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Anal cancer has increasing incidence and is preceded by high‐grade anal intraepithelial neoplasia (HGAIN; AIN2–3). Previously, we identified and validated several methylation markers for accurate detection of anal cancer and HGAIN with cancer risk in HIV‐positive (HIV+) men who have sex with men (MSM). This study aimed to evaluate these markers in HIV‐negative risk groups. A cross‐sectional series of 176 tissue samples of anal cancer, AIN3, AIN2, AIN1 and control biopsies obtained in HIV‐negative women and men was tested for six methylation markers (ASCL1, LHX8, SST, WDR17, ZIC1 and ZNF582). Accuracy for detection of AIN3 and cancer (AIN3+) was determined by univariable and multivariable mixed‐effect ordinal logistic regression. Methylation levels of all markers increased with increasing severity of disease (P, Host cell DNA methylation plays a role in anal carcinogenesis in HIV‐negative (HIV‐neg) and HIV‐positive (HIV+) individuals, including men who have sex with men (MSM). Methylation levels are increased in high‐grade anal intraepithelial neoplasia at risk of progression towards anal cancer, making methylation markers promising prognostic biomarkers.

Purpose We investigated changes in ARDS severity and associations with outcome in COVID–19 ARDS patients. Methods We compared outcomes in patients with ARDS classified as ‘mild’, ‘moderate’ or ‘severe’ at calendar day 1, and after reclassification at calendar day 2. The primary endpoint was 28–day mortality. We also identified which ventilatory parameters had an association with presence of severe ARDS at day 2. We repeated the analysis for reclassification at calendar day 4. Results Of 895 patients, 8.5%, 60.1% and 31.4% had mild, moderate and severe ARDS at day 1. These proportions were 13.5%, 72.6% and 13.9% at day 2. 28–day mortality was 25.3%, 31.3% and 32.0% in patients with mild, moderate and severe ARDS at day 1 (p = 0.537), compared to 28.6%, 29.2% and 44.3% in patients reclassified at day 2 (p = 0.005). No ventilatory parameter had an independent association with presence of severe ARDS at day 2. Findings were not different reclassifying at day 4. Conclusions In this cohort of COVID–19 patients, ARDS severity and mortality between severity classes changed substantially over the first 4 days of ventilation. These findings are important, as reclassification could help identify target patients that may benefit from alternative approaches., Graphical abstract Unlabelled Image

Diabetes mellitus is the number one cause of blindness among adults aged 20 - 64 in the United States. The Center for Disease Control estimates that 9.4% of the US population meets diagnostic criteria for diabetes. Among patients with the disease, over one-fourth will have findings of diabetic retinopathy, ranging from mild non-proliferative diabetic retinopathy (rare dot-blot hemorrhages) to the most severe form, proliferative diabetic retinopathy (PDR). Despite diabetes being recognized as a unique disease entity as early as the 2nd century AD, no physician was capable of identifying the connection between this mysterious endocrine disorder and its ocular manifestations until the 19th century, mainly due to limitations in the ocular examination. As imaging modalities have developed over the decades of research, so have our various treatments; which now include a wide range of options such as anti-VEGF injections, laser treatment, and microsurgeries. Here we review the evolution of imaging modalities, pathophysiology of proliferative vs. non-proliferative diabetic retinopathy complications, and commonly used treatment options.

In Spring 2011 the Department of Health (DH) received a request to review European Union Directive 2005/36 EU – the directive relating to the recognition of professional qualifications. The Department of Health lawyer raised concerns that the existing shortened dental courses may be in breach of EU law. There were three shortened dental courses in the UK: 4 year graduate entry courses in Liverpool/Peninsula and 3-year Dental Programme for Medical Graduates (DPMG) in Kings, London. During the summer the General Dental Council (GDC) was made aware of these concerns. In autumn 2011 the Chief Dental Officer for England with the GDC, told the Dental Deans’ Council (DDC) that shortened dental courses were illegal. On 12th Jan 2012 students on the DPMG were told that they would have to complete a full 5-year dental degree. The GDC said that this interpretation of EU law would also impact on shortened medical courses. In view of the potentially enormous impact that this would have on OMFS training, BAOMS engaged all the resources it could and by assembling legal opinions including written contributions from Sir David Edward, whose opinion was being misinterpreted by the GDC and DH, and by sharing these resources with all the stakeholders, BAOMS was able to preserve shortened dental and medical courses. Now that the UK has left the European Union, negotiations around mutual recognition of qualifications may mean this issue will resurface. We should remain vigilant.

For decades, the complicated energy surfaces found in macromolecular protein:ligand structures, which require large amounts of computational time and resources for energy state sampling, have been an inherent obstacle to fast, routine free energy estimation in industrial drug discovery efforts. Beginning in 2013, the Merz research group addressed this cost with the introduction of a novel sampling methodology termed “Movable Type” (MT). Using numerical integration methods, the MT method reduces the computational expense for energy state sampling by independently calculating each atomic partition function from an initial molecular conformation in order to estimate the molecular free energy using ensembles of the atomic partition functions. In this work, we report a software package, the DivCon Discovery Suite with the MovableType module from QuantumBio Inc., that performs this MT free energy estimation protocol in a fast, fully encapsulated manner. We discuss the computational procedures and improvements to the original work, and we detail the corresponding settings for this software package. Finally, we introduce two validation benchmarks to evaluate the overall robustness of the method against a broad range of protein:ligand structural cases. With these publicly available benchmarks, we show that the method can use a variety of input types and parameters and exhibits comparable predictability whether the method is presented with “expensive” X-ray structures or “inexpensively docked” theoretical models. We also explore some next steps for the method. The MovableType software is available at http://www.quantumbioinc.com/, Graphical Abstract

Transgender, gender non-conforming, and non-binary (TGNCNB) people commonly experience disrespect or discrimination from health care providers when attempting to utilize health care services and tend to avoid or postpone obtaining necessary care. Informed by Andersen’s Behavioral Model of Health Services Use and Lerner and Robles’ Adapted Behavioral Model of Health Care Utilization among Transgender People, we examine avoidance of health care utilization among TGNCNB adults based on anticipated disrespect or mistreatment from doctors. Hierarchical logistic regression was used to analyze data from the 2015 United States Trans Survey (N = 27,715), the largest TGNCNB sample, to date, collected in 2015. A total of 21,930 participants were selected for the current study. Nearly one fourth (22%) of the sample reported not utilizing health care when necessary because they anticipated being disrespected or mistreated when visiting a doctor. Cost (OR = 2.51, CI = 2.32–2.72), invasive questions (OR = 2.38, CI = 2.16–2.63), refusal of care (OR = 2.20, CI = 1.78–2.71), being verbally harassed (OR = 2.18, CI = 1.86–2.56), and needing to educate a provider (OR = 1.89, CI = 1.73–2.07) were the strongest predictors of avoidance of health care utilization. Perceived doctor discriminatory behaviors, cost, need to educate a provider, verbal harassment, and perception of gender conformance are major barriers to TGNCNB people utilizing health care. Reducing transphobia among health professionals utilizing cultural safety by developing providers that are comfortable and affirming of TGNCNB people is critical. Federal policy, such as the Equality Act, is also vital so that transphobia is considered an illegal form of discrimination across the USA that will continue to discourage health insurance companies from denying claims for medically necessary, transition-related health care.

