The increased ambulatory training time in an “X + Y” (inpatient + ambulatory) residency schedule affords more opportunities to teach geriatrics principles of care. We describe our internal medicine ...(IM) residency program's experience in teaching the IM–family medicine (FM) minimum geriatrics competencies (MGC) during a longitudinal geriatrics rotation embedded within interns' yearlong “4 + 2” schedule. Interns spend 1 day of the ambulatory block in a geriatrics outpatient setting (Program of All‐Inclusive Care for the Elderly, house calls, nursing home), during which geriatrics division faculty members give core didactic seminars. We revamped core seminars to address MGC related to medication management, cognitive health, complex chronic illnesses, end of life care, and ambulatory care. Three consecutive intern cohorts completed anonymous surveys pre‐ and postrotation, rating their confidence level in MGC addressed by the curriculum on a 5‐point Likert scale. On postrotation surveys, they also rated the curriculum's contribution to geriatrics skills enhancement. Interns who completed both surveys (N = 22, 92%) reported statistically significant improved confidence ratings on all items, with the greatest point gains seen in performance of functional assessment (1.56), practice of optimal geriatric pharmacotherapy (1.78), and identification of older patients eligible for skilled (1.71) and unskilled home‐based services (1.65). They rated geriatrics curricular components as being more helpful than other rotations and conferences in enhancing their geriatric skills. In conclusion, we developed a longitudinal geriatrics curriculum within the context of our “4 + 2” immersion schedule which other programs can easily adapt. Aligning curricular content with the MGC has resulted in interns' improved confidence in several important geriatrics skills.
Nongeriatricians must acquire skills and knowledge in geriatric medicine to ensure coordinated care of older adults' complex conditions by interspecialty and interprofessional teams. Chief residents ...(CRs) are an ideal target for an educational intervention. This study examined whether the Boston Medical Center Chief Resident Immersion Training (CRIT) in the Care of Older Adults was replicable at diverse medical institutions.
Between 2008 and 2010, 12 institutions in 11 states received funding, technical support, and a common program model. Each implemented 2.5-day CRITs, consisting of a patient case, geriatrics-related lectures, CR leadership sessions, action project planning, and networking time. Site faculty conducted 21 CRITs for 295 CRs representing 28 specialties. CRs completed knowledge pre- and posttests, and self-report baseline and six-month follow-up surveys. Outcome measures were change in pre- and posttest score, and change from baseline to six months in self-reported surveys.
Response rate for CRs was 99% (n = 293) for the pre-post tests and 78% (n = 231) for matchable baseline and follow-up surveys. Participants' knowledge increased from 6.32 to 8.39 (P < .001) averaged from 12 questions. CRs' self-reported ability to apply clinical problem-solving skills to older patients (P < .001), number of geriatrics topics taught (P < .001), frequency of geriatrician consultations (P = .017), confidence in leadership skills (P < .001), and confidence to conduct CR work (P < .001) increased from baseline to follow-up.
CRIT is an innovative way to give nongeriatricians knowledge and skills to treat complex older patients.
Web‐based learning methods are being used increasingly to teach core curriculum in medical school clerkships, but few studies have compared the effectiveness of online methods with that of live ...lectures in teaching the same topics to students. Boston University School of Medicine has implemented an online, case‐based, interactive curriculum using videos and text to teach delirium to fourth‐year medical students during their required 1‐month Geriatrics and Home Medical Care clerkship. A control group of 56 students who received a 1‐hour live delirium lecture only was compared with 111 intervention group students who completed the online delirium curriculum only. Evaluation consisted of a short‐answer test with two cases given as a pre‐ and posttest to both groups. The total possible maximum test score was 34 points, and the lowest possible score was −8 points. Mean pre‐ and posttest scores were 10.5 ± 4.0 and 12.7 ± 4.4, respectively, in the intervention group and 9.9 ± 3.5 and 11.2 ± 4.5, respectively, in the control group. The intervention group had statistically significant improvement between the pre‐ and posttest scores (2.21‐point difference; P < .001), as did the control group (1.36‐point difference; P = .03); the difference in test score improvement between the two groups was not statistically significant. An interactive case‐based online curriculum in delirium is as effective as a live lecture in teaching delirium, although neither of these educational methods alone produces robust increases in knowledge.
