Diversity in Dermatology? An Assessment of Undergraduate Medical Education.

BACKGROUND: A lack of representation of skin of color (SoC) in dermatology curricula is well-documented across North American medical schools and may present a barrier to equitable and comprehensive undergraduate medical education. OBJECTIVES: This study aims to examine representation in dermatologic educational materials and appreciate a link between bias in dermatologic education and student diagnostic ability and self-rated confidence. DESIGN: The University of Toronto Dermatology Undergraduate Medical Education curriculum was examined for the percentage photographic representation of SoC. A survey of 10 multiple-choice questions was administered to first- and third-year medical students at the University of Toronto to assess diagnostic accuracy and self-rated confidence in diagnosis of 5 common skin lesions in Fitzpatrick skin phototypes (SPT) I-III (white skin) and VI-VI (SoC). RESULTS: The curriculum audit showed that <7% of all images of skin disease were in SoC. Diagnostic accuracy was fair for both first- (77.8% and 85.9%) and third-year (71.3% and 72.4%) cohorts in white skin and SoC, respectively. Students' overall self-rated confidence was significantly greater in white skin when compared to SoC, in both first- (18.75/25 and 17.78/25, respectively) and third-year students (17.75/25 and 15.79/25, respectively) (P = .0002). CONCLUSIONS: This preliminary assessment identified a lack of confidence in diagnosing dermatologic conditions in SoC, a finding which may impact health outcomes of patients with SoC. This project is an important first step in diversifying curricular materials to provide comprehensive medical education.

Melanoma incidence, stage, and survival after solid organ transplant: A population-based cohort study in Ontario, Canada.

BACKGROUND: Risk of melanoma is increased with potentially worse outcomes after solid organ transplant. OBJECTIVE: To estimate the incidence, stage, and survival in transplant recipients with melanoma. METHODS: Population-based, retrospective, observational study using linked administrative databases. Adults receiving their first solid organ transplant from 1991 through 2012 were followed to December 2013. RESULTS: We identified 51 transplant recipients with melanoma, 11 369 recipients without melanoma, and 255 matched patients with melanoma from the nontransplant population. Transplant recipients were at increased risk of melanoma (standardized incidence ratio, 2.29; 95% confidence interval [CI], 2.07-2.49) and more likely to be diagnosed at stages II through IV (adjusted odds ratio, 4.29; 95% CI, 2.04-9.00) compared with the nontransplant population. Melanoma-specific mortality was increased in transplant recipients compared with the nontransplant population (adjusted hazard ratio, 1.93; 95% CI, 1.03-3.63). Among transplant recipients, all-cause mortality was increased after melanoma compared with those without melanoma (stage T1/T2: adjusted hazard ratio, 2.18; 95% CI, 1.13-4.21; T3/T4: adjusted hazard ratio, 4.07; 95% CI, 2.36-7.04; III/IV: adjusted hazard ratio, 7.92; 95% CI, 3.76-16.70). LIMITATIONS: The databases did not contain data on immunosuppressive drugs; ascertainment of melanoma metastasis relied on pathology reports. CONCLUSION: Melanoma after solid organ transplant is more often diagnosed at a later stage and leads to increased mortality, even for early-stage tumors.

Early Introduction of Dermatology Clinical Skills in Medical Training.

BACKGROUND: Skin diseases are among the most common diseases encountered by healthcare professionals. Despite this, dedicated dermatology teaching is limited in most Canadian medical school training programs. This is especially true of clinical skills training. OBJECTIVES: To determine the impact of early introduction of dermatology clinical skills in Canadian undergraduate medical training. Secondary objectives included examining the impact of having sessions co-led by a clinician with expertise in the field of dermatology. METHODS: A half-day dermatology clinical skills session was introduced in the University of Toronto preclerkship medical school during the dermatology week. Sessions were co-led by staff or resident dermatologists. Sessions were evaluated using student pre- and postclinical skills test scores, as well as experience questionnaires completed by both tutors and students. RESULTS: The clinical skills session was well received by both students and tutors, with no cumulative score less than 4.34 on a 5-point Likert scale. The majority of students agreed or strongly agreed that the introduction of clinical skills in the early years of the curriculum facilitated learning consolidation (99.5%). Comparison of pre- and post-test scores showed that students' dermatology comprehension improved by an average of 12.1% following completion of the session. In questionnaire responses, students and nondermatology co-tutors emphasized the impact of having an expert in the field of dermatology co-lead the session. CONCLUSIONS: Students valued early clinical skills exposure to dermatology and felt it enhanced their knowledge and abilities. This study demonstrates learning consolidation when dermatologic didactic teachings are paired with practical clinical skills sessions.

