Pan AMPK Activation Protects Tubules in Rat Ischemic Acute Kidney Injury.

Acute Kidney Injury (AKI) is characterized by an abrupt decline in kidney function and has been associated with excess risks of death, kidney disease progression, and cardiovascular events. The kidney has a high energetic demand with mitochondrial health being essential to renal function and damaged mitochondria has been reported across AKI subtypes. 5' adenosine monophosphate-activated protein kinase (AMPK) activation preserves cellular energetics through improvement of mitochondrial function and biogenesis when ATP levels are low such as under ischemia-induced AKI. We developed a selective potent small molecule pan AMPK activator, compound 1, and tested its ability to increase AMPK activity and preserve kidney function during ischemia/reperfusion injury in rats. A single administration of 1 caused sustained activation of AMPK for at least 24 hours, protected against acute tubular necrosis, and reduced clinical markers of tubular injury such as NephroCheck and Fractional Excretion of Sodium (FENa). Reduction in plasma creatinine and increased Glomerular Filtration Rate (GFR) indicated preservation of kidney function. Surprisingly, we observed a strong diuretic effect of AMPK activation associated with natriuresis both with and without AKI. Our findings demonstrate that activation of AMPK leads to protection of tubular function under hypoxic/ischemic conditions which holds promise as a potential novel therapeutic approach for AKI. Significance Statement No approved pharmacological therapies currently exist for acute kidney injury. We developed Compound 1 which dose-dependently activated AMPK in the kidney and protected kidney function and tubules after ischemic renal injury in the rat. This was accompanied by natriuresis in injured as well as uninjured rats.

Time to surgical management of distal radius fractures: effects on health care utilization and functional outcomes.

BACKGROUND: Distal radius fractures are common injuries. Open reduction and internal fixation with volar locking plates is the most common approach for surgical fixation. This study investigated the association between time to surgery and health care utilization, income, and functional outcomes among patients undergoing open reduction and internal fixation for distal radius fracture. METHODS: We conducted a retrospective review of patients who underwent open reduction and internal fixation for isolated acute distal radius fracture between 2009 and 2019. Time to surgery was grouped as early (≤ 14 d) and delayed (> 14 d). We performed χ2 (or Fisher exact) and Wilcoxon rank sum (or Kruskal-Wallis) tests to provide statistical comparison of time to surgery by health care utilization and functional outcomes. Univariable and multivariable logistic regression analyses were performed to identify factors significantly associated with time to surgery. We included all significant univariables in the multivariable logistic regression model, which identified factors based on significant adjusted odds ratios (95% confidence intervals excluding the null) after we adjusted for confounding variables. RESULTS: We included 106 patients, with 36 (34.0%) in the group receiving early treatment and 70 (66.0%) in the group receiving delayed treatment. Patients in the delayed-treatment group attended significantly more clinic visits and postoperative hand therapy sessions. The group with delayed treatment demonstrated significantly lower degrees of wrist flexion at the first follow-up, but this difference did not persist. Patients with higher estimated income (> $39 405 per annum) had lower odds of delayed surgery than those with lower estimated income (≤ $39 405). CONCLUSION: Delayed time to surgery was associated with greater health care utilization and lower degrees of early wrist flexion. Access to care for lower-income patients warrants further evaluation.

A Systematic Review of the Cost-Effectiveness of Cleft Care in Low- and Middle-Income Countries: What is Needed?

OBJECTIVE: The objective of this paper is to conduct a systematic review that summarizes the cost-effectiveness of cleft lip and/or palate (CL/P) care in low- and middle-income countries (LMICs) based on existing literature. DESIGN: We searched eleven electronic databases for articles from January 1, 2000 to December 29, 2020. This study is registered in PROSPERO (CRD42020148402). Two reviewers independently conducted primary and secondary screening, and data extraction. SETTING: All CL/P cost-effectiveness analyses in LMIC settings. PATIENTS, PARTICIPANTS: In total, 2883 citations were screened. Eleven articles encompassing 1,001,675 patients from 86 LMICs were included. MAIN OUTCOME MEASURES: We used cost-effectiveness thresholds of 1% to 51% of a country's gross domestic product per capita (GDP/capita), a conservative threshold recommended for LMICs. Quality appraisal was conducted using the Joanna Briggs Institute (JBI) checklist. RESULTS: Primary CL/P repair was cost-effective at the threshold of 51% of a country's GDP/capita across all studies. However, only 1 study met at least 70% of the JBI criteria. There is a need for context-specific cost and health outcome data for primary CL/P repair, complications, and existing multidisciplinary management in LMICs. CONCLUSIONS: Existing economic evaluations suggest primary CL/P repair is cost-effective, however context-specific local data will make future cost-effectiveness analyses more relevant to local decision-makers and lead to better-informed resource allocation decisions in LMICs.