Background Minimal clinically important differences (MCIDs) for different patient outcome scores have been reported for various shoulder diseases, including shoulder arthroplasty and the nonoperative treatment of rotator cuff disease. The purpose of this study was to assess the MCID for the American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) score, the Simple Shoulder Test (SST), and a visual analog scale (VAS) measuring pain, after arthroscopic rotator cuff repair. Methods A total of 202 patients who underwent arthroscopic rotator cuff repair were retrospectively reviewed. ASES, SST, and VAS pain scores were collected preoperatively and at 1 year postoperatively. The MCID was then calculated via a 4-question anchor–based method. Results The MCID results for the ASES, SST, and VAS pain scores were 27.1, 4.3, and 2.4, respectively. Age at time of surgery, sex, anteroposterior tear size, and worker's compensation status were not associated with MCID values (P > .05). Conclusion The MCID values determined in the current study are higher than those previously identified for the nonoperative treatment of rotator cuff disease using the same anchor questions. Use of these higher values should be considered when evaluating improvements of individual patients after rotator cuff repair, to determine comparative effectiveness of various rotator cuff repair techniques and to determine sample sizes for prospective comparative trials of rotator cuff repair methods.

There is growing evidence that there is an increased use of Marijuana (cannabis) during the perinatal period. This review summarizes pertinent legislation (past and present) and the physiology and pathophysiology of cannabis use during pregnancy. The literature which involves issues concerning cannabis and pregnancy is expanding but at present has many gaps and unanswered questions. The effects on the newborn are significant and treatment recommendations including breastfeeding are presented. Also included is a description of developmental delay during the first 2 years of life in infants exposed to prenatal marijuana. In addition, this commentary discusses the increase use of the newer “synthetic” cannabinoids which have greater psychotropic activity and can cause significant harm.

X‐ray regulations and room design methodology vary widely across Canada. The Canadian Organization of Medical Physicists (COMP) conducted a survey in 2016/2017 to provide a useful snapshot of existing variations in rules and methodologies for human patient medical imaging facilities. Some jurisdictions no longer have radiation safety regulatory requirements and COMP is concerned that lack of regulatory oversight might erode safe practices. Harmonized standards will facilitate oversight that will ensure continued attention is given to public safety and to control workplace exposure. COMP encourages all Canadian jurisdictions to adopt the dose limits and constraints outlined in Health Canada Safety Code 35 with the codicil that the design standards be updated to those outlined in NCRP 147 and BIR 2012.

STUDY DESIGN Retrospective study using a national administrative database. OBJECTIVE To define the cohort differences in patient characteristics between patients undergoing cervical disc arthroplasty (CDA) and anterior cervical discectomy and fusion (ACDF) in a large national sample, and to describe the impact of those baseline patient characteristics on analyses of costs and complications. SUMMARY OF BACKGROUND DATA CDA was initially studied in high quality, randomized trials with strict inclusion criteria. Recently a number of non-randomized, observational studies have been published an attempt to expand CDA indications. These trials are predisposed to falsely attributing differences in outcomes to an intervention due to selection bias. METHODS Adults undergoing ACDF or CDA between 2004 and 2014 were identified using International Classification of Diseases, 9, Clinical Modification (ICD-9-CM) diagnosis and procedure codes. Perioperative demographics, comorbidities, complications, and costs were queried. Patient characteristics were compared via chi-square and t tests. Cost, mortality, and complications were compared between ACDF and CDA cohorts using models that adjusted for demographics and comorbidities, as well as "naive" models that did not. RESULTS A total of 290,419 procedures, 98.2% ACDF and 1.8% CDA, were included in the sample. Compared with ACDF patients, CDA patients were younger, healthier as evidenced by number of comorbidities, and had an improved socioeconomic status as measured by income and insurance. The naive logistic regression model showed that hospital costs for CDA were $549 lower than ACDF. In the fully specified model, CDA was $574 more expensive. The naive model for medical complications suggests a protective advantage for CDA over ACDF, odds ratio of 0.627, P

Objective: To examine effects of four different transcranial, red/near-infrared (NIR), light-emitting diode (tLED) protocols on naming ability in persons with aphasia (PWA) due to left hemisphere (...

Colorectal cancer (CRC) is the second leading cause for cancer-related death globally. Clinically, there is an urgent need for non-invasive CRC detection. This study assessed the feasibility of CRC detection by analysis of tumor-derived methylated DNA fragments in urine. Urine samples, including both unfractioned and supernatant urine fractions, of 92 CRC patients and 63 healthy volunteers were analyzed for DNA methylation levels of 6 CRC-associated markers (SEPT9, TMEFF2, SDC2, NDRG4, VIM and ALX4). Optimal marker panels were determined by two statistical approaches. Methylation levels of SEPT9 were significantly increased in urine supernatant of CRC patients compared to controls (p SEPT9 and SDC2 was able to detect up to 70% of CRC cases in urine supernatant at 86% specificity. First evidence is provided for CRC detection in urine by SEPT9 methylation analysis, which combined with SDC2 allows for an optimal differentiation between CRC patients and controls. Urine therefore provides a promising liquid biopsy for non-invasive CRC detection.

Background Patients with COVID-19-related acute respiratory distress syndrome (ARDS) have been postulated to present with distinct respiratory subphenotypes. However, most phenotyping schema have been limited by sample size, disregard for temporal dynamics, and insufficient validation. We aimed to identify respiratory subphenotypes of COVID-19-related ARDS using unbiased data-driven approaches.Methods PRoVENT-COVID was an investigator-initiated, national, multicentre, prospective, observational cohort study at 22 intensive care units (ICUs) in the Netherlands. Consecutive patients who had received invasive mechanical ventilation for COVID-19 (aged 18 years or older) served as the derivation cohort, and similar patients from two ICUs in the USA served as the replication cohorts. COVID-19 was confirmed by positive RT-PCR. We used latent class analysis to identify subphenotypes using clinically available respiratory data cross-sectionally at baseline, and longitudinally using 8-hourly data from the first 4 days of invasive ventilation. We used group-based trajectory modelling to evaluate trajectories of individual variables and to facilitate potential clinical translation. The PRoVENT-COVID study is registered with ClinicalTrials.gov, NCT04346342.Findings Between March 1, 2020, and May 15, 2020, 1007 patients were admitted to participating ICUs in the Netherlands, and included in the derivation cohort. Data for 288 patients were included in replication cohort 1 and 326 in replication cohort 2. Cross-sectional latent class analysis did not identify any underlying subphenotypes. Longitudinal latent dass analysis identified two distinct subphenotypes. Subphenotype 2 was characterised by higher mechanical power, minute ventilation, and ventilatory ratio over the first 4 days of invasive mechanical ventilation than subphenotype 1, but PaO2/FiO(2), pH, and compliance of the respiratory system did not differ between the two subphenotypes. 185 (28%) of 671 patients with subphenotype 1 and 109 (32%) of 336 patients with subphenotype 2 had died at day 28 (p=0.10). However, patients with subphenotype 2 had fewer ventilator-free days at day 28 (median 0, IQR 0-15 vs 5, 0-17; p=0.016) and more frequent venous thrombotic events (109[32%] of 336 patients vs 176 [26%] of 671 patients; p=0.048) compared with subphenotype 1. Group-based trajectory modelling revealed trajectories of ventilatory ratio and mechanical power with similar dynamics to those observed in latent class analysis-derived trajectory subphenotypes. The two trajectories were: a stable value for ventilatory ratio or mechanical power over the first 4 days of invasive mechanical ventilation (trajectory A) or an upward trajectory (trajectory B). However, upward trajectories were better independent prognosticators for 28-day mortality (OR 1.64, 95% CI 1.17-2.29 for ventilatory ratio; 1.82, 1.24-2.66 for mechanical power). The association between upward ventilatory ratio trajectories (trajectory B) and 28-day mortality was confirmed in the replication cohorts (OR 4.65, 95% CI 1. 87-11 6 for ventilatory ratio in replication cohort 1; 1-89, 1.05-3-37 for ventilatory ratio in replication cohort 2).Interpretation At baseline, COVID-19-related ARDS has no consistent respiratory subphenotype. Patients diverged from a fairly homogenous to a more heterogeneous population, with trajectories of ventilatory ratio and mechanical power being the most discriminatory. Modelling these parameters alone provided prognostic value for duration of mechanical ventilation and mortality. Copyright (C) 2021 Published by Elsevier Ltd. All rights reserved.

