OBJECTIVE: The purpose of this study was to develop a model for assessing the 5-year risk of developing type 2 diabetes from a panel of 64 circulating candidate biomarkers. RESEARCH DESIGN AND ...METHODS: Subjects were selected from the Inter99 cohort, a longitudinal population-based study of ~6,600 Danes in a nested case-control design with the primary outcome of 5-year conversion to type 2 diabetes. Nondiabetic subjects, aged greater-than-or-equal39 years, with BMI greater-than-or-equal25 kg/m² at baseline were selected. Baseline fasting serum samples from 160 individuals who developed type 2 diabetes and from 472 who did not were tested. An ultrasensitive immunoassay was used to measure of 58 candidate biomarkers in multiple diabetes-associated pathways, along with six routine clinical variables. Statistical learning methods and permutation testing were used to select the most informative biomarkers. Risk model performance was estimated using a validated bootstrap bias-correction procedure. RESULTS: A model using six biomarkers (adiponectin, C-reactive protein, ferritin, interleukin-2 receptor A, glucose, and insulin) was developed for assessing an individual's 5-year risk of developing type 2 diabetes. This model has a bootstrap-estimated area under the curve of 0.76, which is greater than that for A1C, fasting plasma glucose, fasting serum insulin, BMI, sex-adjusted waist circumference, a model using fasting glucose and insulin, and a noninvasive clinical model. CONCLUSIONS: A model incorporating six circulating biomarkers provides an objective and quantitative estimate of the 5-year risk of developing type 2 diabetes, performs better than single risk indicators and a noninvasive clinical model, and provides better stratification than fasting plasma glucose alone.
Patient‐centered care involves an inseparable set of knowledge, abilities, and professional traits on the part of the health care provider. For practical reasons, health professions education is ...segmented into disciplines or domains like knowledge, technical skills, and critical thinking, and the culture of dental education is weighted toward knowledge and technical skills. Critical thinking, however, has become a growing presence in dental curricula. To guide student learning and assess performance in critical thinking, guidelines have been developed over the past several decades in the educational literature. Prominent among these guidelines are the following: engage the student in multiple situations/exercises reflecting critical thinking; for each exercise, emulate the intended activity for validity; gain agreement of faculty members across disciplines and curriculum years on the learning construct, application, and performance assessment protocol for reliability; and use the same instrument to guide learning and assess performance. The purposes of this article are 1) to offer a set of concepts from the education literature potentially helpful to guide program design or corroborate existing programs in dental education; 2) to offer an implementation model consolidating these concepts as a guide for program design and execution; 3) to cite specific examples of exercises and programs in critical thinking in the dental education literature analyzed against these concepts; and 4) to discuss opportunities and challenges in guiding student learning and assessing performance in critical thinking for dentistry.
The educational application of critical thinking has increased in the last twenty years with programs like problem‐based learning. Performance measurement related to the dental student's capacity for ...critical thinking remains elusive, however. This article offers a model now in use to measure critical thinking applied to patient assessment and treatment planning across the four years of the dental school curriculum and across clinical disciplines. Two elements of the model are described: 1) a critical thinking measurement “cell,” and 2) a list of minimally essential steps in critical thinking for patient assessment and treatment planning. Issues pertaining to this model are discussed: adaptations on the path from novice to expert, the role of subjective measurement, variations supportive of the model, and the correlation of individual and institutional assessment. The critical thinking measurement cell consists of interacting performance tasks and measures. The student identifies the step in the process (for example, chief complaint) with objective measurement; the student then applies the step to a patient or case with subjective measurement; the faculty member then combines the objective and subjective measurements into an evaluation on progress toward competence. The activities in the cell are then repeated until all the steps in the process have been addressed. A next task is to determine consistency across the four years and across clinical disciplines.
Purpose: To assess performance of a biomarker-based score that predicts the five-year risk of diabetes (Diabetes Risk Score, DRS) in an independent cohort that included 15-year follow-up.