Combating the COVID-19 infodemic using Prompt-Based curriculum learning.

The COVID-19 pandemic has been accompanied by a proliferation of online misinformation and disinformation about the virus. Combating this 'infodemic' has been identified as one of the top priorities of the World Health Organization, because false and misleading information can lead to a range of negative consequences, including the spread of false remedies, conspiracy theories, and xenophobia. This paper aims to combat the COVID-19 infodemic on multiple fronts, including determining the credibility of information, identifying its potential harm to society, and the necessity of intervention by relevant organizations. We present a prompt-based curriculum learning method to achieve this goal. The proposed method could overcome the challenges of data sparsity and class imbalance issues. Using online social media texts as input, the proposed model can verify content from multiple perspectives by answering a series of questions concerning the text's reliability. Experiments revealed the effectiveness of prompt tuning and curriculum learning in assessing the reliability of COVID-19-related text. The proposed method outperforms typical text classification methods, including fastText and BERT. In addition, the proposed method is robust to the hyperparameter settings, making it more applicable with limited infrastructure resources.

Optimization of physicochemical properties of pyridone-based EP3 receptor antagonists.

A novel series of pyridone-based EP3 receptor antagonists was optimized for good physical properties and oral bioavailability in rodents. The lead compounds 3h, 3l and 4d displayed good in vitro profiles, moderate to good metabolic stability and good rodent PK profiles with low clearance, high oral exposure and acceptable half-life.

Amino acids are sensitive glucagon receptor-specific biomarkers for glucagon-like peptide-1 receptor/glucagon receptor dual agonists.

AIM: The aim of this study was to evaluate amino acids as glucagon receptor (GCGR)-specific biomarkers in rodents and cynomolgus monkeys in the presence of agonism of both glucagon-like peptide-1 receptor (GLP1R) and GCGR with a variety of dual agonist compounds. MATERIALS AND METHODS: Primary hepatocytes, rodents (normal, diet-induced obese and GLP1R knockout) and cynomolgus monkeys were treated with insulin (hepatocytes only), glucagon (hepatocytes and cynomolgus monkeys), the GLP1R agonist, dulaglutide, or a variety of dual agonists with varying GCGR potencies. RESULTS: A long-acting dual agonist, Compound 2, significantly decreased amino acids in both wild-type and GLP1R knockout mice in the absence of changes in food intake, body weight, glucose or insulin, and increased expression of hepatic amino acid transporters. Dulaglutide, or a variant of Compound 2 lacking GCGR agonism, had no effect on amino acids. A third variant with ~31-fold less GCGR potency than Compound 2 significantly decreased amino acids, albeit to a significantly lesser extent than Compound 2. Dulaglutide (with saline infusion) had no effect on amino acids, but an infusion of glucagon dose-dependently decreased amino acids on the background of GLP1R engagement (dulaglutide) in cynomolgus monkeys, as did Compound 2. CONCLUSIONS: These results show that amino acids are sensitive and translatable GCGR-specific biomarkers.

Pre-operative biomarkers and imaging tests as predictors of post-operative delirium in non-cardiac surgical patients: a systematic review.

