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Rationale and Objectives To date, no clinically useful classification system has been developed for reliably differentiating mucinous cystic neoplasm (MCN) from a benign hepatic cyst (BHC) in the liver. The objective was to use machine learning and a multi-center study design to develop and assess the performance of a novel classification system for predicting whether a hepatic cystic lesion represents MCN or BHC. Materials and Methods A multi-center cohort study identified 154 surgically resected hepatic cystic lesions in 154 subjects which were pathologic confirmed as MCN (43) or BHC (111). Readers at each institution recorded seven pre-determined imaging features previously identified as potential differentiating features from prior publications. The contribution of each of these features to differentiating MCN from BHC was assessed by machine learning to develop an optimal classification system. Results Although several of the assessed imaging features demonstrated statistical significance, only 3 imaging features were found by machine learning to significantly contribute to a potential classification system: (1) solid enhancing nodule (2) all septations arising from an external macro-lobulation (3) whether the lesion was solitary or one of multiple cystic liver lesions. The optimal classification system had only four categories and correctly identified 144/154 lesion (93.5%). Conclusion This multi-center follow-up study was able to use machine learning to develop a highly accurate classification system for differentiation of hepatic MCN from BHC, which could be readily applied to clinical practice.

Background Primary sclerosing cholangitis (PSC) is linked to inflammatory bowel diseases (IBD). Evidence suggests an association between the gut microbiome and PSC. However, the putative relationship between exposure to antibiotics and onset of PSC has never been reported. We observed 3 cases in which patients without antecedent liver or bowel issues developed symptoms leading to diagnosis of IBD and subsequently PSC after being exposed to doxycycline. We aimed to identify, through the PSC Partners national patient registry, additional cases of PSC in which there is a temporal relationship between exposure to doxycycline and onset of PSC or PSC-IBD. Areas of uncertainty The etiopathogenesis of PSC remains an enigma. Data sources We collected data from patients with PSC and PSC-IBD in which there seemed to be a temporal relationship between exposure to doxycycline and PSC. Time from doxycycline exposure to: (1) onset of PSC or PSC-IBD symptoms and (2) diagnosis of PSC were documented for each patient. Descriptive statistical analyses were performed. Results We identified 6 additional patients with PSC or PSC-IBD in whom there was a temporal relationship between exposure to doxycycline and onset of PSC or PSC-IBD. The median age of these 9 patients was 20 years, 6 were female, and 7 had ulcerative colitis. The median time from doxycycline exposure to onset of first symptoms was 3 months, and median time from doxycycline exposure to diagnosis of PSC was 15 months. Therapeutic hypothesis We describe 9 cases of PSC and PSC-IBD in which there seem to be a temporal relationship between exposure to doxycycline and onset of PSC.

This project aimed to design, simulate, and implement a two-axis inertially stabilised platform (ISP) for use in astronomical applications. It aimed to approximate the stabilisation of a Meade ETX-90 3.5" compound telescope at low-cost using a mechanical assembly designed to geometrically and inertially model the telescope. A set of system specifications was developed to guide design decisions and to provide an analysis framework against which the performance of the implemented system was compared. The electro-mechanical structure of the ISP was designed and manufactured, the associated electrical systems were specified and configured, an image processing script capable of detecting and locating the centre of the Moon in a camera field-of-view was written, a complete simulation model for the system was developed and used to design various classical controllers for the ISP control system. These controllers were implemented on a STM32F051 microcontroller and a user interface was written in LabVIEW to facilitate intuitive user control of the system and perform datalogging of the system runtime data., 2019 Southern African Universities Power Engineering Conference/Robotics and Mechatronics/Pattern Recognition Association of South Africa (SAUPEC/RobMech/PRASA)

Objectives This meta-analysis aims to investigate the efficacy and safety of medicines that target neurotrophic factors for low back pain (LBP) or sciatica. Methods We searched published and trial registry reports of randomized controlled trials evaluating the effect of medicines that target neurotrophic factors to LBP or sciatica in seven databases from inception to December 2020. Two reviewers independently identified studies, extracted data, and assessed the risk of bias and certainty in the evidence. Results Nine studies (3370 participants) were included in the meta-analyses. Low certainty evidence showed that anti-nerve growth factor (NGF) may reduce pain at 4 weeks (mean difference [MD] −6.75, 95% CI: −8.61, −4.90) and 12 weeks (MD −6.16, 95% CI: −8.38, −3.94), and may increase adverse effects for chronic LBP (odds ratio [OR] 1.18, 95% CI: 1.01, 1.38). Higher doses of anti-NGF may offer a clinically important reduction in pain at the cost of increased adverse effects for chronic LBP. Very low certainty evidence showed that anti-NGF and glial cell line-derived neurotrophic factor (pro-GDNF) may not reduce pain for sciatica at 4 weeks (MD −1.40, 95% CI: −8.26, 5.46), at 12 weeks (MD −2.91, 95% CI: −13.69, 7.67) and may increase adverse effects for sciatica (OR 3.27, 95% CI: 1.78, 6.00). Conclusion Anti-NGF may offer small reductions in pain intensity for chronic LBP. The effect may depend on the dose and types of medicines. For sciatica, anti-NGF or pro-GDNF may not reduce pain. Medicines that target neurotrophic factors for LBP or sciatica are associated with different adverse effects compared to those observed in commonly prescribed medicines for these conditions.

Emotion dysregulation frequently co-occurs with chronic pain, which in turn leads to heightened emotional and physical suffering. This cycle of association has prompted a recommendation for psychological treatment of chronic pain to target mechanisms for emotion regulation. The current trial addressed this need by investigating a new internet-delivered treatment incorporating emotional skills training from dialectical behavioural therapy (DBT). Using a single-case experimental design that is suited to heterogeneous populations and can demonstrate efficacy with a small sample, three participants with chronic pain were recruited. Participants received four weeks of online DBT skills training (iDBT-Pain intervention) which incorporated one-on-one sessions over Zoom and a web app. Results revealed compelling evidence for the intervention on the primary outcome of emotion dysregulation and were promising for the secondary outcome of pain intensity. Improvement was also identified on pre-and post-measures of depression, coping behaviours, sleep problems, wellbeing, and harm avoidance, indicating that the intervention may positively influence other factors related to chronic pain. Overall, the trial provides preliminary efficacy for the intervention to improve chronic pain. However, we recommend further investigation of the iDBT-Pain intervention, either in single case trials, which when conducted with scientific rigour may be aggregated to derive nomothetic conclusions, or in a group-comparison trial to compare with usual modes of treatment. Perspective: This trial advances understanding of emotion-focused treatment for chronic pain and provides evidence for a viable new technological treatment. Importantly, as an internet-delivered approach, the iDBT-Pain intervention is accessible to those with restricted mobility and remote communities where there are often limited psychological services for people with chronic pain. Trial registration: The trial was registered on the Australian and New Zealand Clinical Trials Registry (ACTRN12620000604909)

OBJECTIVE The surgical management of large and complex tumors of the posterior fossa poses a formidable challenge in neurosurgery. The standard retrosigmoid craniotomy approach has been performed at most neurosurgical centers; however, the retrosigmoid approach may not provide enough working space without significant retraction of the cerebellum. The transsigmoid approach provides wider and shallower surgical fields; however, there have been few clinical and no cadaveric studies on its usefulness. In the present study, the authors describe the transsigmoid approach in clinical cases and cadaveric specimens. METHODS For the clinical study, the authors retrospectively reviewed the medical records and operative charts of patients who had been surgically treated for parabrainstem tumors using the transsigmoid approach between 1997 and 2019. They analyzed patient demographic and clinical data, as well as surgical and clinical outcomes. In the cadaveric study, they compared the surgical views obtained in different approaches (retrosigmoid, presigmoid, retrolabyrinthine, and transsigmoid) and measured the sigmoid sinus width at the level of the endolymphatic sac and the distance between the anterior edge of the sigmoid sinus and the endolymphatic sac on 35 sides in 19 cadaveric specimens. RESULTS A total of 21 patients (6 males and 15 females) with a mean age of 42.2 (range 15–67) years were included in the clinical study. Eleven patients had meningioma, 7 had vestibular schwannoma, 2 had hemangioblastoma, and 1 had epidermoid cyst. Gross-total, near-total, and subtotal removal were achieved in 7 (33.3%), 3 (14.3%), and 11 (52.4%) patients, respectively. In the cadaveric study, 19 cadaveric specimens were used. The sigmoid sinus was cut in the middle, and the incision was extended from the retrosigmoid to the presigmoid dura. The dura was then retracted upward and downward like opening a door. The results indicated that this technique can widen the operative field anteriorly by approximately 2 cm as compared to the retrosigmoid approach and provides a better view anterior to the brainstem. CONCLUSIONS The transsigmoid approach is useful for complex parabrainstem tumors in the posterior fossa because it provides a wider and shallower operative view with less retraction of the cerebellum. This enables safer tumor removal with less damage to important structures in the posterior fossa, resulting in better operative and clinical outcomes.