Case-Based Learning in Dermatology.

IMPORTANCE: The instruction of dermatology can be challenging due to its large scope, heavy clinical nature, and limited curriculum space. Case-based learning (CBL) is an emerging education paradigm and has no current literature on its use in dermatology. OBJECTIVES: Assess CBL in undergraduate dermatology medical education. METHODS: Case-based learning was implemented in the preclerkship dermatology curriculum at the University of Toronto to 3 student cohorts (totaling 710 students and 93 tutors) between May 2016 and April 2017. We analyzed assignment performance, pre- and post-CBL knowledge test scores, and experience surveys on students and tutors. Surveys were evaluated using aggregate descriptive statistics for quantitative data and thematic data analysis for qualitative data. All assessments were anonymous and voluntary. RESULTS: We received strong positive feedback on the CBL experience, with no score less than 3.8 on a 5-point scale (where 5 indicated strongly agree with a positively phrased question). Thematic data analysis revealed several key themes, including positive comments for a specialist tutor, the use of visual media, and the "mini-cases" style of CBL, while challenges included a lack of motivation. Group assignments scored high, ranging from 88.9% to 99.3%. Tracked pre- and post-CBL knowledge test scores showed a 32% (from 42% to 74%) increase in scores after the CBL experience. Conclusion and Relevance: CBL in dermatology medical education was well received by students and tutors, with high scores in content evaluation and knowledge assessment. Future studies should examine optimal delivery methods and its long-term effects on knowledge retention.

Systematic review of melanoma incidence and prognosis in solid organ transplant recipients.

Cutaneous melanoma carries the potential for substantial morbidity and mortality in the solid organ transplant population. We systematically reviewed the literature published from January 1995 to January 2012 to determine the overall relative risk and prognosis of melanoma in transplant recipients. Our search identified 7,512 citations. Twelve unique non-overlapping studies reported the population-based incidence of melanoma in an inception cohort of solid organ transplant recipients. Compared to the general population, there is a 2.4-fold (95% confidence interval, 2.0 to 2.9) increased incidence of melanoma after transplantation. No population-based outcome data were identified for melanoma arising post-transplant. Data from non-population based cohort studies suggest a worse prognosis for late-stage melanoma developing after transplantation compared with the general population. For patients with a history of pre-transplant melanoma, one population-based study reported a local recurrence rate of 11% (2/19) after transplantation, although staging and survival information was lacking. There is a need for population-based data on the prognosis of melanoma arising pre- and post-transplantation. Increased incidence and potentially worse melanoma outcomes in this high-risk population have implications for clinical care in terms of prevention, screening and reduction of immunosuppression after melanoma development post-transplant, as well as transplantation decisions in patients with a history of pre-transplant melanoma.

Facial nerve danger zone in dermatologic surgery: temporal branch.

BACKGROUND: The principal function of cranial nerve 7 (CN VII), the facial nerve, is to provide motor innervation to the muscles of facial expression. The temporal branch of the facial nerve primarily innervates the frontalis muscle, which raises the eyebrow. OBJECTIVE: To present a case that illustrates the importance of facial nerve anatomy to skin surgery practice. CONCLUSION: The relevant surgical anatomy of the temporal branch is reviewed, as well as clinical practice points around nerve damage in skin surgery.

Cutaneous adverse drug reactions in children: an analysis of reports from the Canadian Pharmacogenomics Network for Drug Safety (CPNDS).