BACKGROUND: Post-operative delirium (POD) is a common post-operative complication in elderly individuals and imposes a significant health and financial burden. Identifying predictive biomarkers may help understand the pathophysiology of POD. Our objective is to summarize the evidence of pre-operative biomarkers and imaging tests to predict POD in patients undergoing non-cardiac surgery. METHODS: A systematic search of English language articles in MEDLINE, EMBASE, Cochrane Database, PsychINFO, PubMed and ClinicalTrials. Gov up to January 2018 was performed. Studies that used biomarkers or imaging tests to predict POD and a validated POD assessment tool were included. Animal studies, paediatric, cardiac and intracranial surgery were excluded. Risk of bias was assessed using the Quality In Prognosis Study tool. RESULTS: Thirty-four prospective cohort studies involving 4424 patients were included. Nineteen studies described serum tests [Interleukin-6, Insulin-like Growth Factor 1, C-Reactive Protein (CRP), cholinesterases, apolipoprotein-E genotype, leptin, hypovitaminosis, hypoalbuminaemia, gamma-amino butyric acid], 10 described cerebral-spinal fluid tests (monoamine precursor, melatonin, acute phase proteins, S100B and neurofibrillary tangles), and 5 described imaging tests. Two studies had high risk of bias due to unclear outcome measurement and study participation. CRP was significantly associated with POD in 5 studies. Other biomarkers were either examined by only a single study or two or more studies with conflicting results. CONCLUSION: CRP is the most promising biomarker associated with POD. However, we are still in the early stages in identifying biomarkers and imaging tests that may further understanding of the pathophysiology of POD.

A Computer Vision-Based Roadside Occupation Surveillance System for Intelligent Transport in Smart Cities.

In digital and green city initiatives, smart mobility is a key aspect of developing smart cities and it is important for built-up areas worldwide. Double-parking and busy roadside activities such as frequent loading and unloading of trucks, have a negative impact on traffic situations, especially in cities with high transportation density. Hence, a real-time internet of things (IoT)-based system for surveillance of roadside loading and unloading bays is needed. In this paper, a fully integrated solution is developed by equipping high-definition smart cameras with wireless communication for traffic surveillance. Henceforth, this system is referred to as a computer vision-based roadside occupation surveillance system (CVROSS). Through a vision-based network, real-time roadside traffic images, such as images of loading or unloading activities, are captured automatically. By making use of the collected data, decision support on roadside occupancy and vacancy can be evaluated by means of fuzzy logic and visualized for users, thus enhancing the transparency of roadside activities. The CVROSS was designed and tested in Hong Kong to validate the accuracy of parking-gap estimation and system performance, aiming at facilitating traffic and fleet management for smart mobility.

Patient preference survey: are patients willing to delay surgery if obstructive sleep apnea is suspected?

BACKGROUND: Screening and optimizing patients for OSA in the perioperative period may reduce postoperative complications. However, sleep studies can be difficult to obtain before surgery. Previous surveys reported that the majority of sleep physicians would delay surgery to diagnose and manage OSA, but most anesthesiologists would not. While disagreements exist, the importance of shared decision making and patient preferences have never been studied on this topic. It is unknown whether patients with suspected OSA, when given information about OSA, would be willing to delay surgery to diagnose and manage their condition preoperatively. METHODS: This study consisted of a self-administered questionnaire that surveyed patients, patient relatives, or any accompanying members. The survey was conducted in the preoperative clinic or in the perioperative patient and family waiting area at two hospitals in Canada and in the United States. A hypothetical scenario was used: participants were given information about OSA, and asked about their preferences regarding preoperative management should they be at risk for OSA in the setting of pending elective surgery. The objective of this study was to determine whether respondents preferred to 1) proceed with surgery as planned, 2) delay surgery to ensure the medical condition of OSA is diagnosed and optimized, or 3) let his/her physician decide. RESULTS: The final survey contained 19 questions and the survey was conducted from June 2016 to September 2016. Four hundred and seventy-three surveys were collected. Forty-four percent of respondents, when given information about OSA, preferred to delay surgery pending a sleep study and treatment. Forty percent of respondents who preferred to delay surgery would tolerate delaying up to two months. CONCLUSION: Increasing emphasis and significant value has been placed on shared-decision making between patients and physicians. Educating patients about the risks of OSA and incorporating patient preferences into the perioperative management of OSA may be warranted.

