients for treatment of perinatal depression on at least a monthly basis. Significant differences in knowledge, self-efficacy, current practices, and perceived patient barriers were found across provider specialties. Conclusion: These findings highlight the need for expansion of online training programs to increase awareness of mental health resources in the community, improve confidence related to diagnosis and treatment of perinatal mood disorders, and to enhance communication between mental health specialists and healthcare providers in order to effectively identify and manage maternal depression.

The prevalence of calcification of human aortic valve in populations 65 years old and greater is estimated to be 2–3%. Bicuspid aortic valve disease (BAVD) is a common etiology of aortic stenosis in populations aged 60–75 years of age; 30–50% of operated cases of aortic stenosis were due to calcified BAVD. Dysregulation of the Notch and the canonical Wnt pathway has been well documented to be associated with calcification of the aortic valve. However, recent studies have increased this scope to include the non-canonical pathway where Wnt5a, Wnt5b and Wnt 11 levels were significantly greater in calcified human aortic valves than normal valves, and with Wnt5b specifically being implicated in BAVD pathogenesis. More recently, Lipoprotein(a) [Lp(a)] has been implicated as a key player in the pathogenesis of calcific aortic valve disease. It has been shown that the osteogenic effect of Lp(a) is mediated through the oxidized phospholipid pathway as well as oxidized phospholipid independent pathways involving mitogen-activated protein kinases (MAPK), glycogen synthase kinase (GSK) and Wnt. Moving forward, further work needs to be conducted in order to elucidate the crosstalk between the different signaling cascades, specifically with regard to BAVD.

Myocardial fibrosis is a severe global health problem due to its prevalence in all forms of cardiac diseases and direct role in causing heart failure. The discovery of efficient antifibrotic compounds has been hampered due to the lack of a physiologically relevant disease model. Herein, we present a disease model of human myocardial fibrosis and use it to establish a compound screening system. In the Biowire II platform, cardiac tissues are suspended between a pair of poly(octamethylene maleate (anhydride) citrate) (POMaC) wires. Noninvasive functional readouts are realized on the basis of the deflection of the intrinsically fluorescent polymer. The disease model is constructed to recapitulate contractile, biomechanical, and electrophysiological complexities of fibrotic myocardium. Additionally, we constructed a heteropolar integrated model with fibrotic and healthy cardiac tissues coupled together. The integrated model captures the regional heterogeneity of scar lesion, border zone, and adjacent healthy myocardium. Finally, we demonstrate the utility of the system for the evaluation of antifibrotic compounds. The high-fidelity in vitro model system combined with convenient functional readouts could potentially facilitate the development of precision medicine strategies for cardiac fibrosis modeling and establish a pipeline for preclinical compound screening., The cardiomyocytes/fibroblasts ratio is modulated to develop cardiac fibrosis-on-a-chip. An integrated model is constructed to mimic the interaction between scar lesion and adjacent healthy tissue.

Since identified in December 2019, COVID-19 has remained a pandemic across the globe. Although primarily a respiratory illness, the impact of COVID-19 on other end organs has been increasingly identified. The effect of COVID-19 on the liver has yet to be completely understood. We describe a case of COVID-19 leading to end-stage cholangiopathy and deceased donor liver transplantation (LT). A 64-year-old man with no underlying respiratory or liver disease presented with acute respiratory distress secondary to COVID-19 pneumonia requiring intubation. Several months after resolution of his respiratory symptoms, he developed transaminitis, worsening jaundice, abdominal pain and dark-coloured urine. Hepatic function remained severely impaired warranting LT 259 days following his initial COVID-19 diagnosis. Explant pathology demonstrated diffuse hepatic injury, onion skinning of the bile ducts and bile duct loss in scattered portal tracts. As more patients develop COVID-19-related complications, we suggest LT as an option for COVID-19-related end-stage liver disease.

Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete description of specific immune biomarkers. We present here a comprehensive multi-omic blood atlas for patients with varying COVID-19 severity in an integrated comparison with influenza and sepsis patients versus healthy volunteers. We identify immune signatures and correlates of host response. Hallmarks of disease severity involved cells, their inflammatory mediators and networks, including progenitor cells and specific myeloid and lymphocyte subsets, features of the immune repertoire, acute phase response, metabolism and coagulation. Persisting immune activation involving AP-1/p38MAPK was a specific feature of COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive of severity and outcome. Systems-based integrative analyses including tensor and matrix decomposition of all modalities revealed feature groupings linked with severity and specificity compared to influenza and sepsis. Our approach and blood atlas will support future drug development, clinical trial design and personalized medicine approaches for COVID-19., Graphical Abstract, A multi-omic analysis of patient blood samples reveals both similarities and specific features of COVID-19 when compared with samples obtained from sepsis or influenza patients which could yield better targetted therapies for severe COVID-19.

Individuals diagnosed with psychosis have high rates of smoking-related morbidity and early mortality. Only a small proportion of these smokers will attempt to quit, and many existing cessation interventions have limited effectiveness. To explore the unique and potentially unmet cessation needs of individuals with psychosis, we sought first-person experiences with smoking cessation and reactions to a proposed intervention. Twenty-four smokers with psychosis participated in focus group interviews. Multiple participants reported previous quit attempts using pharmacotherapy or behavioral methods, but few indicated they had previously tried cessation counseling. Though some individuals reported modest success with cessation, most participants tended to express negative perceptions of many available cessation approaches. When informed about the development of a novel smoking cessation intervention, participants had mixed but generally positive perceptions. Smokers diagnosed with psychosis are interested in sustained, individualized delivery of cessation services as part of their broader mental health care.

PurposeWhile there is an established body of literature that discusses the importance of stakeholder management, and also the need for involvement of all stakeholders so that all values of a heritage site can be captured in a heritage management plan, the concepts are not generally developed in ways that make them useful in practice. This research seeks to bring greater clarity to the practice of stakeholder engagement in built heritage, so that organisations can manage their stakeholders in ways that meet their strategic goals. This study proposes a novel method to identify stakeholders, a stakeholder preference mapping approach, which will depict their influence on decisions based on a of power-interest scale.Design/methodology/approachThis research posits a stakeholder preference mapping approach. Virtual Stakeholder Groups (VSG) were identified and stakeholder's significance impacts were measured using the RIBA Plan of Work 2013 to determine in-depth consideration of each stakeholder's power and interest against differing stages of a heritage project. Participants were convened through a 5-day workshop, consisting of 20 Malaysian and 19 international participants (80% academics and 20% Malaysian civil servants). The Multi-Attribute Decision Analysis (MADA) technique was then used to demonstrate how stakeholder identification and analysis can be used to help heritage teams meet their mandates.FindingsThe research identified eight virtual VSG (Extremist, Expert, Economic, Social, Governance and Tourists) and their scale of power-interest influence at different stages of the heritage management process. The findings reveal varying levels of engagement from each of the different groups of stakeholders at each work stage – with Stage 5 (Construction) being the least engaged.Originality/valueIt is anticipated that through stakeholder preference mapping, heritage teams can increase the robustness of their strategies by identifying and effectively managing the important concepts; heritage teams can effectively manage the interface between the many (often competing) demands of differing stakeholders. Using Georgetown as a case study, the research team were able to delineate the interaction and interplay between the various stakeholders in the complex decision-making processes for a UNESCO heritage site. Applying the RIBA 2013 Plan of Work as a framework to the heritage management process enables a formalised mapping approach to the process.