Objectives ABRUPT was a prospective, non-interventional, observational study of resuscitation practices at 21 burn centers. The primary goal was to examine burn resuscitation with albumin or crystalloids alone, in order to design a future prospective randomized trial. Summary background data No modern prospective study has determined whether to use colloids or crystalloids for acute burn resuscitation. Methods Patients ≥ 18 years with burns ≥ 20% total body surface area (TBSA) had hourly documentation of resuscitation parameters for 48 hours. Patients received either crystalloids alone or had albumin supplemented to crystalloid based on center protocols. Results Of 379 enrollees, two-thirds (253) were resuscitated with albumin and one-third (126) were resuscitated with crystalloid alone. Albumin patients received more total fluid than Crystalloid patients (5.2± 2.3 versus 3.7 ± 1.7 mL/kg/% TBSA burn/24 hours) but patients in the Albumin Group were older, had larger burns, higher admission Sequential Organ Failure Assessment (SOFA) scores, and more inhalation injury. Albumin lowered the in-to-out (I/O) ratio and was started ≤ 12 hours in patients with the highest initial fluid requirements, given >12 hours with intermediate requirements, and avoided in patients who responded to crystalloid alone. Conclusion Albumin use is associated with older age, larger and deeper burns, and more severe organ dysfunction at presentation. Albumin supplementation is started when initial crystalloid rates are above expected targets and improves the I/O ratio. The fluid received in the first 24 hours was at or above the Parkland Formula estimate.

BACKGROUND: Pharmacological interventions are the most used treatment for low back pain (LBP). Use of evidence from systematic reviews of the effects of pharmacological interventions for LBP published in the Cochrane Library, is limited by lack of a comprehensive overview.OBJECTIVES: To summarise the evidence from Cochrane Reviews of the efficacy, effectiveness, and safety of systemic pharmacological interventions for adults with non-specific LBP.METHODS: The Cochrane Database of Systematic Reviews was searched from inception to 3 June 2021, to identify reviews of randomised controlled trials (RCTs) that investigated systemic pharmacological interventions for adults with non-specific LBP. Two authors independently assessed eligibility, extracted data, and assessed the quality of the reviews and certainty of the evidence using the AMSTAR 2 and GRADE tools. The review focused on placebo comparisons and the main outcomes were pain intensity, function, and safety.MAIN RESULTS: Seven Cochrane Reviews that included 103 studies (22,238 participants) were included. There is high confidence in the findings of five reviews, moderate confidence in one, and low confidence in the findings of another. The reviews reported data on six medicines or medicine classes: paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), muscle relaxants, benzodiazepines, opioids, and antidepressants. Three reviews included participants with acute or sub-acute LBP and five reviews included participants with chronic LBP. Acute LBP Paracetamol There was high-certainty evidence for no evidence of difference between paracetamol and placebo for reducing pain intensity (MD 0.49 on a 0 to 100 scale (higher scores indicate worse pain), 95% CI -1.99 to 2.97), reducing disability (MD 0.05 on a 0 to 24 scale (higher scores indicate worse disability), 95% CI -0.50 to 0.60), and increasing the risk of adverse events (RR 1.07, 95% CI 0.86 to 1.33). NSAIDs There was moderate-certainty evidence for a small between-group difference favouring NSAIDs compared to placebo at reducing pain intensity (MD -7.29 on a 0 to 100 scale (higher scores indicate worse pain), 95% CI -10.98 to -3.61), high-certainty evidence for a small between-group difference for reducing disability (MD -2.02 on a 0-24 scale (higher scores indicate worse disability), 95% CI -2.89 to -1.15), and very low-certainty evidence for no evidence of an increased risk of adverse events (RR 0.86, 95% CI 0. 63 to 1.18). Muscle relaxants and benzodiazepines There was moderate-certainty evidence for a small between-group difference favouring muscle relaxants compared to placebo for a higher chance of pain relief (RR 0.58, 95% CI 0.45 to 0.76), and higher chance of improving physical function (RR 0.55, 95% CI 0.40 to 0.77), and increased risk of adverse events (RR 1.50, 95% CI 1. 14 to 1.98). Opioids None of the included Cochrane Reviews aimed to identify evidence for acute LBP. Antidepressants No evidence was identified by the included reviews for acute LBP. Chronic LBP Paracetamol No evidence was identified by the included reviews for chronic LBP. NSAIDs There was low-certainty evidence for a small between-group difference favouring NSAIDs compared to placebo for reducing pain intensity (MD -6.97 on a 0 to 100 scale (higher scores indicate worse pain), 95% CI -10.74 to -3.19), reducing disability (MD -0.85 on a 0-24 scale (higher scores indicate worse disability), 95% CI -1.30 to -0.40), and no evidence of an increased risk of adverse events (RR 1.04, 95% CI -0.92 to 1.17), all at intermediate-term follow-up (> 3 months and ≤ 12 months postintervention). Muscle relaxants and benzodiazepines There was low-certainty evidence for a small between-group difference favouring benzodiazepines compared to placebo for a higher chance of pain relief (RR 0.71, 95% CI 0.54 to 0.93), and low-certainty evidence for no evidence of difference between muscle relaxants and placebo in the risk of adverse events (RR 1.02, 95% CI 0.67 to 1.57). Opioids There was high-certainty evidence for a small between-group difference favouring tapentadol compared to placebo at reducing pain intensity (MD -8.00 on a 0 to 100 scale (higher scores indicate worse pain), 95% CI -1.22 to -0.38), moderate-certainty evidence for a small between-group difference favouring strong opioids for reducing pain intensity (SMD -0.43, 95% CI -0.52 to -0.33), low-certainty evidence for a medium between-group difference favouring tramadol for reducing pain intensity (SMD -0.55, 95% CI -0.66 to -0.44) and very low-certainty evidence for a small between-group difference favouring buprenorphine for reducing pain intensity (SMD -0.41, 95% CI -0.57 to -0.26). There was moderate-certainty evidence for a small between-group difference favouring strong opioids compared to placebo for reducing disability (SMD -0.26, 95% CI -0.37 to -0.15), moderate-certainty evidence for a small between-group difference favouring tramadol for reducing disability (SMD -0.18, 95% CI -0.29 to -0.07), and low-certainty evidence for a small between-group difference favouring buprenorphine for reducing disability (SMD -0.14, 95% CI -0.53 to -0.25). There was low-certainty evidence for a small between-group difference for an increased risk of adverse events for opioids (all types) compared to placebo; nausea (RD 0.10, 95% CI 0.07 to 0.14), headaches (RD 0.03, 95% CI 0.01 to 0.05), constipation (RD 0.07, 95% CI 0.04 to 0.11), and dizziness (RD 0.08, 95% CI 0.05 to 0.11). Antidepressants There was low-certainty evidence for no evidence of difference for antidepressants (all types) compared to placebo for reducing pain intensity (SMD -0.04, 95% CI -0.25 to 0.17) and reducing disability (SMD -0.06, 95% CI -0.40 to 0.29).AUTHORS' CONCLUSIONS: We found no high- or moderate-certainty evidence that any investigated pharmacological intervention provided a large or medium effect on pain intensity for acute or chronic LBP compared to placebo. For acute LBP, we found moderate-certainty evidence that NSAIDs and muscle relaxants may provide a small effect on pain, and high-certainty evidence for no evidence of difference between paracetamol and placebo. For safety, we found very low- and high-certainty evidence for no evidence of difference with NSAIDs and paracetamol compared to placebo for the risk of adverse events, and moderate-certainty evidence that muscle relaxants may increase the risk of adverse events. For chronic LBP, we found low-certainty evidence that NSAIDs and very low- to high-certainty evidence that opioids may provide a small effect on pain. For safety, we found low-certainty evidence for no evidence of difference between NSAIDs and placebo for the risk of adverse events, and low-certainty evidence that opioids may increase the risk of adverse events.

Pancreatic cancer has known precursor lesions with potential to develop into malignancy over time. At least 20% of pancreatic cancer evolves from mucinous cystic neoplasms and intraductal papillary mucinous neoplasms, which are often discovered incidentally.1,2 Current guidelines for the management of mucinous cystic neoplasms and intraductal papillary mucinous neoplasms include long-term surveillance, which is expensive and nontherapeutic, or surgical resection, which is associated with major risk and may not be an option for patients with significant concomitant illness.3.

