Diabetes remission and relapse following an intensive metabolic intervention combining insulin glargine/lixisenatide, metformin and lifestyle approaches: Results of a randomised controlled trial.

AIM: Non-surgical options for inducing type 2 diabetes remission are limited. We examined whether remission can be achieved by combining lifestyle approaches and short-term intensive glucose-lowering therapy. METHODS: In this trial, 160 patients with type 2 diabetes on none to two diabetes medications other than insulin were randomised to (a) an intervention comprising lifestyle approaches, insulin glargine/lixisenatide and metformin, or (b) standard care. Participants with glycated haemoglobin (HbA1c) <7.3% (56 mmol/mol) at 12 weeks were asked to stop diabetes medications and were followed for an additional 52 weeks. The primary outcome was diabetes relapse defined as HbA1c ≥6.5% (48 mmol/mol) at 24 weeks or thereafter, capillary glucose ≥10 mmol/L on ≥50% of readings, or use of diabetes medications, analysed as time-to-event. Main secondary outcomes included complete or partial diabetes remission at 24, 36, 48 and 64 weeks defined as HbA1c <6.5% (48 mmol/mol) off diabetes medications since 12 weeks after randomisation. A hierarchical testing strategy was applied. RESULTS: The intervention significantly reduced the hazard of diabetes relapse by 43% (adjusted hazard ratio 0.57, 95% confidence interval 0.40-0.81; p = .002). Complete or partial diabetes remission was achieved in 30 (38.0%) intervention group participants versus 16 (19.8%) controls at 24 weeks and 25 (31.6%) versus 14 (17.3%) at 36 weeks [relative risk 1.92 (95% confidence interval 1.14-3.24) and 1.83 (1.03-3.26), respectively]. The relative risk of diabetes remission in the intervention versus control group was 1.88 (1.00-3.53) at 48 weeks and 2.05 (0.98-4.29) at 64 weeks. CONCLUSIONS: A 12-week intensive intervention comprising insulin glargine/lixisenatide, metformin and lifestyle approaches can induce remission of diabetes.

The Impact of Bariatric Surgery on Assisted Reproductive Technology Outcomes: A Systematic Review.

OBJECTIVE: There is a paucity of literature on the impact of bariatric surgery on artificial reproductive technology (ART) outcomes. This topic should be examined, given that most bariatric surgery candidates are of reproductive age and those with obesity are significantly more likely to experience poor fertility outcomes. This systematic review aimed to determine if bariatric surgery impacts ART outcomes and if effects vary between females and males. DATA SOURCES: MEDLINE, EMBASE, SCOPUS, and the Cochrane Central Register of Controlled Trials were searched for English studies published between January 1978 and May 2021. STUDY SELECTION: Studies with participants who had received bariatric surgery and subsequently underwent ART (i.e., in vitro fertilization or intracytoplasmic sperm injection) were eligible for inclusion. Screening, data abstraction, and risk of bias assessment were conducted independently and in duplicate. DATA EXTRACTION AND SYNTHESIS: Of the 279 articles screened for eligibility, 25 were sought for full text review, and 7 were included for analysis. Four studies (57%) examined ART interventions in females, while 3 (43%) examined interventions in males. Data on cumulative live birth rate (CLBR) was extracted for all 7 studies (N = 169). There were 50 live births with CLBRs ranging from 0.0% to 80.0%. Data on female secondary outcomes were varied. Data on male secondary outcomes were contradictory: 1 study indicated improved sperm parameters following bariatric surgery, while 2 showed decreased parameters, with certain participants seeing improvements after several months. CONCLUSION: Bariatric surgery prior to ART may have an impact on CLBRs; however, high-quality research is needed to delineate the direct effects of bariatric surgery on ART outcomes. Various sex-specific outcomes should be considered prior to recommending ART after bariatric surgery. Future research should determine the optimal type of bariatric surgery and timing of ART following bariatric surgery.

PREDICTIVE MARKERS FOR POSTSURGICAL MEDICAL MANAGEMENT OF ACROMEGALY: A SYSTEMATIC REVIEW AND CONSENSUS TREATMENT GUIDELINE.