Cutaneous adverse drug reactions (CADRs) are the most prevalent adverse drug reactions (ADRs) in hospitalized children, with an estimated rate of 2-3%. The Canadian Pharmacogenomics Network for Drug Safety (CPNDS) is a pan-Canadian active surveillance network identifying genomic biomarkers of risk for serious ADRs. The purpose of this paper is to describe the characteristics of paediatric CADR cases reported to the CPNDS from February 2005 to December 2008. The CPNDS database was mined and details of CADRs and key clinical data from cases were extracted. Reports were individually analyzed and classified in two main groups: severe and non-severe CADRs, with subcategories. In total, 326 CADR cases were included in the study; 214 (65.6%) severe and 112 (34.4%) non-severe CADRs. Overall L-asparaginase (n=56, 16%), amoxicillin (n=29, 8.3%), cotrimoxazole (n=25, 7.2%), carbamazepine (n=17, 4.9%) and lamotrigine (n=13, 3.7%) accounted for 40% of all suspected medications. We have demonstrated the ability to comprehensively collect clinical data on a wide range of severe and non-severe CADRs to drugs commonly used in the care of children. Our study provides additional real world evidence to promote the proactive detection, collection, reporting and assessment of CADRs in children.

Effects of (18)O isotopic substitution on the rotational spectra and potential splitting in the OH-OH2 complex: improved measurements for (16)OH-(16)OH2 and (18)OH-(18)OH2, new measurements for the mixed isotopic forms, and ab initio calculations of the (2)A'-(2)A" energy separation.

Rotational spectra have been observed for (16)OH-(16)OH(2), (16)OH-(18)OH(2), (18)OH-(16)OH(2), and (18)OH-(18)OH(2) with complete resolution of the nuclear magnetic hyperfine structure from the OH and water protons. Transition frequencies have been analyzed for each isotopic form using the model of Marshall and Lester [J. Chem. Phys. 121, 3019 (2004)], which accounts for partial quenching of the OH orbital angular momentum and the decoupling of the electronic spin from the OH molecular axis. The analysis accounts for both the ground ((2)A(')) and first electronically excited ((2)A(")) states of the system, which correspond roughly to occupancy by the odd electron in the p(y) and p(x) orbitals, respectively (where p(y) is in the mirror plane of the complex and p(x) is perpendicular to p(y) and the OH bond axis). The spectroscopic measurements yield a parameter, rho, which is equal to the vibrationally averaged (2)A(')-(2)A(") energy separation that would be obtained if spin-orbit coupling and rotation were absent. For the parent species, rho = -146.560 27(9) cm(-1). (18)O substitution on the water increases /rho/ by 0.105 29(10) cm(-1), while substitution on the OH decreases /rho/ by 0.068 64(11) cm(-1). In the OH-OH(2) complex, the observed value of rho implies an energy spacing between the rotationless levels of the (2)A(') and (2)A(") states of 203.76 cm(-1). Ab initio calculations have been performed with quadratic configuration interaction with single and double excitations (QCISD), as well as multireference configuration interaction (MRCI), both with and without the inclusion of spin-orbit coupling. The MRCI calculations with spin-orbit coupling perform the best, giving a value of 171 cm(-1) for the (2)A(')-(2)A(") energy spacing at the equilibrium geometry. Calculations along the large-amplitude bending coordinates of the OH and OH(2) moieties within the complex are presented and are shown to be consistent with a vibrational averaging effect as the main cause of the observed isotopic sensitivity of rho.

Mesenteric angiography for the localization and treatment of acute lower gastrointestinal bleeding.

