Surgeon Migration Between Developing Countries and the United States: Train, Retain, and Gain from Brain Drain

Background

The critical shortage of surgeons in many low- and middle-income countries (LMICs) prevents adequate responses to surgical needs, but the factors that affect surgeon migration have remained incompletely understood. The goal of this study was to examine the importance of personal, professional, and infrastructural factors on surgeon migration from LMICs to the United States. We hypothesized that the main drivers of surgeon migration can be addressed by providing adequate domestic surgical infrastructure, surgical training programs, and viable surgical career paths.

Methods

We conducted an internet-based nationwide survey of surgeons living in the US who originated from LMICs.

Results

66 surgeons completed the survey. The most influential factors for primary migration were related to professional reasons (p ≤ 0.001). Nonprofessional factors, such as concern for remuneration, family, and security were significantly less important for the initial migration decisions, but adopted a more substantial role in deciding whether or not to return after training in the United States. Migration to the United States was initially considered temporary (44 %), and a majority of the surveyed surgeons have returned to their source countries in some capacity (56 %), often on multiple occasions (80 %), to contribute to clinical work, research, and education.

Conclusions

This study suggests that surgically oriented medical graduates from LMICs migrate primarily for professional reasons. Initiatives to improve specialist education and surgical infrastructure in LMICs have the potential to promote retention of the surgical workforce. There may be formal ways for LMICs to gain from the international pool of relocated surgeons.     

Affinin and hexahydroaffinin: Chemistry and toxicological profile

The present work aimed to determine the safety parameters of two new alkamides, affinin and hexahydroaffinin, with antinociceptive activity. To predict the preliminary acute toxicity, we used the acute and subchronic toxicity (50 mg/kg, orally [po]) in Swiss Webster mice. Genotoxicity assayed via analysis of cell micronuclei of the femoral bone marrow in mice; at the same time, metabolic parameters determined from peripheral blood samples. Furthermore, to discard the neuropharmacological effects, we assessed the ambulatory activity in mice to determine the possible effects in the central nervous system. Finally, we used capsaicin as a positive control of alkamides. According to our results, hexahydroaffinin (LD₅₀ ≥ 5,000 mg/kg, po) is significantly less noxious than affinin (LD₅₀ = 1,442.2 mg/kg, po) or capsaicin (LD₅₀ = 489.9 mg/kg, po). In subchronic administration, we did not observe any changes in hematological or biochemical parameters in any compound analyzed from peripheral blood samples. Finally, the data from the genotoxicity assay showed micronuclei formation in 28%, 5%, and 3% of mice in the capsaicin, affinin, and hexahydroaffinin groups, respectively. With the results obtained in the present investigation, we suggest that affinin and hexahydroaffinin are not only useful candidates for possible new drugs but also safe compounds.     

Head-to-head comparison between the EQ-5D-5L and the EQ-5D-3L in general population health surveys

Background

The EQ-5D has been frequently used in national health surveys. This study is a head-to-head comparison to assess how expanding the number of levels from three (EQ-5D-3L) to five in the new EQ-5D-5L version has improved its distribution, discriminatory power, and validity in the general population.

Methods

A representative sample (N?=?7554) from the Catalan Health Interview Survey 2011–2012, aged ≥18, answered both EQ-5D versions, and we evaluated the response redistribution and inconsistencies between them. To assess validity of this redistribution, we calculated the mean of the Visual Analogue Scale (VAS), which measures perceived health. The discriminatory power was examined with Shannon Indices, calculated for each dimension separately. Spanish preference value sets were applied to obtain utility indices, examining their distribution with statistics of central tendency and dispersion. We estimated the proportion of individuals reporting the best health state in EQ-5D-5L and EQ-5D-3L within groups of specific chronic conditions and their VAS mean.

Results

A very small reduction in the percentage of individuals with the best health state was observed, from 61.8% in EQ-5D-3L to 60.8% in EQ-5D-5L. In contrast, a large proportion of individuals reporting extreme problems in the 3 L version moved to severe problems (level 4) in the 5 L version, particularly for pain/discomfort (75.5%) and anxiety/depression (66.4%). The average proportion of inconsistencies was 0.9%. The pattern of the perceived health VAS mean confirmed the hypothesis established a priori, supporting the validity of the observed redistribution. Shannon index showed that absolute informativity was higher in the 5 L version for all dimensions. The means (SD) of the Spanish EQ-5D-3L and EQ-5D-5L indices were 0.87 (0.25) and 0.89 (0.22). The proportion of individuals with the best health state within each specific chronic condition was very similar, regardless of the EQ-5D version (≤?30% in half of the 28 chronic conditions).