Made available in DSpace on 2022-05-01T08:44:42Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-09-01 In this work, an optical fiber was coated by a thin-film metal layer to work as a fiber optical phase modulator based on thermal effect. This device was assembled in one of the arms of an all-fiber Michelson interferometer stabilized by a nonlinear control system based on variable structure and sliding modes. The frequency response reached 200 Hz, which can be considered high for a device based on the thermal effect. Compared with a fiber optical phase modulator based on the piezoelectric effect, the thermal modulator presented a higher scale factor per meter of optical fiber, showing the potential to work as a simple, low-cost, small-sized, short length, lightweight, and low-voltage fiber optical phase modulator. Aeronautics Institute of Technology [Instituto Tecnológico de Aeronáutica-ITA], Praça Mal. Eduardo Gomes 50, SP Division of Photonics Institute for Advanced Studies [Instituto de Estudos Avançados-IEAv], Trevo Cel. Av. José A. A. do Amarante 1, SP Universidade Federal de São Paulo (UNIFESP), Av. Cesare Mansueto Giulio Lattes 1201, SP Department of Electrical Engineering São Paulo State University (UNESP), José Carlos Rossi Avenue 1370, SP Department of Electrical Engineering São Paulo State University (UNESP), José Carlos Rossi Avenue 1370, SP

BACKGROUND The evolutionary processes that drive progression in patients with IDH-mutant astrocytoma remain unclear. The GLASS-NL consortium, as part of the larger worldwide GLASS consortium, was initiated to gain insight into the molecular mechanisms underlying glioma evolution and to identify markers of progression in IDH-mutant astrocytomas. Such markers can ultimately assist clinical decision making. Here, we present the first results of genome wide methylation profiling of samples included in the GLASS-NL study. MATERIAL AND METHODS 110 adult patients were identified with an IDH-mutant astrocytoma at first diagnosis. All patients underwent a surgical resection of the tumor at least twice, separated by at least 6 months with a median of 40.9 months (IQR: 24.0, 64.7), in 37% and 18% of the cases, patients were treated with radiotherapy or chemotherapy respectively, before surgical resection of the recurrent tumor. Methylation profiling was done on (macro dissected) DNA isolated of 235 samples from 103 patients (102 1st, 101 2nd, 29 3rd, and 3 4th resection), using the Infinium MethylationEPIC BeadChip array. Copy number variations were also derived from these data. Methylation classes were determined according to Capper et al. (2018). Overall survival (OS) was measured from date of first surgery. RESULTS Of all primary tumors, the methylation-classifier assigned 85 (87%) to the A_IDH (‘low grade’) subclass and 10 (10%) to the A_IDH_HG (‘high grade’) subclass. The relative proportion of high grade tumors increased ~three-fold at tumor recurrence (32/101, 32%) and even further in the second recurrence (15/29, 52%). The overall DNA-methylation levels of recurrent samples was lower than that of primary samples. This difference is explained by the increased number of high grade samples at recurrence, since near identical DNA-methylation levels were observed in samples that remained low grade. In an unsupervised analysis, methylation data derived from first and second resections of individual patients mostly (79%) cluster together. This indicates that variability between tumors is larger than temporal heterogeneity within tumors. Recurrent samples that do not cluster with their primary tumor, form a separate cluster and have relatively low genome-wide DNA-methylation. CONCLUSION Our data demonstrate that methylation profiling identifies a shift towards a higher grade at tumor progression coinciding with reduced genome-wide DNA-methylation levels.

OBJECTIVE: To understand whether the Comprehensive Care for Joint Replacement (CJR) program induces participating hospitals to (1) preferentially select lower risk patients, (2) reduce 90‐day episode‐of‐care costs, (3) improve quality of care, and (4) achieve greater cost reduction during its second year, when downside financial risk was applied. DATA SOURCES: We identified beneficiaries of age 65 years or older undergoing hip or knee joint replacement in the 100% sample of Medicare fee‐for‐service inpatient (Part A) claims from January 1, 2013 to August 31, 2017. Cases were linked to subsequent outpatient, Part B, home health agency, and skilled nursing facility claims, as well as publicly available participation status for CJR. STUDY DESIGN: We estimated the effect of CJR for hospitals in the 67 metropolitan statistical areas (MSA) selected to participate in CJR (785 hospitals), compared to those in 104 non‐CJR MSAs (962 hospitals; maintaining fee‐for‐service). A difference‐in‐differences approach was used to detect patient selection, as well as to compare 90‐day episode‐of‐care costs and quality of care between CJR and non‐CJR hospitals over the first two performance years. DATA COLLECTION: We excluded 172 hospitals from our analysis due to their preexisting BPCI participation. We focused on elective admissions in the main analysis. PRINCIPAL FINDINGS: While reductions in 90‐day episode‐of‐care costs were greater among CJR hospitals (−$902, 95% CI: −$1305, −$499), largely driven by a 16.8% (p

Background There is a concern that the Oncology Care Model (OCM), a voluntary bundled payment program, may incentivize mergers and acquisitions among physician practices leading to reduced competition and price increases. These concerns are heightened if OCM is preferentially adopted in competitive health care markets because it could result in reduced competition, but little is known about the characteristics of markets where OCM is adopted. Objective To measure the association between regional market competition among medical oncologists with the initial adoption of OCM. Research design The Herfindahl-Hirschman Index (HHI), a measure of competition, was calculated for hospital referral regions (HRRs) using secondary data from the Centers for Medicare and Medicaid Services. The relationship between HHI and OCM adoption was assessed using a 2-part regression model adjusting for the market-level number of practices, physician density, average practice size, sociodemographic characteristics, and medical resources. A count model on all HRRs was also estimated to assess an overall effect. Subjects A total of 10,788 physicians in 3,537 practices who billed Medicare for oncology services in 2015. Results OCM was adopted in 114 (37%) of the 306 HRRs. We found that practices in competitive health care markets were more likely to adopt OCM than in noncompetitive markets. Two-part regression analysis indicated a nonlinear relationship between HHI and OCM adoption. Average practice size, number of practices in an HRR, and the hospital bed rate were positively associated with adoption, whereas the rate of full-time equivalent hospital employees to 1000 residents was negatively associated with adoption. Conclusions OCM adoption was higher in HRRs with greater competition. Careful monitoring of market-level changes among OCM adopters should be undertaken to ensure that the benefits of the OCM outweigh the negative consequences of possible changes in competition.