Objective: To clarify the selection of medical therapy following transsphenoidal surgery in patients with acromegaly, based on growth hormone (GH)/insulin-like growth factor 1 (IGF-1) response and glucometabolic control. Methods: We carried out a systematic literature review on three of the best studied and most practical predictive markers of the response to somatostatin analogues (SSAs): somatostatin receptor (SSTR) expression, tumor morphologic classification, and T2-weighted magnetic resonance imaging (MRI) signal intensity. Additional analyses focused on glucose metabolism in treated patients. Results: The literature survey confirmed significant associations of all three factors with SSA responsiveness. SSTR expression appears necessary for the SSA response; however, it is not sufficient, as approximately half of SSTR2-positive tumors failed to respond clinically to first-generation SSAs. MRI findings (T2-hypo-intensity) and a densely granulated phenotype also correlate with SSA efficacy, and are advantageous as predictive markers relative to SSTR expression alone. Glucometabolic control declines with SSA monotherapy, whereas GH receptor antagonist (GHRA) monotherapy may restore normoglycemia. Conclusion: We propose a decision tree to guide selection among SSAs, dopamine agonists (DAs), and GHRA for medical treatment of acromegaly in the postsurgical setting. This decision tree employs three validated predictive markers and other clinical considerations, to determine whether SSAs are appropriate first-line medical therapy in the postsurgical setting. DA treatment is favored in patients with modest IGF-1 elevation. GHRA treatment should be considered for patients with T2-hyperintense tumors with a sparsely granulated phenotype and/or low SSTR2 staining, and may also be favored for individuals with diabetes. Prospective analyses are required to test the utility of this therapeutic paradigm. Abbreviations: DA = dopamine agonist; DG = densely granulated; GH = growth hormone; GHRA = growth hormone receptor antagonist; HbA1c = glycated hemoglobin; IGF-1 = insulin-like growth factor-1; MRI = magnetic resonance imaging; SG = sparsely granulated; SSA = somatostatin analogue; SSTR = somatostatin receptor.

Thyroid-Stimulating Hormone-Stimulated Human Adipocytes Express Thymic Stromal Lymphopoietin.

When recombinant human (rh) thyroid-stimulating hormone (TSH) is administered to thyroid cancer survivors, an acute extra-thyroidal effect raises pro-inflammatory cytokines and activates platelets. Thymic stromal lymphopoietin (TSLP) is a cytokine recently implicated in platelet activation. Our aim was to measure platelet microparticle levels after rhTSH stimulation in vivo, and to investigate TSLP expression in TSH-stimulated human adipocytes in culture. Blood samples for total and platelet microparticle analysis were obtained from thyroid cancer survivors before (day 1) and after rhTSH administration (day 5). Adipocytes, differentiated from stromal preadipocytes isolated from adipose tissue from surgical patients, were stimulated with TSH. TSLP mRNA expression, protein expression, and protein release into the adipocyte medium were measured. The level of platelet microparticles in thyroid cancer patients rose 5-fold after rhTSH stimulation. TSH upregulated TSLP mRNA expression in adipocytes in culture through a pathway that was inhibited by 66% by H89, a protein kinase A inhibitor. TSLP protein expression rose in response to TSH, and TSH-stimulated TSLP release into the medium was completely blocked by dexamethasone. In conclusion, TSLP is a novel TSH-responsive adipokine. Future studies will be needed to address the potential role of adipocyte-derived TSLP and whether it is linked to TSH-dependent platelet activation.

Randomized Trial of the Effect of Mindfulness-Based Stress Reduction on Pain-Related Disability, Pain Intensity, Health-Related Quality of Life, and A1C in Patients With Painful Diabetic Peripheral Neuropathy.

IN BRIEF Painful diabetic peripheral neuropathy (PDPN) has a large negative impact on patients' physical and mental functioning, and pharmacological therapies rarely provide more than partial relief. Mindfulness-based stress reduction (MBSR) is a group psychosocial intervention that was developed for patients with chronic illness who were not responding to existing medical treatments. This study tested the effects of community-based MBSR courses for patients with PDPN. Among patients whose PDPN pharmacotherapy had been optimized in a chronic pain clinic, those randomly assigned to treatment with MBSR experienced improved function, better health-related quality of life, and reduced pain intensity, pain catastrophizing, and depression compared to those receiving usual care.

Deprescribing antihyperglycemic agents in older persons: Evidence-based clinical practice guideline.

