The Prospective Implementation of the 2015 ATA Guidelines and Modified ATA Recurrence Risk Stratification System for Treatment of Differentiated Thyroid Cancer in a Canadian Tertiary Care Referral Setting.

Objective: To present clinical outcomes of the prospective implementation of the 2015 American Thyroid Association (ATA) guidelines for the management of thyroid nodules and differentiated thyroid cancer (DTC) using the modified ATA recurrence risk (RR) stratification system. Methods: We prospectively analyzed 612 patients with DTC treated between April 2017 and December 2021 in Calgary, Alberta. Each patient was prospectively assigned a modified ATA RR and American Joint Committee Cancer 8th edition stage. Initial risk stratification and consideration of the 2015 ATA guidelines guided surgical management as well as the indication for and dose of radioiodine (RAI) and other adjuvant therapies. Patients were assessed for their response to treatment (RTT) at 2-years postoperatively. Results: There were 479 patients who had 2-year follow-up data and were included in the study. Of these patients, there were 253 (53%) low-, 129 (27%) intermediate-, and 97 (20%) high-RR patients. Of these, 227 patients (47%) underwent total thyroidectomy (TTX) plus RAI, 178 (37%) underwent TTX only, and 74 (16%) underwent lobectomy. The RTT at 2 years was excellent for 89% (66) of patients with lobectomy, 84% (149) for TTX only, and 53% (121) for TTX plus RAI. Among 253 patients who were deemed low RR, 85% (216) had excellent RTT, 13% (32) indeterminate RTT, 2% (4) biochemical incomplete RTT, and 1 patient had structural incomplete RTT. The intermediate RR group had the following RTT outcomes: 64% (83) excellent, 23% (30) indeterminate, 6% (7) biochemical incomplete, and 7% (9) structural incomplete. The high RR group had the worst RTT outcomes, with 38% (37) excellent, 19% (18) indeterminate, 10% (10) biochemical incomplete, and 33% (32) structural incomplete RTT. Conclusions: The 2015 ATA RR stratification system is useful for predicting disease status at 2-year post-treatment in patients with DTC. The 2015 ATA guidelines and modified ATA RR stratification treatment recommendations may reduce thyroid cancer overtreatment by including lobectomy as a definitive treatment option for low-risk thyroid cancers and selective use of RAI for intermediate and high-risk patients.

Performance of Confirmatory Tests for Diagnosing Primary Aldosteronism: a Systematic Review and Meta-Analysis.

BACKGROUND: Confirmatory tests are recommended for diagnosing primary aldosteronism, but the supporting evidence is unclear. METHODS: We searched Medline, EMBASE, and the Cochrane Central Register of Controlled Trials. Studies evaluating any guideline-recommended confirmatory test (ie, saline infusion test, salt loading test, fludrocortisone suppression test, and captopril challenge test), compared with a reference standard were included. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to assess the risk of bias. Meta-analyses were conducted using hierarchical summary receiver operating characteristic models. RESULTS: Fifty-five studies were included, comprising 26 studies (3654 participants) for the recumbent saline infusion test, 4 studies (633 participants) for the seated saline infusion test, 2 studies (99 participants) for the salt loading test, 7 studies (386 participants) for the fludrocortisone suppression test, and 25 studies (2585 participants) for the captopril challenge test. Risk of bias was high, affecting more than half of studies, and across all domains. Studies with case-control sampling overestimated accuracy by 7-fold (relative diagnostic odds ratio, 7.26 [95% CI, 2.46-21.43]) and partial verification or use of inconsistent reference standards overestimated accuracy by 5-fold (5.12 [95% CI, 1.48-17.77]). There were large variations in how confirmatory tests were conducted, interpreted, and verified. Under most scenarios, confirmatory testing resulted in an excess of missed cases. The certainty of evidence underlying each test (Grading of Recommendations, Assessment, Development, and Evaluations) was very low. CONCLUSIONS: Recommendations for confirmatory testing in patients with abnormal screening tests and high probability features of primary aldosteronism are based on very low-quality evidence and their routine use should be reconsidered.

A retrospective review of the community medicine needs from osteoporosis services in Canada.