A ubiquitous research finding in regional and national studies is that at least 40% of persons with mental disorders cannot access mental health services, and pharmacotherapy in particular. The American Psychological Association's (APA) designated programs for the provision of education and training in clinical psychopharmacology can be of great help in alleviating this national need. We address key developments relevant to the foundation of a predoctoral model of clinical psychopharmacology education and training. To this end, an overview of the Master of Science in Clinical Psychopharmacology (MSCP) program at The Chicago School of Professional Psychology (TCSPP) is presented. TCSPP is now enrolling its eleventh consecutive cohort of MSCP students, many of whom are doctoral students who are concurrently attending various APA accredited Health Service Psychology (HSP) programs. We provide two predoctoral routes for completing MSCP training: (a) a route allowing for the creation of concentrations in clinical psychopharmacology in Health Service Psychology (HSP) doctoral programs, providing up to half of MSCP coursework; and (b) a joint doctoral PsyD or PhD/MSCP program meeting APA accreditation and designation standards integrated into a 5-year curriculum to impart HSP graduates with the competencies to provide both psychotherapy and pharmacotherapy. We conclude with a discussion about the future direction of predoctoral clinical psychopharmacology education and training. Given its emphasis on neuroscience and interdisciplinary health care, such curricular models may help to address the nation's immediate mental health care needs, while serving to enhance the sustainability of HSP education and professional practice in the 21st Century. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The performance of a three-channel, 100-kW nested Hall thruster was evaluated on xenon propellant for total powers up to 102 kW. The thruster demonstrated stable operation in all seven available ch...

Prognostics predicts the future performance progression and remaining useful life (RUL) of in-service systems based on historical and contemporary data. One of the challenges in prognostics is the development of methods that are capable of handling real-world uncertainties that typically lead to inaccurate predictions. To alleviate the impacts of uncertainties and to achieve accurate degradation trajectory and RUL predictions, a novel sequence-to-sequence predictive model is proposed based on a variational autoencoder that is trained with generative adversarial networks. A long short-term memory network and a Gaussian mixture model are utilized as building blocks so that the model is capable of providing probabilistic predictions. Correlative and monotonic metrics are applied to identify sensitive features in the degradation progress, in order to reduce the uncertainty induced from raw data. Then, the selected features are concatenated with one-hot health state indicators as training data for the model to learn end of life without the need for prior knowledge of failure thresholds. Performance of the proposed model is validated by health monitoring data collected from real-world aeroengines, wind turbines, and lithium-ion batteries. The results demonstrate that significant performance improvement can be achieved in long-term degradation progress and RUL prediction tasks.

OBJECTIVE: Despite a shared degenerative vascular phenotype, Marfan syndrome (MFS), Loeys-Dietz syndrome (LDS), and other genetically distinct connective tissue diseases (CTDs) have unique extravascular pathologies that impact the outcomes of aortic replacement. The aim of our study was to investigate the association of CTD genotype with postoperative outcomes and branch patency following open thoracoabdominal aortic replacement in a large institutional cohort. METHODS: All patients undergoing open branched thoracoabdominal aortic replacement at a single academic center from 2006 to 2020 were included and classified as CTD or non-CTD based on the presence of genotypic documentation. Outcomes were compared using analysis of variance and χ(2) testing for continuous and discrete variables, respectively. Kaplan-Meier curves were utilized to examine patency of graft branches over time. RESULTS: Overall, 172 patients were included, with a mean follow-up of 30.5 ± 34.9 months. CTD was present in 45 patients (26%); specifically, 32 had MFS, five had LDS, and eight had another CTD. Patients with CTDs had more extent II thoracoabdominal aneurysms (40% vs 15%), more reconstructed branches (3.5 vs 1.8), more frequently reconstructed visceral branches (86.7% vs 22.7%), and higher intraoperative blood loss (13.3 vs 6.8 L; all P < .05) compared with non-CTD patients. Patients with MFS were more frequently systemically anticoagulated preoperatively (50% vs 5%) and demonstrated higher rates of postoperative deep vein thrombosis/pulmonary embolism compared with non-CTD patients (9% vs 2%; both P < .05). Five-year renal branch patency was decreased among all patients compared with visceral branches (87.3% vs 95.6%; P = .05), but there were no individual branch patency differences between patients with and without CTDs (P = .086). Overall branch patency at 1 and 5 years was significantly higher in patients with MFS than in non-CTD patients (98.9% vs 89.1% at 5 years); there were no significant patency differences between non-CTD patients and any other CTD subgroup, mostly due to early patency loss. CONCLUSIONS: Open thoracoabdominal reconstruction in patients with CTD is technically challenging and associated with increased transfusion and postoperative thromboembolic events when compared with non-CTD patients. Technical outcomes of the procedure are excellent and are differentially associated with genotype, with patients with MFS experiencing significantly improved branch patency over both non-CTD patients and patients with other CTDs, a finding which has multifactorial drivers.

Contains fulltext : 283453.pdf (Publisher’s version ) (Closed access) Cardiovascular (CV) disease (CVD) remains the leading cause of major morbidity and CVD- and all-cause mortality in most of the world. It is now clear that regular physical activity (PA) and exercise training (ET) induces a wide range of direct and indirect physiologic adaptations and pleiotropic benefits for human general and CV health. Generally, higher levels of PA, ET, and cardiorespiratory fitness (CRF) are correlated with reduced risk of CVD, including myocardial infarction, CVD-related death, and all-cause mortality. Although exact details regarding the ideal doses of ET, including resistance and, especially, aerobic ET, as well as the potential adverse effects of extreme levels of ET, continue to be investigated, there is no question that most of the world's population have insufficient levels of PA/ET, and many also have lower than ideal levels of CRF. Therefore, assessment and promotion of PA, ET, and efforts to improve levels of CRF should be integrated into all health professionals' practices worldwide. In this state-of-the-art review, we discuss the exercise effects on many areas related to CVD, from basic aspects to clinical practice.

Introduction: Information regarding availability of electronic healthcare databases in the Asia-Pacific region is critical for planning vaccine safety assessments particularly, as COVID-19 vaccines are introduced. This study aimed to identify data sources in the region, potentially suitable for vaccine safety surveillance. This manuscript is endorsed by the International Society for Pharmacoepidemiology (ISPE). Methods: Nineteen countries targeted for database reporting were identified using published country lists and review articles. Surveillance capacity was assessed using two surveys: a 9-item introductory survey and a 51-item full survey. Survey questions related to database characteristics, covariate and health outcome variables, vaccine exposure characteristics, access and governance, and dataset linkage capability. Other questions collated research/regulatory applications of the data and local publications detailing database use for research. Results: Eleven databases containing vaccine-specific information were identified across 8 countries. Databases were largely national in coverage (8/11, 73%), encompassed all ages (9/11, 82%) with population size from 1.4 to 52 million persons. Vaccine exposure information varied particularly for standardized vaccine codes (5/11, 46%), brand (7/11, 64%) and manufacturer (5/11, 46%). Outcome data were integrated with vaccine data in 6 (55%) databases and available via linkage in 5 (46%) databases. Data approval processes varied, impacting on timeliness of data access. Conclusions: Variation in vaccine data availability, complexities in data access including, governance and data release approval procedures, together with requirement for data linkage for outcome information, all contribute to the challenges in building a distributed network for vaccine safety assessment in the Asia-Pacific and globally. Common data models (CDMs) may help expedite vaccine safety research across the region. Refereed/Peer-reviewed

Background Antidepressant medicines are used to manage symptoms of low back pain. The efficacy, acceptability, and safety of antidepressant medicines for low back pain (LBP) are not clear. We aimed to evaluate the efficacy, acceptability, and safety of antidepressant medicines for LBP. Methods We searched CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.gov, the EU Clinical Trials Register, and the WHO International Clinical Trial Registry Platform from inception to May 2020. We included published and trial registry reports of RCTs that allocated adult participants with LBP to receive an antidepressant medicine or a placebo medicine. Pairs of authors independently extracted data in duplicate. We extracted participant characteristics, study sample size, outcome values, and measures of variance for each outcome. We data using random-effects meta-analysis models and calculated estimates of effects and heterogeneity for each outcome. We formed judgments of confidence in the evidence in accordance with GRADE. We report our findings in accordance with the PRISMA statement. We prespecified all outcomes in a prospectively registered protocol. The primary outcomes were pain intensity and acceptability. We measured pain intensity at end-of-treatment on a 0–100 point scale and considered 10 points the minimal clinically important difference. We defined acceptability as the odds of stopping treatment for any reason. Results We included 23 RCTs in this review. Data were available for pain in 17 trials and acceptability in 14 trials. Treatment with antidepressants decreased pain intensity by 4.33 points (95% CI − 6.15 to − 2.50) on a 0–100 scale, compared to placebo. Treatment with antidepressants increased the odds of stopping treatment for any reason (OR 1.27 [95% CI 1.03 to 1.56]), compared to placebo. Conclusions Treatment of LBP with antidepressants is associated with small reductions in pain intensity and increased odds of stopping treatment for any reason, compared to placebo. The effect on pain is not clinically important. The effect on acceptability warrants consideration. These findings provide Level I evidence to guide clinicians in their use of antidepressants to treat LBP. Trial registration We prospectively registered the protocol for this systematic review on PROSPERO (CRD42020149275).

