Genomic Education – Bench to Bedside: A Novel Approach to Teaching Genetic Diagnosis

Problem: Teaching genetic diagnosis is required in all medical schools and physician assistant programs. However, with thousands of relevant findings and thousands more rare diseases, lectures and narrative resources are inadequate for the task. Whatever information that is taught is easily forgotten and does not carry over into the clinic. Many rare disease patients suffer through “diagnostic odysseys” (3 to 30 years to correct diagnosis). Approach: We used a commercially available diagnostic decision support system (DDSS) that encompasses all Mendelian disorders with known genes, together with other conditions in their differential diagnosis, and a case-based educational approach to teach diagnostic skills in a way that could then be replicated in the clinic. After a lecture, which included a demonstration using the DDSS with a sample case, 74 students were assigned to replicate the sample case at home and then complete 7 other anonymized cases, all with known rare diagnoses. After each case, students saved the “patient summary” that included the findings entered and differential diagnosis list and submitted it as homework. Students also completed a questionnaire about their experience, including satisfaction. Outcomes: Students were effective at diagnosing rare diseases in 483 of the 514 testing instances, a 94% success rate, with success defined as the correct diagnosis being listed in the differential diagnosis. Eighty-five percent of students rated this interactive learning session “highly,” encouraged us to repeat the assignment next year, and 89% reported that they wanted to use the DDSS during their clinical rotations in the coming year. Next Steps: We plan to refine the cases, add more material on findings, and ensure that all the synonyms students might use are in the software tool. We plan to repeat the program next year and recommend its use more widely in medical education

Evidence-based decision support for pediatric rheumatology reduces diagnostic errors.

BACKGROUND: The number of trained specialists world-wide is insufficient to serve all children with pediatric rheumatologic disorders, even in the countries with robust medical resources. We evaluated the potential of diagnostic decision support software (DDSS) to alleviate this shortage by assessing the ability of such software to improve the diagnostic accuracy of non-specialists. METHODS: Using vignettes of actual clinical cases, clinician testers generated a differential diagnosis before and after using diagnostic decision support software. The evaluation used the SimulConsult® DDSS tool, based on Bayesian pattern matching with temporal onset of each finding in each disease. The tool covered 5405 diseases (averaging 22 findings per disease). Rheumatology content in the database was developed using both primary references and textbooks. The frequency, timing, age of onset and age of disappearance of findings, as well as their incidence, treatability, and heritability were taken into account in order to guide diagnostic decision making. These capabilities allowed key information such as pertinent negatives and evolution over time to be used in the computations. Efficacy was measured by comparing whether the correct condition was included in the differential diagnosis generated by clinicians before using the software ( unaided ), versus after use of the DDSS ( aided ). RESULTS: The 26 clinicians demonstrated a significant reduction in diagnostic errors following introduction of the software, from 28% errors while unaided to 15% using decision support (p \u3c 0.0001). Improvement was greatest for emergency medicine physicians (p = 0.013) and clinicians in practice for less than 10 years (p = 0.012). This error reduction occurred despite the fact that testers employed an open book approach to generate their initial lists of potential diagnoses, spending an average of 8.6 min using printed and electronic sources of medical information before using the diagnostic software. CONCLUSIONS: These findings suggest that decision support can reduce diagnostic errors and improve use of relevant information by generalists. Such assistance could potentially help relieve the shortage of experts in pediatric rheumatology and similarly underserved specialties by improving generalists\u27 ability to evaluate and diagnose patients presenting with musculoskeletal complaints. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02205086

Human capital and national institutional quality: Are TIMSS, PISA, and national average IQ robust predictors?

Is human capital a robust predictor of good institutions? Using a new institutional quality measure, the International Property Rights Index (IPRI), we find that cognitive skill measures are significant, robust, and large in magnitude. We use two databases of cognitive skills: estimates of national average IQ from Lynn and Vanhanen (2012a) and estimates of cognitive ability based on Programme for International Student Assessment (PISA) and Trends in International Mathematics and Science Study (TIMSS) scores estimated by Rindermann et al. (2009). The Rindermann cognitive ability scores estimate mean performance as well as performance at the 5th and 95th percentiles of the national population. National average IQ and the 95th percentile of cognitive ability are both robust predictors of overall institutional quality controlling for legal system, GDP per capita, geography dummies, and years of total schooling. Some possible microfoundations of this relationship are discussed