OBJECTIVE: To develop an evidence-based guideline to help clinicians make decisions about when and how to safely taper, stop, or switch antihyperglycemic agents in older adults. METHODS: We focused on the highest level of evidence available and sought input from primary care professionals in guideline development, review, and endorsement processes. Seven clinicians (2 family physicians, 3 pharmacists, 1 nurse practitioner, and 1 endocrinologist) and a methodologist comprised the overall team; members disclosed conflicts of interest. We used a rigorous process, including the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach, for guideline development. We conducted a systematic review to assess evidence for the benefits and harms of deprescribing antihyperglycemic agents. We performed a review of reviews of the harms of continued antihyperglycemic medication use, and narrative syntheses of patient preferences and resource implications. We used these syntheses and GRADE quality-of-evidence ratings to generate recommendations. The team refined guideline content and recommendation wording through consensus and synthesized clinical considerations to address common front-line clinician questions. The draft guideline was distributed to clinicians and stakeholders for review and revisions were made at each stage. A decision-support algorithm was developed to accompany the guideline. RECOMMENDATIONS: We recommend deprescribing antihyperglycemic medications known to contribute to hypoglycemia in older adults at risk or in situations where antihyperglycemic medications might be causing other adverse effects, and individualizing targets and deprescribing accordingly for those who are frail, have dementia, or have a limited life expectancy. CONCLUSION: This guideline provides practical recommendations for making decisions about deprescribing antihyperglycemic agents. Recommendations are meant to assist with, not dictate, decision making in conjunction with patients.

Thyroid-stimulating hormone acutely increases monocyte gene expression in vivo.

OBJECTIVES: Thyroid-stimulating hormone (TSH) acts in an extra-thyroidal fashion and induces a pro-inflammatory, pro-coagulant state. Blood monocytes can be activated by vascular stress, but it is not known if this occurs upon TSH administration. Our aim was to determine if recombinant human (rh) TSH, administered acutely to patients being screened for thyroid cancer recurrence, alters blood monocyte gene expression. DESIGN AND SETTING: Patients (14 women, 1 man) had a mean (±SD) age of 48±10 years, a body mass index of 26±6 kg/m2, a history of total thyroidectomy and radioablation for thyroid cancer, and were on L-thyroxine therapy at a university teaching hospital. They received 2 intramuscular doses of rhTSH (0.9 mg), administered on days 1 and 2. Blood samples were obtained at baseline on day1, and on days 3 and 5. RESULTS: Monocyte MCP-1 mRNA (mean±SE) increased significantly by 1.7±0.3 fold on day 5 following rhTSH stimulation (p=0.03, n=15). IL-1ß and CD36 mRNA expression also increased on day 5 (1.9±0.4 fold, p=0.07, n=14) and 2.5±0.4 fold, p=0.1, n=10), respectively, although did not quite reach statistical significance. Significant correlations were detected between the BMI of patients and their TSH-stimulated monocyte mRNA responses at day 5 for CD11a, (r=0.66, n=14, p=0.01); CD14 (r=0.638, n=13, p=0.019), and CD16, r=0.84, n=13, p=0.0003). CONCLUSION: TSH administration increases pro-atherogenic monocyte gene expression.

Effects of intensive glycaemic control on ischaemic heart disease: analysis of data from the randomised, controlled ACCORD trial.

BACKGROUND: Hyperglycaemia could substantially increase the risk of ischaemic heart disease in patients with type 2 diabetes. We investigated whether intensive lowering of glucose concentrations affects risk. METHODS: We assessed 10,251 adults aged 40-79 years with established type 2 diabetes, mean glycated haemoglobin A1c (HbA1c) concentration of 67 mmol/mol (8·3%), and risk factors for ischaemic heart disease enrolled in the ACCORD trial. Participants were assigned to intensive or standard therapy (target HbA1c less than 42 or 53-63 mmol/mol [less than 6·0% or 7·0-7·9%], respectively). We assessed fatal or non-fatal myocardial infarction, coronary revascularisation, unstable angina, and new angina during active treatment (mean 3·7 years) plus a further mean 1·2 years. This trial is registered with ClinicalTrials.gov, number NCT00000620. FINDINGS: Myocardial infarction was less frequent in the intensive than in the standard therapy group during active treatment (hazard ratio [HR] 0·80, 95% CI 0·67-0·96; p=0·015) and overall (0·84, 0·72-0·97; p=0·02). Findings were similar for combined myocardial infarction, coronary revascularisation, and unstable angina (active treatment HR 0·89, 95% CI 0·79-0·99, overall 0·87 0·79-0·96) and for coronary revascularisation alone (0·84, 0·75-0·94) and unstable angina alone (0·81, 0·67-0·97) during full follow-up. With lowest achieved HbA1C concentrations included as a time-dependent covariate, all hazards became non-significant. INTERPRETATION: Raised glucose concentration is a modifiable risk factor for ischaemic heart disease in middle-aged people with type 2 diabetes and other cardiovascular risk factors. FUNDING: National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute on Aging, National Eye Intitute, and Centers for Disease Control and Prevention.