Chief residents (CRs) play a crucial role in training residents and students but may have limited geriatrics training or formal preparation for their CR role. A 2‐day off‐site chief resident ...immersion training (CRIT) addressed these challenges. Objectives were to foster collaboration between disciplines in the management of complex older patients, increase knowledge of geriatrics principles to incorporate into teaching, enhance leadership skills, and help CRs develop an achievable project for implementation in their CR year. Three cohorts totaling 47 trainees and 18 faculty mentors from 13 medical and surgical disciplines participated over 3 successive years. The curriculum, developed and taught by a multidisciplinary team, featured an interactive surgical case, mini‐lectures on geriatrics topics, seminars to enhance teaching and leadership skills, and one‐on‐one mentoring to develop a project in geriatric care or education. Evaluation included pre‐ and postprogram tests and self‐report surveys and two follow‐up surveys or interviews. In 2006 and 2007, scores on a 12‐item objective knowledge test increased significantly (P<.001) from before to immediately after CRIT. Self‐report knowledge and confidence in teaching geriatrics also increased significantly (P<.05) in all formally covered topics. Mean enhancement of CR skills was 4.3 (1=not at all, 5=very much). Eleven months after CRIT, all but five CRs had implemented at least part of their action projects. CRs reported improved care of older patients, better leadership skills, more and better geriatrics teaching, and more collaboration between disciplines. A 2‐day interactive program for CRs can increase institutional capacity regarding geriatrics teaching and care of elderly patients across medical specialties.
Geriatrics as a field has been fortunate to have the support of several philanthropic organizations to advance geriatrics education and training in the past two decades. Awardees of such grants were ...presented with unparalleled opportunities to develop new and innovative educational initiatives affecting learners at multiple levels and in multiple disciplines and specialties. The lessons learned from the Donald W. Reynolds Foundation initiatives about effect and sustainability are invaluable to the ongoing strategic development of geriatrics nationally. This article highlights successful educational initiatives developed at four institutions with past and current Donald W. Reynolds Foundation funding. Following an ice hockey playbook, this article identifies 10 strategies and initiatives to “stay in the geriatrics game” by training hospitalists and subspecialty providers. The authors' collective experience suggests that geriatrics educational initiatives can not only influence provider education, but also improve the care of older adults in multiple settings.
As the population ages, it is important that graduating medical students be properly prepared to treat older adults, regardless of their chosen specialty. To this end, the Association of American ...Medical Colleges (AAMC) and the John A. Hartford Foundation convened a consensus conference to establish core competencies in geriatrics for all graduating medical students. An ambulatory geriatric clerkship for fourth‐year medical students that successfully teaches 24 of the 26 AAMC core competencies using an interdisciplinary, team‐based approach is reported here. Graduating students (N=158) reported that the clerkship was successful at teaching the core competencies, as evidenced by positive responses on the AAMC Graduation Questionnaire (GQ). More than three‐quarters (80–93%) of students agreed or strongly agreed that they learned the seven geriatrics concepts asked about on the GQ, which cover 14 of the 26 core competencies. This successful model for a geriatrics clerkship can be used in many institutions to teach the core competencies and in any constellation of geriatric ambulatory care sites that are already available to the faculty.
Scavenger receptor BI (SR-BI) is the major receptor for high-density lipoprotein (HDL) cholesterol (HDL-C). In humans, high amounts of HDL-C in plasma are associated with a lower risk of coronary ...heart disease (CHD). Mice that have depleted Scarb1 (SR-BI knockout mice) have markedly elevated HDL-C levels but, paradoxically, increased atherosclerosis. The impact of SR-BI on HDL metabolism and CHD risk in humans remains unclear. Through targeted sequencing of coding regions of lipid-modifying genes in 328 individuals with extremely high plasma HDL-C levels, we identified a homozygote for a loss-of-function variant, in which leucine replaces proline 376 (P376L), in SCARB1, the gene encoding SR-BI. The P376L variant impairs posttranslational processing of SR-BI and abrogates selective HDL cholesterol uptake in transfected cells, in hepatocyte-like cells derived from induced pluripotent stem cells from the homozygous subject, and in mice. Large population-based studies revealed that subjects who are heterozygous carriers of the P376L variant have significantly increased levels of plasma HDL-C. P376L carriers have a profound HDL-related phenotype and an increased risk of CHD (odds ratio = 1.79, which is statistically significant).
Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 ...HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with other glucose-related traits). In this study, we tested the hypotheses that, in a very large scale GWAS, we would identify more genetic variants associated with HbA1c and that HbA1c variants implicated in erythrocytic biology would affect the diagnostic accuracy of HbA1c. We therefore expanded the number of HbA1c-associated loci and tested the effect of genetic risk-scores comprised of erythrocytic or glycemic variants on incident diabetes prediction and on prevalent diabetes screening performance. Throughout this multiancestry study, we kept a focus on interancestry differences in HbA1c genetics performance that might influence race-ancestry differences in health outcomes.