Non-pharmaceutical interventions including physical distancing and restriction on public gatherings were the cornerstone in controlling the COVID-19 pandemic, in the absence of effective vaccines and available treatment options. Many sport mega-events and sport leagues were canceled or indefinitely postponed, leaving stadiums globally empty or converted to be used as part of the COVID-19 response. There were calls for exit strategies to be developed. With the early containment of COVID-19 in South Australia, various restrictions were lifted in a staged and controlled manner, including the reopening of the Adelaide Oval for recommencement of sport leagues with spectator attendance. This involved the collaboration between public health authorities, other governmental agencies, Adelaide Oval Stadium Management Authority, various sporting leagues etc. Recommencement of sport leagues with staged increase in number of attending spectators allowed various measures to be introduced, revisited, and implemented accordingly, demonstrating that a case-by-case risk assessment can be conducted for mega-events during COVID-19, accounting for the epidemiological context at the time. Economic impacts and non-economic benefits of this recommencement were documented. This globally unprecedented, staged and controlled approach in returning spectators to sporting events during the COVID-19 pandemic could inform the reopening strategy of stadiums, recommencement of sport leagues and mega-events all over the world before herd immunity is achieved or in the event of future outbreaks.

Rectal prolapse has a diverse symptom profile that affects patients of all ages.We sought to identify bothersome symptoms and clinical presentation that motivated patients who have rectal prolapse to seek care, characterize differences in symptom severity with age, and determine factors associated with bothersome symptoms.This study is a retrospective analysis of a prospectively maintained registry.This study was conducted at a tertiary referral academic center.Included were 129 consecutive women with full-thickness rectal prolapse.The main outcomes measured were primary bothersome symptoms, 5-item Cleveland Clinic/Wexner Fecal Incontinence questionnaire, and the 5-item Obstructed Defecation Syndrome questionnaire. Patients were categorized by age65 vs age ≥65 years.Cleveland Clinic/Wexner Fecal Incontinence score9 was more common in older patients (87% vs 60%, p = 0.002). Obstructed Defecation Syndrome score8 was more common in younger patients (57% vs 28%, p0.001). Older patients were more likely than younger patients to report bothersome symptoms of pain (38% vs 19%, p = 0.021) and bleeding (12% vs 2%, p = 0.046). Mucus discharge was reported by most patients (older, 72% vs younger, 66%, p = 0.54) but was bothersome for only 18%, regardless of age. Older patients had more severe prolapse expression than younger patients (at rest, 33% vs 11%; during activity, 26% vs 19%; only with defecation, 40% vs 64%, p = 0.006). Older patients were more likely to seek care within 6 months of prolapse onset (29% vs 11%, p = 0.056). On multivariable regression, increasing age, narcotic use, and nonprotracting prolapse at rest were associated with reporting pain as a primary concern.This was a single-center study with a small sample size.Rectal prolapse-related bothersome symptoms and health care utilization differ by age. Although rectal pain is often not commonly associated with prolapse, it bothers many women and motivates older women to undergo evaluation. Patient-reported functional questionnaires may not reflect patients' primary concerns regarding specific symptoms and could benefit from supplementation with questionnaires to elicit individualized symptom priorities. See Video Abstract at http://links.lww.com/DCR/B492.INFLUENCIA DE LA EDAD EN DIFERENCIAS VINCULADAS CON LA PRESENTACIÓN CLÍNICA Y LOS SÍNTOMAS MAS DESAGRADABLES: El prolapso de recto tiene una gran variedad de síntomas que afectan a pacientes con edades diferentes.Identificar los síntomas mas molestos y la presentación clínica que motivaron a los pacientes con un prolapso de recto a consultar por atención médica, caracterizar las diferencias de gravedad de los síntomas con relación a la edad y determinar los factores asociados con los síntomas mas molestos.Análisis retrospectivo de un registro prospectivo.Centro académico de referencia terciaria.Consecutivamente 129 mujeres que presentaban un prolapso rectal completo.Síntomas y molestias primarias, cuestionario de incontinencia fecal de la Cleveland Clinic / Wexner de 5 ítems, cuestionario de síndrome de defecación obstruida de 5 ítems. Los pacientes fueron categorizados en65 años versus ≥ 65 años.El puntaje de incontinencia fecal de la Cleveland Clinic / Wexner9 fue más común en pacientes mayores (87% vs 60%, p = 0.002). La puntuación del síndrome de defecación obstructiva8 fue más común en pacientes más jóvenes (57% vs 28%, p0,001). Los pacientes mayores fueron más propensos que los pacientes jóvenes a informar síntomas y molestias de dolor (38% vs 19%, p = 0.021) y sangrado (12% vs 2%, p = 0.046). La mayoría de los pacientes informaron secresión de moco (mayores, 72% frente a más jóvenes, 66%, p = 0,54), pero sólo el 18% tuvo molestias, independientemente de la edad. Los pacientes mayores tenían una exteriorización de prolapso más grave que los pacientes jóvenes (en reposo, 33% frente a 11%; durante la actividad, 26% frente a 19%; solo con defecación, 40% frente a 64%, p = 0,006). Los pacientes mayores tenían más probabilidades de buscar atención médica dentro de los 6 meses posteriores al inicio del prolapso (29% frente a 11%, p = 0.056). Tras la regresión multivariable, el aumento de la edad, el uso de narcóticos y el prolapso no prolongado en reposo se asociaron con la notificación de dolor como queja principal.Centro único; tamaño de muestra pequeño.Los síntomas y molestias relacionadas con el prolapso rectal y la solicitud de atención médica difieren según la edad. Aunque el dolor rectal a menudo no se asocia comúnmente con el prolapso, incomoda a muchas pacientes y motiva a las mujeres mayores a someterse a un examen médico. Los cuestionarios funcionales con las respuestas de las pacientes pueden no reflejar las preocupaciones principales de éstos con respecto a los síntomas específicos y podrían requerir cuestionarios complementarios para así obtener prioridades individualizadas con relación a los síntomas identificados. Consulte Video Resumen en http://links.lww.com/DCR/B492. (Traducción-Dr. Xavier Delgadillo).