Electroencephalographic (EEG) neurofeedback has been utilised to regulate abnormal brain activity associated with chronic pain. In this systematic review, we synthesised the evidence from randomised controlled trials (RCTs) to evaluate the effect of EEG neurofeedback on chronic pain using random effects meta-analyses. Additionally, we performed a narrative review to explore the results of non-randomised studies. The quality of included studies was assessed using Cochrane risk of bias tools, and the GRADE system was used to rate the certainty of evidence. Ten RCTs and 13 non-randomised studies were included. The primary meta-analysis on nine eligible RCTs indicated that although there is low confidence, EEG neurofeedback may have a clinically meaningful effect on pain intensity in short-term. Removing the studies with high risk of bias from the primary meta-analysis resulted in moderate confidence that there remained a clinically meaningful effect on pain intensity. We could not draw any conclusion from the findings of non-randomised studies, as they were mostly non-comparative trials or explorative case series. However, the extracted data indicated that the neurofeedback protocols in both RCTs and non-randomised studies mainly involved the conventional EEG neurofeedback approach, which targeted reinforcing either alpha or sensorimotor rhythms and suppressing theta and/or beta bands on one brain region at a time. A post-hoc analysis of RCTs utilising the conventional approach resulted in a clinically meaningful effect estimate for pain intensity. Although there is promising evidence on the analgesic effect of EEG neurofeedback, further studies with larger sample sizes and higher quality of evidence are required.

Background Thoracic outlet syndrome (TOS) takes on heterogenous upper extremity manifestations depending on whether the artery, vein or brachial plexus is primarily compressed. As a result of these variable vascular and neurogenic symptoms, these patients present to surgeons of various training backgrounds for surgical decompression. Surgeon specialty is known to correlate with outcomes for numerous vascular procedures, but its role in TOS is unclear. In this work we examine the association of surgeon specialty with short-term outcomes following first rib resection (FRRS) for TOS. Methods Using the American College of Surgeons National Surgical Quality Improvement Program database, 3,070 patients were identified who underwent FRRS for TOS between 2006-2017. The primary outcomes of the study were 30-d complications, including postoperative hemorrhage requiring transfusion, wound complications, pneumothorax and deep venous thrombosis. Arterial, venous, and neurogenic TOS were distinguished with ICD-9 and 10 codes while patient characteristics, provider specialty, and postoperative outcomes were classified through a combination of standard National Surgical Quality Improvement Program variables and ICD data. Results Most FRRS were performed by vascular surgeons (87.9%), general (6.9%) and thoracic surgeons (4.4%). The relative distribution of vascular TOS between the specialties was not significantly different, with non-vascular surgeons performing an equivalent amount of FRRS for arterial (1.1% versus 2.4%) and venous TOS (8.6% versus 9.1%, both P> 0.05). Patients who underwent FRRS with non-vascular surgeons experienced more frequent perioperative transfusions (3.2% versus 1.2%, P = 0.001) and wound infections (1.9% versus 0.8%, P= 0.04). On multivariable regression, patients undergoing FRRS for venous TOS were more likely to require blood transfusion (odds ratios:3.63, 95% CI 1.43-9.25). Patients operated on by surgeons whose specialty was not among the top three most common specialties performing FRRS had a 40% longer operative time (incidence rate ratios:1.42, 95% CI 1.15-1.74) as well as a significantly increased odds of requiring a transfusion (odds ratios:9.87, 95% CI 2.28-42.68). Conclusions The significantly increased operative times and transfusion requirements associated with specialties who uncommonly perform FRRS suggest the role of surgeon experience and volume in this procedure may play more of a role than specialty training. These data also suggest that vascular TOS carries unique risks that should be kept in mind when performing FRRS.

Objective To evaluate the effect of an arthritis center on patient care and operational throughput. Methods A single-institution, retrospective review was conducted of patients with hip or knee osteoarthritis from January 2016 to October 2019. Our physician assistant (PA) led arthritis center opened in November 2017, and manages nonoperative treatment of osteoarthritis by formulating individualized treatment plans. Descriptive and inferential statistics comparing operational measures, treatment patterns, and patient satisfaction pre- and postcenter opening were performed. Results Overall patient volume, new patient volume, and the proportion of new patients seen increased after the arthritis center opened. Encounters per patient and clinicians seen per patient decreased, while the rate of injections and surgery increased. Patient satisfaction improved after opening of the arthritis center. Conclusions The establishment of a dedicated PA-led arthritis center is associated with improved access to care, operational efficiency, and patient satisfaction in patients with hip and knee osteoarthritis.

Atrial fibrillation (AF) is the most common clinically significant arrhythmia, and it increases stroke risk. A preventive approach to AF is needed because virtually all treatments such as cardioversion, antiarrhythmic drugs, ablation, and anticoagulation are associated with high cost and carry significant risk. A systematic review was performed to identify effective lifestyle-based strategies for reducing primary and secondary AF. A PubMed search was performed using articles up to March 1, 2021. Search terms included atrial fibrillation, atrial flutter, exercise, diet, metabolic syndrome, type 2 diabetes mellitus, obesity, hypertension, stress, tobacco smoking, alcohol, Mediterranean diet, sodium, and omega-3 fatty acids. Additional articles were identified from the bibliographies of retrieved articles. The control of hypertension, ideally with a renin-angiotensin-aldosterone system inhibitor, is effective for preventing primary AF and recurrence. Obstructive sleep apnea is a common cause of AF, and treating it effectively reduces AF episodes. Alcohol increases the risk of AF in a dose-dependent manner, and abstinence reduces risk of recurrence. Sedentary behavior and chronic high-intensity endurance exercise are both risk factors for AF; however, moderate physical activity is associated with lower risk of AF. Recently, sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 agonists have been associated with reduced risk of AF. Among overweight/obese patients, weight loss of ≥10% is associated with reduced AF risk. Lifestyle changes and risk factor modification are highly effective for preventing AF.

BACKGROUND: There are substantial racial and socioeconomic disparities underlying endovascular abdominal aortic aneurysm repair (EVAR) in the United States. To date, race-based variations in reinterventions following elective EVAR have not been studied. Here, we aim to examine racial disparities associated with reinterventions following elective EVAR in a real-world cohort. MATERIALS AND METHODS: We used the Vascular Quality Initiative (VQI) EVAR dataset to identify all patients undergoing elective EVAR between January 2009 and December 2018 in the United States. We compared the association of race with reinterventions after EVAR and all-cause mortality using Welch two-sample t-tests, multivariate logistic regression, and Cox proportional hazards analyses adjusting for baseline differences between groups. RESULTS: At median follow-up of 1.1±1.1 years (1.3±1.4 years Black, 1.1±1.1 years White; P=0.02), a total of 1,164 of 42,481 patients (2.7%) underwent reintervention after elective EVAR, including 2.7% (n = 1,096) White vs. 3.2% (n = 68) Black (P = 0.21). Black patients requiring reintervention were more frequently female, more frequently current or former smokers, and less frequently insured by Medicare/Medicaid (P

Zoonotic orthopoxvirus outbreaks have occurred repeatedly worldwide, including monkeypox in Africa and the United States, cowpox in Europe, camelpox in the Middle East and India, buffalopox in India, vaccinia in South America, and novel emerging orthopoxvirus infections in the United States, Europe, Asia, and South America. Waning smallpox immunity may increase the potential for animal-to-human transmission followed by further community transmission person-to-person (as demonstrated by monkeypox and buffalopox outbreaks) and by contact with fomites (as demonstrated by camelpox, cowpox, and, possibly, Alaskapox). The objectives of this review are to describe the disease ecology, epidemiology, clinical manifestations, prevention, and control of human infections with animal orthopoxviruses and to discuss the association with diminished population herd immunity formerly induced by vaccinia vaccination against smallpox. Internet search engines were queried with key words, and case reports, case series, seroprevalence studies, and epidemiologic investigations were found for review.