BACKGROUND: Comprehensive, real-world osteoporosis care has many facets not explicitly addressed in practice guidelines. We sought to determine the areas of knowledge and practice needs in osteoporosis medicine for the purpose of developing an osteoporosis curriculum for specialist trainees and knowledge translation tools for primary care. METHODS: This was a retrospective review of referral questions received from primary care and specialists to an academic, multi-disciplinary tertiary osteoporosis and metabolic bone clinic. There were 400 referrals in each of 5 years (2015-2019) selected randomly for review. The primary referral question was elucidated and assigned to one of 16 pre-determined referral topics reflecting questions in the care of osteoporosis and metabolic bone patients. The top 7 referral topics by frequency were determined while recording the referral source. RESULTS: The majority of referrals (71%) came from urban primary care. The most common specialists to request care included rheumatology, oncology, gastroenterology and orthopedic surgery (fracture liaison services). Primary care referrals predominantly requested assistance with routine osteoporosis assessments, bisphosphonate holidays, bisphosphonate adverse effects/alternatives, fractures occurring despite therapy and adverse changes on bone densitometry despite treatment. Specialists most often referred patients with complex secondary bone diseases or cancer. The main study limitation was that knowledge needs of referring physicians were inferred from the referral question rather than tested directly. CONCLUSION: By assessing actual community demand for services, this study identified several such topics that may be useful targets to develop high quality knowledge translation tools and curriculum design in programs training specialists in osteoporosis care.

Accuracy of Thyroid Fine-Needle Aspiration Cytology: A Cyto-Histologic Correlation Study in an Integrated Canadian Health Care Region with Centralized Pathology Service.

INTRODUCTION: The reported ROM within TBSRTC categories varies widely and depends on several factors in the clinical care pathway for thyroid nodules, including sonographic risk stratification, cytology expertise, selection criteria for surgical resection, and definitions of malignancy used. METHODS: We present 5,867 consecutive thyroid FNAC and corresponding surgical pathology in the context of a comprehensive, single-payer health care system with centralized cytology and surgical pathology services for over 1.5 million inhabitants. RESULTS: We report higher usage of ND and AUS/FLUS categories than the literature (19% vs. <10% and 15% vs. <10%, respectively). Our surgical resection rate for malignant cytology is substantially higher than the literature (94% vs. 50%, respectively). The ROM by the TBSRTC category in our cohort was similar to the literature. The overall diagnostic accuracy of thyroid FNAC was 92%, which is similar to other studies. Inclusion of incidental PMC as histologically malignant raised the ROM in the ND, benign, and AUS/FLUS categories. DISCUSSION: The diagnostic performance of thyroid FNAC in our study is similar to the reported literature. Differences in TBSRTC category usage likely arise from cytologist variability and expertise. Our higher surgical resection rate in the malignant cytology category reflects the greater capture of surgical follow-up within our healthcare region with centralized pathology and a single EMR system. Keeping in mind the method of calculation of ROM, the malignancy rate by TBSRTC is similar to previous reports.

Comparison of k-wire insertion using oscillatory and unidirectional drilling modes under constant thrust force.

Heat generation during the Kirschner wire (K-wire) insertion process, under either unidirectional or oscillatory drilling mode, places bone at risk of thermal osteonecrosis which can lead to infection. There is a lack of quantitative understanding of the heat generation difference between the two drilling modes and knowledge of optimal thrust force level under each mode is missing. The goal of this study is to investigate the effects of drilling modes and thrust force levels on the bone drilling outcomes. Controlled machine-based constant thrust force K-wire insertion experiments were conducted with key process parameters monitored and compared quantitatively. Statistical analysis showed that the oscillatory mode consumed 2.6 times more electricity than the unidirectional mode but generated 53% less thermal energy and 23% lower peak temperature. However, the oscillation also led to 18% higher peak torque in the transient drilling stage and 23% shallower drilling depth. The optimal choice of the drilling mode depends on specific surgical needs to minimize bone damage (control of peak temperature vs. exposure time and torque control). Heat generation was dominated by the torque and corresponding rotational power under both modes. To minimize the bone temperature while keeping high drilling speed efficiency, a moderate thrust force is preferred under the unidirectional mode to balance between feed force and compressed debris resistance. For oscillatory mode, a small thrust force to keep the K-wire engaged with the bone is optimal.

Comparison of 2 fracture risk estimation processes in Alberta: a cross-sectional chart review.