Socialization to professionalism in medical schools: a Canadian experience.

BACKGROUND: Accrediting bodies now recognize the importance of developing the professionalism competency, by setting standards that require medical schools to identify where professionalism is addressed and how it is evaluated within the formal curriculum. The objective of this study was to compare how professionalism competency is formally addressed in the curricula of Canadian medical schools, and to better understand the Canadian approach to reporting and remediation of lapses. METHODS: A literature review was performed and with the input of the AFMC(Association of Faculties of Medicine of Canada) Professionalism group, questionnaires were generated. An electronic survey was circulated to key leaders across the country at all the medical schools. In-depth telephone interviews were used to further explore themes, and a subsequent focus group was held to discuss challenges, particularly related to reporting and remediation. RESULTS: The preponderance of formal professionalism teaching remains in the form of lectures and small group sessions in the preclinical years. Formal teaching declines significantly in the clerkship/clinical years. Evaluation is usually performed by a clinical supervisor, but OSCE, portfolio, and concern notes are increasingly used. Role modeling is heavily relied upon in clinical years, suggesting faculty training can help ensure clinical teachers recognize their influence on trainees. Formal remediation strategies are in place at most schools, and often involve essay writing, reflection exercises, or completion of learning modules about professionalism. Lack of clarity on what defines a lapse and fear of reprisal (for both trainees and faculty) limits reporting. CONCLUSIONS: This study provides an overview of how professional identity formation is supported in the Canadian context, guided by the standards set out by CanMEDS. Despite a rich literature that describes the definition, program design and evaluation methods for professionalism, in some areas of the curriculum there is still an opportunity to ensure programs embrace the suggested framework. Examples of teaching and evaluation methods, deficiencies in the clinical years of study (clerkship) and challenges in addressing lapses and organizational structure are identified. The results help identify the gaps that need to be addressed and some solutions that can be modeled at other academic institutions.

Serum fetuin-A levels following recombinant human thyroid-stimulating hormone stimulation.

PURPOSE: Fetuin-A is a hepatokine that is linked to lipid metabolism, obesity, insulin resistance, type 2 diabetes and cardiovascular disease. Elevated thyroid-stimulating hormone (TSH) levels are associated with metabolic and cardiovascular disturbances. Our aim was to determine if TSH can regulate fetuin-A levels. METHODS: Fetuin-A serum levels were examined in 26 subjects (19 women; previous thyroidectomy and radioactive iodine ablation) undergoing recombinant human TSH (rhTSH) stimulation to screen for thyroid cancer recurrence. Their age was 49±10 years, and body mass index (BMI) was 28±6 (both expressed as mean±SD). The patients received two doses of rhTSH (0.9 mg), administered 24 hours apart on days 1 and 2, without discontinuation of ongoing L-thyroxine therapy. Morning blood samples were obtained on days 1 (prior to the first dose of rhTSH), 3 and 5. RESULTS: The baseline value of fetuin-A (mean±SD) for all participants was 527±186 mg/L. Values of fetuin-A did not change in response to rhTSH administration. The lack of response was not dependent on gender, age, baseline free thyroxine level or BMI. CONCLUSION: Fetuin-A has been implicated in metabolic and inflammatory conditions, but there have been no reports on whether fetuin-A is influenced by TSH. Within the context of rhTSH administration for surveillance of thyroid cancer recurrence, there was no effect on serum levels of fetuin-A.

Teaching Observation as a Faculty Development Tool in Medical Education: A Scoping Review.

INTRODUCTION: Health professions education often includes teaching observation to inform faculty development (FD) and indirectly improve student performance. Although these FD approaches are well received by faculty, they remain underused and/or underreported, with limited opportunities to receive feedback in workplace contexts. The goal of our study was to map the depth and breadth of education literature on the use of observation of teaching as a tool of professional development in medical education. METHODS: Following the methodology by Arksey and O'Malley, we conducted a scoping review and searched four databases for articles published in English (final searches in April 2022). RESULTS: Of 2080 articles identified, 45 met the inclusion criteria. All observation activities were associated with one of the following FD approaches: peer observation of teaching (23 articles, 51%), peer coaching (12, 27%), peer review (9, 20%), and the critical friends approach (1, 2%). Thirty-three articles (73%) concerned formative versions of the observation model that took place in clinical settings (21, 47%), and they tended to be a voluntary (27, 60%), one-off (18, 40%), in-person intervention (29, 65%), characterized by limited institutional support (13, 29%). Both barriers and challenges of teaching observation were identified. DISCUSSION: This review identified several challenges and shortcomings associated with teaching observation, such as inadequate methodological quality of research articles, inconsistent terminology, and limited understanding of the factors that promote long-term sustainability within FD programs. Practical strategies to consider when designing an FD program that incorporates teaching observation are outlined.