STUDY DESIGN Surgeon survey. OBJECTIVE To examine factors influencing surgeons' definition of instability in grade 1 degenerative spondylolisthesis (DS) and assess treatment preferences for both stable and unstable DS. SUMMARY OF BACKGROUND DATA DS treatment options are broadly classified as decompression with or without fusion. In surgical decision-making, "instability" is frequently considered as a key factor. However, no consensus on the definition of instability exists. METHODS A survey was conducted to ascertain the minimum amounts of static translation, dynamic translation, and angulation change that surgeons considered significant for determining instability. The importance of other clinical and radiographic features were also assessed, and respondents' standard treatment for stable and unstable DS. RESULTS Out of 226 respondents, 99% deemed dynamic translation moderately to extremely influential for determining instability, whereas only 55% found static translation as important. The most prevalent cut-off values for dynamic (57%) and static translation (32%) were at least 2-4 mm and for angulation change at least 10-15 degrees (43%). Facet angulation was considered moderately to extremely important to determine instability by 69% of the surgeons, disk height by 67%, patient age by 64%, severity of stenosis by 55%, severity of back pain by 50%, patient-reported function by 49%, pelvic incidence by 47%, and severity of neurogenic claudication by 42%.Decompression with fusion was the preferred treatment method for unstable DS in 99% of the respondents. For stable DS, 40% would still perform fusion, whereas 60% preferred treatment with decompression-alone. Those who preferred fusion for stable DS reported significantly lower thresholds for static (P

Analysis of National Inpatient Sample (NIS), 2004 to 2015.Describe recent trends in US rates of lumbar fusion procedures and associated costs, by surgical indication.Spinal fusion is appropriate for spinal deformity and instability, but evidence of effectiveness is limited for primary disc herniation and spinal stenosis without instability. It remains controversial for treatment of axial pain secondary to degenerative disc disease. There are potential non-instability, non-deformity indications for fusion surgery, including but not limited to severe foraminal stenosis and third-time disc herniation.Elective lumber fusion trends were reported using Poisson regression, grouped by indication as degenerative scoliosis, degenerative spondylolisthesis, spinal stenosis, disc herniation, and disc degeneration. Generalize linear regression was used to estimate trends in hospital costs, adjusted for age, sex, indication, comorbidity, and inflation.Volume of elective lumbar fusion increased 62.3% (or 32.1% per 100,000 US adults), from 122,679 cases (60.4 per 100,000) in 2004 to 199,140 (79.8 per 100,000) in 2015. Increases were greatest among age 65 or older, increasing 138.7% by volume (73.2% by rate), from 98.3 per 100,000 (95% confidence interval [CI] 97.2, 99.3) in 2004 to 170.3 (95% CI 169.2, 171.5) in 2015. Although the largest increases were for spondylolisthesis (+47,390 operations, 111%) and scoliosis (+16,129 operations, 186.6%), disc degeneration, herniation, and stenosis combined to accounted for 42.3% of total elective lumbar fusions in 2015. Aggregate hospital costs increased 177% during these 12 years, exceeding $10 billion in 2015, and averaging more than $50,000 per admission.While the prevalence of spinal pathologies is not known, the rate of elective lumbar fusion surgery in the United States increased most for spondylolisthesis and scoliosis, indications with relatively good evidence of effectiveness. The proportion of fusions coded for indications with less evidence of effectiveness has slightly decreased in the most recent years.3.

Background: Numerous studies have reported the incidence and outcomes of injuries in the men’s and women’s National Basketball Association (NBA and WNBA, respectively). Purpose: To synthesize published data regarding the incidence and outcomes of all injuries in the NBA and WNBA in a comprehensive review. Study Design: Systematic review; Level of evidence, 4. Methods: Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we searched 3 electronic databases (PubMed, MEDLINE, Embase) for studies of all levels of evidence since 1990 pertaining to injuries sustained by active players in the NBA and WNBA. Studies were excluded if the cohort of interest included ≤3 active players. Results: The initial search of the 3 databases yielded 1253 unique studies, of which 49 met final inclusion criteria for this review. Only 4 studies included athletes in the WNBA. Based on the mean annual incidence, the 5 most common orthopaedic sports injuries sustained in the NBA were concussions (9.5-14.9 per year), fractures of the hand (3.5-5.5 per year), lower extremity stress fractures (4.8 per year), meniscal tears (2.3-3.3 per year), and anterior cruciate ligament tears (1.5-2.6 per year). Cartilage defects treated using microfracture, Achilles tendon ruptures, and anterior cruciate ligament injuries were 3 injuries that led to significant reductions in performance measurements after injury. Conclusion: With advances in sports technology and statistical analysis, there is rapidly growing interest in injuries among professional basketball athletes. High-quality prospective studies are needed to understand the prevalence and effect of injuries on player performance and career length. This information can inform preventative and treatment measures taken by health care providers to protect players and guide safe return to play at a high level.

Nicotinamide N-methyltransferase (NNMT) methylates nicotinamide (NA) to generate 1-methyl nicotinamide. Since its discovery 70 years ago, the appreciation of the role of NNMT in human health has evolved from serving only metabolic functions to also being a driving force in diseases, including a variety of cancers. Despite the increasing evidence indicating NNMT as a viable therapeutic target, the development of cell-active inhibitors against this enzyme is lacking. In this review, we provide an overview of the current status of NNMT inhibitor development, relevant in vitro and in vivo studies, and a discussion of the challenges faced in the development of NNMT inhibitors.