BACKGROUND: In Canada, decisions regarding osteoporosis pharmacotherapy are based on estimated 10-year risk of osteoporotic fracture. We aimed to determine how frequently 2 common approaches (Canadian Association of Radiologists and Osteoporosis Canada [CAROC] tool and Fracture Risk Assessment Tool [FRAX]) produced different estimates and to seek possible explanations for differences. METHODS: We conducted a cross-sectional chart review at a tertiary osteoporosis centre (Dr. David Hanley Osteoporosis Centre in Calgary). Included patients were women referred for consideration of osteoporosis pharmacotherapy who attended a consultation between 2016 and 2019 and whose charts contained 10-year osteoporotic fracture risk estimates using both the CAROC tool (based on bone mineral density [BMD] results) and FRAX (based on BMD results and clinically assessed fracture risk factors). Risk estimates provided on BMD reports (calculated with CAROC) and generated through osteoporosis clinic consultation (calculated with FRAX, including BMD) were categorized as low (< 10.0%), moderate (10.0%-19.9%) or high (≥ 20.0%). Estimates were considered discordant when they placed the patient in different risk categories. RESULTS: Of 190 patients evaluated, 99 (52.1%) had discordant risk estimates. Although a similar proportion were considered high risk by BMD reports using the CAROC tool (17.9%) and clinic charts using FRAX (19.5%), the 2 methods identified different patients as being high risk. Around the crucial high-risk (20.0%) treatment threshold, discordance was present in 37 patients (19.5%, 95% confidence interval [CI] 14.5%-25.7%); discordance around the moderate-risk (10.0%) threshold was present in 69 (36.3%, 95% CI 29.5%-43.2%) patients. Disagreement regarding fracture history between BMD reports and clinic charts was observed in 19.8% of patients. INTERPRETATION: Fracture risk estimates on BMD reports (using the CAROC tool) and those calculated in the clinical setting (using FRAX) frequently result in different risk classification. Osteoporosis treatment decisions may differ in up to half of patients depending on which estimate is used, highlighting the need for a consistent and accurate assessment process for fracture risk.

Levothyroxine prescribing and laboratory test use after a minor change in reference range for thyroid-stimulating hormone.

BACKGROUND: Prescribing of levothyroxine and rates of thyroid function testing may be sensitive to minor changes in the upper limit of the reference range for thyroid-stimulating hormone (TSH) that increase the proportion of abnormal results. We evaluated the population-level change in levothyroxine prescribing and TSH testing after a minor planned decrease in the upper limit of the reference range for TSH in a large urban centre with a single medical laboratory. METHODS: Using provincial administrative data, we compared predicted volumes of TSH tests with actual TSH test volumes before and after a planned change in the TSH reference range. We also determined the number of new levothyroxine prescriptions for previously untreated patients and the rate of changes to the prescribed dose for those on previously stable, long-term levothyroxine therapy before and after the change in the TSH reference range. RESULTS: Before the change in the TSH reference range, actual and predicted monthly volumes of TSH testing followed an identical course. After the change, actual test volumes exceeded predicted test volumes by 7.3% (95% confidence interval [CI] 5.3%-9.3%) or about 3000 to 5000 extra tests per month. The proportion of patients with newly "abnormal" TSH results almost tripled, from 3.3% (95% CI 3.2%-3.4%) to 9.1% (95% CI 9.0%-9.2%). The rate of new levothyroxine prescriptions increased from 3.24 (95% CI 3.15-3.33) per 1000 population in 2013 to 4.06 (95% CI 3.96-4.15) per 1000 population in 2014. Among patients with preexisting stable levothyroxine therapy, there was a significant increase in the number of dose escalations (p < 0.001) and a total increase of 500 new prescriptions per month. INTERPRETATION: Our findings suggest that clinicians may have responded to mildly elevated TSH results with new or increased levothyroxine prescriptions and more TSH testing. Knowledge translation efforts may be useful to accompany minor changes in reference ranges.

Ultrafast photodissociation dynamics of pyrazole, imidazole and their deuterated derivatives using ab initio multiple cloning.

