Seven ways to get a grip on implementing Competency-Based Medical Education at the program level.

Competency-based medical education (CBME) curricula are becoming increasingly common in graduate medical education. Put simply, CBME is focused on educational outcomes, is independent of methods and time, and is composed of achievable competencies.1 In spite of widespread uptake, there remains much to learn about implementing CBME at the program level. Leveraging the collective experience of program leaders at Queen's University, where CBME simultaneously launched across 29 specialty programs in 2017, this paper leverages change management theory to provide a short summary of how program leaders can navigate the successful preparation, launch, and initial implementation of CBME within their residency programs.

Les programmes de formation médicale fondée sur les compétences (FMFC) sont de plus en plus répandus dans les études supérieures en médecine. En termes simples, la FMFC est centrée sur les résultats scolaires, elle est indépendante des méthodes et du temps, et est constituée de compétences réalisables.1 Malgré cette adoption généralisée, il reste encore beaucoup à apprendre sur la mise en œuvre de la FMFC au niveau des programmes. Tirant profit de l'expérience collective des responsables de programmes à l'Université Queen, où la FMFC a été lancée simultanément dans 29 programmes de spécialité en 2017,le présent article s'appuie sur la théorie de la gestion du changement pour produire un court résumé de la manière dont les responsables de programmes peuvent gérer avec succès la préparation, le lancement et la mise en œuvre initiale de la FMFC au sein de leurs programmes de résidence.

Evaluating Population Coverage in a Regional Distributed Data Network: Implications for Electronic Health Record-Based Public Health Surveillance.

OBJECTIVE: Electronic health records (EHRs) hold promise as a public health surveillance tool, but questions remain about how EHR patients compare with populations in health and demographic surveys. We compared population characteristics from a regional distributed data network (DDN), which securely and confidentially aggregates EHR data from multiple health care organizations in the same geographic region, with population characteristics from health and demographic surveys. METHODS: Ten health care organizations participating in a Colorado DDN contributed data for coverage estimation. We aggregated demographic and geographic data from 2017 for patients aged ≥18 residing in 7 counties. We used a cross-sectional design to compare DDN population size, by county, with the following survey-estimated populations: the county population, estimated by the American Community Survey (ACS); residents seeking any health care, estimated by the Colorado Health Access Survey; and residents seeking routine (eg, primary) health care, estimated by the Behavioral Risk Factor Surveillance System. We also compared data on the DDN and survey populations by sex, age group, race/ethnicity, and poverty level to assess surveillance system representativeness. RESULTS: The DDN population included 609 840 people in 7 counties, corresponding to 25% coverage of the general adult population. Population coverage ranged from 15% to 35% across counties. Demographic distributions generated by DDN and surveys were similar for many groups. Overall, the DDN and surveys assessing care-seeking populations had a higher proportion of women and older adults than the ACS population. The DDN included higher proportions of Hispanic people and people living in high-poverty neighborhoods compared with the surveys. CONCLUSION: The DDN population is not a random sample of the regional adult population; it is influenced by health care use patterns and organizations participating in the DDN. Strengths and limitations of DDNs complement those of survey-based approaches. The regional DDN is a promising public health surveillance tool.

Accelerated DNA methylation age in adolescent girls: associations with elevated diurnal cortisol and reduced hippocampal volume.

Numerous studies have linked exposure to stress to adverse health outcomes through the effects of cortisol, a product of the stress response system, on cellular aging processes. Accelerated DNA methylation age is a promising epigenetic marker associated with stress and disease risk that may constitute a link from stress response to changes in neural structures. Specifically, elevated glucocorticoid signaling likely contributes to accelerating DNA methylation age, which may signify a maladaptive stress-related cascade that leads to hippocampal atrophy. We examined the relations among diurnal cortisol levels, DNA methylation age and hippocampal volume in a longitudinal study of 46 adolescent girls. We computed area under the curve from two daily cortisol collection periods, and calculated DNA methylation age using previously established methods based on a set of CpG sites associated with chronological age. We computed a residual score by partialling out chronological age; higher discrepancies reflect relatively accelerated DNA methylation age. We assessed hippocampal volume via T1-weighted images and automated volumetric segmentation. We found that greater diurnal cortisol production was associated with accelerated DNA methylation age, which in turn was associated with reduced left hippocampal volume. Finally, accelerated DNA methylation age significantly mediated the association between diurnal cortisol and left hippocampal volume. Thus, accelerated DNA methylation age may be an epigenetic marker linking hypothalamic-pituitary-adrenal axis dysregulation with neural structure. If these findings are replicated, the current study provides a method for advancing our understanding of mechanisms by which glucocorticoid signaling is associated with cellular aging and brain development.