ObjectivesFamilial adenomatous polyposis (FAP) is a condition caused by a constitutional pathogenic variant of the adenomatous polyposis coli (APC) gene that results in intestinal adenoma formation and colorectal cancer (CRC), necessitating pre-emptive colectomy. We sought to examine interaction between the mucosal immune system and commensal bacteria in FAP to test for immune dysfunction that might accelerate tumorigenesis.MethodsColonic biopsies were obtained from macroscopically normal mucosal tissue from 14 healthy donors and 13 patients with FAP during endoscopy or from surgical specimens. Intraepithelial and lamina propria lymphocytes were phenotyped. Intraepithelial microbes were labelled with anti-IgA/IgG and analyzed by flow cytometry.ResultsProportions of resident memory CD103-expressing CD8+ and γδ T cell receptor+ intraepithelial lymphocytes were dramatically reduced in both left and right colon of patients with FAP compared to healthy controls. In lamina propria, T-cells expressed less CD103 and CD4+ CD103+ cells expressed less CD73 ectonucleotidase. IgA coating of epithelia-associated bacteria, IgA+ peripheral B cells and CD4 T-cell memory responses to commensal bacteria were increased in FAP.ConclusionsLoss of resident memory T-cells and γδ T-cells in mucosal tissue of patients with FAP accompanies intestinal microbial dysbiosis previously reported in this pre-cancerous state and suggests impaired cellular immunity and tumor surveillance. This may lead to barrier dysfunction, possible loss of regulatory T-cell function and excess IgA antibody secretion. Our data are the first to implicate mucosal immune dysfunction as a contributing factor in this genetically driven disease and identify potentially critical pathways in the etiology of CRC.

Background and importance There are several types of renal cell tumours, the most frequent being clear cell renal carcinoma (ccRCC) which represents 80% of malignant renal tumours in adults. Pembrolizumab, in combination with axitinib, is indicated for the firstline treatment of advanced RCC in adults. Aim and objectives To describe and analyse the effectiveness and safety of pembrolizumab and axitinib in a tertiary hospital clinical practice. Material and methods An observational retrospective study was conducted in all patients diagnosed with ccRCC and treated with pembrolizumab and axitinib from March 2019 to October 2020. All patients gave their informed consent. Data sources were the electronic medical records. Variables analysed were: sex, age, PDL-1, prior lines of treatments, IMDC risk and presence of metastases at the start therapy, duration of treatment and interruption causes, grade and type of toxicities and best TAC response. Results 13 patients were included, 76.9% men, mean age 60.4±8.8 years. Among the four patients with tumour samples that were evaluated for PD-L1 expression, 75% had a score ≥1. Three patients were treated with at least one previous line. Previous treatments were: sunitinib (n=3) cabozantinib (n=1) or nivolumab (n=1). IMDC risk classification: 7.7% favourable, 53.8% intermediate and 38.5% poor risk. Presence of metastases: lung (7/13), bone (5/13), liver (3/13), ganglionar (2/13), cerebral (1/13) and unknown (2/13). All patients were treated with pembrolizumab 200 mg every 3 weeks and axitinib 5 mg twice daily until progression, unacceptable toxicity or death. Mean duration of treatment was 28.7 weeks. 46% are continuing with active treatment. Discontinuation causes included: death (n=3), adverse effects (n=3) and progression (n=1). Toxicities included: asthenia grade (G)1–3 (n=11), anorexia G1–2 (n=6), diarrhoea G1–4 (n=5), liver profile alterations G1–3 (n=3), hyperthyroidism G1–3 (n=3), abdominal pain G1–2 (n=3), palmar–plantar erythrodysesthesia G2–3 (n=2), pruritus G1 (n=1), dizziness and paraesthesia G1 (n=1), vomiting G1 (n=1), thrombopenia G2 (n=1) and arthralgias G1 (n=1). Best TAC responses obtained were: 50% stable disease, 25% partial response and 12.5% progressive disease. In five patients the response rate was not evaluated. Conclusion and relevance Effectiveness in our patients resulted in a higher objective response rate than that in the KEYNOTE-426 trial. The combination treatment was well tolerated. To rationalise the use of novel medicines and optimise efficiency, measuring health results is crucial. References and/or acknowledgements Conflict of interest No conflict of interest

Introduction The lifetime risk of colorectal cancer in familial adenomatous polyposis (FAP) approaches 100%. In patients who have undergone prophylactic colectomy, duodenal cancer is 100-300 times more common than in the general population, and an important cause of death. We aimed to develop in vitro models of mucosal crypt-derived organoids from patients with FAP. Method Biopsies from apparent healthy duodenal mucosa of FAP patients undergoing upper gastrointestinal endoscopy or surgery yielded crypts that were immobilised in Matrigel Basement Membrane Matrix (Corning) and cultured in IntestiCult Organoid Growth Medium (StemCell Technologies) to generate organoids for further morphologic and immunocytochemistry analyses (Dako and Abcam antibodies). Result Duodenal crypt-derived organoids from one healthy volunteer formed ring structures (days 1 -2) that progressed to expected branched structures (days 4-7). FAP-derived organoids from 9 patients all generated organoids with aberrant morphologies. These organoids expressed markers of Paneth cells (lysozyme), proliferation (Ki-67), goblet cells (Muc-2) and the single cell layer of mucosal epithelium (CK18). Conclusion This is the first report of duodenal crypt-derived organoids generated from FAP patients. Aberrant organoid morphologies were observed in all 9 patients. Immunocytochemistry confirmed markers of duodenal epithelium, suggesting a promising in vitro model to study disease aetiology in FAP. Take-home message This is a step towards a personalised model of disease for patients with familial adenomatous polyposis.

Supplemental Digital Content is available in the text., Background: In anticipation of a demand surge for hospital beds attributed to the coronavirus pandemic (COVID-19) many US states have mandated that hospitals postpone elective admissions. Objectives: To estimate excess demand for hospital beds due to COVID-19, the net financial impact of eliminating elective admissions in order to meet demand, and to explore the scenario when demand remains below capacity. Research Design: An economic simulation to estimate the net financial impact of halting elective admissions, combining epidemiological reports, the US Census, American Hospital Association Annual Survey, and the National Inpatient Sample. Deterministic sensitivity analyses explored the results while varying assumptions for demand and capacity. Subjects: Inputs regarding disease prevalence and inpatient utilization were representative of the US population. Our base case relied on a hospital admission rate reported by the Center for Disease Control and Prevention of 137.6 per 100,000, with the highest rates in people aged 65 years and older (378.8 per 100,000) and 50–64 years (207.4 per 100,000). On average, elective admissions accounted for 20% of total hospital admissions, and the average rate of unoccupied beds across hospitals was 30%. Measures: Net financial impact of halting elective admissions. Results: On average, hospitals COVID-19 demand for hospital bed-days fell well short of hospital capacity, resulting in a substantial financial loss. The net financial impact of a 90-day COVID surge on a hospital was only favorable under a narrow circumstance when capacity was filled by a high proportion of COVID-19 cases among hospitals with low rates of elective admissions. Conclusions: Hospitals that restricted elective care took on a substantial financial risk, potentially threatening viability. A sustainable public policy should therefore consider support to hospitals that responsibly served their communities through the crisis.

