The Ethics of Physician Migration and Their Implications for the United States

Currently, the United States trains only three quarters of the physicians it requires to fill its entry-level residency positions. The other quarter of residents employed by its hospitals is composed of immigrants who have been trained in other countries. This reliance of our healthcare system on foreign physicians puts a tremendous strain on the healthcare systems of developing nations. At the same time, by replacing American medical school graduates with graduates of foreign schools, the policy prevents a significant number of Americans who desire to practice medicine from doing so. An alarming shortage of physicians by the year 2020 has been forecasted. Discussion of how this shortage will be addressed is long overdue. The options are clear: either the United States can increase its dependence on foreign medical training programs or it can expand its own. It should choose the latter

Serendipitous Discovery of Light-Induced \u3cem\u3e(In Situ)\u3c/em\u3e Formation of An Azo-Bridged Dimeric Sulfonated Naphthol as a Potent PTP1B Inhibito

Background Protein tyrosine phosphatases (PTPs) like dual specificity phosphatase 5 (DUSP5) and protein tyrosine phosphatase 1B (PTP1B) are drug targets for diseases that include cancer, diabetes, and vascular disorders such as hemangiomas. The PTPs are also known to be notoriously difficult targets for designing inihibitors that become viable drug leads. Therefore, the pipeline for approved drugs in this class is minimal. Furthermore, drug screening for targets like PTPs often produce false positive and false negative results. Results Studies presented herein provide important insights into: (a) how to detect such artifacts, (b) the importance of compound re-synthesis and verification, and (c) how in situ chemical reactivity of compounds, when diagnosed and characterized, can actually lead to serendipitous discovery of valuable new lead molecules. Initial docking of compounds from the National Cancer Institute (NCI), followed by experimental testing in enzyme inhibition assays, identified an inhibitor of DUSP5. Subsequent control experiments revealed that this compound demonstrated time-dependent inhibition, and also a time-dependent change in color of the inhibitor that correlated with potency of inhibition. In addition, the compound activity varied depending on vendor source. We hypothesized, and then confirmed by synthesis of the compound, that the actual inhibitor of DUSP5 was a dimeric form of the original inhibitor compound, formed upon exposure to light and oxygen. This compound has an IC50 of 36 μM for DUSP5, and is a competitive inhibitor. Testing against PTP1B, for selectivity, demonstrated the dimeric compound was actually a more potent inhibitor of PTP1B, with an IC50 of 2.1 μM. The compound, an azo-bridged dimer of sulfonated naphthol rings, resembles previously reported PTP inhibitors, but with 18-fold selectivity for PTP1B versus DUSP5. Conclusion We report the identification of a potent PTP1B inhibitor that was initially identified in a screen for DUSP5, implying common mechanism of inhibitory action for these scaffolds

Medical Comorbidities and Functional Dependent Living Are Independent Risk Factors for Short-Term Complications Following Osteotomy Procedures about the Knee

© The Author(s) 2018. Objective: To characterize rates and risk factors for adverse events following distal femoral osteotomy (DFO), high tibial osteotomy (HTO), and tibial tubercle osteotomy (TTO) procedures. Design: Patients undergoing DFO, HTO, or TTO procedures during 2005 to 2016 were identified in the American College of Surgeons National Surgical Quality Improvement Program. Rates of adverse events were characterized for each procedure. Demographic, comorbidity, and procedural factors were tested for association with occurrence of any adverse events. Results: A total of 1,083 patients were identified. Of these, 305 (28%) underwent DFO, 273 (25%) underwent HTO, and 505 (47%) underwent TTO. Mean ages for patients undergoing each procedure were the following: DFO, 51 ± 23 years; HTO, 40 ± 13 years; and TTO, 31 ± 11 years. The most common comorbidities for DFO were hypertension (34%) and smoking (17%); for HTO, hypertension (22%) and smoking (21%); and for TTO, smoking (20%) and hypertension (11%). Independent risk factors for occurrence of any adverse event were age ⩾45 years for DFO (odds ratio [OR] = 3.1, P \u3c 0.001) and HTO (OR = 2.3, P = 0.029), and body mass index \u3e30 for HTO (OR = 2.5, 95% confidence interval = 1.1-5.7, P = 0.031). When all osteotomy procedures were analyzed collectively, additional variables including diabetes mellitus (OR = 2.2, P = 0.017), chronic obstructive pulmonary disease (OR = 5.5, P = 0.003), and dependent functional status (OR = 3.0, P = 0.004) were associated with adverse events. Conclusions: The total rate of adverse events was not independently associated with the type of osteotomy procedure. In addition, patients with age \u3e45, diabetes mellitus, chronic obstructive pulmonary disease, and dependent functional status have greater odds for adverse events and should be counseled and monitored accordingly