Because mushroom poisonings are increasing worldwide after ingestions of known, newly described, and formerly considered edible species, the objectives of this review are to describe the global epidemiology of nephrotoxic mushroom poisonings, to identify nephrotoxic mushrooms, to present a toxidromic approach to earlier diagnoses of nephrotoxic mushroom poisonings based on the onset of acute renal failure, and to compare the outcomes of renal replacement management strategies. Internet search engines were queried with the keywords to identify scientific articles on nephrotoxic mushroom poisonings and their management during the period of 1957 to the present. Although hepatotoxic, amatoxin-containing mushrooms cause most mushroom poisonings and fatalities, nephrotoxic mushrooms, most commonly Cortinarius species, can cause acute renal insufficiency and failure. Several new species of nephrotoxic mushrooms have been identified, including Amanita proxima and Tricholoma equestre in Europe and Amanita smithiana in the United States and Canada. In addition, the edible, hallucinogenic mushroom Psilocybe cubensis has been noted recently via mass spectrometry as a rare cause of acute renal insufficiency. Renal replacement therapies including hemodialysis are often indicated in the management of nephrotoxic mushroom poisonings, with renal transplantation reserved for extracorporeal treatment failures.

Transnasal swab testing for the detection of SARS-CoV-2 is well established. The Centers for Disease Control and Prevention advocates swabbing either of the anterior nares, middle turbinate, or nasopharynx for specimen collection depending on available local resources. The purpose of this review is to investigate complications related to transnasal SARS-CoV-2 testing with specific attention to specimen collection site and swab approach. The literature demonstrates that while nasopharyngeal swabbing is associated with an increased risk of complications, it should remain the gold-standard test due to greater diagnostic accuracy relative to anterior nasal and middle turbinate swabs.

Background and aims Noninvasive predictors of choledocholithiasis have generally exhibited marginal performance characteristics. We aimed to identify noninvasive independent predictors of endoscopic retrograde cholangiopancreatography (ERCP)-confirmed choledocholithiasis and accordingly developed predictive machine learning models (MLMs). Methods Clinical data of consecutive patients undergoing first-ever ERCP for suspected choledocholithiasis from 2015 to 2019 were abstracted from a prospectively-maintained database. Multiple logistic regression was used to identify predictors of ERCP-confirmed choledocholithiasis. MLMs were then trained to predict ERCP-confirmed choledocholithiasis using pre-ERCP ultrasound (US) imaging only as well as using all available noninvasive imaging (US, computed tomography, and/or magnetic resonance cholangiopancreatography). The diagnostic performance of American Society for Gastrointestinal Endoscopy (ASGE) “high-likelihood” criteria was compared to MLMs. Results We identified 270 patients (mean age 46 years, 62.2% female, 73.7% Hispanic/Latino, 59% with noninvasive imaging positive for choledocholithiasis) with native papilla who underwent ERCP for suspected choledocholithiasis, of whom 230 (85.2%) were found to have ERCP-confirmed choledocholithiasis. Logistic regression identified choledocholithiasis on noninvasive imaging (odds ratio (OR) = 3.045, P = 0.004) and common bile duct (CBD) diameter on noninvasive imaging (OR = 1.157, P = 0.011) as predictors of ERCP-confirmed choledocholithiasis. Among the various MLMs trained, the random forest-based MLM performed best; sensitivity was 61.4% and 77.3% and specificity was 100% and 75.0%, using US-only and using all available imaging, respectively. ASGE high-likelihood criteria demonstrated sensitivity of 90.9% and specificity of 25.0%; using cut-points achieving this specificity, MLMs achieved sensitivity up to 97.7%. Conclusions MLMs using age, sex, race/ethnicity, presence of diabetes, fever, body mass index (BMI), total bilirubin, maximum CBD diameter, and choledocholithiasis on pre-ERCP noninvasive imaging predict ERCP-confirmed choledocholithiasis with good sensitivity and specificity and outperform the ASGE criteria for patients with suspected choledocholithiasis.

BACKGROUND We have previously shown that the initiation of antiretroviral therapy (ART) is associated with a decrease in skeletal muscle density (greater fat accumulation), suggesting that gains in lean body mass seen in many ART studies may reflect gains in low quality, fatty muscle. Here, we explore whether skeletal muscle density and area are associated with markers of inflammation and immune activation. METHODS ART-naive people with HIV were randomized to raltegravir or ritonavir-boosted atazanavir or darunavir, each with tenofovir disoproxil fumarate/emtricitabine. Abdominal computed tomography scans from baseline and week 96 were reanalyzed for psoas density and area and correlations explored with inflammation [interleukin-6 (IL-6) and high-sensitivity C-reactive protein] and immune activation [soluble CD14 (sCD14), soluble CD163 (sCD163), and %CD38+HLADR+ on CD4+ or CD8+ T cells]. RESULTS Two hundred twenty-two participants had available inflammation/immune activation markers and paired computed tomography scans. At baseline, lower psoas density (greater fat) correlated with higher IL-6 (r = -0.26, P < 0.001) and sCD163 (r -0.15, P = 0.03) and lower lean psoas area correlated with higher IL-6, high-sensitivity C-reactive protein, sCD14, sCD163, and %CD38+HLADR+ on CD4+ T cells (r = -0.30-0.13; all P ≤ 0.05). From baseline to week 96, greater percent decrease in total psoas density (more fat) correlated with greater increase in IL-6 (r = -0.14; P = 0.04); greater % decrease in lean psoas area correlated greater increases in IL-6, sCD14, sCD163, and %CD38+HLADR+ on CD8+ T cells (r = -0.15 to -0.18; all P < 0.04). CONCLUSIONS Greater fat infiltration within the psoas muscle (lower density) and greater loss in lean psoas muscle area were associated with higher inflammation and immune activation, which may portend important effects on muscle function and cardiometabolic risk.

To evaluate the noninferiority of intraocular pressure (IOP)-lowering latanoprost without benzalkonium chloride (BAK) versus latanoprost with BAK (for treatment of open-angle glaucoma or ocular hypertension).Overall, 578 patients were randomized 1:1 to latanoprost without BAK or latanoprost with BAK once daily in the affected eye(s) for 12 weeks. The primary efficacy endpoint was IOP, measured on days 0, 7, 28, 56, and 84 (8 am, 10 am, and 4 pm). Noninferiority was established if the following criteria were met: 95% confidence interval (CI) of the mean difference between treatments included 0 mm Hg for all time points (N1), 95% CI upper limit less than 1.5 mm Hg (N2), and less than 1 mm Hg for≥7 of 12 time points (N3). Primary efficacy analysis was performed on the intent-to-treat population. Safety measurements included ocular and systemic adverse event (AE).The 95% CI included 0 mm Hg for 7/12 time points (N1), 95% CI upper limit was less than 1.5 mm Hg for 12/12 time points (N2), and less than 1.0 mm Hg for 4/7 time points (N3). AEs were mild and similarly distributed between groups.Latanoprost without BAK did not meet two of three criteria for noninferiority and showed a similar safety profile relative to latanoprost with BAK.

Purpose of review Late-onset Fuchs endothelial corneal dystrophy (FECD) is seen in approximately 4% of individuals over the age of 40. With the growing population of adults over the age of 65, ophthalmologists need to be aware of the preoperative, perioperative, and postoperative considerations involved in cataract surgery in Fuchs patients. Recent findings Management of cataract patients with FECD requires preoperative assessment of endothelial cell size, density, and morphology. Considerations for perioperative endothelial cell loss include patients with hyperopia and shallow anterior chambers, phacoemulsification technique, transfer of ultrasonic energy to the cornea, corneal-protective perioperative agents, as well as thermal and mechanical damage. Summary Ophthalmologists performing cataract surgery on patients with FECD must carefully consider the risks of endothelial cell loss during surgery and minimize the risk of corneal decompensation after surgery. Preoperative management should evaluate the severity of the FECD as well as individual factors such as cataract density, the health and thickness of the cornea, and the anterior chamber depth. Perioperative techniques, adjustments to biometry calculations, and intraocular lens (IOL) selection may help optimize visual outcomes and recovery time.