Introduction Gut microbiota dysbiosis may modify the inflammatory state, which could trigger the development of acute coronary syndrome (ACS). Moreover, cardiovascular risk factors may alter the microbiota profile involved in ACS development. Purpose To address the potential role of alterations in microbiota as triggers of ACS and their cardiovascular comorbidities in patients with ACS. Methods Patients admitted for ACS were prospectively included. Stool samples were collected in the first 24 hours after admission. For microbiota analysis, Operational Taxonomic Unit (OTUs) method from V4 amplicon of 16S rRNA was employed. Identification, quantification, clusterization and taxonomic classification of OTUs was performed in Mothur through RDP database. ACS patient microbiota was compared with the microbiota of 10 healthy controls. The microbiota changes analyses were evaluated with ANOVA analysis. Results 41 ACS patients with a mean age of 62±11 years old were included. 34 (83%) were males, 17 (42%) suffered arterial hypertension, 18 (44%) dyslipidaemia, 37 (90%) diabetes mellitus and 16 (39%) were current smokers. A multidimensional scaling model allowed us to clearly delineate different clusters between patients with ACS and healthy controls. This was due to important differences in the main phylum of the human microbiota (Table) Bacteroidetes, Firmicutes / Bacteroidetes ratio and Actinobacteria. In addition, there was a significant decrease in protective Cyanobacteria (p=0.03) and Proteobacteria (p=0.04) in men. Hypertensive and dyslipidaemic patients had a significantly higher amount of Firmicutes, Clostridia (p=0.05) and Erysipelotrichia (p=0.03) classes, respectively. Patients with diabetes had significantly less protective Proteobacteria (p=0.002) and Spirochaetes (p=0.04). Finally, smoking was associated with a significant increase in pathogenic Lentisphaerae (p=0.04). Conclusions Patients with ACS have clear pathogenic alterations of their gut microbiota. Classical cardiovascular risk factors induce different patterns of gut dysbiosis. Gut microbiota profile. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Carlos III Health Institute

BACKGROUND: There is increasing interest in the development of statistical models that can be used to estimate risk of adverse patient outcomes after joint arthroplasty. Competing risk approaches have been recommended to estimate risk of longer-term revision, which is often likely to be precluded by the competing risk of death. However, a common approach is to ignore the competing risk by treating death as a censoring event and using standard survival models such as Cox regression. It is well-known that this approach can overestimate the event risk for population-level estimates, but the impact on the estimation of a patient’s individualized risk after joint arthroplasty has not been explored. QUESTIONS/PURPOSES: We performed this study to (1) determine whether using a competing risk or noncompeting risk method affects the accuracy of predictive models for joint arthroplasty revision and (2) determine the magnitude of difference that using a competing risks versus noncompeting risks approach will make to predicted risks for individual patients. METHODS: The predictive performance of a standard Cox model, with competing risks treated as censoring events, was compared with the performance of two competing risks approaches, the cause-specific Cox model and Fine-Gray model. Models were trained and tested using data pertaining to 531,304 TKAs and 274,618 THAs recorded in the Australian Orthopaedic Association National Joint Replacement Registry between January 1, 2003 and December 31, 2017. The registry is a large database with near-complete capture and follow-up of all hip and knee joint arthroplasty in Australia from 2003 onwards, making it an ideal setting for this study. The performance of the three modeling approaches was compared in two different prediction settings: prediction of the 10-year risk of all-cause revision after TKA and prediction of revision for periprosthetic fracture after THA. The calibration and discrimination of each approach were compared using the concordance index, integrated Brier scores, and calibration plots. Calibration of 10-year risk estimates was further assessed within subgroups of age by comparing the observed and predicted proportion of events. Estimated 10-year risks from each model were also compared in three hypothetical patients with different risk profiles to determine whether differences in population-level performance metrics would translate into a meaningful difference for individual patient predictions. RESULTS: The standard Cox and two competing risks models showed near-identical ability to distinguish between high-risk and low-risk patients (c-index 0.64 [95% CI, 0.64 to 0.64] for all three modeling approaches for TKAs and 0.66 [95% CI 0.66 to 0.66] for THA). All models performed similarly in patients younger than 75 years, but for patients aged 75 years and older, the standard Cox model overestimated the risk of revision more than the cause-specific Cox and Fine-Gray model did. These results were echoed when predictions were made for hypothetical individual patients. For patients with a low competing risk of mortality, the 10-year predicted risks from the standard Cox, cause-specific Cox, and Fine-Gray models were similar for TKAs and THAs. However, a larger difference was observed for hypothetical 89-year-old patients with increased mortality risk. In TKAs, the revision risk for an 89-year-old patient was so low that this difference was negligible (0.83% from the cause-specific Cox model versus 1.1% from the standard Cox model). However, for THAs, where older age is a risk factor for both death and revision for periprosthetic fracture, a larger difference was observed in the 10-year predicted risks for a hypothetical 89-year-old patient (3.4% from the cause-specific Cox model versus 5.2% from the standard Cox model). CONCLUSION: When developing models to predict longer-term revision of joint arthroplasty, failing to use a competing risks modeling approach will result in overestimating the revision risk for patients with a high risk of mortality during the surveillance period. However, even in an extreme instance, where both the frequency of the event of interest and the competing risk of death are high, the largest absolute difference in predicted 10-year risk for an individual patient was just 1.8%, which may not be of consequence to an individual. Despite these findings, when developing or using risk prediction models, researchers and clinicians should be aware of how competing risks were handled in the modeling process, particularly if the model is intended for use populations where the mortality risk is high. LEVEL OF EVIDENCE: Level III, therapeutic study.

Highlights • Children with COVID 19 disease are less symptomatic but they can be potential agents of transmission. • Most children with symptoms from COVID 19 disease (cough, fever, respiratory difficulties) show bnormalities in CXR. • Findings in CXR are non-specific and superimpose on other viral pneumonias. • Peripheral distribution of lung abnormalities is not a distinctive feature in paediatric population. • CXR have a role in the management of the disease in children., BACKGROUND The outbreak of COVID-19 has become pandemic. Pediatric population has been less studied than adult population and prompt diagnosis is challenging due to asymptomatic or mild episodes. Radiology is an important complement to clinical and epidemiological features. OBJECTIVE To establish the most common CXR patterns in children with COVID-19, evaluate interobserver correlation and to discuss the role of imaging techniques in the management of children. MATERIALS AND METHODS Forty-four patients between 0 and 16 years of age with confirmed SARS-Cov-2 infection and CXR were selected. Two paediatric radiologists independently evaluated the images and assessed the type of abnormality, distribution and evolution when available. RESULTS Median age was 79.8 months (ranging from 2 weeks to 16 years of age). Fever was the most common symptom (43.5 %). 90 % of CXR showed abnormalities. Peribronchial cuffing was the most common finding (86.3 %) followed by GGOs (50 %). In both cases central distribution was more common than peripheral. Consolidations accounted for 18.1 %. Normal CXR, pleural effusion, and altered cardiomediastinal contour were the least common. CONCLUSION The vast majority of CXR showed abnormalities in children with COVID-19. However, findings are nonspecific. Interobserver correlation was good in describing consolidations, normal x-rays and GGOs. Imaging techniques have a role in the management of children with known or suspected COVID-19, especially in those with moderate or severe symptoms or with underlying risk factors.