Association of STOP-Bang Questionnaire as a Screening Tool for Sleep Apnea and Postoperative Complications: A Systematic Review and Bayesian Meta-analysis of Prospective and Retrospective Cohort Studies.

BACKGROUND: The risk of postoperative complications increases with undiagnosed obstructive sleep apnea (OSA). The high-risk OSA (HR-OSA) patients can be easily identified using the STOP-Bang screening tool. The aim of this systematic review and meta-analysis is to determine the association of postoperative complications in patients screened as HR-OSA versus low-risk OSA (LR-OSA). METHODS: The following data bases were searched from January 1, 2008, to October 31, 2016, to identify the eligible articles: Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, Cochrane Databases of Systematic Reviews, Medline-in-Process & other nonindexed citations, Google Scholar, Embase, Web of Sciences and Scopus. The search included studies with adult surgical patients screened for OSA with STOP-Bang questionnaire that reported at least 1 cardiopulmonary or any other complication requiring intensive care unit admission as diagnosis of outcome. We used a Bayesian random-effects analysis to evaluate the existing evidence of STOP-Bang in relation to OSA and to assess the association of postoperative complications with the identified HR-OSA patients by study design and methodologies. RESULTS: This systematic review and meta-analysis was conducted using 10 cohort studies: 23,609 patients (HR-OSA, 7877; LR-OSA, 15,732). The pooled odds of perioperative complications were higher in the HR-OSA versus LR-OSA patients (odds ratio 3.93, 95% credible interval, 1.85-7.77, P= .003; 6.86% vs 4.62%). The length of hospital stay was longer in HR-OSA by 2 days when compared with LR-OSA (5.0 ± 4.2 vs 3.4 ± 2.8 days; mean difference 2.01; 95% credible interval, 0.77-3.24; P= .005). Meta-regression to adjust for baseline confounding factors and subgroup analysis did not materially change the results. CONCLUSIONS: This systematic review and meta-analysis suggests that HR-OSA is related with higher risk of postoperative adverse events and longer length of hospital stay when compared with LR-OSA patients. Our findings support the implementation of the STOP-Bang screening tool for perioperative risk stratification.

Postoperative Outcomes in Obstructive Sleep Apnea Patients Undergoing Cardiac Surgery: A Systematic Review and Meta-analysis of Comparative Studies.

BACKGROUND: Obstructive sleep apnea (OSA) is a common comorbidity in patients undergoing cardiac surgery and may predispose patients to postoperative complications. The purpose of this meta-analysis is to determine the evidence of postoperative complications associated with OSA patients undergoing cardiac surgery. METHODS: A literature search of Cochrane Database of Systematic Reviews, Medline, Medline In-process, Web of Science, Scopus, EMBASE, Cochrane Central Register of Controlled Trials, and CINAHL until October 2016 was performed. The search was constrained to studies in adult cardiac surgical patients with diagnosed or suspected OSA. All included studies must report at least 1 postoperative complication. The primary outcome is major adverse cardiac or cerebrovascular events (MACCEs) up to 30 days after surgery, which includes death from all-cause mortality, myocardial infarction, myocardial injury, nonfatal cardiac arrest, revascularization process, pulmonary embolism, deep venous thrombosis, newly documented postoperative atrial fibrillation (POAF), stroke, and congestive heart failure. Secondary outcome is newly documented POAF. The other exploratory outcomes include the following: (1) postoperative tracheal intubation and mechanical ventilation; (2) infection and/or sepsis; (3) unplanned intensive care unit (ICU) admission; and (4) duration of stay in hospital and ICU. Meta-analysis and meta- regression were conducted using Cochrane Review Manager 5.3 (Cochrane, London, UK) and OpenBUGS v3.0, respectively. RESULTS: Eleven comparative studies were included (n = 1801 patients; OSA versus non-OSA: 688 vs 1113, respectively). MACCEs were 33.3% higher odds in OSA versus non-OSA patients (OSA versus non-OSA: 31% vs 10.6%; odds ratio [OR], 2.4; 95% confidence interval [CI], 1.38-4.2; P = .002). The odds of newly documented POAF (OSA versus non-OSA: 31% vs 21%; OR, 1.94; 95% CI, 1.13-3.33; P = .02) was higher in OSA compared to non-OSA. Even though the postoperative tracheal intubation and mechanical ventilation (OSA versus non-OSA: 13% vs 5.4%; OR, 2.67; 95% CI, 1.03-6.89; P = .04) were significantly higher in OSA patients, the length of ICU stay and hospital stay were not significantly prolonged in patients with OSA compared to non-OSA. The majority of OSA patients were not treated with continuous positive airway pressure therapy. Meta-regression and sensitivity analysis of the subgroups did not impact the OR of postoperative complications for OSA versus non-OSA groups. CONCLUSIONS: Our meta-analysis demonstrates that after cardiac surgery, MACCEs and newly documented POAF were 33.3% and 18.1% higher odds in OSA versus non-OSA patients, respectively.