Training Traditional Birth Attendants on the Use of Misoprostol and a Blood Measurement Tool to Prevent Postpartum Haemorrhage: Lessons Learnt from Bangladesh

A consensus emerged in the late 1990s among leaders in global maternal health that traditional birth attendants (TBAs) should no longer be trained in delivery skills and should instead be trained as promoters of facility-based care. Many TBAs continue to be trained in places where home deliveries are the norm and the potential impacts of this training are important to understand. The primary objective of this study was to gain a more nuanced understanding of the full impact of training TBAs to use misoprostol and a blood measurement tool (mat) for the prevention of postpartum haemorrhage (PPH) at home deliveries through the perspective of those involved in the project. This qualitative study, conducted between July 2009 and July 2010 in Bangladesh, was nested within larger operations research, testing the feasibility and acceptability of scaling up community-based provision of misoprostol and a blood measurement tool for prevention of PPH. A total of 87 in-depth interviews (IDIs) were conducted with TBAs, community health workers (CHWs), managers, and government-employed family welfare visitors (FWVs) at three time points during the study. Computer-assisted thematic data analysis was conducted using ATLAS.ti (version 5.2). Four primary themes emerged during the data analysis, which all highlight changes that occurred following the training. The first theme describes the perceived direct changes linked to the two new interventions. The following three themes describe the indirect changes that interviewees perceived: strengthened linkages between TBAs and the formal healthcare system; strengthened linkages between TBAs and the communities they serve; and improved quality of services/service utilization. The data indicate that training TBAs and CHW supervisors resulted in perceived broader and more nuanced changes than simply improvements in TBAs\u2019 knowledge, attitudes, and practices. Acknowledgeing TBAs\u2019 important role in the community and in home deliveries and integrating them into the formal healthcare system has the potential to result in changes similar to those seen in this study

Model Based Targeting of IL-6-Induced Inflammatory Responses in Cultured Primary Hepatocytes to Improve Application of the JAK Inhibitor Ruxolitinib.

IL-6 is a central mediator of the immediate induction of hepatic acute phase proteins (APP) in the liver during infection and after injury, but increased IL-6 activity has been associated with multiple pathological conditions. In hepatocytes, IL-6 activates JAK1-STAT3 signaling that induces the negative feedback regulator SOCS3 and expression of APPs. While different inhibitors of IL-6-induced JAK1-STAT3-signaling have been developed, understanding their precise impact on signaling dynamics requires a systems biology approach. Here we present a mathematical model of IL-6-induced JAK1-STAT3 signaling that quantitatively links physiological IL-6 concentrations to the dynamics of IL-6-induced signal transduction and expression of target genes in hepatocytes. The mathematical model consists of coupled ordinary differential equations (ODE) and the model parameters were estimated by a maximum likelihood approach, whereas identifiability of the dynamic model parameters was ensured by the Profile Likelihood. Using model simulations coupled with experimental validation we could optimize the long-term impact of the JAK-inhibitor Ruxolitinib, a therapeutic compound that is quickly metabolized. Model-predicted doses and timing of treatments helps to improve the reduction of inflammatory APP gene expression in primary mouse hepatocytes close to levels observed during regenerative conditions. The concept of improved efficacy of the inhibitor through multiple treatments at optimized time intervals was confirmed in primary human hepatocytes. Thus, combining quantitative data generation with mathematical modeling suggests that repetitive treatment with Ruxolitinib is required to effectively target excessive inflammatory responses without exceeding doses recommended by the clinical guidelines

