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The analysis of big healthcare data has enormous potential as a tool for advancing oncology drug development and patient treatment, particularly in the context of precision medicine. However, there are challenges in organizing, sharing, integrating, and making these data readily accessible to the research community. This review presents five case studies illustrating various successful approaches to addressing such challenges. These efforts are CancerLinQ, the American Association for Cancer Research Project GENIE, Project Data Sphere, the National Cancer Institute Genomic Data Commons, and the Veterans Health Administration Clinical Data Initiative. Critical factors in the development of these systems include attention to the use of robust pipelines for data aggregation, common data models, data deidentification to enable multiple uses, integration of data collection into physician workflows, terminology standardization and attention to interoperability, extensive quality assurance and quality control activity, incorporation of multiple data types, and understanding how data resources can be best applied. By describing some of the emerging resources, we hope to inspire consideration of the secondary use of such data at the earliest possible step to ensure the proper sharing of data in order to generate insights that advance the understanding and the treatment of cancer.

Whether chlorthalidone is superior to hydrochlorothiazide for preventing major adverse cardiovascular events in patients with hypertension is unclear.In a pragmatic trial, we randomly assigned adults 65 years of age or older who were patients in the Department of Veterans Affairs health system and had been receiving hydrochlorothiazide at a daily dose of 25 or 50 mg to continue therapy with hydrochlorothiazide or to switch to chlorthalidone at a daily dose of 12.5 or 25 mg. The primary outcome was a composite of nonfatal myocardial infarction, stroke, heart failure resulting in hospitalization, urgent coronary revascularization for unstable angina, and non-cancer-related death. Safety was also assessed.A total of 13,523 patients underwent randomization. The mean age was 72 years. At baseline, hydrochlorothiazide at a dose of 25 mg per day had been prescribed in 12,781 patients (94.5%). The mean baseline systolic blood pressure in each group was 139 mm Hg. At a median follow-up of 2.4 years, there was little difference in the occurrence of primary-outcome events between the chlorthalidone group (702 patients [10.4%]) and the hydrochlorothiazide group (675 patients [10.0%]) (hazard ratio, 1.04; 95% confidence interval, 0.94 to 1.16; P = 0.45). There were no between-group differences in the occurrence of any of the components of the primary outcome. The incidence of hypokalemia was higher in the chlorthalidone group than in the hydrochlorothiazide group (6.0% vs. 4.4%, P0.001).In this large pragmatic trial of thiazide diuretics at doses commonly used in clinical practice, patients who received chlorthalidone did not have a lower occurrence of major cardiovascular outcome events or non-cancer-related deaths than patients who received hydrochlorothiazide. (Funded by the Veterans Affairs Cooperative Studies Program; ClinicalTrials.gov number, NCT02185417.).

Background The existence of a close association between disease of the biliary tract and heart‘s disease is known from the mists of time. Acute acalculous cholecystitis (AAC) is a challenging diagnosis. The atypical clinical onset associated to a paucity and similarity of symptoms and to laboratory data mimicking cardiovascular disease (CVD) often results in under and misdiagnosed cases. Moreover, AAC is often associated with gangrene, perforation and empyema as well as considerable morbidity and mortality(up 50%). Early diagnosis is crucial to increase survivability. Even today, there is still a lot of confusion regarding the relationship and consequently the clinical management AAC and CVD. Aim The aim of this review was to provide evidence regarding epidemiology, pathophysiology, clinical presentation and treatment of the complex association between AAC and CVD. Methods we searched for publications addressing Acalculous cholecystitis and cardiovascular disease, consulting Medline and Scopus databases. Any retrospective or prospective study design or systematic review focusing on the aforementioned topic was accepted. This study was conducted in accordance with the PRISMA and AMSTAR Guidelines. Our search rendered 1422 hits (995 from Medline and 427 from Scopus). After progressive screening, 268 full texts were assessed for eligibility and 135 studies were included in qualitative synthesis. Results According to the literature, 11 cases of AAC were reported after cardiopulmonary bypass surgery. Similarly, in 6 of 7 patients following aortic reconstruction. Small vessel occlusion has shown to be the predominant phenomenon in AAC. Histological analysis suggest involvement of ischaemia and reperfusion mediated injury. The most common ECG alterations noted in AAC are changes in T waves in significant leads, slurring and notching of the QRS complex and elevation or depression of the S–T segment, hypothesizing a vagally reflex mechanism, due to the distention of the common bile duct, with a reduced coronary blood flow. Finally it was reported a resolution of ECG changes due to AAC after cholecystectomy or antibiotic treatment within a few days. Conclusion AAC should be suspected after each general disease leading to hypoperfusion such as cardiovascular diseases and major heart or aortic surgery. ECG changes in absence of significant laboratory data for IMA could be related to a misdiagnosed AAC.