Despite the extensive usage of the internet, little is known about internet addiction among Americans during the pandemic. A valid and reliable questionnaire was deployed online via MTurk to recruit a national sample of adult Americans to understand the nature and extent of internet addiction. A total of 1305 individuals participated in the study where the majority were males (64%), whites (78%), non-Hispanic (70%), married (72%), 18–35 years old (57%), employed full time (86%), and with a Bachelor’s degree or higher (83%). The prevalence of internet addiction was distributed as no addiction (45%), probable addiction or risk of addiction (41%), and definite or severe addiction (14%). More than a fourth of the population had depression (28%) or anxiety (25%). Despite adjusting for sociodemographic characteristics, definite/severe internet addiction was strongly predictive of depression, anxiety, and psychological distress in multiple regression analyses. Those who were probably addicted or at risk of addiction were also more likely to have depression or anxiety. Compared to estimates before the pandemic, this study suggests an increase in internet addiction among U.S. adults during the COVID-19 pandemic. Population-based interventions and mental health promotion strategies should focus on a reduction in internet consumption and screen time.

Antipsychotic treatment resistance affects up to a third of individuals with schizophrenia. Of those affected, 70–84% are reported to be treatment resistant from the outset. This raises the possibility that the neurobiological mechanisms of treatment resistance emerge before the onset of psychosis and have a neurodevelopmental origin. Neuropsychological investigations can offer important insights into the nature, origin and pathophysiology of treatment-resistant schizophrenia (TRS), but methodological limitations in a still emergent field of research have obscured the neuropsychological discriminability of TRS. We report on the first systematic review and meta-analysis to investigate neuropsychological differences between TRS patients and treatment-responsive controls across 17 published studies (1864 participants). Five meta-analyses were performed in relation to (1) executive function, (2) general cognitive function, (3) attention, working memory and processing speed, (4) verbal memory and learning, and (5) visual−spatial memory and learning. Small-to-moderate effect sizes emerged for all domains. Similarly to previous comparisons between unselected, drug-naïve and first-episode schizophrenia samples v. healthy controls in the literature, the largest effect size was observed in verbal memory and learning [dl = −0.53; 95% confidence interval (CI) −0.29 to −0.76; z = 4.42; p < 0.001]. A sub-analysis of language-related functions, extracted from across the primary domains, yielded a comparable effect size (dl = −0.53, 95% CI −0.82 to −0.23; z = 3.45; p < 0.001). Manipulating our sampling strategy to include or exclude samples selected for clozapine response did not affect the pattern of findings. Our findings are discussed in relation to possible aetiological contributions to TRS.

We examined the effect of varying multimodal pain management (MMPM) combinations on oral morphine milligram equivalents (OMME) and length of stay (LOS) after total knee arthroplasty (TKA). Five groups were compared based on the combination of multimodal analgesics ranging from no MMPM to full MMPM with acetaminophen, gabapentinoids, and celecoxib. After risk adjustment, MMPM was associated with decreased odds of LOS ≥2 days and OMME ≥75th percentile. MMPM protocols are effective at reducing LOS and postoperative narcotic requirements post-TKA. Patients appear to derive similar benefit from receiving all three medications, as well as various combinations of these drugs.

Background Many people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) never develop substantial symptoms. With more than 34 million people in the United States already infected and highly transmissible variants rapidly emerging, it is highly probable that post- and presymptomatic people will form an important fraction of those seeking dental care. Salivary carriage rates in these populations are not known. Moreover, although preventing transmission is critical for controlling spread, the efficacy of mouthrinses in reducing oral viral load is poorly studied. Methods The authors recruited 201 asymptomatic, presymptomatic, postsymptomatic, and symptomatic people and measured copy numbers of SARS-CoV-2 in unstimulated saliva using real-time reverse transcriptase quantitative polymerase chain reaction. Subsequently, the authors inducted 41 symptomatic people into a randomized, triple-blinded study and instructed them to rinse with saline, 1% hydrogen peroxide, 0.12% chlorhexidine, or 0.5% povidone-iodine for 60 seconds. The authors measured viral load 15 and 45 minutes after rinsing. Results Salivary SARS-CoV-2 was detected in 23% of asymptomatic, 60% of postsymptomatic, and 28% of presymptomatic participants. Neither carriage rate nor viral load correlated with COVID-19 symptomatology, age, sex, or race or ethnicity. All 4 mouthrinses decreased viral load by 61% through 89% at 15 minutes and by 70% through 97% at 45 minutes. The extent of reduction correlated significantly with initial viral load. Conclusions Nonsymptomatic people can pose a risk of transmitting the virus, and mouthrinses are simple and efficacious means of reducing this risk, especially when the load is less than 104 copies per milliliter. Practical Implications At a time when resources are stretched, the findings of this study contribute to evidence-based selection of personal protection equipment and simple infection-control practices to reduce contagion at source. This clinical trial was registered at ClinicalTrials.gov . The registration number is NCT04603794.

Objective To investigate whether patients with clozapine treatment are at an increased risk of a more severe COVID-19 infection as compared with patients on other antipsychotic drugs. Methods In this register-based cohort study, all residents (age 18 or older) in the Stockholm Region with a psychotic disorder diagnosis and antipsychotic treatment were included (N = 8 233) and followed from March 1, 2020 to January 14, 2021. The exposure was defined as clozapine treatment and the outcome measures (indicating a more severe COVID-19 infection) were: inpatient care, care within intensive care unit or death due to COVID-19 infection. Differences in outcome rates between exposed (n = 966) and unexposed (other antipsychotics; n = 7 267) were examined using Cox proportional hazards models and expressed as hazard ratios (HR) with 95% confidence intervals (CI). Results No statistically significant differences in outcome rates were found between the two groups of patients after adjusting for age, sex, and residence in retirement homes. The adjusted HR for the exposed compared to the unexposed was 0.96 (95% CI: 0.54, 1.70) for inpatient care; 1.69 (0.48, 5.93) for care in intensive care unit (ICU); and 0.86 (0.26, 2.80) for death. Regarding inpatient care, additional adjusting for country of birth, living in socioeconomically vulnerable areas, number of care visits during the previous year, and comorbid medical illnesses did not alter the results. Conclusions Our results may add support to the present guidelines, recommending sustained clozapine treatment during the current COVID-19 pandemic with careful monitoring and readiness to alter drug doses as needed.

Purpose: Soft-tissue sarcomas (STS) are a rare, heterogeneous group of mesenchymal tumors. For decades the mainstay of treatment for advanced, unresectable STS has been palliative chemotherapy. High levels of activated MET receptor have been reported in various sarcoma cell lines, together with elevated vascular endothelial growth factor (VEGF) levels in patients with STS, suggesting that dual targeting of the VEGF and MET pathways with the multi-receptor tyrosine kinase inhibitor cabozantinib would result in clinical benefit in this population. Patients and Methods: We performed an open-label, multi-institution, single-arm phase II trial of single-agent cabozantinib in adult patients with advanced STS and progressive disease after at least 1 standard line of systemic therapy. Patients received 60 mg oral cabozantinib once daily in 28-day cycles, and dual primary endpoints of overall response rate and 6-month progression-free survival (PFS) were assessed. Changes in several circulating biomarkers were assessed as secondary endpoints. Results: Six (11.1%; 95% CI, 4.2%–22.6%) of the 54 evaluable patients enrolled experienced objective responses (all partial responses). Six-month PFS was 49.3% (95% CI, 36.2%–67.3%), with a median time on study of 4 cycles (range, 1–99). The most common grade 3/4 adverse events were hypertension (7.4%) and neutropenia (16.7%). Patients' levels of circulating hepatocyte growth factor (HGF), soluble MET, and VEGF-A generally increased after a cycle of therapy, while soluble VEGFR2 levels decreased, regardless of clinical outcome. Conclusions: Cabozantinib single-agent antitumor activity was observed in patients with selected STS histologic subtypes (alveolar soft-part sarcoma, undifferentiated pleomorphic sarcoma, extraskeletal myxoid chondrosarcoma, and leiomyosarcoma) highlighting the biomolecular diversity of STS.