Conclusion

Although the proportion of individuals with the best possible health state is still very high, our findings support that the increase of levels provided by the EQ-5D-5L contributed to the validity and discriminatory power of this new version to measure health in general population, as in the national health surveys.

     

Improved pharmacokinetic profile of lipophilic anti-cancer drugs using ανβ3-targeted polyurethane-polyurea nanoparticles

Glutathione degradable polyurethane-polyurea nanoparticles (PUUa NP) with a disulfide-rich multiwalled structure and a cyclic RGD peptide as a targeting moiety were synthesized, incorporating a very lipophilic chemotherapeutic drug named Plitidepsin. In vitro studies indicated that encapsulated drug maintained and even improved its cytotoxic activity while in vivo toxicity studies revealed that the maximum tolerated dose (MTD) of Plitidepsin could be increased three-fold after encapsulation. We also found that pharmacokinetic parameters such as maximum concentration (Cmax), area under the curve (AUC) and plasma half-life were significantly improved for Plitidepsin loaded in PUUa NP. Moreover, biodistribution assays in mice showed that RGD-decorated PUUa NP accumulate less in spleen and liver than non-targeted conjugates, suggesting that RGD-decorated nanoparticles avoid sequestration by macrophages from the reticuloendothelial system. Overall, our results indicate that polyurethane-polyurea nanoparticles represent a very valuable nanoplatform for the delivery of lipophilic drugs by improving their toxicological, pharmacokinetic and whole-body biodistribution profiles.     

Plasma troponins as markers of myocardial damage during cardiac surgery with extracorporeal circulation

All types of cardiac surgery involve considerable injury to the myocardium. However, it is difficult to differentiate, in the immediate post-operative state, between ischemic alterations associated with the cardiac surgery itself and the pathological alterations of a peri-operative myocardial infarction. The diagnosis of damaged myocardium, classically performed with the enzymatic markers creatine kinase (CK) and its muscle fraction (CK-MB), has become more precise with the option of measuring cardiac troponins T and I. We measured these markers in 58 patients undergoing elective cardiac surgery with extra-corporeal circulation (ECC). The patients included 37 cases undergoing valve surgery, 14 for coronary revascularization, 6 for mixed procedures, and 1 for closure of an inter-atrial communication. The markers were measured in plasma at baseline (at anesthesia initiation), 5 min post-ECC commencement, following aorta de-clamping, during the surgical closure, and 6, 18 and 42 hrs after surgery. All the markers were increased significantly relative to the baseline values. Troponin I, CK and CK-MB values peaked between 6 and 18 hrs after surgery, troponin T between 18 and 42 hrs, and myoglobin at the surgical closure. The values of all markers were higher in patients undergoing coronary surgery compared to those in patients undergoing valve surgery. In the evaluation of myocardial damage after surgery, the measurement of classical markers such as CK and myoglobin remain valid, but other markers such as troponins provide significant additional diagnostic benefit and, thus, need to be included in the routine biochemical measurements for monitoring myocardial damage associated with the surgical procedure.     

Effectiveness of manual lymphatic drainage vs. perineal massage in secundigravida women with gestational oedema: A randomised clinical trial

Perineal trauma (PT) may be considered as a very common injury during the childbirth. The incidence of PT was estimated in 30% to 85%, with 60% to 70% requiring suture. The present study was a prospective, single‐blinded, randomised, clinical trial carried out from January 2015 to January 2016. For this study, 49 secundigravida women diagnosed with gestational oedema were recruited and randomly divided into two groups (A and B). Group A (n = 30) received the conventional treatment plus perineal massage and group B (n = 19) the conventional treatment plus manual lymphatic drainage (MLD). Visual analogue scale (VAS) and King Health's Questionnaire (KHQ) were performed to assess pain intensity and quality of life‐related with urinary incontinence (UI). Pain intensity measurements showed statistically significant differences for a decrease after 30‐weeks (P = .037), after 36‐weeks (P = .000), and at the end of puerperium (P = .014) for MLD with respect to perineal massage group. Moreover, inter‐groups repeated measures ANOVA for the values related statistically significant differences to the interaction of each applied treatment (perineal massage and MLD group, separately) over the pain intensity variable. MLD treatment reduced pain intensity with respect to perineal massage in secundigravida women with gestational oedema from 25‐weeks of gestation to the end of puerperium.     