Method: DRS ...was developed on the Inter99 cohort, and validated on the Botnia cohort. Performance was benchmarked against other risk-assessment tools comparing calibration, time to event analysis, and net reclassification.
Results: The area under the receiver-operating characteristic curve (AUC) was 0.84 for the Inter99 cohort and 0.78 for the Botnia cohort. In the Botnia cohort, DRS provided better discrimination than fasting plasma glucose (FPG), homeostasis model assessment of insulin resistance, oral glucose tolerance test or risk scores derived from Framingham or San Antonio Study cohorts. Overall reclassification with DRS was significantly better than using FPG and glucose tolerance status (p < 0.0001). In time to event analysis, rates of conversion to diabetes in low, moderate, and high DRS groups were significantly different (p < 0.001).
Conclusion: This study validates DRS performance in an independent population, and provides a more accurate assessment of T2DM risk than other methods.
A concise overview of an institution's aspirations for its students becomes increasingly elusive because dental education has evolving emphases on priorities like critical thinking and adapting to ...new technology. The purpose of this article is to offer a learner‐oriented matrix that gives a focus for discussion and an overview of an institution's educational outcomes. On one axis of the matrix, common educational outcomes are listed: knowledge, technical skills, critical thinking, ethical and professional values, patient and practice management, and social responsibility awareness. On the other axis, methodologies are listed: definition, cultivation strategies, measures (summative/formative, objective/subjective), institutional coordination, and competency determination. By completing the matrix, an overview of the process by which students reach these outcomes emerges. Each institution would likely complete the matrix differently and, ideally, with active discussion. While the matrix can first be used to establish “Where are we now?” for an institution, it can also be a starting point for more extensive matrices and further discussion. Vertical and horizontal analyses of the matrix provide a unique lens for viewing the institution's learning environment.
Risks of Complication Following Thyroidectomy Burge, Mark R.; Zeise, Tanja‐Maria; Johnsen, Michael W. ...
Journal of general internal medicine,
January 1998, 1998, 1998-Jan, 1998-1-00, 19980101, Letnik:
13, Številka:
1
Journal Article, Conference Proceeding
Recenzirano
Odprti dostop
OBJECTIVE:
Because hypoparathyroidism is a serious complication of thyroidectomy, we attempted to elucidate factors determining the risk of this postoperative outcome.
SETTING:
Four tertiary care ...hospitals in Albuquerque, New Mexico.
PATIENTS:
A retrospective study of 142 patients who underwent total or subtotal thyroidectomy between 1988 and 1995.
MEASUREMENTS AND MAIN RESULTS:
Permanent hypoparathyroidism was defined as hypocalcemic symptoms plus a requirement for oral vitamin D or calcium 6 months after thyroidectomy. Factors analyzed to determine their contribution to the risk of persistent postoperative hypoparathyroidism were the indication for thyroidectomy, performance of a preoperative thyroid needle biopsy, type of surgery, postoperative pathology, presence and stage of thyroid carcinoma, resident surgeon involvement, and specialty of the surgeon performing the procedure. Surgical specialty and stage of thyroid carcinoma were independent risk factors for persistent postoperative hypoparathyroidism by multivariate analysis. Nine (29%) of 31 patients who had thyroidectomy by otolaryngologists met criteria for permanent hypoparathyroidism, and 6 (5%) of 111 patients who had thyroidectomy by general surgeons met the same criteria ( p < .001). Adjustment for the effect of stage did not eliminate the effect of specialty ( p= .006), and adjustment for the effect of specialty did not eliminate the effect of stage ( p= .02), on the occurrence of postoperative hypoparathyroidism.
CONCLUSIONS:
We conclude from our data that patients undergoing thyroidectomy by an otolaryngologist may be at a higher risk of permanent postoperative hypoparathyroidism than patients who undergo thyroidectomy by a general surgeon. This may reflect differences in case selection or surgical approach or both.