Analysis Of Adverse Event Rates Following Orthopaedic Surgery In The United States

In the setting of the recent increase in the use of nationwide databases to study rates of adverse events in orthopaedic surgery, the purposes of this thesis are three-fold. (1) To demonstrate how nationwide databases can be optimally used to answer research questions in orthopaedics. (2) To determine how the two most commonly used databases in orthopaedic research compare in terms of documented rates of comorbidities and adverse events. (3) To provide an alternative outcome to the currently dominant composite adverse event outcomes for use in orthopaedic database research. The following methods were used. (1) Patients undergoing intertrochanteric hip fracture surgery were identified and their perioperative outcomes were compared between treatment with intramedullary and extramedullary implants using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. (2) Patients undergoing lumbar fusion surgery were identified in the ACS-NSQIP and the Nationwide Inpatient Sample (NIS) and documented rates of comorbidities and adverse events were compared between databases. (3) Faculty at two large orthopaedic institutions were surveyed regarding their perceptions of severity of adverse events in orthopaedics, and their responses were used to generate a severity-weighting scheme that can be applied to orthopaedic patients in databases and used as an outcome in future database research. Findings were as follows. (1) The rates of adverse events did not differ by implant type. Postoperative length of stay was shorter with intramedullary than extramedullary implants (5.4 versus 6.5 days; p\u3c0.001). (2) There were large differences between databases in the rates at which specific comorbidities and adverse events were documented, with relative risks ranging from 0.25 to 8.47. (3) Of the 50 orthopaedic faculty who were invited to participate, 47 (94%) completed the exercise. Generated severity weights were highly disparate, ranging from 0.23% of death for urinary tract infection (least severe) to 15.14% of death for coma (most severe). Conclusions are as follows. (1) The finding of increased length of stay among patients undergoing treatment with intramedullary implants may negate or reverse the excess cost perceived to be associated with intramedullary treatment. When the optimal dataset and statistical methods are used to answer appropriate research questions in orthopaedics, databases can be a powerful research tool. (2) The differences between databases are likely the result of the very different mechanisms through which the databases collect their comorbidity and adverse event data. Findings highlight concerns regarding the validity of administratively coded data. (3) The presentation of this severity-weighted outcome score fills an important gap in orthopaedic database research methodology. Future studies may benefit from using the severity-weighted outcome score presented here

Is Insurance Status a Predictor for the Development of Nonunion Following Scaphoid Fracture?