Background: The design of a videolaryngoscope blade may affect its efficacy. We classified videolaryngoscope blades as standard and non-standard shapes to compare their efficacy performing tracheal intubation in children enrolled in the Paediatric Difficult Intubation Registry. Methods: Cases entered in the Registry from March 2017 to January 2020 were analysed. We compared the success rates of initial and eventual tracheal intubation, complications, and technical difficulties between the two groups and by weight stratification. Results: Videolaryngoscopy was used in 1313 patients. Standard and non-standard blades were used in 529 and 740 patients, respectively. Both types were used in 44 patients. In children weighing

Background: Orotracheal intubation of infants using direct laryngoscopy can be challenging. We aimed to investigate whether video laryngoscopy with a standard blade done by anaesthesia clinicians improves the first-attempt success rate of orotracheal intubation and reduces the risk of complications when compared with direct laryngoscopy. We hypothesised that the first-attempt success rate would be higher with video laryngoscopy than with direct laryngoscopy. Methods: In this multicentre, parallel group, randomised controlled trial, we recruited infants without difficult airways abnormalities requiring orotracheal intubation in operating theatres at four quaternary children's hospitals in the USA and one in Australia. We randomly assigned patients (1:1) to video laryngoscopy or direct laryngoscopy using random permuted blocks of size 2, 4, and 6, and stratified by site and clinician role. Guardians were masked to group assignment. The primary outcome was the proportion of infants with a successful first attempt at orotracheal intubation. Analysis (modified intention-to-treat [mITT] and per-protocol) used a generalised estimating equation model to account for clustering of patients treated by the same clinician and institution, and adjusted for gestational age, American Society of Anesthesiologists physical status, weight, clinician role, and institution. The trial is registered at ClinicalTrials.gov, NCT03396432. Findings: Between June 4, 2018, and Aug 19, 2019, 564 infants were randomly assigned: 282 (50%) to video laryngoscopy and 282 (50%) to direct laryngoscopy. The mean age of infants was 5·5 months (SD 3·3). 274 infants in the video laryngoscopy group and 278 infants in the direct laryngoscopy group were included in the mITT analysis. In the video laryngoscopy group, 254 (93%) infants were successfully intubated on the first attempt compared with 244 (88%) in the direct laryngoscopy group (adjusted absolute risk difference 5·5% [95% CI 0·7 to 10·3]; p=0·024). Severe complications occurred in four (2%) infants in the video laryngoscopy group compared with 15 (5%) in the direct laryngoscopy group (–3·7% [–6·5 to –0·9]; p=0·0087). Fewer oesophageal intubations occurred in the video laryngoscopy group (n=1 [

We assessed the impact of policy-based and institutional interventions to limit postoperative opioid prescribing.Retrospective cohort study of patients who underwent laparoscopic/open appendectomies, laparoscopic/open cholecystectomies, and laparoscopic/open inguinal hernia repair during a 6-month interval in 2018 (control), 2019 (post-policy intervention), and 2020 (post-institutional intervention) to assess changes in postoperative opioid prescribing patterns. A survey was collected for the 2020 cohort.Comparing the 762 patients identified in 2018, 2019, and 2020 cohorts there was a significant decrease in mean opioid tabs prescribed (23.5 ± 8.9 vs. 16.2 ± 7.0 vs. 12.8 ± 4.9, p 0.01) and mean OME dosage (148.0 ± 68.0 vs. 108.6 ± 51.8 vs. 95.4 ± 38.0, p 0.01), without a difference in refill requests. Patient survey (response rate 63%) indicated 91.4% of patients reported sufficient pain control.Formalized opioid-prescribing guidelines and statewide regulations can significantly decrease postoperative opioid prescribing with good patient satisfaction. Surgeon education may facilitate efforts to minimize narcotic over-prescription without compromising pain management.

Atrial fibrillation, the most common cardiac arrhythmia, is an important contributor to mortality and morbidity, and particularly to the risk of stroke in humans1. Atrial-tissue fibrosis is a central pathophysiological feature of atrial fibrillation that also hampers its treatment; the underlying molecular mechanisms are poorly understood and warrant investigation given the inadequacy of present therapies2. Here we show that calcitonin, a hormone product of the thyroid gland involved in bone metabolism3, is also produced by atrial cardiomyocytes in substantial quantities and acts as a paracrine signal that affects neighbouring collagen-producing fibroblasts to control their proliferation and secretion of extracellular matrix proteins. Global disruption of calcitonin receptor signalling in mice causes atrial fibrosis and increases susceptibility to atrial fibrillation. In mice in which liver kinase B1 is knocked down specifically in the atria, atrial-specific knockdown of calcitonin promotes atrial fibrosis and increases and prolongs spontaneous episodes of atrial fibrillation, whereas atrial-specific overexpression of calcitonin prevents both atrial fibrosis and fibrillation. Human patients with persistent atrial fibrillation show sixfold lower levels of myocardial calcitonin compared to control individuals with normal heart rhythm, with loss of calcitonin receptors in the fibroblast membrane. Although transcriptome analysis of human atrial fibroblasts reveals little change after exposure to calcitonin, proteomic analysis shows extensive alterations in extracellular matrix proteins and pathways related to fibrogenesis, infection and immune responses, and transcriptional regulation. Strategies to restore disrupted myocardial calcitonin signalling thus may offer therapeutic avenues for patients with atrial fibrillation.

Background: Psychological stress is a risk factor for cardiovascular disease (CVD). Despite advancements in CV-prevention, CVD remains the global leading cause of disease burden, suggesting that additional factors contribute to sustained CV risk. The mechanisms by which stress contributes to increased CVD are largely unknown. However, in preclinical models increased sympathetic nervous system activity promotes systemic inflammation (e.g. monocyte activation, cytokine production), and may underlie increased CVD risk. We investigated perceived stress in women with MI and its association with platelet activity, and validated our findings in a murine model. Methods: Monocyte-platelet aggregates (MPA) and psychological stress, using the validated Perceived Stress Scale (PSS4), were measured in women post MI (n=96; median age 62.2 years) and in control women (n=31; 66.7 years). A mouse model of chronic variable stress was utilized to explore the impact of stress on platelet activity and risk of thrombosis-mediated death. Results: Perceived stress was higher in MI patients than matched women (p=0.009). Platelet activity, assessed by MPA, was significantly elevated in MI vs. controls (p=0.0025). MPA significantly correlated with PSS4 scores (R=0.412, p =0.009). In a female mouse model of chronic variable stress, circulating MPA was increased in stressed mice compared to controls (p Conclusion: Platelet activity was increased at the time of MI in women, and positively associated with stress. In a mouse model, we find that stress is a significant contributor to increased platelet reactivity, and promotes thrombosis-mediated death. Cross-talk between platelets and monocytes is a critical mechanism linking thrombosis and inflammation, thus stress-induced MPAs may represent an unexplored pathway linked to stress-mediated CVD-risk. Future studies will examine whether reducing stress reduces platelet hyperactivity and MI risk.

Background: COVID-19 is a global pandemic with patients at increased risk for all-cause mortality. Virus-platelet interactions are linked to viral pathogenesis and increased risk of adverse events. Aim: To investigate the relationship between in vivo platelet activity markers and all-cause mortality in hospitalized patients with COVID-19. Method: Plasma samples were collected from 100 hospitalized patients on the day of PCR-confirmed COVID-19 diagnosis. Thromboxane B 2 (TxB 2 ), P-selectin, and soluble CD40 ligand (sCD40L) were measured in plasma, and mean platelet volume (MPV) assessed. Subjects were followed until discharge or death. Results: Among 100 patients, the median age was 65 years (IQR: 55, 75), 39% were female, and 32 died or experienced a thrombotic event. The baseline platelet activation markers, P-selectin (p=0.02), sCD40L (p=0.03) and MPV (p=0.005) were higher in patients who died. After adjustment for age, sex, race/ethnicity, platelet count, antiplatelet therapy, and chronic obstructive pulmonary disease, TxB 2 (p=0.036), P-selectin (p=0.007), sCD40L (p=0.02) and MPV (p=0.01) were each independently associated with death after multivariable adjustment ( Table 1 ). Conclusions: Biomarkers of platelet activation are significantly associated with death or thrombosis in patients hospitalized with COVID-19. Our findings suggest multiple platelet activation mechanisms may contribute to adverse events. Further investigation into the mechanistic role of platelets in COVID-19 pathogenesis and the potential role of antiplatelet therapy is warranted. Table 1. Multivariable regression models of all-cause mortality. Odds ratios (OR) from logistic regression analysis per SD increase for biomarker levels adjusted for age, sex, race, antiplatelet therapy, platelet count, and chronic obstructive pulmonary disease (COPD).