BACKGROUND AND AIMS There is a higher prevalence of unhealthy alcohol use among Indigenous populations, but there have been few studies of the effectiveness of screening and treatment in primary health care. Over 24 months, we tested whether a model of service-wide support could increase screening and any alcohol treatment. DESIGN Cluster-randomized trial with 24-month implementation (12 months active, 12 months maintenance). SETTING Australian Aboriginal Community Controlled primary care services. PARTICIPANTS Twenty-two services (83 032 clients) that use Communicare practice software and see at least 1000 clients annually, randomized to the treatment arm or control arm. INTERVENTION AND COMPARATOR Multi-faceted early support model versus a comparator of waiting-list control (11 services). MEASUREMENTS A record (presence = 1, absence = 0) of: (i) Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) screening (primary outcome), (ii) any-treatment and (iii) brief intervention. We received routinely collected practice data bimonthly over 3 years (1-year baseline, 1-year implementation, 1-year maintenance). Multi-level logistic modelling was used to compare the odds of each outcome before and after implementation. FINDINGS The odds of being screened within any 2-month reference period increased in both arms post-implementation, but the increase was nearly eight times greater in early-support services [odds ratio (OR) = 7.95, 95% confidence interval (CI) = 4.04-15.63, P

Suicides are among the 10 leading causes of death in U.S. children 12 years of age and younger. The purpose of this study was to examine trends and methods of suicide in children by race and gender from 2010 to 2019, the most recent years of data available from the Centers for Disease Control and Prevention. Child suicides statistically significantly increased for black (95%), white (158%), male (95%), and female (300%) children during the decade. Additionally, the methods children used to commit suicide did not significantly differ by race or gender. The leading method of suicide used by children was strangulation/suffocation depending on race and gender (67%-85%). The second most common method of suicide was by the use of a firearm, again depending on race and gender (11%-30%). Northeastern states had the fewest child suicides during the decade and Texas and California had the most child suicides. Policymakers need to commit more resources and research funding to better detect risk factors, protective factors, and effective interventions for reducing child suicides.

The therapeutic efficacy of temozolomide (TMZ) is hindered by inherent and acquired resistance. Biomarkers such as MGMT expression and MMR proficiency are used as predictors of response. However, not all MGMTlow/−ve/MMRproficient patients benefit from TMZ treatment, indicating a need for additional patient selection criteria. We explored the role of ATR in mediating TMZ resistance and whether ATR inhibitors (ATRi) could reverse this resistance in multiple cancer lines. We observed that only 31% of MGMTlow/−ve/MMRproficient patient-derived and established cancer lines are sensitive to TMZ at clinically relevant concentrations. TMZ treatment resulted in DNA damage signaling in both sensitive and resistant lines, but prolonged G2/M arrest and cell death were exclusive to sensitive models. Inhibition of ATR but not ATM, sensitized the majority of resistant models to TMZ and resulted in measurable DNA damage and persistent growth inhibition. Also, compromised homologous recombination (HR) via RAD51 or BRCA1 loss only conferred sensitivity to TMZ when combined with an ATRi. Furthermore, low REV3L mRNA expression correlated with sensitivity to the TMZ and ATRi combination in vitro and in vivo. This suggests that HR defects and low REV3L levels could be useful selection criteria for enhanced clinical efficacy of an ATRi plus TMZ combination.

Enhancement of fluorescence through the application of plasmonic metal nanostructures has gained substantial research attention due to the widespread use of fluorescence-based measurements and devices. Using a microfabricated plasmonic silver nanoparticle-organic semiconductor platform, we show experimentally the enhancement of fluorescence intensity achieved through electro-optical synergy. Fluorophores located sufficiently near silver nanoparticles are combined with diphenylalanine nanotubes (FFNTs) and subjected to a DC electric field. It is proposed that the enhancement of the fluorescence signal arises from the application of the electric field along the length of the FFNTs, which stimulates the pairing of low-energy electrons in the FFNTs with the silver nanoparticles, enabling charge transport across the metal-semiconductor template that enhances the electromagnetic field of the plasmonic nanoparticles. Many-body perturbation theory calculations indicate that, furthermore, the charging of silver may enhance its plasmonic performance intrinsically at particular wavelengths, through band-structure effects. These studies demonstrate for the first time that field-activated plasmonic hybrid platforms can improve fluorescence-based detection beyond using plasmonic nanoparticles alone. In order to widen the use of this hybrid platform, we have applied it to enhance fluorescence from bovine serum albumin and

Background Chagas disease affects an estimated 326 000–347 000 people in the United States and is severely underdiagnosed. Lack of awareness and clarity regarding screening and diagnosis is a key barrier. This article provides straightforward recommendations, with the goal of simplifying identification and testing of people at risk for US healthcare providers. Methods A multidisciplinary working group of clinicians and researchers with expertise in Chagas disease agreed on 6 main questions, and developed recommendations based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, after reviewing the relevant literature on Chagas disease in the United States. Results Individuals who were born or resided for prolonged time periods in endemic countries of Mexico and Central and South America should be tested for Trypanosoma cruzi infection, and family members of people who test positive should be screened. Women of childbearing age with risk factors and infants born to seropositive mothers deserve special consideration due to the risk of vertical transmission. Diagnostic testing for chronic T. cruzi infection should be conducted using 2 distinct assays. Conclusions Increasing provider-directed screening for T. cruzi infection is key to addressing this neglected public health challenge in the United States.

This article is the work product of the Continuous Ketone Monitoring Consensus Panel, which was organized by Diabetes Technology Society and met virtually on April 20, 2021. The panel consisted of 20 US-based experts in the use of diabetes technology, representing adult endocrinology, pediatric endocrinology, advanced practice nursing, diabetes care and education, clinical chemistry, and bioengineering. The panelists were from universities, hospitals, freestanding research institutes, government, and private practice. Panelists reviewed the medical literature pertaining to ten topics: (1) physiology of ketone production, (2) measurement of ketones, (3) performance of the first continuous ketone monitor (CKM) reported to be used in human trials, (4) demographics and epidemiology of diabetic ketoacidosis (DKA), (5) atypical hyperketonemia, (6) prevention of DKA, (7) non-DKA states of fasting ketonemia and ketonuria, (8) potential integration of CKMs with pumps and automated insulin delivery systems to prevent DKA, (9) clinical trials of CKMs, and (10) the future of CKMs. The panelists summarized the medical literature for each of the ten topics in this report. They also developed 30 conclusions (amounting to three conclusions for each topic) about CKMs and voted unanimously to adopt the 30 conclusions. This report is intended to support the development of safe and effective continuous ketone monitoring and to apply this technology in ways that will benefit people with diabetes.

Suicides are among the leading causes of death in elderly Americans. The problem is expected to grow with an aging population in the U.S. Suicides in African-American elderly are not well studied. This article enumerates the risk factors for suicidal behaviors in elderly African-Americans; presents an epidemiological assessment of suicides in elderly African-Americans from 2010 to 2018 with gender-specific differences, and explores public health considerations for helping to reduce the growing numbers of suicides in elderly African-Americans. Currently, there are very limited evidence-based interventions to reduce or prevent suicides in older African-Americans. This article also provides implications and recommendations for prevention practice and research that is needed to help alleviate suicides in older African-Americans.

Background/ Purpose There is a dearth of studies that have examined unintentional firearm-related mortality in African–American (AA) youths. The purpose of this article is to assess the epidemiology of unintentional firearm mortality in AA youth, examine the risk factors associated with unintentional AA youth firearm mortality, and explore the evidence for preventing unintentional firearm-mortality in AA youths. Methods In this cross-sectional study, the Web-Based Injury Statistics Query and Reporting System (WISQARS) data from the Centers for Disease Control and Prevention (CDC) was used. Data were analyzed from the years 2010–2019 using descriptive statistics. Results Between the years 2010 and 2019, the AA youth unintentional firearm mortality rate increased by 48% while the rate for White youths declined by 29%. The decade from 2010 to 2019 saw almost 400 AA youths lose their lives to unintentional firearm trauma. AA male children averaged 87% of all AA unintentional firearm deaths during this time. The years of potential life lost due to unintentional firearm mortality ranged between 21,200 and 24,300 years. The risk factors for unintentional firearm mortality in AA youths include living in states with high rates of firearm ownership, living in a home with firearms, being an older adolescent, and being of lower socioeconomic status. Of all the strategies to prevent unintentional firearm mortality in youths, the most effective include strong (felony penalty) Child Access Prevention laws, the absence of Stand-Your-Ground laws, and physicians engaging in anticipatory guidance with patients regarding safe storage of firearms. Conclusions Despite the limited scale of unintentional firearm mortality in AA youths, primary prevention dictates that public health professionals intervene to keep this public health problem from becoming an epidemic and a larger contributor to health disparities.