Using Spatial Analysis to Inform Community Immunization Strategies.

INTRODUCTION: Recent pertussis outbreaks in the United States suggest our response to local disease outbreaks (eg, vaccine-preventable Bordetella pertussis) may benefit from understanding and applying spatial analytical methods that use data from immunization information systems at a subcounty level. METHODS: A 2012 study on Denver, CO, residents less than 19 years of age confirmed pertussis cases and immunization information system records were geocoded and aggregated to the census tract (CT) level. An algorithm assessed whether individuals were up-to-date (UTD) for pertussis vaccines. Pearson, Spearman, and Kendall correlations assessed relations between disease incidence and pertussis vaccine coverage. Using spatial analysis software, disease incidence and UTD rates were spatially weighted, and smoothed. Global and local autocorrelations based on univariate Moran's I spatial autocorrelation statistics evaluated whether a CT's rate belong to a cluster based on incidence or UTD measures. RESULTS: Overall disease incidence rate was 116.8/100 000. Assessment of pertussis vaccination coverage was available for 90% of the population. Among 134 672 Denver residents less than 19 years old, 103 496 (77%) were UTD for pertussis vaccines. Raw correlation coefficients showed weak relationships between incidence and immunization rates due to the presence of outliers. With geospatial and clustering analysis, estimates and correlation coefficients were improved with statistically significant Moran's I values for global and local autocorrelations rejecting the null hypothesis that incidence or UTD rates were randomly distributed. With evidence indicating the presence of clusters, smoothed and weighted disease incidence and UTD rates in 144 CTs identified 21 CTs (15%) for potential public health intervention. CONCLUSIONS: Correlation of raw disease incidence and vaccine UTD rates in subcounty regions showed limited association, providing limited information for decision making. By assessing for clusters using spatial analysis methods, we identified CTs with higher incidence and lower immunization coverage for targeted public health interventions.

Indomethacin administered early in the postnatal period results in reduced glomerular number in the adult rat.

Indomethacin and ibuprofen are administered to close a patent ductus arteriosus (PDA) during active glomerulogenesis. Light and electron microscopic glomerular changes with no change in glomerular number were seen following indomethacin and ibuprofen treatment during glomerulogenesis at 14 days after birth in a neonatal rat model. This present study aimed to determine whether longstanding renal structural changes are present at 30 days and 6 mo (equivalent to human adulthood). Rat pups were administered indomethacin or ibuprofen antenatally on days 18-20 (0.5 mg·kg(-1)·dose(-1) indomethacin; 10 mg·kg(-1)·dose(-1) ibuprofen) or postnatally intraperitoneally from day 1 to 3 or day 1 to 5 (0.2 mg·kg(-1)·dose(-1) indomethacin; 10 mg·kg(-1)·dose(-1) ibuprofen). Control groups received no treatment or normal saline intraperitoneally. Pups were killed at 30 days of age and 6 mo of age. Tissue blocks from right kidneys were prepared for light and electron microscopic examination, while total glomerular number was determined in left kidneys using unbiased stereology. Eight pups were included in each group from 14 maternal rats. At 30 days and 6 mo, there were persistent electron microscopy abnormalities of the glomerular basement membrane in those receiving postnatal indomethacin and ibuprofen. There were no significant light microscopy findings at 30 days or 6 mo. At 6 mo, there were significantly fewer glomeruli in those receiving postnatal indomethacin but not ibuprofen (P = 0.003). In conclusion, indomethacin administered during glomerulogenesis appears to reduce the number of glomeruli in adulthood. Alternative options for closing a PDA should be considered including ibuprofen as well as emerging therapies such as paracetamol.

Is the physical functioning of older adults with diabetes associated with the processes and outcomes of care? Evidence from Translating Research Into Action for Diabetes (TRIAD).