Introduction: Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) responsible for the COVID-19 pandemic has spread from Wuhan, China in December, 2019 to 216 countries and territories as of September 10, 2020 with 27.74 million cases and 899,911 confirmed deaths. The spectrum of disease is most commonly seen as a viral pneumonia with high grade fevers, shortness of breath, dry cough, and chest pain with radiologic evidence of bilateral, interstitial, ground glass opacities, and peripheral lung consolidation. Liver chemistries are frequently abnormal, with transaminases shown to be one-two times the upper limit of normal in most instances. The full spectrum of gastrointestinal involvement of the SARS-CoV-2 infection has yet to be fully seen. Patient concerns: We present a case of a young woman with SLE who developed severe abdominal pain, nausea and vomiting, rapidly progressing to acute hepatic failure and tested positive for SARS-CoV-2 infection. She had no respiratory symptoms. Diagnosis: A thorough work-up of acute liver failure including liver biopsy confirmed acute hepatitis with viral like changes. Common viral causes of liver failure were ruled out. The patient had no recent travel history. Interventions: The patient was started on hydroxychloroquine due to SLE, treated with N-Acetyl-Cysteine, and methylprednisolone. Outcomes: The patient improved with resolution of encephalopathy and normalization of her liver chemistries without any development of respiratory illness. Conclusion: This case details a unique presentation of likely SARS-CoV-2 infection. Until now, the literature has primarily described a respiratory illness and liver injury with mild transaminase elevations. Significant liver injury progressing to acute liver failure should be considered in those with SARS-CoV-2 infection.

The COVID-19 pandemic has brought to light significant failures and fragilities in our food, health, and market systems. Concomitantly, it has emphasized the urgent need for a critical re-evaluation of many of the policies and practices that have created the conditions in which viral pathogens can spread. However, there are many factors that are complicating this process; among others, the uncertain, rapidly evolving, and often poorly reported science surrounding the virus' origins has contributed to a politically charged and often rancorous public debate, which is concerning insofar as the proliferation of divisive discourse may hinder efforts to address complex and collective concerns in a mutually cooperative manner. In developing ethical and effective responses to the disproportionate risks associated with certain food production and consumption practices, we argue that the focus should be on mitigating such risks wherever they arise, instead of seeking to ascribe blame to specific countries or cultures. To this end, this article is an effort to inject some nuance into contemporary conversations about COVID-19 and its broader implications, particularly when it comes to trade in wildlife, public health, and food systems reform. If COVID-19 is to represent a turning point towards building a more equitable, sustainable, and resilient world for both humans and nonhuman animals alike, the kind of fractioning that is currently being exacerbated by the use of loaded terms such as "wet market" must be eschewed in favour of a greater recognition of our fundamental interconnectedness.

Background and Aims Veverimer is an investigational drug being developed as an orally administered hydrochloric acid binder for the treatment of metabolic acidosis associated with chronic kidney disease (CKD). In clinical studies, treatment with veverimer safely and effectively increased serum bicarbonate and improved objective and subjective measures of physical functioning1-3. Veverimer, a free-amine polymer, is not systemically absorbed; therefore, its potential for drug-drug interactions (DDIs) is limited to those that occur in the gastrointestinal (GI) tract (i.e., direct binding or indirect effects resulting from transient increases in gastric pH). We assessed the potential for DDIs with veverimer both in vitro and in vivo in healthy subjects. Methods In vitro binding to veverimer was evaluated with 16 drugs of varying molecular weight and charge. In a separate study, the effect of veverimer on gastric pH was measured continuously in vivo in healthy subjects using a microelectrode pH probe placed in the gastric compartment. Human DDI studies were conducted with 4 orally administered drugs, including those that demonstrated the most in vitro binding to veverimer and those with pH-dependent solubility (furosemide, aspirin, warfarin, dabigatran). Results Veverimer did not bind to any of the positively charged, neutral or zwitterionic drugs tested in vitro. It bound to 3 small (MW Veverimer increased gastric pH by ∼3.0 and 1.5 pH units in fasted and fed subjects, respectively. The increase in gastric pH was short-lived, with a peak within 1 hour after dosing and a return to baseline after ∼1.5 hours and ∼3 hours under fasting and fed conditions, respectively. The effect of veverimer on gastric pH was similar in the presence and absence of omeprazole. No clinically meaningful changes in systemic exposure, as indicated by Cmax and AUC, were observed when 3 drugs with pH-dependent solubility were coadministered with veverimer in human DDI studies (Figure 1). Conclusions In human DDI studies, we observed: a) no effect of veverimer on the bioavailability of drugs with physicochemical characteristics most susceptible to direct binding to the polymer; b) small, short-lived effects of veverimer on gastric pH; and c) no effect of veverimer on the bioavailability of drugs with pH-sensitive solubility. Therefore, it is concluded that there is a negligible risk of veverimer involvement in clinically significant DDIs.

PurposeThis paper aims to identify key performance indicators (KPIs), and their corresponding attributes, required to successfully manage asset management sustainably in a built environment context. Improving the sustainability of existing housing stock is a major challenge facing the UK social housing sector. There is a lack of support to navigate the growing and often incongruent information relating to sustainable development and how to operationalise it. The problem is twofold; first, the current (single criterion) condition-based approach to maintenance planning constrains asset managers and does not fully address the social, environmental and economic aspects of sustainability. Second, the toolkits available for assessing the sustainability of housing are often generic and are time consuming and expensive to implement.Design/methodology/approachThis paper reports the findings of a participatory research project with a leading London-based housing association, using a series of landlord and tenant workshops to derive a set of attributes associated with KPIs to fully reflect the local requirements of the landlord and their interpretation of the sustainability agenda. Five KPIs are considered to be measurable, directly affected by maintenance work and independent of each other were identified by this landlord (comfort, running costs, adaptability, maintenance costs and community).FindingsThe resulting outputs, in a policy context, will provide a clear route map to social housing landlords of how to improve the sustainability of their housing stock with the additional benefits of addressing fuel poverty and carbon emission targets, whilst at the same time, help create and maintain housing in which people want to live.Originality/valueThe proposed approach is flexible enough to incorporate the individual requirements of landlords and be able to adapt to changes in government policy (local and central) in a timely, robust, transparent and inclusive format.