The long history of artificial reefs has stimulated diversity in their physical properties and deployment for a range of purposes. A systematic literature search yielded 804 scientific publications on artificial reefs. A database of their characteristics was constructed and used to investigate geographical and historical trends. A total of 1074 unique artificial reefs from 71 countries were identified, with 89% located in the northern hemisphere, but equally distributed between eastern and western hemispheres. Reefs were assigned to one of three categories: (A) unintentional deployment, (B) intentional deployment but unintentional reef, and (C) intentional artificial reef. Category A reefs consisted predominantly of accidental shipwrecks. Category B reefs were primarily coastal defense structures in shallow waters and active oil and gas infrastructures at greater depths. The number of Category C reefs increased after 1965, with most in depths of 10–30 m. Most were constructed from concrete or steel, followed by rock and rubber. Usage of concrete as a material steadily increased, while those of steel and rubber decreased, coinciding with the transition from objects (materials) of opportunity to purpose- built reefs. Most reefs were deployed to enhance faunal communities or fisheries, particularly recreational fishing in North America and Australia. Monitoring was most often performed using underwater visual census but transitioned to more technologically advanced methods, particularly in more affluent countries over recent decades. We present a standardized protocol for describing artificial reefs and urge authors to include all relevant data in their publications to allow future comparisons to enhance our understanding and evaluation of these structures.

Recent reports have questioned the efficacy of intraosseous (IO) drug administration for out-of-hospital cardiac arrest (OHCA) resuscitation. Our aim was to determine whether prehospital administration of resuscitative medications via the IO route was associated with lower rates of return of spontaneous circulation (ROSC) and survival to hospital discharge than peripheral intravenous (IV) infusion in the setting of OHCA.We obtained data on all OHCA patients receiving prehospital IV or IO drug administration from the three most populous counties in Michigan over three years. Data was from the Michigan Cardiac Arrest Registry to Enhance Survival (CARES) database. The association between route of drug administration and outcomes was tested using a matched propensity score analysis.From a total of 10,626 OHCA patients, 6869 received parenteral drugs during their prehospital resuscitation (37.8% by IO) and were included in analysis. Unadjusted outcomes were lower in patients with IO vs. IV access: 18.3% vs. 23.8% for ROSC (p0.001), 3.2% vs. 7.6% for survival to hospital discharge (p0.001), and 2.0% vs. 5.8% for favorable neurological function (p0.001). After adjustment, IO route remained associated with lower odds of sustained ROSC (OR 0.72, 95% CI 0.63-0.81, p0.001), hospital survival (OR 0.48, 95% CI 0.37-0.62, p0.001), and favorable neurological outcomes (OR 0.42, 95% CI 0.30-0.57, p0.001).In this cohort of OHCA patients, the use of prehospital IO drug administration was associated with unfavorable clinical outcomes.

Refereed/Peer-reviewed Background and Aims: This cross-sectional study evaluated the nature of pain curriculum being taught in accredited exercise physiology degrees across Australian universities and its perceived usefulness for preparing exercise physiologists to treat people with chronic pain. Materials & Methods: Universities and graduates were asked about the nature and sufficiency of pain curriculum taught, with particular emphasis on competencies for physical therapists as outlined by the International Association for the Study of Pain. Results: Ten universities and 101 graduates responded. Median (interquartile range) instruction time on pain curriculum was 12 (7.25–18.75) hours. Few universities (30%) were aware of the guidelines for physical therapy pain curricula, although most (70%) agreed their degrees contained adequate instruction on pain assessment and management. In contrast, 74% of graduates felt their degree did not adequately prepare them to treat people with chronic pain. Half the graduates (51%) were not aware of the guidelines for physical therapy pain curricula. Discussion & Conclusion: There is a disconnect between perceptions of Australian universities and their graduates regarding the sufficiency of pain curriculum taught to student exercise physiologists. Benchmarking pain curriculum in Australian university programs against relevant international recommendations may enhance the suitability of pain curricula taught to exercise physiologists, thereby better preparing new graduates to treat people with pain.

Herbal-induced liver injury (HILI) is an important and increasingly concerning cause of liver toxicity, and this study presents recent updates to the literature. An extensive literature review was conducted encompassing September 2019 through March 2021. Studies with clinically significant findings were analyzed and included in this review. We emphasized those studies that provided a causality assessment methodology, such as Roussel Uclaf Causality Assessment Method scores. Our review includes reports of individual herbals, including Garcinia cambogia, green tea extract, kratom as well as classes such as performance enhancing supplements, Traditional Chinese medicine, Ayurvedic medicine and herbal contamination. Newly described herbals include ashwagandha, boldo, skyfruit, and ‘Thermo gun’. Several studies discussing data from national registries, including the United States Drug-Induced Liver Injury (DILI) Network, Spanish DILI Registry, and Latin American DILI Network were incorporated. There has also been a continued interest in hepatoprotection, with promising use of herbals to counter hepatotoxicity from anti-tubercular medications. We also elucidated the current legal conversation surrounding use of herbals by presenting updates from the Federal Drug Administration. The highlights of the literature over the past year indicate interest in HILI that will continue as the supplement industry in the United States grows.

The hyperbolic phonon polaritons supported in hexagonal boron nitride (hBN) with long scattering lifetimes are advantageous for applications such as super-resolution imaging via hyperlensing. Yet, hyperlens imaging is challenging for distinguishing individual and closely spaced objects and for correlating the complicated hyperlens fields with the structure of an unknown object underneath. Here, we make significant strides to overcome each of these challenges. First, we demonstrate that monoisotopic h11BN provides significant improvements in spatial resolution, experimentally resolving structures as small as 44 nm and those with sub 25 nm spacings at 6.76 μm free-space wavelength. We also present an image reconstruction algorithm that provides a structurally accurate, visual representation of the embedded objects from the complex hyperlens field. Further, we offer additional insights into optimizing hyperlens performance on the basis of material properties, with an eye toward realizing far-field imaging modalities. Thus, our results significantly advance label-free, high-resolution, spectrally selective hyperlens imaging and image reconstruction methodologies.

Drug-induced liver injury (DILI) remains an important, yet challenging diagnosis for physicians. Each year, additional drugs are implicated in DILI and this year was no different, with more than 1400 articles published on the subject. This review examines some of the most significant highlights and controversies in DILI-related research over the past year and their implications for clinical practice. Several new drugs were approved by the US Food and Drug Administration including a number of drugs implicated in causing DILI, particularly among the chemotherapeutic classes. The COVID-19 pandemic was also a major focus of attention in 2020 and we discuss some of the notable aspects of COVID-19-related liver injury and its implications for diagnosing DILI. Updates in diagnostic and causality assessments related to DILI such as the Roussel Uclaf Causality Assessment Method are included, mindful that there is still no single biomarker or diagnostic tool to unequivocally diagnose DILI. Glutamate dehydrogenase received renewed attention as being more specific than alanine aminotransferase. There were a few new reports of previously unrecognized hepatotoxins, including immune modulators and novel gene therapy drugs that we highlight. Updates and new developments of previously described hepatotoxins, such as immune checkpoint inhibitors and anti-tuberculosis drugs are reviewed. Finally, novel technologies such as organoid culture systems to better predict DILI preclinically may be coming of age and determinants of hepatocyte loss, such as calculating PALT are poised to improve our current means of estimating DILI severity and the risk of acute liver failure.

Introduction:The COVID-19 pandemic response limited access to many traditional forms of physical activity (PA). Purpose:To assess changes in objectively measured PAofUniversity staff during the initial stageofthe COVID-19 pandemic.Methods:We implemented a repeated measures natural experiment design. PA data (walking distance, steps∙d#x2D;1, and Moderate#x2D;to#x2D;Vigorous PA (MVPA) time) from commercial grade triaxial accelerometers were collected from employees (N#x3D;625) of a large, public university in the southeast United States during the months of Jan#x2D;May in calendar years 2019 and 2020.Results#x3A;Walking distance (6#x2D;9#x25;, p#x3C;0.001) and steps∙d#x2D;1(7#x2D;11#x25;, p#x3C;0.001) were lower during April and May 2020 compared to 2019. However, MVPA time was not significantly different among calendar years for the months of March#x2D;May. Steps∙d#x2D;1significantly decreased after WHO's worldwide pandemic declaration (10,348#xB1;171 v. 9551#xB1;156 steps∙d#x2D;1, p#x3C;0.001) and campus closure (10,100#xB1;160 v. 9,186#xB1;167 steps∙d#x2D;1, p#x3C;0.001). Conversely, steps∙d#x2D;1significantly increased after implementation of the state's "Healthy at Home" order (9,693#xB1;177 vs. 10,156#xB1;185 steps∙d#x2D;1, p#x3C;0.001).Conclusion: A decrease in daily steps, but not MVPA, suggests increased sedentary behavior, not reduced participation in exercise, during the early stages of the COVID#x2D;19 pandemic. Specific pandemic response policies may positively or negatively affect PA and sedentary behavior.