Search

Purpose: The MER proto-oncogene tyrosine kinase (MERTK) helps maintain the homeostasis of the retinal pigmented epithelium (RPE). Additionally, MERTK regulates the innate immune system. As such inhibition of MERTK has gained recent interest as a target for cancer therapeutics. Herein, we present on MERTK inhibitor associated retinal toxicity in a human., Methods: A 43-year-old male with past medical history of esophageal adenocarcinoma was enrolled in a trial studying the MERTK inhibitor PF-07265807. As part of the study protocol, the patient was seen every two to three weeks for dilated fundus exams and ancillary testing. Data on the patient's relevant past medical history, ophthalmic exam findings, and imaging performed at baseline and subsequent ophthalmology visits was obtained via retrospective chart review., Results: At the patient's baseline visit, his dilated exam and testing were normal. Seven months after starting the MERTK inhibitor the patient developed subtle but reproducible signs of retinal toxicity with disruption of the extrafoveal ellipsoid zone on optical coherence tomography and extrafoveal hyper-autofluorescence on short wavelength fundus autofluorescence. The patient's vision remained stable throughout the study; however, the medication was stopped due to the unknown ocular effects as well as progression of the patient's cancer., Discussion: Patients taking MERTK inhibitors should be monitored by an ophthalmologist while on the drug. If toxicity develops, discussion of whether to continue the medication should take place between the patient, ophthalmologist, and oncologist, with consideration of the risks of vision loss versus benefits of taking the medication from a cancer perspective., Competing Interests: Conflicts of Interest: The authors have no conflicts to declare.

Purpose: To determine which spectral domain optical coherence tomography biomarkers of idiopathic macular hole (MH) correlate with the postoperative best-corrected visual acuity (BCVA) in anatomically closed MH., Methods: Retrospective analysis of spectral domain optical coherence tomography scans of 44 patients presenting with MH followed for a mean of 17 months. Widths of MH aperture, base, and ellipsoid zone disruption were calculated from presenting foveal spectral domain optical coherence tomography B-scans. Macular hole base area and ellipsoid zone disruption area were calculated through the custom in-house software., Results: Poorer postoperative BCVA correlated with increased preoperative choroidal hypertransmission (r = 0.503, P = 0.0005), minimum diameter (r = 0.491, P = 0.0007), and base diameter (r = 0.319, P = 0.0348), but not with preoperative ellipsoid zone width (r = 0.199, P = 0.2001). Applying en-face analysis, the BCVA correlated weakly with preoperative ellipsoid zone loss area (r = 0.380, P = 0.013), but not with preoperative MH base area (r = 0.253, P = 0.1058)., Conclusion: Increased MH minimum diameter, base diameter, base area, and choroidal hypertransmission are correlated with a poorer postoperative BCVA. Ellipsoid zone loss measurements were not consistently correlated with a BCVA. Choroidal hypertransmission width may be an easy-to-visualize predictive imaging biomarker in MH surgery.

Clinicians are bombarded with information daily by social media, mainstream television news, e-mail, and print and online reports. They usually do not have much control over these information streams and thus are passive recipients, which means they get more noise than signal. Accessing, absorbing, organizing, storing, and retrieving useful medical information can improve patient care. The authors outline how to create a personalized stream of relevant information that can be scanned regularly and saved so that it is readily accessible., (Copyright © 2016 Cleveland Clinic.)

For all its traditional successes, the current model of medical education in the United States and Canada is being challenged on issues of quality, throughput, and cost, a process that has exposed numerous shortcomings in its efforts to meet the needs of the nations' health care systems. A radical change in direction is required because the current path will not lead to a solution.The 2010 publication Educating Physicians: A Call for Reform of Medical School and Residency identifies several goals for improving the medical education system, and proposals have been made to reform medical education to meet these goals. Enacting these recommendations practically and efficiently, while training more health care providers at a lower cost, is challenging.To advance solutions, the authors review innovations that are disrupting higher education and describe a vision for using these to create a new model for competency-based, learner-centered medical education that can better meet the needs of the health care system while adhering to the spirit of the above proposals. These innovations include collaboration amongst medical schools to develop massive open online courses for didactic content; faculty working in small groups to leverage this online content in a "flipped-classroom" model; and digital badges for credentialing entrustable professional activities over the continuum of learning.

