Bias in IGF-1 concentrations and interpretation across three different clinical laboratory assays.

In this study, we compared the DiaSorin LiaisonXL IGF-1 immunoassay to both the Roche Elecsys IGF-1 immunoassay and to the liquid chromatography-high resolution mass spectrometry (LC-MS) IGF-1 assay. Our study shows a constant positive bias in DiaSorin compared to the Roche immunoassay (mean 42 µg/L, 24%), and a proportional positive bias in DiaSorin compared to the LC-MS method (mean 49 µg/L, 29%). Further, we demonstrate the potential clinical impact of this bias by evaluating 43 adult samples, collected over a 2-month period, which were shown to be discrepant based on a chart review. Despite the positive analytical bias in the Diasorin assay compared to the LC-MS assay, the Diasorin assay upper reference limits were lower than those of the LC-MS assay. This effect caused nine out of forty-three samples to show falsely elevated results when they were clinically diagnosed as negative for acromegaly. Discussed in the context of previous literature, our findings emphasize the importance of adjusting reference intervals for IGF-1 assays based on the clinical needs of a patient population.

Resection of the medial wall of the cavernous sinus in functioning pituitary adenomas: Technical note and outcomes in a matched-cohort study.

BACKGROUND: Parasellar dural invasion can be associated with treatment failure after excision of functioning pituitary adenomas. Because the medial wall of the cavernous sinus is a common site of microscopic disease, we hypothesize that its resection may lead to improvement in biochemical remission and recurrence rates. We aim to describe our technique in the resection of the medial wall of the cavernous sinus using binasal endoscopic transsphenoidal surgery (BETS); and compare tumor control and biochemical remission rates against a matched cohort. METHODS: Patients with functioning pituitary adenomas who underwent resection of the medial cavernous wall in addition to tumor excision via BETS were compared to a cohort matched for tumor type, size, and Knosp grade. Biochemical remission rates, tumor control at follow-up, and complication rates were assessed. RESULTS: Sixteen patients underwent resection of the medial wall of the cavernous sinus. Of 14 cases with wall specimens deemed adequate for histopathologic analysis, 43 % had microscopic evidence of tumor. Two of three patients with Knosp grade 0 scores had microscopic tumor invasion of the medial wall. The mean blood loss in the cohort was 175 mL (comparable to control, p = 0.895), with no operative complications noted. Gross total excision was achieved in 81 % of cases in the treatment cohort. At a median follow-up of 11 months, no statistical difference was noted in the biochemical remission and oncologic control rates between groups. CONCLUSION: Resection of the medial wall of the cavernous sinus is safe and technically feasible using BETS when performed by experienced surgeons. The Knosp classification may not be reliable for microscopic tumor invasion. The effect of this technique on clinical outcomes remains to be determined by larger cohorts with matched controls and long-term follow-up.

Recovery Room Cortisol Predicts Long-Term Glucocorticoid Need After Transsphenoidal Surgery for Pituitary Tumors.

BACKGROUND: Accurate assessment of the need for glucocorticoid therapy is essential after transsphenoidal surgery (TSS) for pituitary tumors. Agreement on the best test to use in the early postoperative setting is lacking. OBJECTIVE: To examine recovery room (RR) cortisol as a predictor of long-term need for glucocorticoids. METHODS: We conducted a retrospective cohort study of 149 patients who underwent TSS for pituitary tumors between January 2007 and December 2014. Pathological tumor diagnoses were confirmed. Endocrinologists assessed the need for glucocorticoid supplementation within 6 to 8 wk after TSS. We extracted data on preoperative, RR, and day 1 to 3 post-TSS morning serum cortisol (MSC). We reported areas under the receiver operating characteristic curve (AUC) and diagnostic measures for different cortisol measures. We also conducted a logistic regression to identify the most predictive variables. RESULTS: Eighteen patients required glucocorticoid supplementation at follow-up. RR cortisol was the most accurate measurement in the early postoperative period (AUC [95% confidence interval (CI)], .92 [.85-.99]; P < .001), followed by day 1, 2, and 3 post-TSS MSC, respectively. A threshold RR cortisol of 744.0 nmol/L (26.97 µg/dL) had 90.9% sensitivity and 73.7% specificity for detecting patients in the hypocortisolism group, while 757.5 nmol/L (27.46 µg/dL) had 100% and 70.0%, respectively. The logistic regression identified RR cortisol as the sole significant predictor (odds ratio [CI], .36[.18-.71] for every 100 nmol/L increase; P = .0033). CONCLUSION: The RR cortisol is accurate in predicting long-term glucocorticoid supplementation and may be the best early postoperative measure. Future larger studies should validate these findings and derive optimal RR cortisol threshold values.