The Canadian Study of Arterial Inflammation in Patients with Diabetes and Recent Vascular Events, Evaluation of Colchicine Effectiveness (CADENCE): protocol for a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Inflammation is a key mediator in the development and progression of the atherosclerotic disease process as well as its resultant complications, like myocardial infarction (MI), stroke and cardiovascular (CV) death, and is emerging as a novel treatment target. Trials involving anti-inflammatory medications have demonstrated outcome benefit in patients with known CV disease. In this regard, colchicine appears to hold great promise. However, there are potential drawbacks to colchicine use, as some studies have identified an increased risk of infection, and a non-significant trend for increased all-cause mortality. Thus, a more thorough understanding of the underlying mechanism of action of colchicine is needed to enable a better patient selection for this novel CV therapy. OBJECTIVE: The primary objective of the Canadian Study of Arterial Inflammation in Patients with Diabetes and Recent Vascular Events, Evaluation of Colchicine Effectiveness (CADENCE) trial is to assess the effect of colchicine on vascular inflammation in the carotid arteries and ascending aorta measured with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in patients with type 2 diabetes mellitus (T2DM) or pre-diabetes who have experienced a recent vascular event (acute coronary syndrome (ACS)/MI, transient ischaemic attack (TIA) or stroke). Secondary objectives include determining colchicine's effect on inflammatory biomarkers (high-sensitivity C reactive protein (hs-CRP) and interleukin-6 (IL-6)). Additionally, we will assess if baseline inflammation imaging or biomarkers are associated with a treatment response to colchicine determined by imaging. Exploratory objectives will look at: (1) the difference in the inflammatory response to colchicine in patients with coronary events compared with patients with cerebral events; (2) the difference in the inflammatory response to colchicine in different vascular beds; (3) the relationship of FDG-PET imaging markers with serum biomarkers and (4) assessment of quality-of-life changes. METHODS AND DESIGN: CADENCE is a multicentre, prospective, randomised, double-blinded, placebo-controlled study to determine the effect of colchicine on arterial inflammation as assessed with imaging and circulatory biomarkers, specifically carotid arteries and aortic FDG uptake as well as hs-CRP and IL-6 among others. Patients with T2DM or pre-diabetes who have recently experienced a CV event (within 30-120 days after an ACS (ie, ST-elevation MI (STEMI) or non-STEMI)) or TIA/stroke with documented large vessel atherosclerotic disease will be randomised to treatment with either colchicine 0.6 mg oral daily or placebo. Participants will undergo baseline clinical evaluation including EQ5D assessment, blood work for inflammatory markers and FDG PET/CT scan of the ascending aorta and left and right carotid arteries. Patients will undergo treatment for 6 months and have repeat clinical evaluation including EQ5D assessment, blood work for inflammatory markers and FDG PET/CT scan at the conclusion of the study. The primary outcome will be the change in the maximum target to background ratio (TBRmax) in the ascending aorta (or carotid arteries) from baseline to follow-up on FDG PET/CT imaging. DISCUSSION: Colchicine is an exciting potential new therapy for CV risk reduction. However, its use is associated with side effects and greater understanding of its underlying mechanism of action is needed. Importantly, the current study will determine whether its anti-inflammatory action is an indirect systemic effect, or a more local plaque action that decreases inflammation. The results will also help identify patients who will benefit most from such therapy. TRIAL REGISTRATION NUMBER: NCT04181996.

Déprescription des antihyperglycémiants chez les personnes âgées: Guide de pratique clinique fondé sur les données probantes.