4-Bicyclic heteroaryl-piperidine derivatives as potent, orally bioavailable stearoyl-CoA desaturase-1 (SCD1) inhibitors: part 2. Pyridazine-based analogs.

Design, synthesis, and biological evaluation of pyridazine-based, 4-bicyclic heteroaryl-piperidine derivatives as potent stearoyl-CoA desaturase-1 (SCD1) inhibitors are described. In a chronic study of selected analog (3e) in Zucker fa/fa (ZF) rat, dose-dependent decrease of body weight gain and plasma fatty acid desaturation index (DI) in both C16 and C18 are also demonstrated. The results indicate that the plasma fatty acid DI may serve as an indicator for direct target engagement and biomarker for SCD1 inhibition.

4-Bicyclic heteroaryl-piperidine derivatives as potent, orally bioavailable Stearoyl-CoA desaturase-1 (SCD1) inhibitors. Part 1: urea-based analogs.

A new series of urea-based, 4-bicyclic heteroaryl-piperidine derivatives as potent SCD1 inhibitors is described. The structure-activity relationships focused on bicyclic heteroarenes and aminothiazole-urea portions are discussed. A trend of dose-dependent decrease in body weight gain in diet-induced obese (DIO) mice is also demonstrated.

A new species of the genus Interphasma Chen & He, 2008 (Phasmida: Clitumninae: Medaurini) from Sichuan, China.

Chen and He erected the genus Interphasma in 2008 (Chen & He, 2008). Thirteen species are recognized in this Chinese endemic genus which is distributed in eastern to south-western China (Chen & He, 2008; Chen & Zhang, 2008; Xu et al., 2010). In this paper, a new species, I. lizipingense sp. nov., is described and illustrated from Sichuan, China. A key to the species of the genus is given. The types are deposited in the Museum of Hebei University (HBU) and Hong Kong Entomological Society (HKEM). Full measurements are given to all the types in millimeter (mm.).

Ambient Room Temperatures in a Burn Intensive Care Unit-A Quality Improvement Project.

Introduction: Patients with major burn injuries are particularly susceptible to hypothermia. The ability to maintain and rapidly increase ambient temperatures may reduce the impact of hypothermia and the hypermetabolic response. The purpose of this study was to determine ambient patient room temperatures in a burn intensive care unit (ICU) and to evaluate our ability to adjust these temperatures. Methods: The ambient temperatures of 9 burn ICU patient rooms were recorded hourly over a 6-month period in an American Burn Association-verified burn centre. Temperatures were recorded using wall-mounted smart sensors, transmitted to a mobile smartphone application via Bluetooth, and then exported to Excel for analysis. On 2 predetermined dates, thermostats in all rooms were simultaneously set to maximum, and monitored over 3 h. This represented a sound change initiative, and replicated a medical order to increase the ambient temperature during critical stages of patient care. Results: We recorded 4394 individual hourly temperature measurements for each of the 9 rooms. The mean ambient temperature was 23.5 ± 0.3 °C (range 22.8-24). After intervention 1, ambient temperatures increased <2 °C in 7 rooms and by only 2 °C-3 °C in the other 2 rooms. The overall mean increase in temperature over 3 h across all rooms was 1.03 °C ± 1.19 °C (range -0.88 to 3.26). Following intervention 2, temperatures could be increased by ≥2 °C in only 2 rooms with an overall mean increase in temperature of only 0.76 °C ± 0.99 °C (range -0.29 to 2.43) across all rooms. Conclusions: The burn ICU rooms were relatively cool and our ability locally to adjust ambient temperatures quickly was limited. Burn centres should have regular facility assessments to assess whether ambient temperatures can be adjusted expeditiously when required.