BACKGROUND: There is limited evidence regarding the effectiveness and complications of mesenteric angiography in the diagnosis and management of acute lower gastrointestinal bleeding (ALGIB). Our objective was to determine the complications and outcomes of mesenteric angiography in patients with ALGIB and to identify predictors of a positive result at angiography. METHODS: We identified and reviewed the records of all patients who underwent mesenteric angiography for ALGIB at our institution during a 10-year period. We compared potential predictors of positive versus negative angiograms. RESULTS: Of 47 mesenteric angiograms in 35 patients, 22 (47%, 95% confidence interval [CI] 33%-61%) revealed a source of bleeding, most commonly the colon. Hematomas developed in the groins of 3 patients (6.4%, 95% CI 0%-18%), and 1 of these patients also experienced a myocardial infarction during the procedure. None of the potential predictors were significantly associated with a positive result at angiography, although the confidence intervals were wide. Twenty patients (57%, 95% CI 41%-74%) continued to bleed after the angiogram, and 18 of the patients (51%, 95% CI 35%-68%) were discharged without a definitive diagnosis. CONCLUSION: With a diagnostic success of about 50%, mesenteric angiography may play an important part in the diagnosis and management of patients with ALGIB; however, one or more large, prospective multicentre studies are needed to more clearly define its role. Canadian surgeons have the opportunity to initiate collaborative multicentre studies to address such diagnostic and therapeutic clinical questions.

Assessment of the accuracy of density functionals for prediction of relative energies and geometries of low-lying isomers of water hexamers.

Water hexamers provide a critical testing ground for validating potential energy surface predictions because they contain structural motifs not present in smaller clusters. We tested the ability of 11 density functionals (four of which are local and seven of which are nonlocal) to accurately predict the relative energies of a series of low-lying water hexamers, relative to the CCSD(T)/aug'-cc-pVTZ level of theory, where CCSD(T) denotes coupled cluster theory with an interative treatment of single and double excitations and a quasi-perturbative treatment of connected triple excitations. Five of the density functionals were tested with two different basis sets, making a total of 16 levels of density functional theory (DFT) tested. When single-point energy calculations are carried out on geometries obtained with second-order Møller-Plesset perturbation theory (MP2), only three density functionals, M06-L, M05-2X, and M06-2X, are able to correctly predict the relative energy ordering of the hexamers. These three functionals predict that the range of energies spanned by the six isomers is 3.2-5.6 kcal/mol, whereas the other eight functionals predict ranges of 1.0-2.4 kcal/mol; the benchmark value for this range is 3.1 kcal/mol. When the hexamers are optimized at each level of theory, all methods are able to reproduce the MP2 geometries well for all isomers except the boat and bag isomers, and DFT optimization changes the energy ordering for seven of the 16 methods tested. The addition of zero-point energy changes the energy ordering for all of the density functionals studied except for M05-2X and M06-2X. The variation in relative energies predicted by the different methods highlights the necessity for exercising caution in the choice of density functionals used in future studies. Of the 11 density functionals tested, the most accurate results for energies were obtained with the PWB6K, MPWB1K, and M05-2X functionals.

Assessment of multicoefficient correlation methods, second-order Møller-Plesset perturbation theory, and density functional theory for H3O(+)(H2O)n (n = 1-5) and OH(-)(H2O)n (n = 1-4).

We have assessed the ability of 52 methods including 15 multicoefficient correlation methods (MCCMs), two complete basis set (CBS) methods, second-order Møller-Plesset perturbation theory (MP2) with 5 basis sets, the popular B3LYP hybrid functional with 6 basis sets, and 24 combinations of local density functional and basis set to accurately reproduce reaction energies obtained at the Weizmann-1 level of theory for hydronium, hydroxide, and pure water clusters. The three best methods overall are BMC-CCSD, G3SX(MP3), and M06-L/aug-cc-pVTZ. If only microsolvated ion data is included, M06-L/aug-cc-pVTZ is the best method; it has errors only half as large as the other density functionals. The deviations between the three best performing methods are larger for the larger hydronium- and hydroxide-containing clusters, despite a decrease in the average reaction energy, making it impossible to determine which of the three methods is overall the best, so they might be ranked in order of increasing cost, with BMC-CCSD least expensive, followed by M06-L/aug-cc-pVTZ. However, the cost for M06-L will increase more slowly as cluster size increases. This study shows that the M06-L functional is very promising for condensed-phase simulations of the transport of hydronium and hydroxide ions in aqueous solution.

Electrostatically Embedded Many-Body Expansion for Simulations.