Objective: Patients with psoriasis have impaired vascular health and increased cardiovascular disease (CVD). Platelets are key players in the pathogenesis of vascular dysfunction in cardiovascular disease and represent therapeutic targets in cardiovascular prevention. The object of this study was to define the platelet phenotype and effector cell properties on vascular health in psoriasis and evaluate whether aspirin modulates the platelet-induced phenotype. Approach and Results: Platelets from psoriasis patients (n=45) exhibited increased platelet activation (relative to age- and gender-matched controls, n=18), which correlated with psoriasis skin severity. Isolated platelets from psoriasis patients demonstrated a 2- to 3-fold ( P IL 8 (interleukin 8), IL1β , and Cox (cyclooxygenase)-2 Platelet RNA sequencing revealed an interferon signature and elevated expression of COX-1 , which correlated with psoriasis disease severity ( r =0.83, P =0.01). In a randomized trial of patients with psoriasis, 2 weeks of 81 mg low-dose aspirin, a COX-1 inhibitor, reduced serum thromboxane (Tx) B 2 and reduced brachial vein endothelial proinflammatory transcript expression >70% compared with the no-treatment group ( P 2 ( r =0.48, P =0.02). Conclusions: In patients with psoriasis, platelets are activated and induce endothelial cell inflammation. Low-dose aspirin improved endothelial cell health in psoriasis via platelet COX-1 inhibition. These data demonstrate a previously unappreciated role of platelets in psoriasis and endothelial cell inflammation and suggests that aspirin may be effective in improving vascular health in patients with psoriasis. Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT03228017.

This retrospective case series details early experience with intra-arterial (IA) and intravenous (IV) contrast-enhanced ultrasound (CEUS) in 8 patients (mean age, 70.4 years) who underwent prostatic arterial embolizations from July 2014 to March 2017. Technical success was achieved in 7 of the 8 patients. IA CEUS demonstrated ipsilateral prostatic perfusion in 15 out of 20 interrogated prostatic arteries (PAs), confirming proper catheter placement. Four of the 20 interrogated PAs demonstrated extraprostatic perfusion. One PA was not successfully interrogated owing to a localized wire perforation. IV CEUS, performed on 4 of the 8 patients, demonstrated decreased enhancement after embolization in all 4 patients, confirming the procedural end point.

It was argued that either the construction industry to continue to be conservative and inefficient on the premise that it was distinctive or it should have opened-up to learn lessons from the best practices models in other sectors like manufacturing. This paper is a comparative study of the sustainable end-of-life management practices in the automobile and the Nigerian building sector with the aim of examining the feasibility of construction industry learning lessons from model of the automobile industry. While the practices in the automobile sector were obtained from literature, the practices in the Nigerian construction industry were investigated using in-depth, semi-structured interviews. The participants were construction industry experts with experience in building demolition as directly identified by the researchers or identified using snowball technique. The results of a comparative evaluation of the practices in the two industries shows that the practices in the construction industry can be improved by adopting five sustainable practices from the automobile industry. These are materials sorting techniques, maintaining materials database, reverse logistics and extended manufacturer responsibility, standardisation, and application of advanced material handling technology. Key words: End-of-life, waste management, automobile, construction, Kano Nigeria.

Objective We directly compared the Villalta scale and the Venous Clinical Severity Score (VCSS) to determine which of the two measures would be better at capturing clinically important cases of post-thrombotic syndrome (PTS) and PTS severity compared with patient-reported quality of life (QOL) scores. Methods We performed a secondary analysis of the ATTRACT (acute venous thrombosis: thrombus removal with adjunctive catheter-directed thrombolysis) trial study population. We calculated the correlations of the Villalta scores and VCSSs with QOL scores (short-form 36-item health survey [SF-36] physical component summary [PCS] and mental component summary [MCS]; and VEINES [venous insufficiency epidemiological and economic study]-QOL/symptom [VEINES-QOL/Sym] questionnaire) at each study visit (6, 12, 18, and 24 months of follow-up). The correlation of the random intercept (mean scores) and random slope (rate of change of the scores) among the Villalta scores, VCSS, and VEINES-QOL/Sym scores was assessed using a multivariate longitudinal model. Results The median correlation between Villalta scores and VCSSs was 0.72. The median correlation between the Villalta scores and VEINES-QOL and VEINES-Sym scores at all follow-up visits was −0.68 and −0.71, respectively. The median correlation between the Villalta scores and SF-36 PCS and MCS scores was −0.51 and −0.31, respectively. For the VCSSs, the median correlation with the VEINES-QOL and VEINES-Sym scores at all follow-up visits was −0.39 and −0.41, respectively. The median correlation between the VCSSs and SF-36 PCS and MCS scores was −0.32 and −0.13, respectively. The correlations between the random effects in the multivariate longitudinal models showed a similar pattern. The effect of covariate adjustment by age, sex, and body mass index was minor. Conclusions The Villalta scores and VCSSs correlated strongly. The Villalta scale showed a substantially greater correlation with venous disease-specific and general QOL scores compared with the correlation with the VCSS. Our findings suggest that when a single scale is used to assess for clinically meaningful PTS, the Villalta scale will better capture the effects of PTS on patient-reported QOL.

Background and objectives Metabolic acidosis is common in patients with CKD and has significant adverse effects on kidney, muscle, and bone. We tested the efficacy and safety of TRC101, a novel, sodium-free, nonabsorbed hydrochloric acid binder, to increase serum bicarbonate in patients with CKD and metabolic acidosis. Design, setting, participants, & measurements One hundred thirty-five patients were enrolled in this randomized, double-blind, placebo-controlled, multicenter, in-unit study (designated the TRCA-101 Study). Patients had a mean baseline eGFR of 35 ml/min per 1.73 m 2 , a mean baseline serum bicarbonate of 17.7 mEq/L, and comorbidities, including hypertension (93%), diabetes (70%), and heart failure (21%). Patients ate a controlled diet and were treated for 14 days with placebo or one of four TRC101 dosing regimens (1.5, 3, or 4.5 g twice daily or 6 g once daily). After treatment, patients were discharged and followed for 7–14 days. Results All TRC101 treatment groups had a mean within-group increase in serum bicarbonate of ≥1.3 mEq/L ( P P Conclusions TRC101 safely and significantly increased the level of serum bicarbonate in patients with metabolic acidosis and CKD.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the U.S. There is a strong association between COPD and cardiovascular (CV) disease; however, the relation between COPD and CV health factors is not well defined. We examined the relation between lung function and CV health factors defined by American Heart Association's (AHA) Life's Simple 7 (LS7).We studied 6352 adults aged ≥20 from the National Health and Nutrition Examination Survey (NHANES) 2009-2012. Analysis of variance was used to compare mean FEV1% of predicted across levels of each LS7 metric and population attributable risk was calculated based on COPD prevalence. We also conducted linear regression and logistic regression analyses to determine the association between lung function, COPD and LS7 score.Overall 19.9% of subjects were defined as having COPD. Subjects in the highest categories of the LS7 metrics had the highest mean values of FEV1% of predicted (p 0.0001 except for total cholesterol). Current smoking and hypertension had a population attributed risk of 21.8% and 21.1% of COPD, respectively. Compared to subjects with 0 ideal health factors, the gender and ethnicity-adjusted odds (95% CI) for COPD were 0.45 (0.22-0.93), 0.22 (0.11-0.43) for those with 4 and 5-7 factors, but adjustment for age attenuated this relation.LS7 score is associated with lung function as well as the odds of COPD that is largely explained by age. Studies are needed to show if promotion of CV health will preserve healthy lung function.