International audience; Background: Several observational studies have reported elevated baseline D-dimer levels in patients hospitalized for moderate to severe coronavirus disease 2019 (COVID-19). These elevated baseline D-dimer levels have been associated with disease severity and mortality in retrospective cohorts.Objectives: To review current available data on the association between D-Dimer levels and mortality in patients admitted to hospital for COVID-19.Methods: We performed a systematic review of published studies using MEDLINE and EMBASE through 13 April 2020. Two authors independently screened all records and extracted the outcomes. A random effects model was used to estimate the standardized mean difference (SMD) with 95% confidence intervals (CI).Results: Six original studies enrolling 1355 hospitalized patients with moderate to critical COVID-19 (391 in the non-survivor group and 964 in the survivor group) were considered for the final pooled analysis. When pooling together the results of these studies, D-Dimer levels were found to be higher in non-survivors than in-survivors. The SMD in D-Dimer levels between non-survivors and survivors was 3.59μg/L (95% CI 2.79-4.40μg/L), and the Z-score for overall effect was 8.74 (P

ObjectiveExposure to persistent organic pollutants is consistently associated with increased diabetes risk in humans. We investigated the short- and long-term impact of chronic low-dose dioxin (aka 2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) exposure during pregnancy and lactation on glucose homeostasis and beta cell function in female mice, including their response to a metabolic stressor later in life.MethodsFemale mice were injected with either corn oil (CO; vehicle control) or 20 ng/kg/d TCDD 2x/week throughout mating, pregnancy, and lactation, and then tracked for 6-10 weeks after chemical exposure stopped. A subset of CO- and TCDD-exposed dams were then transferred to a 45% high fat diet (HFD) or remained on standard chow diet for an additional 11 weeks to assess long-term effects of TCDD on adaptability to a metabolic stressor.ResultsDioxin-exposed dams were hypoglycemic at birth but otherwise had normal glucose homeostasis during and post-dioxin exposure. However, dioxin-exposed dams on chow diet were modestly heavier than controls starting 5 weeks after the last dioxin injection, and their weight gain accelerated after transitioning to a HFD. Dioxin-exposed dams also had accelerated onset of hyperglycemia, dysregulated insulin secretion, reduced islet size, increased MAFA-beta cells, and increased proinsulin accumulation following HFD feeding compared to control dams.ConclusionsOur mouse model suggests that chronic low-dose dioxin exposure may be a contributing factor to obesity and diabetes pathogenesis in females.

Introduction: Approximately 25–30% of veterans deployed to Kuwait, 1990-91, report persistent multi-symptom Gulf War Illness (GWI) likely from neurotoxicant exposures. Photobiomodulation (PBM) in red/near-infrared (NIR) wavelengths is a safe, non-invasive modality shown to help repair hypoxic/stressed cells. Red/NIR wavelengths are absorbed by cytochrome C oxidase in mitochondria, releasing nitric oxide (increasing local vasodilation), and increasing adenosine tri-phosphate production. We investigated whether PBM applied transcranially could improve cognition, and health symptoms in GWI.Materials and Methods: Forty-eight (40 M) participants completed this blinded, randomized, sham-controlled trial using Sham or Real, red/NIR light-emitting diodes (LED) applied transcranially. Fifteen, half-hour transcranial LED (tLED) treatments were twice a week (7.5 weeks, in-office). Goggles worn by participant and assistant maintained blinding for visible red. Pre-/Post- testing was at Entry, 1 week and 1 month post- 15th treatment. Primary outcome measures were neuropsychological (NP) tests; secondary outcomes, Psychosocial Questionnaires, including PTSD.Results: Primary Analyses (all participants), showed improvement for Real vs. Sham, for Digit Span Forwards (p < 0.01); and a trend for Trails 4, Number/Letter Sequencing (p < 0.10). For secondary outcomes, Real group reported more improvement on the SF-36V Plus, Physical Component Score (p < 0.08). Secondary Analyses included only subjects scoring below norm (50%ile) at Entry, on specific NP test/s. Real and Sham improved at 1 week after 15th treatment; however, at 1 month, only those receiving Real improved further: Digit Span Total, Forwards and Backwards; Trails 4, Number/Letter Sequencing; California Verbal Learning Test-II, long delay free recall; Continuous Performance Test-II, False Alarm Rate; and Color-Word Interference, Stroop, Trial 3, Inhibition; Sham group worsened, toward Entry values. Only those with more post-traumatic stress disorder (PTSD) symptomatology at Entry, receiving Real, continued to have additional PTSD reduction at 1 month; Sham regressed.Conclusion: This study was underpowered (n = 48), with large heterogeneity at Entry. This likely contributed to significance or trend to significance, for only two of the NP tests (Digit Span Forwards; Trails 4, Number/Letter Sequencing) and only one general health measure, the SF-36V Plus, Physical Component Score. More subjects receiving Real, self-reported increased concentration, relaxation and sleep. Controlled studies with newer, transcranial LED home treatment devices are warranted; this is expected to increase enrollment.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT01782378.

Background:. The optimal surgical treatment for scapholunate advanced collapse (SLAC) and scaphoid nonunion advanced collapse (SNAC) remains unclear. To inform clinical decision-makers, we conducted a cost-effectiveness analysis comparing proximal row carpectomy (PRC) and four-corner arthrodesis (FCA). Methods:. A Markov microsimulation model was used to compare clinical outcomes, costs, and health utilities between PRC and FCA. The model used a 10-year time horizon and a 1-month cycle length, and it was evaluated from the societal perspective. Utilities and clinical parameters including transition probabilities for debridement for infection, removal of implants, conversion to total wrist arthrodesis, revision FCA, and revision total wrist arthrodesis were obtained from published literature. Timing of complications was estimated from the literature. Direct medical costs were derived from Medicare ambulatory surgical cost data, and indirect costs for missed work due to surgical procedures and complications were included. The effectiveness outcome was quality-adjusted life years (QALYs). Probabilistic sensitivity analysis and 1-way threshold analysis for utilities were performed. Results:. In the base-case model, PRC dominated FCA (i.e., PRC had lower cost and greater effectiveness). The mean (and standard deviation) for the total cost and QALYs per patient were $30,970 ± $5,931 and 8.24 ± 1.28, respectively, for PRC and $44,526 ± $11,205 and 8.23 ± 1.26, respectively, for FCA. In the probabilistic sensitivity analysis, PRC dominated FCA in 57% of the 1 million iterations. The cost-effectiveness acceptability curve indicated that PRC is the most cost-effective strategy regardless of the willingness-to-pay threshold up to $100,000/QALY. Conclusions:. PRC dominated FCA in the base-case analysis and in the probabilistic sensitivity analysis. These results suggest that PRC is the optimal strategy for Stage-I or II SLAC and for SNAC in patients ≥55 years of age. Level of Evidence:. Economic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Our orthopaedic surgery department at Montefiore Medical Center and Albert Einstein College of Medicine is located within the Bronx, a borough of New York City, and serves a densely populated urban community. Since the beginning of the novel coronavirus outbreak in New York City, the medical center was forced to rapidly adapt to the projected influx of critically ill patients. The aim of this report is to outline how our large academic orthopaedic surgery department adopted changes and alternative practices in response to the most daunting challenge to public health in our region in over a century. We hope that this report provides insight for others facing similar challenges.