Introduction:  Scaphoid nonunion is a common precursor to radiocarpal arthrosis. Several factors have been associated with development of scaphoid nonunion, including delayed diagnosis, inadequate initial management, proximal location, and carpal instability. We hypothesized that insurance status would also be a risk factor for development of scaphoid nonunion. Methods:  A case-control study was performed on patients who presented to a single surgeon at a tertiary referral center during the period 2006–2015. Cases were defined as patients presenting with nonunions. Controls were defined as patients presenting with primary fractures. Insurance status was characterized as underinsured if the patient lacked any type of insurance or if the patient was on Medicaid. Case/control status was tested for association with patient and fracture characteristics, including age, sex, fracture displacement, fracture location, laterality of fracture, and insurance status. Results:  A total of 71 patients were identified. Of these, 39 (55%) were nonunions (cases) and 32 (45%) were primary fractures (controls). Cases were more likely than controls to have had displaced fractures (72% versus 41%, p  = 0.008; Table 1 ). Cases were also more likely than controls to have fractures located at the proximal aspect (18% versus 0%) and less likely than controls to have fractures located at the distal aspect (0% versus 19%; p  < 0.001). Finally, cases were more likely than controls to be underinsured (46% versus 19%, odds ratio = 3.7, 95% confidence interval = 1.3–11.0, p  = 0.015, Fig. 1 ). Conclusion:  Patients presenting with nonunions were more likely than patients presenting with primary fractures to be underinsured. This finding suggests that underinsurance is a risk factor for development of nonunion. Given that delay between fracture and intervention is a known risk factor for development of nonunion, it is likely that the association between nonunion and underinsurance is mediated through this delay. Increased attention should be turned to timely and standard-of-care management of primary fractures in those who lack adequate insurance. Fig. 1 Primary fracture(controls; N  = 32) Nonunion(cases; N  = 39) P -value Age (years ± standard deviation) 29.7 ± 19.1 25.7 ± 13.5 0.302 Sex 0.482 Male 25 (78%) 33 (85%) Female 7 (22%) 6 (15%) Fracture displacement 0.008 Nondisplaced 19 (59%) 11 (28%) Displaced 13 (41%) 28 (72%) Fracture location <0.001 Proximal pole 0 (0%) 7 (18%) Mid/waist 26 (81%) 32 (82%) Distal pole 6 (19%) 0 (0%) Laterality 0.801 Left 13 (41%) 17 (44%) Right 19 (59%) 22 (56%) Insurance status 0.015 Adequately insured 26 (81%) 21 (54%) Underinsured 6 (19%) 18 (46%

The Impact of Insurance Status on the Development of Nonunion following Scaphoid Fracture

Purpose  Certain factors have been associated with the development of scaphoid nonunion, including delayed diagnosis, smoking, inadequate initial management, proximal location, and carpal instability. We hypothesized that insurance status would also be a risk factor for the development of scaphoid nonunion. Methods  A case–control study was performed on patients who presented to a single surgeon at a tertiary referral center during 2006 to 2015. Cases were patients presenting with nonunions, controls, and patients with acute fractures. Patients were characterized as underinsured if they lacked any type of insurance or if they were on Medicaid. Results  Patients (39 nonunions [cases] and 32 primary fractures [controls]) presenting with nonunions were more likely than controls to have had displaced fractures (72 vs. 41%) and fractures located at the proximal aspect of the scaphoid (18 vs. 0%), and to be underinsured (46 vs. 19%). Conclusion  Patients presenting with nonunions were more likely to be underinsured than patients presenting with primary fractures. This finding suggests that underinsurance is a risk factor for the development of nonunion. Assuming delay between fracture and intervention is a known risk factor for the development of nonunion, and it is likely that the association between nonunion and underinsurance is mediated through this delay. Level of Evidence  Prognostic, level III, case-control study

Routine Imaging after Operatively Repaired Distal Radius and Scaphoid Fractures: A Survey of Hand Surgeons

Background There is currently no standard of care for imaging after hand and upper-extremity procedures, and current imaging practices have not been characterized. Questions/Purposes To characterize current imaging practices and to compare those practices to the best available evidence. Patients and Methods A survey was distributed to attending-level surgeons at a regional hand and upper-extremity surgery conference in the United States in 2013. 40 out of 75 surgeons completed the survey (53%). Results All results are presented for distal radius and scaphoid fractures, respectively. There was a high degree of variability between respondents in the number of radiographic series routinely ordered during follow-up of asymptomatic patients, with the number of series ranging from 1–6 and 1–6. On average, respondents did not order an excessive number of follow-up radiographs for asymptomatic patients, with means (± standard deviations) of 2.6 ± 1.0 and 3.3 ± 1.2 radiographic series. Radiographic series were taken at only 74% and 81% of postoperative visits with asymptomatic patients. Only 10% and 8% of respondents felt it was acceptable medical practice to save costs by ordering postoperative radiographs only when patients are symptomatic. Conclusions Among a sample of 40 fellowship-trained hand surgeons, these findings demonstrate a high degree of variability in number of radiographs obtained after operative repair of distal radius and scaphoid fractures. On average, respondents were relatively efficient with respect to total number of postoperative radiographs ordered. Level of Evidence Diagnostic study, level IV