Introduction : Les patients ayant des brûlures importantes (>20% de la surface corporelle totale) sont particulièrement exposés au risque d'hypothermie. La capacité à maintenir et à rapidement augmenter la température ambiante peut réduire la répercussion négative de l'hypothermie et de la réponse hypermétabolique. L'objectif de cette étude était de déterminer la température ambiante des chambres de patients dans une unité de soins intensifs (USI) pour brûlés et d'évaluer notre capacité à ajuster ces températures. Méthodes : La température ambiante de neuf chambres de patients en USI pour brûlés a été enregistrée heure par heure pendant une période de 6 mois dans un centre pour brûlés vérifié par l'ABA. Les températures ont été consignées en utilisant des capteurs intelligents montés sur les murs avec transmission par Bluetooth à une application mobile pour téléphone intelligent, puis exportées dans un tableau Excel pour analyse. À deux dates prédéterminées, les thermostats de toutes les chambres ont été simultanément réglés au maximum et contrôlés pendant 3 heures. Cela représentait une initiative de changement réfléchie, répliquant une consigne médicale d'augmentation de la température ambiante pendant les phases critiques de soins aux patients. Résultats : Nous avons enregistré 4394 relevés horaires de la température pour chacune des neuf chambres. La température ambiante moyenne était de 23,5 ± 0,3 °C (écart : 22,8 à 24). Après la première intervention, les températures ambiantes ont augmenté de moins de 2 °C dans 7 chambres et de seulement 2 °C à 3 °C dans les deux autres chambres. L'augmentation moyenne globale pendant les 3 heures dans toutes les chambres était de 1,03 °C ± 1,19 °C (écart : −0,88 à 3,26). Après la deuxième intervention, les températures ont pu être augmentées de ≥ 2 °C dans seulement deux chambres avec une augmentation globale moyenne de la température de seulement 0,76 °C ± 0,99 °C (écart : −0,29 à 2,43) pour l'ensemble des chambres. Conclusions : Les chambres de l'USI pour brûlés étaient relativement fraîches et notre capacité à ajuster rapidement les températures ambiantes était limitée. Les centres pour brûlés devraient faire l'objet d'évaluations régulières d'établissement pour déterminer si la température ambiante peut être ajustée dans des délais très brefs en cas de besoin.

Improving hand therapy delivery during care transitions in multisystem trauma patients.

High-quality hand therapy is critical to maximising functional capacity and optimising overall outcomes following hand injuries. Therapy delivery requires clear communication between surgeons and occupational therapists. At Sunnybrook Health Sciences Centre (SHSC), Canada's largest tertiary care centre, suboptimal communication is a significant barrier to efficient hand therapy delivery in acute multisystem trauma patients. A baseline audit at SHSC found that 41% of hand therapy orders required clarification and 35% of patients waited over 24 hours before their order was fulfilled. In many cases, communication errors created unacceptably long delays that were suspected by surgeon stakeholders to impede patient outcomes. This highlighted an opportunity for investigation and system improvement.Using process mapping methodology, we outlined standard process involved in patient care and identified barriers to successful communication. We collaborated with key stakeholders to codesign a standardised template for care orders. We aimed to improve order clarity and consistency with the goal of reducing the incidence of clarification and delays.Postimplementation, the percentage of hand therapy orders requiring clarification was decreased to 24%. The number of patients waiting over 24 hours for therapy was also reduced; however, further investigation is required to verify this finding. In addition, essential order components were more consistently and comprehensively included. Next steps of this work include expanding the use of the order template outside of the multisystem trauma population and improving the communication of hand therapy at discharge from hospital.

Accelerating L1-penalized expectation maximization algorithm for latent variable selection in multidimensional two-parameter logistic models.