We have applied the electrostatically embedded many-body (EE-MB) method truncated at the two-body level (also called the pairwise additive EE-MB method or the EE-PA approximation) and the three-body level (called EE-3B) to calculate the gradient of the potential energy for a simulation box containing 64 water molecules. We employed the B3LYP density functional with the 6-31+G(d,p) basis set for this test case. We found that the EE-PA method is able to reproduce the magnitude of the gradient from a B3LYP/6-31+G(d,p) calculation on the entire system to within 1.0% with a 1.3% error for the maximum component of the gradient. Furthermore, the EE-3B method is able to reproduce the magnitude of the gradient to within 0.1% with a 0.2% error for the maximum component of the gradient. The good performance of the EE-MB methods for calculating forces and the highly parallel nature of these methods make them well suited for use in molecular dynamics simulations. Furthermore, since the methods can be used for efficient and accurate calculations of forces with any level of electronic structure theory that has analytic gradients and with any electronic structure package that allows for the presence of a field of point charges, these methods can readily be used with a wide variety of density functional theory and wave function theory methods.

Evaluation of the Electrostatically Embedded Many-Body Expansion and the Electrostatically Embedded Many-Body Expansion of the Correlation Energy by Application to Low-Lying Water Hexamers.

We have applied a many-body (MB) expansion, the electrostatically embedded many-body (EE-MB) approximation, and the electrostatically embedded many-body expansion of the correlation energy (EE-MB-CE), each at the two-body (MB = PA, where PA denotes pairwise additive) and three-body (MB = 3B) levels, to calculate total energies for a series of low-lying water hexamers using eight correlated levels of theory including second-order and fourth-order Møller-Plesset perturbation theory (MP2 and MP4) and coupled cluster theory with single, double, and quasipertubative triple excitations (CCSD(T)). Comparison of the expansion methods to energies obtained from full (i.e., unexpanded) calculations shows that the EE-3B-CE method is able to reproduce the full cluster energies to within 0.03 kcal/mol, on average. We have also found that the deviations of the results predicted by the expansion methods from those obtained with full calculations are nearly independent of the correlated level of theory used; this observation will allow validation of the many-body methods on large clusters at less expensive levels of theory (such as MP2) to be extrapolated to the CCSD(T) level of theory. Furthermore, we have been able to rationalize the accuracies of the MB, EE-MB, and EE-MB-CE methods for the six hexamers in terms of the specific many-body effects present in each cluster.

Application of the Electrostatically Embedded Many-Body Expansion to Microsolvation of Ammonia in Water Clusters.

The electrostatically embedded many-body expansion (EE-MB), at both the second and third order, that is, the electrostatically embedded pairwise additive (EE-PA) approximation and the electrostatically embedded three-body (EE-3B) approximation, are tested for mixed ammonia-water clusters. We examine tetramers, pentamers, and hexamers for three different density functionals and two levels of wave function theory, We compare the many-body results to the results of full calculations performed without many-body expansions. Because of the differing charge distributions in the two kinds of monomers, this provides a different kind of test of the usefulness of the EE-MB method than was provided by previous tests on pure water clusters. We find only small errors due to the truncation of the many-body expansion for the mixed clusters. In particular, for tests on tetramers and pentamers, the mean absolute deviations for truncation at second order are 0.36-0.98 kcal/mol (average: 0.66 kcal/mol), and the mean absolute deviations for truncation at third order are 0.04-0.28 (average: 0.16 kcal/mol). These may be compared to a spread of energies as large as 4.24 kcal/mol in the relative energies of various structures of pentamers and to deviations of up to 8.57 kcal/mol of the full calculations of relative energies from the best estimates of the relative energies. When the methods are tested on hexamers, the mean unsigned deviation per monomer remains below 0.10 kcal/mol for EE-PA and below 0.03 kcal/mol for EE-3B. Thus the additional error due to the truncation of the expansion is small compared to the accuracy needed or the other approximations involved in practical calculations. This means that the EE-MB expansion in combination with density functional theory or wave function theory for the oligomers provides a useful practical model chemistry for making electronic structure calculations and simulations more affordable by improving the scaling with respect to system size.