Introduction Transfusion protocols are not well-studied for pediatric patients with acute liver failure (ALF). This study evaluates the utility of an international normalized ratio (INR)-based transfusion threshold for these patients. Methods Forty-four ALF pediatric patients from 2009 to 2018 were reviewed and divided into two groups: (a) a threshold group including patients between 2009 and 2015 who were transfused for an INR above 3.0, per institutional policy (n = 30), and (b) a post-threshold group including patients after 2015 through 2018 who were transfused based on clinical judgment (n = 14). Preoperative INRs, preoperative transfusions, intraoperative transfusions, early reoperation, renal function, graft function and deaths were compared. Results Liver failure severity was similar between threshold and post-threshold groups. Threshold patients had a lower average INR prior to transplantation, 2.8 (range 1.8-3.8) vs 4.4 (range 2.1-9.0), respectively (P = .01). Twenty-six threshold patients (87%) received preoperative FFP compared with seven post-threshold patients (50%, P = .0088). Two threshold patients (7%) received preoperative cryoprecipitate compared with five post-threshold patients (36%, P = .014). The incidence of pre-transplant bleeding, operative transfusions, and 1-year patient and graft survival did not differ significantly. Conclusion Clinical judgment vs an INR-based threshold for transfusions did not increase perioperative complications in children with ALF.

Background Taste changes are commonly reported by people with cancer undergoing radio- or chemotherapy. Taste changes may compromise dietary intake and nutritional status. Objective To understand whether or not taste change is associated with cancer diagnosis or treatment modality in adults. Methods A systematic literature search up to December 31, 2019, was conducted using PubMed, Embase, and PsycInfo (International Prospective Register of Systematic Reviews protocol no. CRD42019134005). Studies in adults with cancer objectively assessing the effect of a cancer diagnosis or chemotherapy and/or radiotherapy treatment on taste function compared with healthy controls or within participant changes were included. Additional outcomes were food liking, appetite, dietary intake, nutritional status, and body composition. Reference lists of relevant articles were searched to identify additional articles. Quality was assessed using the Academy of Nutrition and Dietetics quality criteria checklist. Results A total of 24 articles were included, one of which consisted of two studies that reported the effects of radiotherapy and chemotherapy separately. From the total 25 studies reported in 24 published articles, 14 studies examined effects of radiotherapy, and remaining 11 studies examined chemotherapy. There is limited evidence of a cancer diagnosis per se contributing to taste dysfunction. Impaired taste function was reported in almost all radiotherapy studies, occurring as early as Week 3 of treatment and lasting for 3 to 24 months posttreatment. During chemotherapy, impairment of taste function was less consistently reported, occurring as early as the first few days of chemotherapy, and persisting up to 6 months posttreatment. Taxane-based chemotherapy was reported to affect taste function more than other treatments. Several studies reported reduced liking for food, appetite, and dietary intake. Only one study reported nutritional status of participants, finding no association between taste function and nutritional status. No studies examined associations between taste changes and body composition. Conclusions This review highlights the importance of considering treatment modality in practice. Research is required to identify factors contributing to taste alteration and to inform evidence-based interventions.

INTRODUCTION Urinary diversion in pediatric renal transplant candidates with bladders not amenable to primary reconstruction can be achieved by pre-transplant ileal conduit creation. We performed cutaneous ureterostomies to limit pre-transplant surgery, protect the peritoneum for dialysis, transplant patients sooner, and preserve ureter length for future surgical reconstruction. METHODS We compared four pediatric transplant recipients with ureterostomies to four recipients with ileal conduits from 2009 to 2017. RESULTS All patients with ileal conduits developed at least one urinary tract infection (UTI) within 1 year of transplant and three of four patients had recurrent UTIs within the first year. Two patients required ileal conduit revisions for redundant conduits and recurrent UTIs. Of the four ureterostomy patients, two patients had UTIs within one year of transplant. Two patients developed ureterostomy strictures requiring revision at the fascial level; one was associated with a UTI. CONCLUSION In our small case series, ureterostomy allowed for a single operative intervention with preservation of ureter length for later reconstruction. Ureterostomy is safe and recurrent UTI may be lower in the ureterostomy group. Long-term evaluation of ureterostomy for urinary diversion in pediatric kidney transplant is warranted.

Surgery remains the only known treatment option for rectal prolapse. Although over 100 abdominal and perineal procedures are available, there is no consensus as to which intervention is best suited for an individual. This retrospective cohort study describes the patient- and disease-related factors involved in making surgical recommendations around rectal prolapse in a single surgeon experience.91 consecutive patients ≥18 years old diagnosed with external and/or high-grade internal rectal prolapse were assessed and were prospectively entered into an IRB approved registry. Information on patient symptoms, comorbidities, exam findings, surgeon judgment, and patient preference was collected. Treatment recommendations (abdominal, perineal, or no operation) were analyzed and compared.Surgical intervention was recommended to 93% of patients. Of those, 66% were recommended robotic abdominal procedures: 75%, robotic ventral mesh rectopexies; 16%, resection rectopexies; and 9%, suture rectopexies. On univariate analysis, patients with older age, higher ASA scores, presence of cardiopulmonary morbidity, pain as a primary rectal prolapse symptom, rectal prolapse always descended, and surgeon concern for frailty and general anesthesia were associated with recommendations for perineal operations (p0.05 for all). However, on multivariate analysis, only age and concern over prolonged anesthesia remained correlated with a recommendation for perineal surgery. Of patients80 years of age, 15% were recommended an abdominal approach.With multiple options available for the treatment of rectal prolapse, treatment recommendations remain surgeon-dependent and may be influenced by many factors. In our practice, robotic ventral mesh rectopexy was the most commonly recommended operation and was offered to carefully selected patients of advanced age. Although robotic surgery and ventral mesh rectopexy may not be accessible to all patients and surgeons, this represents a single surgeon's practice bias. This study reinforces the importance of perineal procedures for higher-risk individuals.

Background Recovery-oriented models of care are evidence based and have been shown to improve patient satisfaction and outcomes as well as decrease the percentage of readmissions to inpatient psychiatric units. Methods This quality improvement project was implemented on a 16-bed inpatient adult mental health unit in a Veterans Affairs Medical Center. Percentages of readmissions were compared throughout the course of implementation of the recovery model. Readmissions during the months of July-September were tabulated over 3 subsequent years and compared readmission percentages before recovery implementation, during the early stage of recovery implementation, and finally, during ongoing recovery implementation. Results A decrease in readmission percentages was seen with implementation of recovery-oriented care when comparing the same 3-month period over 3 years. Conclusion After implementation of recovery-oriented care measures, there was a decrease in percentage of readmissions to the unit. In addition, this decrease was sustained and was shown to improve over time as recovery-oriented programming was further developed on the unit. These data suggest that Veterans Affairs Medical Centers should consider adding tools and procedures to successfully implement recovery programming on inpatient units and efforts should include direct involvement of patients in their own recovery journey, revision of policies and procedures to reflect the importance of recovery, thorough training of frontline staff regarding recovery principles, and transfer of recovery information directly from inpatient units to outpatient providers.