Tools for Enhancement and Quality Improvement of Peer Assessment and Clinical Care in Endocrinology and Metabolism.

Members of the College of Physicians and Surgeons of Ontario Endocrinology and Metabolism Peer Review Network have been involved in a quality improvement project to help standardize the peer assessment of physicians practicing in endocrinology and metabolism. This has included developing state-of-the-art summaries of common endocrine problems by Canadian experts in endocrinology and metabolism. These tools have been developed in response to the educational needs, as identified by peer reviewers, of practicing endocrinologists in Ontario. These pedagogical tools aim not only to standardize the documentation of the clinical performance of endocrinologists but also to make the process more transparent and to improve the quality of patient care in Ontario. This article summarizes the project and also provides the tools developed for the endocrinology and metabolism section of the College of Physicians and Surgeons of Ontario.

Canadian Cardiovascular Society Position Statement on Familial Hypercholesterolemia: Update 2018.

Familial hypercholesterolemia (FH) is the most common monogenic disorder causing premature atherosclerotic cardiovascular disease. It affects 1 in 250 individuals worldwide, and of the approximately 145,000 Canadians estimated to have FH, most are undiagnosed. Herein, we provide an update of the 2014 Canadian Cardiovascular Society position statement on FH addressing the need for case identification, prompt recognition, and treatment with statins and ezetimibe, and cascade family screening. We provide a new Canadian definition for FH and tools for clinicians to make a diagnosis. The risk of atherosclerotic cardiovascular disease in patients with "definite" FH is 10- to 20-fold that of a normolipidemic individual and initiating treatment in youth or young adulthood can normalize life expectancy. Target levels for low-density lipoprotein cholesterol are proposed and are aligned with the Canadian Cardiovascular Society guidelines on dyslipidemia. Recommendation for the use of inhibitors of proprotein convertase kexin/subtilisin type 9 are made in patients who cannot achieve therapeutic low-density lipoprotein cholesterol targets on maximally tolerated statins and ezetimibe. The writing committee used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology in the preparation of the present document, which offers guidance for practical evaluation and management of patients with FH. This position statement also aims to raise awareness of FH nationally, and to mobilize patient support, promote knowledge translation, and availability of treatment and health care resources for this under-recognized, but important medical condition.

Developing a set of indicators to monitor quality in ambulatory diabetes care using a modified Delphi panel process.

OBJECTIVE: There is a large evidence to practice gap in diabetes care with limited performance assessments that capture the full spectrum of care delivery. Our study aimed to develop a set of ambulatory diabetes quality indicators across six domains (effectiveness, safety, patient-centered, timely, equitable and efficient) to provide a broad view of quality. DESIGN: A modified Delphi panel process was conducted. Phase I involved compiling a list of indicators through literature review and generation of patient and healthcare provider-derived indicators through interviews and surveys, respectively. Phase II involved panelists rating indicators using the Agency for Healthcare Research and Quality measure attributes on 9-point Likert scale, attending a face-to-face meeting followed by re-rating, and final ranking. SETTING: This study was conducted across five adult academic medical centers affiliated with the University of Toronto. PARTICIPANTS: A multi-disciplinary Delphi panel (n = 16) including patients was assembled. MAIN OUTCOME MEASURE: For indicator advancement for ranking, ≥75% of panelists' responses in the top tertile (between 7 and 9) with a median composite score of ≥7 was required. RESULTS: There were 202 indicators included in the Delphi panel process including 171 from a comprehensive literature review, 14 from patient interviews, and 17 from healthcare provider surveys. Following the first round, 40 indicators proceeded directly to ranking, while 162 indicators were re-rated and distilled down to 12 for ranking. In the final ranking round, the 52 indicators were reduced to 35 including 13 effective, 10 safe, 6 patient-centered, 1 equitable, 3 efficient and 2 timely indicators. CONCLUSION: Thirty-five selected indicators developed with broad stakeholder engagement can be used to monitor quality in diabetes care.