Changes in the multidisciplinary management of rectal cancer from 2009 to 2015 and associated improvements in short‐term outcomes

Aim: Significant recent changes in management of locally advanced rectal cancer include preoperative staging, use of extended neoadjuvant therapies, and minimally invasive surgery (MIS). This study was aimed at characterizing those changes and associated short‐term outcomes. Method: We retrospectively analysed treatment and outcome data from patients with T3/4 or N+ locally advanced rectal cancer ≤15 cm from the anal verge who were evaluated at a comprehensive cancer center in 2009–2015. Results: In total, 798 patients were identified and grouped into five cohorts based on treatment year: 2009‐2010, 2011, 2012, 2013, and 2014‐2015. Temporal changes included increased reliance on MRI staging, from 57% in 2009‐2010 to 98% in 2014‐2015 (p < 0.001); increased use of total neoadjuvant therapy, from 17% to 76% (p < 0.001); and increased use of MIS, from 33% to 70% (p < 0.001). Concurrently, median hospital stay decreased (from 7 to 5 days; p < 0.001), as did the rates of grade III‐V complications (from 13% to 7%; p < 0.05), surgical site infections (from 24% to 8%; p < 0.001), anastomotic leak (from 11% to 3%; p < 0.05), and positive circumferential resection margin (from 9% to 4%; p < 0.05). TNM downstaging increased from 62% to 74% (p = 0.002). Conclusion: Shifts toward MRI‐based staging, total neoadjuvant therapy, and MIS occurred between 2009 and 2015. Over the same period, treatment responses improved, and lengths of stay and the incidence of complications decreased

Mental health care and resistance to fascism

Mental health nurses have a critical stake in resisting the right-wing ideology of British fascism. Particularly concerning is the contemporary effort of the British National Party (BNP) to gain credibility and electoral support by the strategic re-packaging of a racist and divisive political manifesto. Evidence that some public sector workers are affiliated with the BNP has relevance for nursing at a series of levels, not least the incompatibility of party membership with a requirement of the Professional Code to avoid discrimination. Progressive advances, though, need to account for deep rooted institutionalized racism in the discourse and practice of healthcare services. The anomalous treatment of black people within mental health services, alongside racial abuse experienced by ethnic minority staff, is discussed in relation to the concept of race as a powerful social category and construction. The murder of the mentally ill and learning disabled in Nazi Germany, as an adjunct of racial genocide, is presented as an extreme example where professional ethics was undermined by dominant political ideology. Finally, the complicity of medical and nursing staff in the state sanctioned, bureaucratic, killing that characterized the Holocaust is revisited in the context of ethical repositioning for contemporary practice and praxis

The spontaneous release of a high-molecular-weight aggregate containing immunoglobulin G from the surface of Ehrlich ascites tumor cells

The spontaneous release of tumor cell antigens from the cell surface into the circulation has been proposed as a mechanism whereby tumors may escape the immune response of the host. In this study we have found that Ehrlich ascites tumor cells after removal from the host (mouse) spontaneously release significant amounts of cell surface components during incubation for 1 h in cold isotonic buffer. Immunodiffusion studies revealed that immunoglobulin G (IgG) and a complement component (C3) are included in this spontaneously released material. These surface-bound humoral immune components are apparently released in the form of a high-molecular-weight aggregate (cell coat particle) as shown by ultracentrifugation and ultrafiltration experiments. Precipitation of IgG from the cell coat particle preparation with antibodies directed against mouse IgG followed by detergent gel electrophoresis of the immune precipitate revealed five major bands in addition to the heavy and light chains of IgG. These results suggest that host IgG is tightly bound to several other components at the cell surface, perhaps in the form of immune complexes. IgG is localized on the tumor cell surface in a highly heterogeneous pattern with the appearance of patches and caps in some cells as shown by immuno-fluorescence analysis. The possibility that humoral immune components bind to the tumor cell surface and result in the shedding of high-molecular-weight aggregates of cell surface antigens into extracellular fluids is discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38207/1/400090311_ftp.pd

Tracking potentiating states of dissociation: An intensive clinical case study of sleep, daydreaming, mood, and depersonalization/derealization