Background Guidelines remain unclear over whether patients with early stage oral cancer without overt neck disease benefit from upfront elective neck dissection (END), particularly those with the smallest tumours. Methods We conducted a randomised trial of patients with stage T1/T2 N0 disease, who had their mouth tumour resected either with or without END. Data were also collected from a concurrent cohort of patients who had their preferred surgery. Endpoints included overall survival (OS) and disease-free survival (DFS). We conducted a meta-analysis of all six randomised trials. Results Two hundred fifty randomised and 346 observational cohort patients were studied (27 hospitals). Occult neck disease was found in 19.1% (T1) and 34.7% (T2) patients respectively. Five-year intention-to-treat hazard ratios (HR) were: OS HR = 0.71 (p = 0.18), and DFS HR = 0.66 (p = 0.04). Corresponding per-protocol results were: OS HR = 0.59 (p = 0.054), and DFS HR = 0.56 (p = 0.007). END was effective for small tumours. END patients experienced more facial/neck nerve damage; QoL was largely unaffected. The observational cohort supported the randomised findings. The meta-analysis produced HR OS 0.64 and DFS 0.54 (p Conclusion SEND and the cumulative evidence show that within a generalisable setting oral cancer patients who have an upfront END have a lower risk of death/recurrence, even with small tumours. Clinical Trial Registration NIHR UK Clinical Research Network database ID number: UKCRN 2069 (registered on 17/02/2006), ISCRTN number: 65018995, ClinicalTrials.gov Identifier: NCT00571883.

We used multicenter international data from the International Society of Heart and Lung Transplantation Mechanically Assisted Circulation Support (IMACS) registry to determine bloodstream infection (BSI) event rate, independent risk factors, and association with mortality.Included were patients registered in IMACS from January 2013 through December 2015, assessed BSI event rate of mechanical circulatory support (MCS) and non-MCS-related BSIs, and conducted univariate and multivariate analyses between BSI with baseline characteristics and mortality.We documented 1,606 BSIs in 1,231 of 10,171 MCS recipients (12%), with an event rate of 2.43 BSIs/100 patient-months within 3 months after implant (early onset) and 1.03 BSIs/100 patient-months after 3 months (late onset). Of these episodes, 1,378 (85.8%) were non- MCS-related BSI. Increasing body mass index and bilirubin were independent correlates of MCS-related BSI. Independent correlates of non-MCS-related BSI included older age, higher body mass index, previous cardiac surgery, baseline chronic renal disease and dialysis, pre-implant frailty, presence of biventricular assist device, total artificial heart or right ventricular assist device, and Interagency Registry for Mechanically Assisted Circulatory Support category 1. Survival after 3 months after implant of patients who developed early-onset BSI was 56.9% at 24 months vs 77.4% in patients without early-onset BSI (p0.001). Early-onset BSI was an independent correlate of mortality at 3 months after implantation (hazard ratio, 2.56; 95% confidence interval, 2.09-3.15; p0.001).Early-onset BSI was associated with significantly increased 24-month mortality. More than 85% of these BSIs were not device related. There is an opportunity for infection prevention practices to decrease the BSI event rate, which may affect 24-month survival. These data can also serve as benchmarking for individual institutions.

Objective The purpose of this study was to identify factors that influence a patient's decision to use physical therapy (PT) services for a low back pain (LBP) complaint. Methods Semi-structured qualitative phone interviews were conducted with patients who were offered an early outpatient PT visit secondary to patients’ primary appointment for LBP with a non-operative sports medicine specialist physician. Interviews were recorded, transcribed, and analyzed to identify themes using an iterative process. Results Forty participants were interviewed; 20 accepted early PT services, and 20 did not. Patients' decisions were influenced by perceived provider training, costs, doctor recommendations, wait times, symptoms, and a desire for a diagnosis. Patients preferred the care of non-operative sports medicine doctors over physical therapists for LBP due to their beliefs that favored doctors’ diagnosis and management of LBP. Patients perceived exercise as an effective treatment for back pain. Physical therapists were viewed as an adjunct service, despite positive comments about PT and the belief that exercise is one of the most effective treatments for LBP. Conclusion Barriers including costs, patient preferences, and knowledge about physical therapists limited patients' use of PT. Value-based care strategies aimed at improving the management of LBP increasingly promote the early use of PT. For these strategies to be effective, it is critical that patient perceptions and the influence of barriers on PT use are further understood. This study highlights the need to promote confidence in physical therapists’ expertise in the management and diagnosis of lower back pain.

BACKGROUND CONTEXT Spine surgery in Medicare patients has increased in recent years and its use is variable across geographic regions. Corresponding wide variation in costs are also well-documented. Provider care intensity, a marker for discretionary care (eg, unnecessary imaging, tests, injections, and visits), is the component of spending variation that is independent of patient severity, age, and regional pricing. It is unknown if greater provider care intensity is associated with improved safety, as we might expect from value-based care. PURPOSE To determine if increased provider care intensity was associated with safety among five Medicare cohorts undergoing spinal surgery. STUDY DESIGN/SETTING Retrospective analysis of Medicare claims, 2013-2017. PATIENT SAMPLE We included beneficiaries (age 65+) undergoing inpatient spinal surgery as defined by the Center for Medicare and Medicaid Innovation, including “cervical fusion,” “fusion, except cervical,” “anterior-posterior combined fusion,” “complex fusion,” and “back or neck surgery, except fusion.” Claims included variables on age, sex and race, as well as codes from the International Classification of Diseases, used to calculate the Charlson Comorbidity Index. Regional 90-day episode costs for the five cohorts ranged from a low of $32,384 for cervical fusion to a high of $123,388 for complex fusion. OUTCOME MEASURES Safety was measured as mortality, pulmonary embolism, deep vein thrombosis, and all-cause readmission over the first 90-days following surgery. METHODS Patients were classified by the Hospital Referral Region (HRR) where surgery occurred. Regions were grouped into quintiles based on the Dartmouth Atlas End-of-Life Expenditure Index (EOL), reflecting spending variation due to practice care intensity. Multivariable regression examined the association between care intensity and our safety measures, controlling for age, sex, race, and comorbidity. To further mitigate unobserved confounding by indication, we also added year and hospital fixed-effects parameters, and applied EOL as an instrumental variable. RESULTS Within each cohort, we observed a 4-fold variation in 90-day episode cost across HRRs. Spine-specific spending was correlated with EOL quintile, confirming that spending variation is due to provider care intensity more than pricing, age, or illness severity. Greater spending across EOL quintile was not associated with improved safety, and in-fact, was associated with significantly worse outcomes in some cohorts. For example, all-cause readmission was greater in the high spending quintile relative to the low spending quintile among the “Fusion, except cervical” cohort (14.2% vs 13.1%; OR 1.10; 95% CI 1.05 – 1.20; p CONCLUSIONS Wide variation in regional 90-day episode-of-care spine spending was not explained by differences in patient severity, age, or regional pricing. Hospitals in the highest spending quintile spent between $10,378 (back & neck) to $35,533 (complex fusion) more per patient than those in the lowest quintile, but increased spending did not result in enhanced safety. These findings point to inefficient and potentially wasteful use of health care resources, which should be a focus of payment reforms. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.