Background: Healthcare institutions spend enormous time and effort to train their workforce. Web-based training can potentially streamline this process. However the deployment of web-based training in a large-scale setting with a diverse healthcare workforce has not been evaluated. The aim of this study was to evaluate the satisfaction of healthcare professionals with web-based training and to determine the predictors of such satisfaction including age, education status and computer proficiency., Methods: Observational, cross-sectional survey of healthcare professionals from six hospital systems in an integrated delivery network. We measured overall satisfaction to web-based training and response to survey items measuring Website Usability, Course Usefulness, Instructional Design Effectiveness, Computer Proficiency and Self-learning Attitude., Results: A total of 17,891 healthcare professionals completed the web-based training on HIPAA Privacy Rule; and of these, 13,537 completed the survey (response rate 75.6%). Overall course satisfaction was good (median, 4; scale, 1 to 5) with more than 75% of the respondents satisfied with the training (rating 4 or 5) and 65% preferring web-based training over traditional instructor-led training (rating 4 or 5). Multivariable ordinal regression revealed 3 key predictors of satisfaction with web-based training: Instructional Design Effectiveness, Website Usability and Course Usefulness. Demographic predictors such as gender, age and education did not have an effect on satisfaction., Conclusion: The study shows that web-based training when tailored to learners' background, is perceived as a satisfactory mode of learning by an interdisciplinary group of healthcare professionals, irrespective of age, education level or prior computer experience. Future studies should aim to measure the long-term outcomes of web-based training.

Although e-mail is supposed to help save time and increase efficiency, for many it has become a burden. You can fight e-mail overload by taking steps to decrease the amount of unwanted e-mail you receive and by managing your in-box in an organized manner.

Electronic health records (EHRs) offer a number of advantages over the old paper record. They have the potential to improve the quality of patient care, reduce the cost of health care, and expedite the transfer of information. Yet fewer than 20% of hospitals and physician practices now use them. We discuss the advantages of EHRs, reasons for adopting this system, current barriers to the adoption of EHRs, and issues to consider when choosing a system.

The synthesis of the enantiomers of bupropion, (rac)-2-tert-butylamino-3'-chloropropiophenone 1 (Wellbutrin) is described. The enantiomers were compared with the racemate in both the tetrabenazine-induced sedation model and the inhibition of uptake of biogenic amine assay. No significant differences were found in their potencies to reverse tetrabenazine-induced sedation in mice or in their IC50 values as inhibitors of biogenic amine uptake into nerve endings obtained from mouse brain.

A radioimmunoassay (RIA) procedure for the quantification of bupropion (dl-2-tert-butylamino-3'-chloropropiophenone) in biological fluids is described. Immunization of rabbits with conjugates of bovine serum albumin and p-succinoyl propylbupropion or p-carbomethoxybupropion resulted in the production of antisera which are capable of detecting less than 1 ng ml-1 (100 pg actual mass) of bupropion in the RIA, utilizing [6-3H] bupropion as radioligand. The antisera used in these studies have low cross-reaction (approximately 0.1% or less) with known side chain metabolites of bupropion, but exhibit significant cross-reaction with p-hydroxybupropion (30.3%). Excellent agreement was obtained between RIA and high-pressure liquid chromatography determinations of bupropion concentrations in human plasma samples, but plasma or serum from bupropion-treated dogs, rats and mice required extraction from basic medium to remove some interference before RIA. The assay was applied to a study of bupropion disposition in two beagles of each sex after i.v. and p.o. administrations of bupropion hydrochloride (100 mg). The pharmacokinetic profile in dogs was best described by an open two-compartment model after either route of drug administration. Peak plasma bupropion levels after oral dosing were highly variable, ranging from 12.9 to 63.5 ng ml-1 at 26 to 32 min after drug administration. The mean terminal phase half-life of bupropion was calculated to be 1.73 hr after either route and the absolute oral bioavailability of the drug varied from 2.0 to 6.5%.

A selected group of alkoxy- and halogen-substituted 5-benzylidino- and 5-benzylhydantoins was prepared and screened for anticonvulsant activity as measured by the ability of the compound to prevent maximal electroshock and metrazol-induced threshold clonic seizures in rats. The structure-activity studies revealed 5-[3-(trifluoromethyl)benzyl]hydantoin (14) to be the most potent member of the series.

The chemical structure and synthesis of bupropion are described and compared with typical polycyclic antidepressants to point up the novelty and simplicity of this drug. The features of bupropion's substructure are discussed to help in understanding the observed pharmacological differences among bupropion, tricyclic antidepressants, and psychostimulants.

The synthesis of a hapten useful in the radioimmunoassay of bupropion is described. Since bupropion has no functional group that can be easily derivatized, a hydroxypropyl group was incorporated into the molecule. Studies in cross-reactivity with possible metabolites required the synthesis of the 4'-hydroxy analogue of bupropion. This synthesis is also described.