Faculty-Resident "Co-learning": A Longitudinal Exploration of an Innovative Model for Faculty Development in Quality Improvement.

PURPOSE: To examine the effectiveness of co-learning, wherein faculty and trainees learn together, as a novel approach for building quality improvement (QI) faculty capacity. METHOD: From July 2012 through September 2015, the authors conducted 30 semistructured interviews with 23 faculty participants from the Co-Learning QI Curriculum of the Department of Medicine, Faculty of Medicine, University of Toronto, and collected descriptive data on faculty participation and resident evaluations of teaching effectiveness. Interviewees were from 13 subspecialty residency programs at their institution. RESULTS: Of the 56 faculty participants, the Co-Learning QI Curriculum trained 29 faculty mentors, 14 of whom taught formally. Faculty leads with an academic QI role, many of whom had prior QI training, reinforced their QI knowledge while also developing QI mentorship and teaching skills. Co-learning elements that contributed to QI teaching skills development included seeing first how the QI content is taught, learning through project mentorship, building experience longitudinally over time, a graded transition toward independent teaching, and a supportive program lead. Faculty with limited QI experience reported improved QI knowledge, skills, and project facilitation but were ambivalent about assuming a teacher role. Unplanned outcomes for both groups included QI teaching outside of the curriculum, applying QI principles to other work, networking, and strengthening one's QI professional role. CONCLUSIONS: The Co-Learning QI Curriculum was effective in improving faculty QI knowledge and skills and increased faculty capacity to teach and mentor QI. Findings suggest that a combination of curriculum and contextual factors were critical to realizing the curriculum's full potential.

Epistemology, culture, justice and power: non-bioscientific knowledge for medical training.

CONTEXT: While medical curricula were traditionally almost entirely comprised of bioscientific knowledge, widely accepted competency frameworks now make clear that physicians must be competent in far more than biomedical knowledge and technical skills. For example, of the influential CanMEDS roles, six are conceptually based in the social sciences and humanities (SSH). Educators frequently express uncertainty about what to teach in this area. This study concretely identifies the knowledge beyond bioscience needed to support the training of physicians competent in the six non-Medical Expert CanMEDS roles. METHODS: We interviewed 58 non-clinician university faculty members with doctorates in over 20 SSH disciplines. We abstracted our transcripts (meaning condensation, direct quotations) resulting in approximately 300 pages of data which we coded using top-down (by CanMEDS role) and bottom-up (thematically) approaches and analysed within a critical constructivist framework. Participants and clinicians with SSH PhDs member-checked and refined our results. RESULTS: Twelve interrelated themes were evident in the data. An understanding of epistemology, including the constructed nature of social knowledge, was seen as the foundational theme without which the others could not be taught or understood. Our findings highlighted three anchoring themes (Justice, Power, Culture), all of which link to eight more specific themes concerning future physicians' relationships to the world and the self. All 12 themes were cross-cutting, in that each related to all six non-Medical Expert CanMEDS roles. The data also provided many concrete examples of potential curricular content. CONCLUSIONS: There is a definable body of SSH knowledge that forms the academic underpinning for important physician competencies and is outside the experience of most medical educators. Curricular change incorporating such content is necessary if we are to strengthen the non-Medical Expert physician competencies. Our findings, particularly our cross-cutting themes, also provide a pedagogically useful mechanism for holistically teaching the underpinnings of physician competence. We are now implementing our findings into medical curricula.

Examining the "Killer K" of Diabetic Ketoacidosis at a Tertiary Care Hospital: An Exploratory Study.