Dieulafoy’s lesions (DLs) are a rare and difficult-to-identify cause of acute gastrointestinal bleeding that can lead to hemorrhagic shock. We present a case of a 23-year-old previously healthy male presenting with melenic stools and hemorrhagic shock. Computed tomography of abdomen and pelvis with oral and intravenous contrast showed a possible source of hemorrhage as a hyperdense intraluminal material within the stomach. Initial urgent esophagogastroduodenoscopy showed a large, nonbleeding distal esophageal DL, which was treated successfully with 10 mL of 1:10,000 epinephrine and bipolar cauterization with 10 Fr Gold Probe™. Hemorrhage recurred 2 d later, prompting another esophagogastroduodenoscopy, which found another DL within the gastric fundus. Treatment with epinephrine, Gold Probe™, and through-the-scope Hemoclips was unsuccessful because of difficult visualization and positioning. A subsequent attempt was made using the over-the-scope clip (OTSC) Padlock™ Clip Defect Closure System with successful hemostasis and stabilization of the patient. His hospital course was complicated by left lower lobe segmental pulmonary embolism without right heart strain for which he was discharged on 3 months of anticoagulation with apixaban. On follow-up, there was no recurrence of gastrointestinal bleeding (GIB) despite 3 months of anticoagulation. He did not complete the Basic Underwater Demolition/SEAL (BUD/S) Training. This case report demonstrates the evaluation and management of a patient with hemorrhagic shock from two DLs and sustained hemostasis with the Padlock™ OTSC in the setting of apixaban anticoagulation.

This paper focuses on the understanding of the Random Telegraph Signal (RTS) in Single-Photon Avalanche Diodes (SPAD). We studied the RTS of two different SPAD layouts, designed and implemented in a 150-nm CMOS process, after proton irradiation. The two structures are characterized by different junction types: the first structure is constituted by a P+/Nwell junction, while the second is formed by a Pwell/Niso junction. RTS occurrence has been measured in about one thousand SPAD pixels and the differences addressed in two layouts are motivated and discussed. Hypotheses on the RTS origin are drawn by analyzing the RTS time constants and the RTS occurrence evolution as a function of the annealing temperature.

Recent US guidelines recommend chlorthalidone over other thiazide-type diuretics for the treatment of hypertension based on its long half-life and proven ability to reduce CVD events. Despite recommendations most clinicians prescribe hydrochlorothiazide (HCTZ) over chlorthalidone (CTD). No randomized controlled data exist comparing these two diuretics on cardiovascular outcomes.The Diuretic Comparison Project (DCP) is a multicenter, two-arm, parallel, Prospective Randomized Open, Blinded End-point (PROBE) trial testing the primary hypothesis that CTD is superior to HCTZ in the prevention of non-fatal CVD events and non-cancer death. Patients with hypertension taking HCTZ 25 or 50 mg were randomly assigned to either continue their current HCTZ or switch to an equipotent dose of CTD. The primary outcome is time to the first occurrence of a composite outcome consisting of a non-fatal CVD event (stroke, myocardial infarction, urgent coronary revascularization because of unstable angina, or hospitalization for acute heart failure) or non-cancer death. The trial randomized 13,523 patients at 72 VA medical centers. The study is conducted by a centralized research team with site procedures embedded in the electronic health record and all data collected through administrative claims data, with no study related visits for participants. The trial will have 90% power to detect an absolute reduction in the composite event rate of 2.4%.Enrollment ended in November 2021. There are 4128 participting primary care providers and 16,595 patients individually consented to participate, 13,523 of whom were randomized.DCP should provide much needed evidence as to whether CTD is superior to HCTZ in preventing cardiovascular events in hypertensive patients.NCT02185417 [https://clinicaltrials.gov/ct2/show/NCT02185417].

The DoD Instruction 6130.03, Volume 2, outlines the retention standards for the U.S. Military, providing guidance on medical conditions and treatments that are disqualifying for all branches of the military. This document states that patients with conditions requiring immunomodulating or immunosuppressant medications do not meet retention standards. Eosinophilic esophagitis is a common, chronic inflammatory disease of the esophagus that typically presents with dysphagia. Although proton pump inhibitors are effective at treating this disease in some cases, swallowed topical steroids are the most frequently used therapy within the DoD. These medications act locally in the esophagus and do not cause systemic side effects typical of oral steroid therapy, including immunosuppression. They are effective at inducing and maintaining disease remission and are generally well tolerated, with minimal side effects. We propose a brief amendment to this document to clarify the language used and avoid inappropriate Medical Evaluation Board referrals.

This paper investigates the effects of the numerical method employed to solve the system of differential equations that characterise a closed-loop inverse kinematics (CLIK) algorithm in the discrete-time domain. The paper presents a detailed comparison between a 4th order method, namely the Runge-Kutta 4 (RK4) and the explicit Euler 1-st order method, that is the one most often used in applications. In spite of a lower complexity of the mathematical model, simulations on a 7-Degree-Of-Freedom (DOF) show that using explicit Euler produces better performance in some conditions, such as when considering a constant Cartesian reference. On the other hand, significantly lower tracking error is observed for time-varying Cartesian reference when using RK4. This method also generates smoother joint trajectories when moving through a kinematic singularity. Finally, the results suggest that the stability of the closed-loop algorithm is retained for larger gain values when using RK4.