OBJECTIF: Formuler des lignes directrices fondées sur les données probantes afin d'aider les cliniciens à décider du moment et de la façon sécuritaire de réduire la dose des antihyperglycémiants, de mettre fin au traitement ou de passer à un autre agent chez les personnes âgées. MÉTHODES: Nous nous sommes concentrés sur les données les plus probantes disponibles et avons cherché à obtenir les commentaires des professionnels de première ligne durant le processus de rédaction, de révision et d'adoption des lignes directrices. L'équipe était formée de 7 professionnels de la santé (2 médecins de famille, 3 pharmaciens, 1 infirmière praticienne et 1 endocrinologue) et d'une spécialiste de la méthodologie; les membres ont divulgué tout conflit d'intérêts. Nous avons eu recours à un processus rigoureux, y compris l'approche GRADE (Grading of Recommendations Assessment, Development and Evaluation) pour formuler les lignes directrices. Nous avons effectué une revue systématique dans le but d'évaluer les données probantes indiquant les bienfaits et les torts liés à la déprescription des antihyperglycémiants. Nous avons révisé les revues des torts liés à la poursuite du traitement antihyperglycémiant, et effectué des synthèses narratives des préférences des patients et des répercussions sur les ressources. Ces synthèses et évaluations de la qualité des données selon l'approche GRADE ont servi à formuler les recommandations. L'équipe a peaufiné le texte sur le contenu et les recommandations des lignes directrices par consensus et a synthétisé les considérations cliniques afin de répondre aux questions courantes des cliniciens de première ligne. Une version préliminaire des lignes directrices a été distribuée aux cliniciens et aux intervenants aux fins d'examen, et des révisions ont été apportées au texte à chaque étape. Un algorithme d'appui décisionnel a été conçu pour accompagner les lignes directrices. RECOMMANDATIONS: Nous recommandons de déprescrire les antihyperglycémiants reconnus pour contribuer à l'hypoglycémie chez les personnes âgées à risque ou dans les situations où les antihyperglycémiants pourraient causer d'autres effets indésirables, et d'individualiser les cibles et de déprescrire en conséquence chez les personnes frêles, atteintes de démence ou dont l'espérance de vie est limitée. CONCLUSION: Les présentes lignes directrices émettent des recommandations pratiques pour décider du moment et de la façon de déprescrire les antihyperglycémiants. Elles visent à contribuer au processus de décision conjointement avec le patient et non à le dicter.

The impact of bariatric surgery on assisted reproductive technology outcomes: a systematic review protocol.

BACKGROUND: Individuals with obesity are at higher risk of experiencing complications during their pregnancy and may also experience infertility, requiring assisted reproductive technologies (ART) to conceive. The current body of literature demonstrates that bariatric surgery decreases an individual's risk of developing a variety of obesity-related obstetrical conditions during and after pregnancy. However, the effects of bariatric surgery on ART outcomes are not well understood. Therefore, the paucity in the literature warrants a need to determine these effects. METHODS: We will search electronic databases, including MEDLINE, Embase, Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL), as well as the gray literature and the reference lists of included articles. We will screen all studies published between January 1978 and the present day that explore the impact of bariatric surgery on ART outcomes for women and men. We will include observational studies. Two independent reviewers will assess the studies for inclusion and extract data for each article. The main outcome that will be analyzed is live birth rate. Secondary outcomes such as time to conception, number of rounds of ART, type of bariatric surgery, and length of time between bariatric surgery and initiation of ART will also be recorded. Risk of bias will be conducted using the National Institutes of Health Study Quality Assessment Tools. A random effects model will be used to account for statistical analysis and results will be pooled with forest plots. In the event of statistical and reporting heterogeneity, we will provide a qualitative synthesis and narrative review of the results. DISCUSSION: This review will provide information on the outcomes of ART following bariatric surgery and may help healthcare professionals make informed decisions about the length of time between bariatric surgery and initiation of ART. The study findings may be of interest to various stakeholders including patients, bariatric surgeons, obstetricians, and gynecologists, and those who specialize in obesity medicine and reproductive endocrinology and infertility. We plan to disseminate our findings through presentations, publications, and social media releases to individuals who are navigating infertility and are interested in undergoing or have undergone bariatric surgery, healthcare professionals, policymakers, and researchers. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021252561.

Routine Screening for Central and Primary Adrenal Insufficiency during Immune-Checkpoint Inhibitor Therapy: An Endocrinology Perspective for Oncologists.