We present results obtained using the ab initio multiple cloning (AIMC) method to simulate fully quantum dynamics for imidazole and its structural isomer pyrazole along with their selectively deuterated species. We simulate the ultrafast dissociation of the N-H/D bond for these molecules along the repulsive 1πσ* state which agrees well with previous experimental results. Our results give evidence for a two-stage dissociation of the N-H/D bond on the sub-50 fs regime for imidazole, pyrazole and their selectively deuterated species, and give evidence for the importance of the repulsive 1πσ* state along the N-H/D bond coordinate for the relaxation of both imidazole and pyrazole. The ability of these calculations to reproduce experimental results lends confidence that larger complex systems could be explored with predictive capabilities with the AIMC method. These results also confirm the ability of the AIMC method to add detailed insights into which experiments are blind.

Ultrafast photodissociation dynamics of 2-ethylpyrrole: adding insight to experiment with ab initio multiple cloning.

The ultrafast photodissociation dynamics of 2-ethylpyrrole (2-EP) is simulated in a fully quantum manner on the S1 and S2 πσ* states by the ab initio multiple cloning (AIMC) method. AIMC treats electrons with accurate electronic structure methods "on the fly", and nuclear dynamics with wavefunction propagation via a basis set of Ehrenfest trajectory guided Gaussian wavepackets. Total kinetic energy release (TKER) spectra are produced, as well as velocity map images and N-H dissociation times. These are compared to results from time-resolved velocity map imaging studies, and the AIMC method is able to provide quantitative reproduction of experimental data, including dissociation times of 50-80 fs. Novel insight into the dissociation mechanism is then obtained, with the experimentally obtained time constant shown to be composed of two components. Firstly, there is a contribution in <50 fs from 2-EP molecules that have sufficient energy in the N-H stretch coordinate to dissociate almost immediately over the barrier, and this is followed by a second slower contribution from 2-EP molecules that must sample the potential energy surface before finding a way around the barrier to dissociate. This two component mechanism is not observed experimentally due to the temporal widths of the laser pulses obscuring the dynamics in the <50 fs window, and is shown for the first time via theory. Calculations are also performed on selectively deuterated 2-EP, demonstrating that AIMC is able to produce a kinetic isotope effect for the dissociation time constant, and correctly predict a shift to lower energy in the TKER spectrum. The S2 πσ* state is also shown to be unstable with respect to the S1 πσ* state, with the N-H dissociation proceeding along S1 when initially excited to S2. This work demonstrates that the combination of state of the art theory and experiments can provide unprecedented novel insight into the N-H dissociation mechanism, with the tantalising prospect of providing insight into more general heteroatom hydride bond dissociation.

The Calgary Audit and Feedback Framework: a practical, evidence-informed approach for the design and implementation of socially constructed learning interventions using audit and group feedback.

BACKGROUND: Audit and feedback interventions may be strengthened using social interaction. The Calgary office of the Alberta Physician Learning Program (CPLP) developed a process for audit and group feedback for physicians. This paper extends previous work in which we developed a conceptual model of physician responses to audit and group feedback based on a qualitative analysis of six audit and group feedback sessions. The present study explored the mediating factors for successfully engaging physician groups in change planning through audit and group feedback. METHODS: To understand why some groups were more interactive than others, we completed a comparative case analysis of the six audit and group feedback projects from the prior study. We used framework analysis to build the case studies, triangulated our observations across data sources to validate findings, compared the case studies for similarities and differences that influenced social interaction (mediating factors), and thematically categorized mediating factors into an organizing framework. RESULTS: Mediating factors for socially interactive AGFS were a pre-existing relationship between the program team and the physician group, projects addressing important, actionable questions, easily interpretable data visualization in the reports, and facilitation of the groups that included reflective questioning. When these factors were in place (cases 1, 2A, 3), the audit and group feedback sessions were dynamic, with physicians sharing and comparing practices, and raising change cues (such as declaring commitments to de-prescribing, planning educational interventions, and improving documentation). In cases 2C-D, the mediating factors were less well established and in these cases, the sessions showed little physician reflection or change planning. We organized the mediating factors into a framework linking the factors for successful sessions to the conceptual model of physician behaviors which these mediating factors drive. CONCLUSIONS: We propose the Calgary Audit and Feedback Framework as a practical tool to help foster socially constructed learning in audit and group feedback sessions. Ensuring that the four factors, relationship, question choice, data visualization, and facilitation, are considered for design and implementation of audit and group feedback will help physicians move from reactions to their data towards planning for change.