AIMS: To examine the relationship between physical function limitations and diabetes self-management, processes of care and intermediate outcomes in adults ≥ 65 years of age with Type 2 diabetes. METHODS: We studied 1796 participants 65 years of age and older in managed care health plans enrolled in Translating Research into Action for Diabetes (TRIAD). Physical functioning was assessed at baseline with the Physical Component Summary of the Short Form-12 Health Survey. Diabetes self-management was assessed with follow-up surveys, and processes of care (eye examinations, urine microalbumin testing, foot examinations, etc.) and intermediate health outcomes (HbA(1c), blood pressure, LDL cholesterol) were assessed with medical chart reviews. Multivariate regression models were constructed to examine the associations between physical function limitations and outcomes. RESULTS: Frequency of eye examinations (odds ratio 0.69, 95% CI 0.49-0.99) was the only process of care that was worse for participants with physical function limitations (n = 573) compared with those without limitations (n = 618). Neither self-management nor intermediate outcomes differed by whether patients had or did not have physical function limitations. CONCLUSION: Limitations in physical functioning as assessed by the Short Form-12 were not associated with substantial difference in diabetes care in adults ≥ 65 years of age enrolled in managed care health plans.

Nephron endowment in glial cell line-derived neurotrophic factor (GDNF) heterozygous mice.

BACKGROUND: The exact molecular mechanisms that regulate ureteric branching morphogenesis in the developing metanephros have not been fully elucidated. However, in vivo and in vitro evidence indicates that glial cell line-derived neurotrophic factor (GDNF) is a key regulator of the initiation of ureteric branching. GDNF knockout mice show renal agenesis or severe dysgenesis and die 24 hours after birth from renal failure. Inhibition of GDNF activity in metanephric organ culture inhibits ureteric branching. Since nephron initiation only occurs at the tips of ureteric branches, the aim of the present study was to determine whether nephron number in GDNF heterozygous mice is reduced. METHODS: Male GDNF heterozygous mice of hybrid 129/Sv and C57/BL genetic background were mated with C57BL/6 females. Offspring were genotyped at postnatal day 30 (PN30) by polymerase chain reaction. Left kidneys were used for estimating kidney volume and total nephron number. We also estimated absolute and relative volumes of ureteric duct epithelium. Unbiased stereological methods were used throughout (Cavalieri method, physical disector/fractionator combination). RESULTS: GDNF wild-type and heterozygous mice had similar body weights at PN30. However, heterozygous kidneys were 25% smaller than wild-type kidneys (wild-type, 114.75 +/- 16.46 mm3; heterozygous, 87.11 +/- 21.84 mm3, P < 0.001) and contained approximately 30% fewer nephrons (wild-type, 11886 +/- 1277; heterozygous, 8573 +/- 2240, P < 0.01). In addition, the absolute ureteric duct volume was significantly reduced in heterozygous mice (P < 0.001). CONCLUSIONS: : These results indicate that the loss of one GDNF allele results in reduced nephron endowment in the adult kidney, presumably as the result of reduced branching morphogenesis of the ureteric bud.

Effect of preseasonal enzyme potentiated desensitisation (EPD) on plasma-IL-6 and IL-10 of grass pollen-sensitive asthmatic children.

EPD is a method of preventive immunotherapy which employs b-glucuronidase as a biological response modifier. Plasma IL-6 and IL-10 were measured before a single injection of EPD, 24 hours later and 15 days after in a group of 17 children suffering from grass pollen asthma. 17 normal untreated children were used as controls. Although the study was conducted before the grass pollen season when the allergic children were free of symptoms, their plasma IL-6 and IL-10 were significantly elevated before the injection of EPD. 24 hours after treatment the plasma IL-10 had increased significantly and there was also a slight rise in IL-6. 15 days after treatment IL-6 had fallen to normal but IL-10 was still elevated. These findings suggest antigen-specific and non-specific mechanisms by which EPD may produce clinical improvement.

Retinyl ester hydrolytic activity associated with human intestinal brush border membranes.

Hydrolysis of retinyl esters in the lumen of the small intestine is required before absorption. Previously, rat brush border membranes (BBMs) were found to contain a pancreatic-derived esterase preferring retinyl esters with short fatty acyl chains and an intrinsic esterase preferring esters with long fatty acyl chains. Here, similar activities were found for preparations of human BBMs. Long-chain ester hydrolysis was stimulated best by deoxycholate, a dihydroxy bile salt, whereas short-chain ester hydrolysis was stimulated best by taurocholate, a trihydroxy bile salt. A 10-fold difference in KM values for retinyl palmitate (0.53 mumol/L) and caproate (5.5 mumol/L) also indicated distinguishable long-chain and short-chain activities. Differences between retinyl butyrate and retinyl caproate hydrolysis suggested the possible presence of two short-chain esterase activities associated with both rat and human BBMs, in addition to the long-chain activity. Similarities between human BBM retinyl ester hydrolytic activities and those observed for rat BBMs suggest that the rat is a good model for humans in this step of vitamin A metabolism.