KEY WORDS:
thyroidectomy; surgical complications; hypoparathyroidism; hypocalcemia; thyroid carcinoma.
Tumor genetic testing is standard of care for patients with advanced lung adenocarcinoma, but the fraction of patients who derive clinical benefit remains undefined. Here, we report the experience of ...860 patients with metastatic lung adenocarcinoma analyzed prospectively for mutations in >300 cancer-associated genes. Potentially actionable genetic events were stratified into one of four levels based upon published clinical or laboratory evidence that the mutation in question confers increased sensitivity to standard or investigational therapies. Overall, 37.1% (319/860) of patients received a matched therapy guided by their tumor molecular profile. Excluding alterations associated with standard-of-care therapy, 14.4% (69/478) received matched therapy, with a clinical benefit of 52%. Use of matched therapy was strongly influenced by the level of preexistent clinical evidence that the mutation identified predicts for drug response. Analysis of genes mutated significantly more often in tumors without known actionable mutations nominated
and
as possible targetable mitogenic drivers.
An increasing number of therapies that target molecular alterations required for tumor maintenance and progression have demonstrated clinical activity in patients with lung adenocarcinoma. The data reported here suggest that broader, early testing for molecular alterations that have not yet been recognized as standard-of-care predictive biomarkers of drug response could accelerate the development of targeted agents for rare mutational events and could result in improved clinical outcomes.
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Bardet-Biedl syndrome (BBS) is a genetically heterogeneous developmental disorder whose molecular basis is largely unknown. Here, we show that mutations in the Caenorhabditis elegans bbs-7 and bbs-8 ...genes cause structural and functional defects in cilia. C. elegans BBS proteins localize predominantly at the base of cilia, and like proteins involved in intraflagellar transport (IFT), a process necessary for cilia biogenesis and maintenance, move bidirectionally along the ciliary axoneme. Importantly, we demonstrate that BBS-7 and BBS-8 are required for the normal localization/motility of the IFT proteins OSM-5/Polaris and CHE-11, and to a notably lesser extent, CHE-2. We propose that BBS proteins play important, selective roles in the assembly and/or function of IFT particle components. Our findings also suggest that some of the cardinal and secondary symptoms of BBS, such as obesity, diabetes, cardiomyopathy, and learning defects may result from cilia dysfunction.
Abstract Purpose Development of secondary central nervous system involvement (SCNS) in patients with diffuse large B-cell lymphoma is associated with poor outcomes. The CNS International Prognostic ...Index (CNS-IPI) has been proposed for identifying patients at greatest risk, but the optimal model is unknown. Methods We retrospectively analysed patients with diffuse large B-cell lymphoma diagnosed between 2001 and 2013, staged with PET/CT and treated with R-CHOP(-like) regimens. Baseline clinicopathologic characteristics, treatments, and outcome data were collected from clinical databases and medical files. We evaluated the association between candidate prognostic factors and modelled different risk models for predicting SCNS. Results Of 1532 patients, 62 (4%) subsequently developed SCNS. By multivariate analysis, disease stage III/IV, elevated serum LDH, kidney/adrenal and uterine/testicular involvement were independently associated with SCNS. There was a strong correlation between absolute number of extranodal sites and risk of SCNS; the 144 patients (9%) with >2 extranodal sites had a 3-year cumulative incidence of SCNS of 15.2% (95% confidence interval CI 9.2–21.2%) compared with 2.6% (95% CI 1.7–3.5) among those with ≤2 sites ( P < 0.001). The 3-year cumulative risks of SCNS for CNS-IPI defined risk groups were 11.2%, 3.1% and 0.4% for high-, intermediate- and low-risk patients, respectively. All risk models analysed had high negative predictive values, but only modest positive predictive values. Conclusions Patients with >2 extranodal sites or high-risk disease according to the CNS-IPI should be considered for baseline CNS staging. Clinical risk prediction models suffer from limited positive predictive ability, highlighting the need for more sensitive biomarkers to identify patients at highest risk of this devastating complication.
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