OBJECTIVES: Hypokalemia, a frequently cited complication of diabetic ketoacidosis (DKA) treatment, can have critical implications, including arrhythmias and death. We assessed the prevalence of hypokalemia and its associated factors in patients with DKA at our tertiary-care centre and identified opportunities to improve care. METHODS: We conducted a retrospective chart review to establish the prevalence of hypokalemia in patients diagnosed with DKA between July 2012 and July 2013. A focused root-cause analysis was subsequently performed to identify Canadian Diabetes Association DKA clinical practice guideline deviations and preventable errors that resulted in significant hypokalemia (K<3.3 mmol/L) during the first 48 hours of management. Clinical and management details were reviewed to determine the type, preventability and root cause(s) of each error. RESULTS: We identified 40 cases of DKA during the study period. The overall prevalence of hypokalemia during DKA treatment was 38% (15/40), with 25% in type 1 and 56% in type 2 diabetes. Males were more likely to experience hypokalemia (87%), and 47% of hypokalemic incidents occurred in the first presentation of diabetes. All 10 cases of significant hypokalemia were reviewed. We identified 23 errors in 6 (60%) cases, of which 87% were deemed to be preventable. The most common errors were noncessation of insulin infusion during hypokalemia (60%), inadequate potassium supplementation (50%) and infrequent biochemical monitoring (50%). CONCLUSIONS: Hypokalemia occurs frequently during acute DKA management and is often preventable. Our findings suggest that interventions targeted at enhancing awareness of guidelines may reduce hypokalemia rates.

Endoscopic versus microscopic approach for surgical treatment of acromegaly.

Transsphenoidal surgery in the setting of acromegaly is quite challenging due to increased soft tissue mass, bony overgrowth, and bleeding. There is a debate on the endoscopic versus microscopic approach for these patients. The purpose of our study is to compare the outcomes for acromegaly after transsphenoidal surgery using both techniques. Retrospective review of 65 acromegalic patients who underwent transsphenoidal surgery in our department. Clinical remission was defined as resolution of typical acromegalic symptoms. Radiological resection was defined by volumetric criteria, and biochemical remission was defined as by the 2010 consensus on the criteria for remission of acromegaly. There was no significant difference in age, preoperative endocrine status, percent of macro adenomas, suprasellar, or infrasellar extension between both groups. Patients were assigned to both groups based on our existing referral pattern. Endoscopic approach was performed in 42 patients, while the microscopic approach was performed in 23 patients. No significant difference in remission rates was found between both groups (45.2 vs. 34.7 %, p = 0.40). The endoscopic group, however, had a significantly higher rate of gross total resections (61 vs. 42 %, p = 0.05). There was also a trend towards higher rates of gross total resections when cavernous sinus was present (48 vs. 14.2 %, p = 0.09). Postoperative diabetes insipidus occurred more in microscopic patients (34.7 vs. 17 %, p = 0.05), otherwise there was no significant difference in rates of complications. The median follow-up period was 56.6 months (range 6-156, mean 66.1). There is no significant difference in the rates of biochemical remission between the endoscopic and microscopic techniques. The endoscope technique, however, seems to be superior in achieving gross total resection especially with tumors invading the cavernous sinus.

Deliberate practice as a framework for evaluating feedback in residency training.

OBJECTIVE: Using the theory of deliberate practice, a key component of Ericsson's theory of expertise development, this study aims to evaluate the quality of written feedback given to learners. METHODS: The authors created a feedback scoring system based on the key elements of deliberate practice and used it to assess the quality of written feedback provided to residents in 205 mini-CEX encounter forms. Scores were assigned to each feedback entry for identification of the following: Task, performance gap and action plan. RESULTS: The scoring system allowed for reliable identification of the components that facilitate deliberate practice in written feedback provided to trainees. However, only one of these components was identified in 70% of the feedback entries. A specific task was identified in 56%, whereas specific performance gaps and action plans were identified in only 3.9% and 13.7% of encounters, respectively. CONCLUSIONS: Scoring written feedback identified that tasks were often specifically described, but performance gaps and action plans were less frequently and specifically mentioned. Educators might improve feedback effectiveness by better articulating to trainees the gap between their performance and an expert standard, as well as by providing them with specific learning plans.

Persistent posttreatment fatigue in thyroid cancer survivors: a scoping review.

The relevance of persistent posttreatment fatigue (PPF) to thyroid cancer (TC) survivor populations is not known. This article presents a scoping review, which is an overview of published research activity. Uncontrolled data suggest that PPF is one of the most common complaints in TC survivors. Furthermore, statistically significantly worse levels of fatigue were reported in TC survivors, compared with the general population or healthy controls. There was some inconsistency among PPF risk factors. More research is needed on PPF in TC survivors, including long-term prospective cohort studies, research on fatigue severity prevalence, and randomized controlled trials of treatment strategies.