How do physicians behave when they participate in audit and feedback activities in a group with their peers?

BACKGROUND: Audit and feedback interventions may be strengthened using social interaction. With this in mind, the Calgary office of the Alberta Physician Learning Program developed a process for audit and group feedback for physician groups. As a part of a larger project to develop a practical approach to the design and implementation of audit and group feedback projects, we explored patterns of physician behavior during facilitated audit and group feedback sessions. METHODS: Six audit and group feedback sessions were recorded, transcribed, and analyzed thematically to derive a conceptual model of physicians' behaviors during audit and group feedback sessions. RESULTS: A predictable cycle of behaviors emerged from audit and group feedback sessions. This cycle would repeat with discussion of each new data element: reacting to the data, questioning and understanding the data, justifying and contextualizing, sharing and reflecting on the data and relevant guidelines, and planning for change. "Change cues" that emerged within groups reliably pivoted the discussion towards action planning. CONCLUSIONS: In audit and group feedback sessions, physicians display a predictable series of behaviors as they move towards commitment to change. Establishing the meaning and credibility of the data is a necessary precursor to reflection. Group reflection leads to "change cues" triggered by group members, which stimulate action planning.

Thyroid nodule ultrasound reports in routine clinical practice provide insufficient information to estimate risk of malignancy.

PURPOSE: Ultrasonographic characteristics of thyroid nodules play an important role in estimating the risk of malignancy (ROM). Guidelines mandate all thyroid nodules be characterized by six key ultrasonographic features to estimate the ROM. Our objective was to evaluate how frequently these characteristics were identified by radiologists and the ensuing utility to estimate ROM. METHODS: We retrospectively reviewed 1930 consecutive diagnostic thyroid ultrasound reports from a large community radiology practice. A total of 1339 individual patients were found to have one or more thyroid nodules. Each report was analyzed for six key ultrasonographic features. A utility score (UtS) was calculated (range 0-6) with a single point given for a comment on each feature. RESULTS: Of the 1339 patients, 75% of the studies reported more than one nodule (mean number of nodules = 3.4). Mean maximal diameter of the largest nodule per patient = 1.8 cm. The mean UtS was 2.57. Nodule size did not influence the UtS.: Nodule <1 cm (UtS: 2.53), 1-2 cm (UtS: 2.68) and >2 cm (UtS: 2.49). We believe a UtS of four or greater is needed to confidently estimate ROM: we found this in 13.7% of reports. CONCLUSIONS: Our retrospective analysis of a large number of consecutive thyroid ultrasound reports in routine clinical practice suggests that the vast majority provide insufficient information to allow the clinician to risk stratify the nodules by estimating the ROM. This could lead to both over-diagnosis and over-treatment of benign/indolent thyroid lesions or under-diagnosis of clinically important thyroid cancers.

Screening with Papanicolaou tests in Alberta: Are we Choosing Wisely?

OBJECTIVE: To describe the prevalence and geographic distribution of cervical cancer screening, as well as the age groups of those undergoing screening, in Alberta, and to determine if screening practices conform to current guidelines and follow Choosing Wisely Canada recommendations. DESIGN: Descriptive study using data from the Alberta Ministry of Health Analytics and Performance Reporting Branch. SETTING: Alberta. PARTICIPANTS: Women who had 1 or more Papanicolaou tests between 2011 and 2013. MAIN OUTCOME MEASURES: Number of women aged 15 to 20 and those aged 70 and older who had 1 or more Pap tests in a 3-year period; year-to-year trends in screening rates for women in these 2 age groups; trends in screening rates in various geographic regions (ie, cities and zones) in Alberta; and the discipline of clinicians who ordered the Pap tests. RESULTS: Between 2011 and 2013, 805 632 women in the province of Alberta had 1 or more Pap tests for cervical cancer screening. Overall, 25 511 (17.5%) women aged 15 to 20 and 16 818 (10.3%) aged 70 and older were screened contrary to most existing guidelines. Screening rates varied markedly in different geographic regions of the province. Most Pap tests were ordered by family physicians or general practitioners. CONCLUSION: Within the geographic regions of Alberta, provincial, national, and international guidelines for screening with Pap tests are inconsistently followed. This strongly echoes the need for clinicians and patients to consider the Choosing Wisely Canada recommendations and current guidelines for cervical cancer screening.