Background: Management of venous thromboembolism (VTE) in patients with central nervous system (CNS) malignancies is challenging as there is an increased risk of recurrent VTE and intracranial hemorrhage (ICH). Low molecular weight heparins (LMWH) have historically been the standard of care for treatment of cancer-associated thrombosis (CAT). Current guidelines recommend direct oral anticoagulants (DOACs) for CAT treatment, but patients with CNS malignancies have limited representation in the supporting clinical trials. This multicenter, retrospective cohort study evaluated the safety and efficacy of DOACs compared to LMWH for CAT in patients with primary brain tumors or secondary brain metastases. Patients/Methods: In this multicenter, retrospective cohort study, adult patients with a diagnosis of primary brain tumor or secondary brain metastases who received either a DOAC or LMWH for CAT were evaluated. The primary outcome was the incidence of any bleeding event within a 6-month period following the initiation of anticoagulation. Secondary outcomes included incidence of recurrent VTE events, major bleeding, clinically relevant non-major bleeding (CRNMB), and minor bleeding, within a 6-month period following the initiation of anticoagulation. Patients were excluded if their indication for anticoagulation was stroke, non-cancer-associated VTE, or VTE prophylaxis, were on LMWH for one week or less while bridging to warfarin, or received a diagnosis of VTE at an outside hospital. All bleeding events were defined by the International Society on Thrombosis and Haemostasis (ISTH) criteria. Primary and secondary outcomes were analyzed using Fisher's exact test for categorical variables and Wilcoxon rank-sum tests for non-parametric continuous variables. Results: Between January 1, 2012 to October 9, 2019, one-hundred eleven patients met inclusion criteria. Of the patients who met inclusion criteria, 26 (23.4%) patients had primary brain tumors and 85 (76.6%) patients had secondary brain metastases. Bleeding events occurred in 7 of 55 patients (12.7%) in the DOAC group compared to 13 of 56 (23.2%) patients in the LMWH group (RR 0.55, 95% CI 0.24-1.27). Recurrent VTE events occurred in 3 of 55 (5.5%) patients in the DOAC group compared to 3 of 56 (5.4%) patients in the LMWH group (RR 1.02, 95% CI 0.21-4.83). Major bleeding occurred in 3 of 55 (5.5%) patients in the DOAC group, compared to 4 of 56 (7.1%) patients in the LMWH group (RR 0.76, 95% CI 0.18-3.26). There were no differences in the rates of CRNMB and rates of minor bleeding between groups. Conclusion: In this multicenter retrospective cohort study, therapeutic anticoagulation with DOACs showed no significant difference in bleeding events or recurrent VTE events when compared to LMWH, in patients with primary brain tumors or secondary brain metastases. We conclude that DOACs may be potentially safe and efficacious for VTE treatment in patients with primary brain tumors or secondary brain metastases. As prescribing practices are expected to continue to shift towards DOACs, this study provides preliminary evidence of the safety of DOACs in this high-bleeding risk patient population. Disclosures No relevant conflicts of interest to declare.

AIMS Most research into reasons for smoking among adults with serious mental illness (SMI) has focused on reasons related to SMI symptoms. The current study reports reasons for smoking and barriers to cessation that are both related and unrelated to SMI symptoms among adults with SMI. METHODS Four focus groups were conducted among current smokers receiving outpatient care for a psychotic disorder in 2017 (N = 24). Participants were asked why they currently smoke and their barriers to quitting smoking. RESULTS Smoking as a coping mechanism and to self-medicate SMI symptoms were reasons for current smoking and barriers to cessation. Avoidance of other unhealthy behaviors, routine, and enjoyment emerged as reasons for smoking and barriers to cessation that were unrelated to mental illness. CONCLUSION Consideration of factors that are both related and unrelated to SMI symptoms in smoking cessation interventions and brief cessation counseling may improve cessation success in this population.

ObjectiveWe investigated genome-wide changes in gene expression and chromatin remodelling induced by tumour necrosis factor (TNF) in fibroblast-like synoviocytes (FLS) and macrophages to better understand the contribution of FLS to the pathogenesis of rheumatoid arthritis (RA).MethodsFLS were purified from patients with RA and CD14+ human monocyte-derived macrophages were obtained from healthy donors. RNA-sequencing, histone 3 lysine 27 acetylation (H3K27ac), chromatin immunoprecipitation-sequencing (ChIP-seq) and assay for transposable accessible chromatin by high throughput sequencing (ATAC-seq) were performed in control and TNF-stimulated cells.ResultsWe discovered 280 TNF-inducible arthritogenic genes which are transiently expressed and subsequently repressed in macrophages, but in RA, FLS are expressed with prolonged kinetics that parallel the unremitting kinetics of RA synovitis. 80 out of these 280 fibroblast-sustained genes (FSGs) that escape repression in FLS relative to macrophages were desensitised (tolerised) in macrophages. Epigenomic analysis revealed persistent H3K27 acetylation and increased chromatin accessibility in regulatory elements associated with FSGs in TNF-stimulated FLS. The accessible regulatory elements of FSGs were enriched in binding motifs for nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), interferon-regulatory factors (IRFs) and activating protein-1 (AP-1). Inhibition of bromodomain and extra-terminal motif (BET) proteins, which interact with histone acetylation, suppressed sustained induction of FSGs by TNF.ConclusionOur genome-wide analysis has identified the escape of genes from transcriptional repression in FLS as a novel mechanism potentially contributing to the chronic unremitting synovitis observed in RA. Our finding that TNF induces sustained chromatin activation in regulatory elements of the genes that escape repression in RA FLS suggests that altering or targeting chromatin states in FLS (eg, with inhibitors of BET proteins) is an attractive therapeutic strategy.

Background With access to surgical care, >90% of today's infants with congenital heart disease (CHD) will reach adulthood. During childhood, survivors accrue a wealth of health care experience and develop strategies for navigating life with a chronic disease. Methods Seeking to learn from this individualized process, we invited adults with complex CHD to participate in narrative analysis-an established qualitative research method for studying how individuals derive meaning from their personal stories. Audio recordings of 2-4 hour free-form interviews were transcribed and iteratively analyzed to identify common themes and detect similarities or differences in language, viewpoint and interpretation. Recruitment continued until saturation was reached (n = 10). Results While each narrative was unique, CHD had a pervasive effect on the autobiography of all participants. Seven themes were discussed consistently: (1) parental/sibling relationships, (2) physical limitations, (3) embarrassment/denial, (4) memories of pediatric health care, (5) transition to adult care, (6) education and career choices, and (7) relationship and reproductive choices. While some of the recalled experiences were negative, all participants also spoke positively about the effect of CHD on their lives. Conclusions Adults with CHD provide the voices of expert witnesses; illuminating how the pediatric journey influences their identity, choices, personal relationships and adult health care interactions. These narratives could inform and improve the contemporary care of children with heart disease.