Impact of technique on cushing disease outcome using strict remission criteria.

BACKGROUND: Cushing disease (CD) constitutes a challenging condition for the pituitary surgeon. Given the variety of factors affecting outcomes in CD, it is uncertain whether the newer endoscopic technique improves the results of surgery. METHODS: A review was conducted of CD cases at our institution between 2000 and 2010. Analysis was done to: determine if surgical technique had an effect on outcome, identify the predictors of outcome and provide details of failed cases. Remission was defined as normal postoperative 24-hour urinary free cortisol (24-h UFC), suppression of morning serum cortisol to <50 nmol/L after 1mg of dexamethasone or being dependent on steroid replacement. RESULTS: Forty-two patients met our inclusion criteria. Average follow-up period was 33 months. There were 15 macroadenomas and 27 microadenomas. Seventeen patients had an endoscopic transsphenoidal surgery and twenty-five patients had a microscopic transsphenoidal procedure. Long-term overall remission was achieved in 26 (62%) patients. There was no significant difference in remission rates between the two techniques (p value 0.757). Patient's subjective symptomatic improvement and drop of morning serum cortisol in the postoperative period to less than 100 nmol/L correlated with long-term remission (p value 0.0031 and 0.0101, respectively) while repeat surgery was the only predictor of the lack of postoperative remission (p value 0.0008). CONCLUSIONS: Revision surgery predicted poor remission rate for CD. Within the power of our study size, there was no difference in outcome between the endoscopic and microscopic approaches. Surgical outcomes should be reviewed in association with remission criteria used in a study.

Building capacity for quality: a pilot co-learning curriculum in quality improvement for faculty and resident learners.

BACKGROUND: Despite a mandate to teach quality improvement (QI) to residents, many training programs lack faculty capacity to deliver a QI curriculum. OBJECTIVE: We piloted a co-learning curriculum in QI to train residents while simultaneously developing QI teachers. We evaluated the curriculum's acceptability and feasibility and its effect on faculty engagement in doing and teaching QI. METHODS: The curriculum involved 2 half-day, interactive sessions, a team-based QI project, and end-of-year project presentations. Key curriculum design principles included (1) residents and faculty co-attend all interactive sessions, (2) residents and faculty work together on team-based QI projects, and (3) QI projects align with divisional QI priorities. Using the Kirkpatrick framework for learner outcomes, we focused our program evaluation on Level 1 (satisfaction) and Level 2 (knowledge and skills acquisition) outcomes using year-end curriculum evaluations. RESULTS: Our study included 14 residents (70%) and 6 faculty members (30%). With respect to satisfaction (Kirkpatrick Level 1 outcome), 93% (13 of 14) of residents and 100% (6 of 6) of faculty participants rated the overall curriculum as "above average" or "outstanding." Regarding faculty knowledge and skills acquisition (Kirkpatrick Level 2 outcomes), faculty self-rated their QI knowledge and interest in QI higher than their intent to incorporate QI into future practice and their comfort in teaching or supervising QI projects. All 5 faculty respondents (100%) rated the co-learning model for faculty development in QI as "above average" or "outstanding." CONCLUSIONS: Teaching QI to residents and faculty as co-learners is feasible and acceptable and offers a promising model for programs to teach QI to residents while concurrently building faculty capacity.

Transphenoidal surgery without steroid replacement in patients with morning serum cortisol below 9 µg/dl (250 Nmol/l).