Exaggerated Waiting Impulsivity Associated with Human Binge Drinking,and High Alcohol Consumption in Mice

There are well-established links between impulsivity and alcohol use in humans and animal models; however, whether exaggerated impulsivity is a premorbid risk factor or a consequence of alcohol intake remains unclear. In a first approach, human young (18–25 years) social binge and non-binge drinkers were tested for motor impulsivity and attentional abilities in a human version of the Five-Choice Serial Reaction Time Task (Sx-5CSRTT), modeled on the rodent 5CSRTT. Participants completed four variants of the Sx-5CSRT, in addition to being screened for impulsive traits (BIS-11 questionnaire) and impulsive behavior (by means of the Delay Discounting Questionnaire, Two-Choice Impulsivity Paradigm (TCIP), Stop Signal Reaction Time, and Time Estimation Task). Using a second approach, we compared one of these impulsivity measures, 5CSRTT performance, in two inbred strains of mice known to differ in alcohol intake. Compared with non-bingers (NBD; n=22), binge drinkers (BD, n=22) showed robust impairments in attention and premature responding when evaluated under increased attentional load, in addition to presenting deficits in decision making using the TCIP. The best predictors for high binge drinking score were premature responding in the Sx-5CSRTT, trait impulsivity in the BIS-11, and decision making in the TCIP. Alcohol-naïve C57BL/6J (B6) mice (alcohol preferring) were more impulsive in the 5CSRTT than DBA2/J (D2) mice (alcohol averse); the degree of impulsivity correlated with subsequent alcohol consumption. Homologous measures in animal and human studies indicate increased premature responding in young social BD and in the ethanol-preferring B6 strain of mice.Impulsivity has been consistently implicated as both a determinant and a consequence of alcohol abuse. Binge patterns of alcohol consumption, in particular, have been associated with impaired attentional function and executive function (Scaife and Duka, 2009; Townshend and Duka, 2005), and increased impulsive behavior in both humans and rodent models (Bell et al, 2013; Duka et al, 2003; Stephens and Duka, 2008). However, it is unclear whether high levels of impulsivity are a cause or consequence of alcohol intake.Given the prevalence of binge drinking in adolescence (Healey et al, 2014), the first aim of our study was to examine the relationship of binge drinking to measures of waiting impulsivity and attentional abilities in human adolescents (18–25 years old) and in rodents, which consume alcohol. Taking the rodent 5CSRTT (Robbins, 2002) as a model, we developed a novel, iPad-based task (Sussex 5CSRTT; Sx-5CSRTT), to assess both attentional performance and anticipatory behavior in humans. BD were also characterized in four additional measures of impulsivity, based on different operational definitions of the construct. The Stop Signal Task, used to assess ability to inhibit a prepotent response (Logan, 1994), served as an additional measure of ‘motoric impulsivity''. The Delay Discounting Questionnaire measured preference for immediate over-delayed rewards (Petry, 2001) and, combined with the Two-Choice Impulsivity paradigm (Dougherty et al, 2005), provided an index of ‘choice'' impulsivity or decision making; the fourth behavioral measure used was the Time Estimation Task. Although each of these five measures has been used in the clinical context as an index of impulsive behavior, the sensitivity of each task to characterize impulsive phenotype in young social BD, and their relationship to one another has not been explored. We anticipated binge drinking might be differentially associated with different aspects of impulsive behavior, but generally that high binge drinking scores would be associated with high levels of trait and behavioral motor impulsivity and aversion to delay.The role of premorbid impulsivity as a predictor of elevated alcohol intake cannot be easily disentangled in human studies, as impulsivity measures are almost inevitably assessed after a period of alcohol use. Animal models are more powerful tools in this respect as they allow the exclusion of alcohol experience as a potential contributor to impulsivity. Therefore, having established that 5CSRTT waiting impulsivity was associated with human binge drinking, we asked whether waiting impulsivity in alcohol-naïve mice predicted alcohol drinking in two widely used B6 and D2 inbred strains, that also differ in alcohol consumption (Crabbe et al, 1994). We have previously reported (Walker et al, 2011) that prior exposure to high alcohol concentrations over several weeks in adulthood has only transitory effects in increasing impulsivity in B6 mice. We predicted greater impulsivity in the high-ethanol-preferring mice indicating a potential causal relationship between waiting impulsivity and high alcohol consumption.Using homologous measures of impulsivity in mouse and humans, we provide evidence that waiting impulsivity is associated with binge drinking in young adult humans, and predicts alcohol consumption in mice.