BACKGROUND: Immune checkpoint inhibitor (ICI)-associated hypothalamic-pituitary-adrenal axis disruption can lead to hypocortisolism. This is a life-threatening but difficult to diagnose condition, due to its non-specific symptoms that overlap with symptoms of malignancy. Currently, there is no consensus on how to best screen asymptomatic patients on ICI therapy for hypophysitis with serum cortisol. METHODS: A retrospective chart review of patients treated with ICI in a tertiary care centre was conducted to assess the rate of screening with cortisol and whether this had an impact on diagnosis of ICI-hypophysitis in the preclinical stage. Patients were identified as having hypophysitis with an adrenocorticotropin hormone (ACTH) deficiency based on chart review of patients with cortisol values ≤ 140 nmol/L (≤5 mcg/dL). We also assessed what proportion of cortisol values were drawn at the correct time for interpretation (between 6 AM and 10 AM). RESULTS: Two hundred and sixty-five patients had 1301 cortisol levels drawn, only 40% of which were drawn correctly (between 6 and 10 AM). Twenty-two cases of hypophysitis manifesting with ACTH deficiency were identified. Eight of these patients were being screened with cortisol following treatment and were detected in the outpatient setting. The remaining 14 patients were not screened and were diagnosed when symptomatic, after an emergency room visit or hospital admission. Sixty percent of the cortisol tests were uninterpretable as they were not drawn within the appropriate time window. CONCLUSION: Measuring morning serum cortisol in asymptomatic patients on ICI therapy is a fast and inexpensive way to screen for hypophysitis and should become the standard of care. Random serum cortisol measurement has no clinical value. Education needs to be provided on when to correctly perform the test and how to interpret it and we provide an algorithm for this purpose. The adoption and validation of such an algorithm as part of routine practice could significantly reduce morbidity and mortality in patients, especially as ICI therapy is becoming increasingly commonplace.

Benefits and Harms of Deprescribing Antihyperglycemics for Adults With Type 2 Diabetes: A Systematic Review.

OBJECTIVES: Contemporary guidelines suggest relaxed glycemic targets in populations with type 2 diabetes mellitus (T2DM) at risk of hypoglycemia, including people with multimorbidity, limited life expectancy or frailty. However, overtreatment remains commonplace. To inform safe deprescribing, a previous systematic review investigated the benefits and harms of deprescribing antihyperglycemics, but identified only limited, very low-quality evidence. We sought to update that review and identify and describe newly published literature on the effects of deprescribing antihyperglycemics in older adults with T2DM. METHODS: We searched MEDLINE, EMBASE and the Cochrane Library (July 2015 to January 2021) for controlled studies published in English addressing the effects of deprescribing vs continuing antihyperglycemics in adults with T2DM. Two independent reviewers performed title, abstract and full-text screening, data extraction and risk-of-bias assessment. Cochrane's risk-of-bias tools, RoB 2 and ROBINS-I, were used. The findings were summarized narratively. GRADE (Grading of Recommendations, Assessment, Development and Evaluations) was used to evaluate the evidence. RESULTS: We identified 4 additional investigations-2 randomized controlled trials and 2 retrospective cohort studies. After deprescribing, 3 studies reported no clinically significant changes in glucose management and 2 studies reported reductions in adverse events (e.g. hypoglycemia, all-cause mortality and nonspine fractures). However, based on GRADE assessment, we found very low certainty of the evidence due to concerns of risk of bias (e.g. unmeasured confounding), imprecision, and indirectness. CONCLUSIONS: Deprescribing antihyperglycemic medications in older adults with T2DM is likely feasible and safe, and benefits may outweigh the harms. However, the evidence indicates very low certainty. Additional deprescribing studies are needed with rigorous methodologies and reporting.

Attributes of excellent clinician teachers and barriers to recognizing and rewarding clinician teachers' performances and achievements: a narrative review.

Background: Over the last 31 years, there have been several institutional efforts to better recognize and reward clinician teachers. However, the perception of inadequate recognition and rewards by clinician teachers for their clinical teaching performance and achievements remains. The objective of this narrative review is two-fold: deepen understanding of the attributes of excellent clinician teachers considered for recognition and reward decisions and identify the barriers clinician teachers face in receiving recognition and rewards. Methods: We searched OVID Medline, Embase, Education Source and Web of Science to identify relevant papers published between 1990 and 2020. After screening for eligibility, we conducted a content analysis of the findings from 43 relevant papers to identify key trends and issues in the literature. Results: We found the majority of relevant papers from the US context, a paucity of relevant papers from the Canadian context, and a declining international focus on the attributes of excellent clinician teachers and barriers to the recognition and rewarding of clinician teachers since 2010. 'Provides feedback', 'excellent communication skills', 'good supervision', and 'organizational skills' were common cognitive attributes considered for recognition and rewards. 'Stimulates', 'passionate and enthusiastic', and 'creates supportive environment', were common non-cognitive attributes considered for recognition and rewards. The devaluation of teaching, unclear criteria, and unreliable metrics were the main barriers to the recognition and rewarding of clinician teachers. Conclusions: The findings of our narrative review highlight a need for local empirical research on recognition and reward issues to better inform local, context-specific reforms to policies and practices.