Background Post-thrombotic syndrome (PTS) occurs in 20-50% of patients following proximal deep vein thrombosis (DVT), despite anticoagulation treatment. The International Society on Thrombosis and Haemostasis recommends using the Villalta scale to standardize the diagnosis of PTS and to quantify its severity. However, many investigators use the Venous Clinical Severity Score (VCSS) to assess PTS. Different to the Villalta score, the VCSS was developed as a measure for chronic venous disease and not PTS specifically. The aim of the study was to determine which of Villalta and VCSS best captures clinically important PTS and PTS severity by analyzing the relationship of each to QoL scores in the Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis (ATTRACT) trial study population. Methods A secondary analysis of the ATTRACT randomized controlled clinical trial was conducted. 621 ATTRACT patients with symptomatic proximal DVT are included in this analysis. Correlations of the Villalta and VCSS scores with QoL scores (Short-Form Health Survey-36 physical component score/mental component score [SF-36 PCS/MCS]; the Venous Insufficiency Epidemiological and Economic Study-QoL/Symptoms [VEINES-QoL/Sym] questionnaire) were examined at study visits. The correlation of the random intercept (mean scores) and random slope (rate of change of the scores) between the Villalta, VCSS and the VEINES-QoL/Sym scores was assessed using a multivariate longitudinal model. Results The mean age at enrolment was 51 years of age, 78% were white, 62% were male, the mean BMI was 32 kg/m2, 57% had iliofemoral DVT, 19% had a previous ipsilateral DVT and 93% were taking one or more anticoagulation therapies prior to randomization. The median (range) correlation coefficients across all follow-up visits for the Villalta scale and VEINES-QOL and the Villalta scale and VEINES-Sym were -0.73 (0.51, -0.73) and -0.75 (-0.50, -0.76), respectively. The median (range) correlation coefficients for the Villalta scale and the SF-36 PCS or the SF-36 MCS across all follow-up visits were -0.51 (-0.35, -0.54) and -0.31 (-0.21, -0.38), respectively. In all correlation analyses between the Villalta scale and QoL measures, correlations at baseline were the weakest, and then increased until 6 months, after which the correlation coefficients remained relatively constant. The median correlation coefficient (range) across all follow-up visits for VCSS and VEINES-QOL and for VCSS and VEINES-Sym were -0.39 (-0.37, -0.39) and -0.41 (-0.36, -0.41), respectively. The median correlation (range) between VCSS and SF-36 PCS and for VCSS and MCS were -0.32 (-0.31, -0.32) and -0.12 (-0.12, -0.14), respectively. The magnitude of the correlations remained relatively constant from 6 months to 24 months follow-up visits. The Villalta scale had a strong negative correlation with VEINES-QoL and VEINES-Sym, a moderate negative correlation with SF-36 PCS, and a weak negative correlation with SF-36 MCS. Conversely, the VCSS had a weak negative correlation with VEINES-QoL, VEINES-Sym and SF-36 PCS, and a very weak negative correlation with SF-36 MCS. Adjustment for age, sex, ethnicity, race, extent of DVT and previous ipsilateral DVT did not change our findings. Each pair of disease severity scales and QoL scales were analyzed as a multivariate outcome in a multivariate longitudinal model. A random intercept (mean scores) and random slope (rate of change of the scores) were present in all these multivariate longitudinal models. The impact of covariates (i.e. age, sex and BMI) was also examined. The Villalta score and VCSS score have a positive correlation between their random intercept and random slope. This suggests that patients with a higher average Villalta score also tend to have a higher average VCSS score (correlation is 0.74 and 0.69 if adjusted). Those that have a higher rate of change in Villalta score over time tend to have a higher rate of change in VCSS (correlation is 0.72 and 0.84 if adjusted). The impact from covariate adjustment by age, sex and BMI was minor. Conclusion For all measures, the Villalta scale has a substantially higher correlation with QOL than the VCSS. Our findings support the use of the Villalta scale to assess PTS in preference to VCSS, as it better captures the impact of PTS on patient reported QoL, a key consideration in patients with chronic PTS.

Purpose– The purpose of this study is to investigate the perception of knowledge workers on practice of knowledge management (POKM) as an organizational knowledge sharing enabler in an information technology shared services company to understand issues faced and provide recommendations on different technological characteristics of the system.Design/methodology/approach– The initial stage of the research involved a preliminary review of the existing knowledge management-related documents. This was followed by a top management interview to understand the organization’s business goals and knowledge management (KM) expectations. A total of 70 knowledge workers took part in the research activity. Twenty-five participants from nine departments took part in the preliminary interview, and 52 successful survey forms were collected from a total of 70 respondents. The entire investigation took close to nine months. Data compilation and research result analysis took about three months to complete.Findings– The outcomes of the research show that the quality of POKM is stable, easy to use and organization of the content is rated as good. However, POKM has poor response time and search capability. The content is found to be difficult to locate in the POKM but most participants agree that knowledge stored in the POKM is helpful, can be accessed anytime and anywhere and useful for their day-to-day job. As for the user interface, POKM is not very pleasant to use with a weak set of functions and features. For user satisfaction toward POKM, it is shown that users are not satisfied with the efficiency and effectiveness of the systems. However, employees generally are satisfied with the ease of access, download and reuse of knowledge contains in POKM. In term of perceived POKM benefits, users agree that POKM is an enabler for acquiring new knowledge and innovative ideas, managing and storing knowledge and accomplishing tasks more efficiently. Lastly, knowledge users agree that POKM functions enable knowledge networking, sharing and creation in the organization.Originality/value– POKM was launched and implemented for close to 10 years; however, the organization has failed to achieve some of the goals such as knowledge sharing among employees, creation of new skills and knowledge, measuring knowledge sharing activities and knowledge sharing strategy. The importance of this study is to understand and highlight the technological perspective of POKM from the knowledge workers. Findings will summarize issues faced by the case company for further action and remedy. The outcomes of the study also provide a comprehensive view and guideline to organizations who are interested to implement a KM system.

Background: Infants have been screened for developmental dysplasia of the hip (DDH) since the 1960s. However, changes to the national screening programme in 2008 have reduced the surveillance of DDH following the removal of the 8-month infant hip check, leaving only the 6–8 week hip check as standard. Aim: The study was to ascertain if parents/carers could be effective screeners in the detection of infant DDH using a self-check guide. Design and setting: A self-check guide for DDH was developed to enlist parents as screeners. The guide highlights common signs used to alert to the possibility of DDH or hip dislocation. It was disseminated during 2008–13 by the Royal Berkshire NHS Foundation Trust in West Berkshire, through maternity services and health centres. Results: Of those infants referred to our clinic as a result of parental screening, 73% were ‘abnormal’; of these, 33% went on to treatment with splintage. The mean age of infants was 5.36 months, and 20% of positive findings were in infants aged 7 months or over at the time seen. None went on to have open surgery. These patients represented 5–10% of the overall group of DDH-positive patients. If left undiagnosed, they may have gone on to late presentation requiring surgery as a child, or undiagnosed acetabular dysplasia and possible surgical treatment in relatively early adulthood. Conclusion: Given the right guidance, parents could assist in detecting DDH in their infant.