Mineral and organic matrix interaction in normally calcifying tendon visualized in three dimensions by high-voltage electron microscopic tomography and graphic image reconstruction.

To define the ultrastructural accommodation of mineral crystals by collagen fibrils and other organic matrix components during vertebrate calcification, electron microscopic 3-D reconstructions were generated from the normally mineralizing leg tendons from the domestic turkey, Meleagris gallopavo. Embedded specimens containing initial collagen mineralizing sites were cut into 0.5-micron-thick sections and viewed and photographed at 1.0 MV in the Albany AEI-EM7 high-voltage electron microscope. Tomographic 3-D reconstructions were computed from a 2 degree tilt series of micrographs taken over a minimum angular range of +/- 60 degrees. Reconstructions of longitudinal tendon profiles confirm the presence of irregularly shaped mineral platelets, whose crystallographic c-axes are oriented generally parallel to one another and directed along the collagen long axes. The reconstructions also corroborate observations of a variable crystal length (up to 170 nm measured along crystallographic c-axes), the presence of crystals initially in either the hole or overlap zones of collagen, and crystal growth in the c-axis direction beyond these zones into adjacent overlap and other hole regions. Tomography shows for the first time that crystal width varies (30-45 nm) but crystal thickness is uniform (approximately 4-6 nm at the resolution limit of tomography); more crystals are located in the collagen hole zones than in the overlap regions at the earliest stages of tendon mineralization; the crystallographic c-axes of the platelets lie within +/- 15-20 degrees of one another rather than being perfectly parallel; adjacent platelets are spatially separated by a minimum of 4.2 +/- 1.0 nm; crystals apparently fuse in coplanar alignment to form larger platelets; development of crystals in width occurs to dimensions beyond single collagen hole zones; and a thin envelope of organic origin may be present along or just beneath the surfaces of individual mineral platelets. Implicit in the results is that the formation of crystals occurs at different sites and times by independent nucleation events in local regions of collagen. These data provide the first direct visual evidence from 3-D imaging describing the size, shape, orientation, and growth of mineral crystals in association with collagen of a normally mineralizing vertebrate tissue. They support concepts that c-axial crystal growth is unhindered by collage hole zone dimensions, that crystals are organized in the tendon in a series of generally parallel platelets, and that crystal growth in width across collagen fibrils may follow channels or grooves formed by adjacent hole zones in register.

Controlled trial of hyposensitisation in children with food-induced hyperkinetic syndrome.

Food intolerance seems to be an important cause of the hyperkinetic syndrome, but restricted diets are expensive, socially disruptive, and often nutritionally inadequate. Enzyme-potentiated desensitisation (EPD) may overcome some of these difficulties. EPD was tested in a double-blind placebo-controlled trial among 40 children with food-induced hyperkinetic behaviour disorder. A total of 185 children with established hyperkinetic syndrome underwent oligoantigenic dietary treatment for four weeks. 116 whose behaviour responded had provoking foods identified by sequential reintroduction. Foods that reproducibly provoked overactivity were avoided. 40 patients who were then invited to take part in the hyposensitisation trial were randomly assigned to treated and control groups. Treated patients received three doses of EPD (beta-glucuronidase and small quantities of food antigens) intradermally at two-monthly intervals. Controls received buffer only. Thereafter, patients were allowed to eat known provoking foods. Of 20 patients who received active treatment, 16 became tolerant towards provoking foods compared with 4 of 20 who received placebo (p less than 0.001). Our results show that EPD permits children with food-induced hyperkinetic syndrome to eat foods that had previously been identified as responsible for their symptoms. These results also support the notion that food allergy is a possible mechanism of the hyperkinetic syndrome.

Enzyme potentiated hyposensitization: IV. effect of protamine on the immunological behavior of beta glucuronidase in mice and patients with hay fever.

The ability of beta glucuronidase and a small dose of antigen to modify the anaphylactic reaction of previously sensitized mice has been further investigated. Protamine has an important effect on the immunological behavior of the enzyme. A trial on hay fever patients shows that the results in mice are relevant and that the method can produce significant clinical hyposensitization.