Severe Thyrotoxicosis Secondary to Povidone-Iodine from Peritoneal Dialysis.

A 73-year-old male on home peritoneal dialysis (PD) with recent diagnosis of atrial fibrillation presented with fatigue and dyspnea. Hyperthyroidism was diagnosed with TSH < 0.01 mIU/L and FT4 > 100 pmol/L. He had no personal or family history of thyroid disease. There had been no exposures to CT contrast, amiodarone, or iodine. Technetium thyroid scan showed diffusely decreased uptake. He was discharged with a presumptive diagnosis of thyroiditis. Three weeks later, he had deteriorated clinically. Possible iodine sources were again reviewed, and it was determined that povidone-iodine solution was used with each PD cycle. Methimazole 25 mg daily was initiated; however, he had difficulty tolerating the medication and continued to clinically deteriorate. He was readmitted to hospital where methimazole was restarted at 20 mg bid with high dose prednisone 25 mg and daily plasma exchange (PLEX) therapy. Biochemical improvement was observed with FT4 dropping to 48.5 pmol/L by day 10, but FT4 rebounded to 67.8 pmol/L after PLEX was discontinued. PLEX was restarted and thyroidectomy was performed. Pathology revealed nodular hyperplasia with no evidence of thyroiditis. Preoperative plasma iodine levels were greater than 5 times the upper limit of normal range. We hypothesize that the patient had underlying autonomous thyroid hormone production exacerbated by exogenous iodine exposure from a previously unreported PD-related source.

Molecular profiling of thyroid nodule fine-needle aspiration cytology.

The differential diagnosis and malignancy risk stratification of thyroid nodules requires multidisciplinary expertise and knowledge of both local ultrasonography practices and the local malignancy rates for a given fine-needle aspiration (FNA) result. Even in such a multidisciplinary setting, FNA cytology has the inherent limitation that indeterminate cytology results cannot distinguish between follicular adenomas, follicular thyroid carcinomas or follicular variant papillary thyroid carcinomas. Accumulating evidence suggests that this limitation can be overcome by using molecular diagnostic approaches. In this Review, we present the advantages and disadvantages of the different molecular diagnostic methodologies, which can be divided into two approaches: those that 'rule out' malignancy (to reduce the overtreatment of benign nodules) and those that 'rule in' malignancy (to optimize surgical planning). We identify microRNA classifiers as potential additional markers for use in a two-step diagnostic approach, consider the potential implications of the reclassification of noninvasive encapsulated follicular variant papillary thyroid carcinomas to noninvasive follicular thyroid neoplasms with papillary-like nuclear features and discuss the cost-effectiveness of molecular testing. Molecular FNA diagnostics is an important complementary addition to FNA cytology that could substantially reduce unnecessary surgery and better define the need for appropriate surgery in patients who have thyroid nodules with indeterminate FNA cytology.

Hypertriglyceridemia-induced pancreatitis: A case-based review.

Hypertriglyceridemia is an established cause of pancreatitis. In a case-based approach, we present a review of hypertriglyceridemia and how it can cause pancreatitis. We outline how to investigate and manage such patients. A 35 year old man presented to the emergency department with abdominal pain and biochemical evidence of acute pancreatitis. There was no history of alcohol consumption and biliary imaging was normal. The only relevant past medical history was that of mild hyperlipidemia, treated with diet alone. Physical exam revealed epigastric tenderness, right lateral rectus palsy, lipemia retinalis, bitemporal hemianopsia and a delay in the relaxation phase of his ankle reflexes. Subsequent laboratory investigation revealed marked hypertriglyceridemia and panhypopituarism. An enhanced CT scan of the head revealed a large suprasellar mass impinging on the optic chiasm and hypothalamus. The patient was treated supportively; thyroid replacement and lipid lowering agents were started. He underwent a successful resection of a craniopharyngioma. Post-operatively, the patient did well on hormone replacement therapy. He has had no further attacks of pancreatitis. This case highlights many of the factors involved in the regulation of triglyceride metabolism. We review the common causes of hypertriglyceridemia and the proposed mechanisms resulting in pancreatitis. The incidence and management of hypertriglyceridemia-induced pancreatitis are also discussed.