One of the main concerns in multidimensional item response theory (MIRT) is to detect the relationship between observed items and latent traits, which is typically addressed by the exploratory analysis and factor rotation techniques. Recently, an EM-based L1-penalized log-likelihood method (EML1) is proposed as a vital alternative to factor rotation. Based on the observed test response data, EML1 can yield a sparse and interpretable estimate of the loading matrix. However, EML1 suffers from high computational burden. In this paper, we consider the coordinate descent algorithm to optimize a new weighted log-likelihood, and consequently propose an improved EML1 (IEML1) which is more than 30 times faster than EML1. The performance of IEML1 is evaluated through simulation studies and an application on a real data set related to the Eysenck Personality Questionnaire is used to demonstrate our methodologies.

Approach to machine learning for extraction of real-world data variables from electronic health records.

Background: As artificial intelligence (AI) continues to advance with breakthroughs in natural language processing (NLP) and machine learning (ML), such as the development of models like OpenAI's ChatGPT, new opportunities are emerging for efficient curation of electronic health records (EHR) into real-world data (RWD) for evidence generation in oncology. Our objective is to describe the research and development of industry methods to promote transparency and explainability. Methods: We applied NLP with ML techniques to train, validate, and test the extraction of information from unstructured documents (e.g., clinician notes, radiology reports, lab reports, etc.) to output a set of structured variables required for RWD analysis. This research used a nationwide electronic health record (EHR)-derived database. Models were selected based on performance. Variables curated with an approach using ML extraction are those where the value is determined solely based on an ML model (i.e. not confirmed by abstraction), which identifies key information from visit notes and documents. These models do not predict future events or infer missing information. Results: We developed an approach using NLP and ML for extraction of clinically meaningful information from unstructured EHR documents and found high performance of output variables compared with variables curated by manually abstracted data. These extraction methods resulted in research-ready variables including initial cancer diagnosis with date, advanced/metastatic diagnosis with date, disease stage, histology, smoking status, surgery status with date, biomarker test results with dates, and oral treatments with dates. Conclusion: NLP and ML enable the extraction of retrospective clinical data in EHR with speed and scalability to help researchers learn from the experience of every person with cancer.

Aromatase Inhibitor-Induced Carpal Tunnel Syndrome and Stenosing Tenosynovitis: A Systematic Review.

BACKGROUND: Although aromatase inhibitors are the first-line treatment in postmenopausal women with hormone receptor-positive breast cancer, there is increasing evidence that they can induce carpal tunnel syndrome and stenosing tenosynovitis. This systematic review summarizes the risk factors, incidence, and management for patients with aromatase inhibitor-induced carpal tunnel syndrome and stenosing tenosynovitis compared to tamoxifen or placebo. METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-guided systematic review of PubMed/MEDLINE, Ovid Embase, and the Cochrane Central Register of Controlled Trials was conducted (to March 19, 2020), supplemented with Google Scholar, Plastic and Reconstructive Surgery, and The Journal of Hand Surgery. Two reviewers independently completed the primary and secondary screens and the quality appraisal. RESULTS: This study reviewed 577 abstracts and included 19 studies. Risk factors for aromatase inhibitor-induced carpal tunnel syndrome or stenosing tenosynovitis included hormone replacement therapy before trial entry, history of musculoskeletal symptoms, age younger than 60 years, prior chemotherapy, and body mass index greater than 25 kg/m2. The incidence can be increased up to 10 times compared to tamoxifen. Patient discontinuation of aromatase inhibitor treatment because of carpal tunnel syndrome and stenosing tenosynovitis was reported. Nonsurgical management led to complete resolution of carpal tunnel syndrome symptoms in up to 67 percent of cases. Although most aromatase inhibitor-induced stenosing tenosynovitis original studies were low quality, all recommended surgical release for symptom resolution. CONCLUSIONS: This study provides current knowledge of the associated risk factors, management options, and quality of literature for aromatase inhibitor-induced carpal tunnel syndrome and stenosing tenosynovitis. Early recognition can prevent self-discontinuation of an aromatase inhibitor and long-term sequelae of poorly treated carpal tunnel syndrome and stenosing tenosynovitis.