This study examined in real time the role of sleep and daydreaming as potentiating states for subsequent dissociation in depersonalization/derealization disorder (DDD). Research and theory suggests that dissociation may be exacerbated and maintained by a labile sleep-wake cycle in which ‘dream-like’ mentation intrudes into waking life and fuels dissociative symptoms. We explore and extend this idea by examining the state of daydreaming in dissociation. Daydreaming is a state of consciousness between dreaming and waking cognition that involves stimulus-independent and task-unrelated mentation. We report the results of a unique intensive N=1 study with an individual meeting diagnostic criteria for DDD. Using experience-sampling methodology, the participant rated (six times daily for 40 days) current daydreaming, mood, and dissociative symptoms. At the start of each day sleep quality and duration was also rated. Daydreaming was reported on 45% of occasions and significantly predicted greater dissociation, in particular when daydreams were repetitive and negative (but not fanciful) in content. These relationships were mediated by feelings of depression and anxiety. Sleep quality but not duration was a negative predictor of daily dissociation and also negatively predicted depression but not anxiety. Findings offer initial evidence that the occurrence and content of daydreams may act as potentiating states for heightened, in the moment, dissociation. The treatment implications of targeting sleep and daydreaming for dissociative disorders are discussed

An Asian viewpoint on the use of vitamin D and calcium in osteoporosis treatment: Physician and patient attitudes and beliefs

<p>Abstract</p> <p>Background</p> <p>Osteoporosis treatment guidelines recommend calcium and vitamin D supplementation for both prevention as well as treatment, however, compliance with these guidelines is often unsatisfactory. This study investigated the opinion of Asian physicians and Asian patients regarding vitamin D and calcium and patients' use of both.</p> <p>Methods</p> <p>Physicians selected from Malaysia, Taiwan, Philippines, Korea and Singapore were asked to grade the significance of vitamin D and calcium in the treatment of osteoporosis and their patients' use of these supplements. In addition, physicians recruited seven eligible osteoporotic women to answer a questionnaire to determine their use of vitamin D and calcium, and their attitudes and beliefs regarding these supplements.</p> <p>Results</p> <p>In total, 237 physicians and 1463 osteoporosis patients completed the questionnaire. The results revealed that 22% of physicians in Malaysia, 12% in Taiwan, 72% in the Philippines, 50% in Korea and 24% in Singapore rated the importance of vitamin D supplementation as being extremely important. For calcium, 27% of physicians in Malaysia, 30% in Taiwan, 80% in the Philippines, 50% in Korea and 38% in Singapore rated the importance as being extremely important. Forty-three percent of patients in Malaysia, 38% in Taiwan, 73% in the Philippines, 35% in Korea and 39% in Singapore rated the importance of vitamin D as being extremely important. For calcium, 69% of patients in Malaysia, 58% in Taiwan, 90% in the Philippines, 70% in Korea and 55% in Singapore rated the importance as being extremely important. In addition, results of the patient questionnaire revealed that only a very small number regularly took both supplements. In addition, the results indicated that, with the exception of patients from the Philippines, the majority of patients had no or infrequent discussion with their physician about vitamin D and calcium.</p> <p>Conclusions</p> <p>There is generally suboptimal appreciation by both physicians and patients of the importance of vitamin D and calcium for maintenance of bone health as reflected in the low number of patients who reported regularly taking these supplements. Recognition of this problem should translate to appropriate action to improve education for both physicians and patients, with a goal to increase use of these supplements among Asian patients with osteoporosis.</p

Influence of sex hormones on the periodontium

Objectives : Sex hormones have long been considered to play an influential role on periodontal tissues, bone turnover rate, wound healing and periodontal disease progression. The objectives of this review article are to (1) address the link between sex hormones and the periodontium, (2) analyse how these hormones influence the periodontium at different life times and (3) discuss the effects of hormone supplements/replacement on the periodontium. Materials and Methods : Two autonomous searches were performed in English language utilizing Medline, Premedline and Pubmed as the online databases. Publications up to 2002 were selected and further reviewed. In addition, a manual search was also performed including specific related journals and books. Results : It is certain that sexual hormones play a key role in periodontal disease progression and wound healing. More specifically, these effects seem to differentiate by gender as well as lifetime period. In addition, the influence of sex hormones can be minimized with good plaque control and with hormone replacement. Conclusion : Despite profound research linking periodontal condition with sex hormones kinetics, more definitive molecular mechanisms and therapy still remain to be determined.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75598/1/j.1600-051X.2003.00055.x.pd