Contexte: Depuis 31 ans, nous sommes témoins d'efforts institutionnels visant à offrir aux cliniciens enseignants une plus grande reconnaissance et à récompenser leur travail. Cependant, d'après leur perception, la valorisation de leurs réalisations en matière d'enseignement clinique demeure insuffisante. Cette revue narrative a un double objectif : d'une part, repérer les qualités qui sont prises en considération en vue de l'octroi d'une reconnaissance officielle ou de l'attribution de récompenses (prix) aux cliniciens enseignants et d'autre part recenser les éléments qui empêchent certains candidats de se voir accorder une telle reconnaissance ou récompense. Méthodes: Nous avons effectué des recherches dans OVID Medline, Embase, Education Source et Web of Science pour repérer les articles pertinents publiés entre 1990 et 2020. Le contenu des résultats des 43 articles sélectionnés a ensuite été analysé pour dégager les principales tendances et questions abordées. Résultats: La plupart des articles pertinents se rapportaient au contexte des États-Unis. En revanche, peu d'articles pertinents concernaient celui du Canada. Sur le plan international, la question des qualités des cliniciens enseignants et des éléments qui peuvent les empêcher d'obtenir la reconnaissance ou une récompense suscite moins d'intérêt depuis 2010. Le fait « d'offrir de la rétroaction ¼, d'avoir « d'excellentes habiletés de communication ¼, d'assurer une « bonne supervision ¼, et un bon « sens de l'organisation ¼ sont des compétences cognitives souvent considérées pour l'octroi de la reconnaissance et l'attribution de récompenses. Parmi les compétences non cognitives, on note le fait d'être « stimulant ¼, d'être « passionné et enthousiaste ¼ et de « créer un environnement offrant du soutien ¼. La dévalorisation de l'enseignement, le manque de critères clairs et l'utilisation de mesures d'évaluation peu fiables sont les principaux obstacles à l'octroi de la reconnaissance ou à l'attribution d'une récompense aux cliniciens enseignants. Conclusions: Les résultats de notre revue narrative mettent en évidence la nécessité de mener des recherches empiriques localement en matière de reconnaissance et de récompense afin d'éclairer les réformes locales des politiques et des pratiques dans le milieu spécifique où elles sont appliquées.

Gastrointestinal Symptoms in Type 1 Diabetes: Relationship With Autoimmune and Microvascular Complications.

PURPOSE: To assess reported rates of gastrointestinal (GI) symptoms and their association with autoimmune diseases and microvascular complications in adults and children with type 1 diabetes. METHODS: The Gastrointestinal Symptom Scale was used to assess GI symptom type and severity in 2370 patients with type 1 diabetes aged 8 to 45 years evaluated as part of a clinical trial screening for celiac disease (CD). The presence and severity of GI symptoms and relationships with demographic, clinical, and other diabetes-related factors were evaluated. RESULTS: Overall, 1368 adults (57.7%) aged 19 to 45 years and 1002 (42.3%) pediatric patients aged 8 to 18 years were studied. At least 1 GI symptom was reported in 34.1% of adults as compared with 21.7% of children (P < 0.0001). Common symptoms in children included upper and lower abdominal pain while adults more frequently reported lower GI symptoms. Participants with GI symptoms had higher hemoglobin A1c (HbA1c) levels (68 ±â€…14mmol/mol; 8.35 ±â€…1.37%) than those without symptoms (66 ±â€…15mmol/mol; 8.22 ±â€…1.40%; P = 0.041). Patients with microvascular complications (nephropathy, retinopathy, and/or neuropathy) were 1.8 times more likely to report GI symptoms (95% CI: 1.26-2.60; P < 0.01) after adjusting for age and sex. No association was observed between GI symptoms and the presence of autoimmune conditions, including thyroid and biopsy-confirmed CD (odds ratio = 1.1; 95% CI: 0.86-1.42; P = 0.45). MAIN CONCLUSIONS: These results highlight that GI symptoms are an important clinical morbidity and are associated with increasing age, duration of type 1 diabetes, HbA1c, and microvascular complications but not with autoimmune comorbidities including CD.