Using genome-wide association meta-analyses in up to 159,940 individuals from 82 cohorts of European, African, East Asian, and South Asian ancestry, we identified 60 common genetic variants associated with HbA1c. We classified variants as implicated in glycemic, erythrocytic, or unclassified biology and tested whether additive genetic scores of erythrocytic variants (GS-E) or glycemic variants (GS-G) were associated with higher T2D incidence in multiethnic longitudinal cohorts (N = 33,241). Nineteen glycemic and 22 erythrocytic variants were associated with HbA1c at genome-wide significance. GS-G was associated with higher T2D risk (incidence OR = 1.05, 95% CI 1.04-1.06, per HbA1c-raising allele, p = 3 × 10-29); whereas GS-E was not (OR = 1.00, 95% CI 0.99-1.01, p = 0.60). In Europeans and Asians, erythrocytic variants in aggregate had only modest effects on the diagnostic accuracy of HbA1c. Yet, in African Americans, the X-linked G6PD G202A variant (T-allele frequency 11%) was associated with an absolute decrease in HbA1c of 0.81%-units (95% CI 0.66-0.96) per allele in hemizygous men, and 0.68%-units (95% CI 0.38-0.97) in homozygous women. The G6PD variant may cause approximately 2% (N = 0.65 million, 95% CI 0.55-0.74) of African American adults with T2D to remain undiagnosed when screened with HbA1c. Limitations include the smaller sample sizes for non-European ancestries and the inability to classify approximately one-third of the variants. Further studies in large multiethnic cohorts with HbA1c, glycemic, and erythrocytic traits are required to better determine the biological action of the unclassified variants.
As G6PD deficiency can be clinically silent until illness strikes, we recommend investigation of the possible benefits of screening for the G6PD genotype along with using HbA1c to diagnose T2D in populations of African ancestry or groups where G6PD deficiency is common. Screening with direct glucose measurements, or genetically-informed HbA1c diagnostic thresholds in people with G6PD deficiency, may be required to avoid missed or delayed diagnoses.
The generation of biologically active proteins by regulated intramembrane proteolysis is a highly conserved mechanism in cell signaling. Presenilin-dependent γ-secretase activity is responsible for ...the intramembrane proteolysis of selected type I membrane proteins, including β-amyloid precursor protein (APP) and Notch. A small fraction of intracellular domains derived from both APP and Notch translocates to and appears to function in the nucleus, suggesting a generic role for γ-secretase cleavage in nuclear signaling. Here we show that the p75 neurotrophin receptor (p75NTR) undergoes presenilin-dependent intramembrane proteolysis to yield the soluble p75-intracellular domain. The p75NTR is a multifunctional type I membrane protein that promotes neurotrophin-induced neuronal survival and differentiation by forming a heteromeric co-receptor complex with the Trk receptors. Mass spectrometric analysis revealed that γ-secretase-mediated cleavage of p75NTR occurs at a position located in the middle of the transmembrane (TM) domain, which is reminiscent of the amyloid β-peptide 40 (Aβ40) cleavage of APP and is topologically distinct from the major TM cleavage site of Notch 1. Size exclusion chromatography and co-immunoprecipitation analyses revealed that TrkA forms a molecular complex together with either full-length p75 or membrane-tethered C-terminal fragments. The p75-ICD was not recruited into the TrkA-containing high molecular weight complex, indicating that γ-secretase-mediated removal of the p75 TM domain may perturb the interaction with TrkA. Independent of the possible nuclear function, our studies suggest that γ-secretase-mediated p75NTR proteolysis plays a role in the formation/disassembly of the p75-TrkA receptor complex by regulating the availability of the p75 TM domain that is required for this interaction.
Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive breast cancer (IBC). Due to a lack of biomarkers able to distinguish high- from low-risk cases, DCIS is treated similar to ...early IBC even though the minority of untreated cases eventually become invasive. Here, we characterized 115 patient-derived mouse-intraductal (MIND) DCIS models reflecting the full spectrum of DCIS observed in patients. Utilizing the possibility to follow the natural progression of DCIS combined with omics and imaging data, we reveal multiple prognostic factors for high-risk DCIS including high grade, HER2 amplification, expansive 3D growth, and high burden of copy number aberrations. In addition, sequential transplantation of xenografts showed minimal phenotypic and genotypic changes over time, indicating that invasive behavior is an intrinsic phenotype of DCIS and supporting a multiclonal evolution model. Moreover, this study provides a collection of 19 distributable DCIS-MIND models spanning all molecular subtypes.
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•Development of a biobank of DCIS-MIND models retaining primary features•Identification of multiple factors associated with invasive progression of DCIS•Identification of two distinct 3D growth patterns associated with outcome•Development of a collection of 19 distributable DCIS models
Hutten et al. generate 115 DCIS-MIND models and characterize them with genomic, transcriptomic, and imaging data. With this biobank they identify risk factors associated with progression of ductal carcinoma in situ to invasive breast cancer and create a collection of 19 distributable DCIS models, providing a resource for further research.
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