BACKGROUND: Adrenal insufficiency is a feared complication in patients undergoing transphenoidal surgery (TSS). Using the insulin tolerance test (ITT) for the preoperative assessment of hypothalamic-pituitary-adrenal (HPA) status is less than ideal, and the morning serum cortisol (MSC) is often used as a proxy for ITT. However, neither the ITT nor the MSC level has been validated to indicate HPA sufficiency compared to a physiological gold standard such as patients' ability to withstand transphenoidal surgery. OBJECTIVE: To evaluate the intraoperative and postoperative course of nine patients with non-ACTH-secreting pituitary adenomas who did not receive intraoperative cortisol replacement despite having a preoperative MSC below 9 µg/dl (250 nmol/l) and to compare this with a set of patients with a preoperative MSC greater than 14.5 µg/dl (400 nmol/l) and another set of patients with MSC below 9 µg/dl (250 nmol/l) who received intraoperative cortisol administration. METHODS: Preoperative and day 1 and day 2 postoperative MSC, intraoperative anesthetic record, vital signs, fluid balance, medications, and complications were recorded. RESULTS: None of the patients experienced the full syndrome of adrenal insufficiency. One patient with a preoperative MSC <9 µg/dl (250 mol/l) had isolated postoperative fatigue and required cortisol replacement. No patient suffered any life-threatening complications. There were no differences among the three groups in their intraoperative or postoperative courses when compared for intraoperative hypotension, acute blood pressure drop, and administration of vasopressors. CONCLUSION: This study suggests that TSS can be performed safely in patients with preoperative MSC less than 9 µg/dl (250 nmol/l) in closely monitored settings without intraoperative cortisol administration. Further studies are warranted.

Outcomes of surgically treated giant pituitary tumours.

OBJECTIVE: To evaluate the outcomes of patients with giant pituitary tumours (GPTs) who underwent a purely binasal endoscopic transsphenoidal surgery (BETS) and compare their outcomes with those achieved through craniotomy and microscopic transsphenoidal surgery (MTS). METHODS: Seventy-two consecutive patients with GPTs (greater than 10 cm3 in volume) who were treated surgically with BETS, craniotomy, or MTS from October 1994 to July 2009 were reviewed for clinical outcomes, degree of tumor resection, recurrence rates, and surgical complications. RESULTS: The BETS group had significantly better mean reduction of tumor volume (91%) than the craniotomy (63%, p = 0.001), and the MTS (63%, p = 0.010) groups. Gross total resection rates were also higher for BETS patients than for craniotomy patients (p = 0.010). Improvements in vision and headaches were noted in 96% and 100% of patients in the BETS group, respectively; these rates were similar to those in the craniotomy and MTS groups. Of the four patients with hormone-secreting tumours in the BETS group, three remained in remission. The median length-of-stay (four days) for the BETS group was shorter (p = 0.010), and surgical complications were less frequent (p = 0.037) and less severe compared to the craniotomy group. There were no differences in the recurrence rates: 79% percent of patients in the BETS group, 69% in the craniotomy group, and 79% in the MTS group were recurrence free at last follow-up (p = 0.829). CONCLUSIONS: Treatment of GPT with BETS offers excellent oncologic and clinical outcomes and can frequently obviate the need for craniotomy in these patients.

The impact of thyroid cancer and post-surgical radioactive iodine treatment on the lives of thyroid cancer survivors: a qualitative study.

BACKGROUND: Adjuvant treatment with radioactive iodine (RAI) is often considered in the treatment of well-differentiated thyroid carcinoma (WDTC). We explored the recollections of thyroid cancer survivors on the diagnosis of WDTC, adjuvant radioactive iodine (RAI) treatment, and decision-making related to RAI treatment. Participants provided recommendations for healthcare providers on counseling future patients on adjuvant RAI treatment. METHODS: We conducted three focus group sessions, including WDTC survivors recruited from two Canadian academic hospitals. Participants had a prior history of WDTC that was completely resected at primary surgery and had been offered adjuvant RAI treatment. Open-ended questions were used to generate discussion in the groups. Saturation of major themes was achieved among the groups. FINDINGS: There were 16 participants in the study, twelve of whom were women (75%). All but one participant had received RAI treatment (94%). Participants reported that a thyroid cancer diagnosis was life-changing, resulting in feelings of fear and uncertainty. Some participants felt dismissed as not having a serious disease. Some participants reported receiving conflicting messages from healthcare providers on the appropriateness of adjuvant RAI treatment or insufficient information. If RAI-related side effects occurred, their presence was not legitimized by some healthcare providers. CONCLUSIONS: The diagnosis and treatment of thyroid cancer significantly impacts the lives of survivors. Fear and uncertainty related to a cancer diagnosis, feelings of the diagnosis being dismissed as not serious, conflicting messages about adjuvant RAI treatment, and treatment-related side effects, have been raised as important concerns by thyroid cancer survivors.