Mary-Anne Doyle

An unusual case of malignancy-related hypercalcemia.

Objective To report the case of a 28-year-old woman who presented with hypercalcemia (total calcium =4.11 mmol/L), elevated parathyroid hormone (PTH) 24.6 pmol/L, normal parathyroid hormone-related peptide 7.8 pg/mL, and a 63 mm × 57 mm, poorly differentiated neuroendocrine carcinoma (small-cell type) pancreatic mass with liver metastases. Investigations and treatment Hypercalcemia was acutely managed with intravenous fluids, pamidronate and calcitonin. Investigations for multiple endocrine neoplasia type 1 and parathyroid adenoma were initiated. The identified neuroendocrine tumor was treated with cisplatinum/etoposide chemotherapy. Results The pancreatic mass (56 mm × 49 mm) and metastases decreased in size with chemotherapy and calcium levels normalized. Eight months later, calcium increased to 3.23 mmol/L, PTH increased to 48.2 pmol/L, and the pancreatic mass increased in size to 67 mm × 58 mm. The patient was given a trial of cinacalcet but was unable to tolerate it. Chemotherapy was restarted and resulted in a decrease in the pancreatic mass (49 mm × 42 mm), a reduction in PTH levels (16.6 pmol/L), and calcium levels (2.34 mmol/L). Conclusion Ectopic PTH secreting tumors should be considered when there is no parathyroid related cause for an elevated PTH. Recognizing the association between PTH and hypercalcemia of malignancy may lead to an earlier detection of an undiagnosed malignancy.

International survey on gestational diabetes

Objective: There is a lack of consensus among guidelines for screening, diagnosis and management of gestational diabetes (GDM). The purpose of this project was to determine current practices around GDM amongst members of the Medical Women’s International Association (MWIA). Methods: The MWIA with the Division of Endocrinology and Metabolism, University of Ottawa, developed an online survey using “Survey Monkey” and distributed it to its members. Results: A total of 125 members completed the survey. Universal screening was recommended by 83% and most followed published guidelines. The 50 g glucose challenge test (GCT) was used for screening by 23% of participants while 25% recommended fasting blood glucose. There was also variability in how to proceed following a positive screening test. Almost 65 % recommended one of the glucose tolerance tests (50 g OGTT 26.7 % vs. 75 g OGTT 25.6% vs. 100 g OGTT 12.2%), while 18.8% recommended starting treatment and 16.7% used other diagnostic measures. Insulin was the most recommended treatment (75%) if diet/lifestyle failed. Conclusions: Our survey highlights the international variability that exists in the screening, diagnosis, and management of women with GDM. These differences impact on true prevalence rates and may underestimate the costs of this disease. The recommendation to move to a single internationally accepted diagnostic algorithm may be hampered by the variation in current practice globally.

Using Standardized Insulin Orders to Improve Patient Safety in a Tertiary Care Centre

OBJECTIVE To standardize insulin prescribing practices for inpatients, improve management of hypoglycemia, reduce reliance on sliding scales, increase use of basal-bolus insulin and improve patient safety. METHODS Patients with diabetes were admitted to 2 pilot inpatient units followed by corporate spread to all insulin-treated patients on noncritical care units in a Canadian tertiary care multicampus teaching hospital. Standardized preprinted insulin and hypoglycemia management orders, decision support tools and multidisciplinary education strategies were developed, tested and implemented by way of the Model for Improvement and The Ottawa Model for Research Process. Clinical and balance measures were evaluated through statistical process control. RESULTS Patient safety was improved through a reduction in hypoglycemia and decreased dependence on correctional scales. Utilization of the preprinted orders approached the target of 70% at the end of the test period and was sustained at 89% corporately 3 years post-implementation. CONCLUSIONS The implementation of a standardized, preprinted insulin order set facilitates best practices for insulin therapy, improves patient safety and is highly supported by treating practitioners. The utilization of formal quality-improvement methodology promoted efficiency, enhanced sustainability, increased support among clinicians and senior administrators, and was effective in instituting sustained practice change in a complex care centre.

Ancillary testing for diagnosis of brain death: a protocol for a systematic review and meta-analysis.

BackgroundThe essential clinical diagnostic components of brain death must include evidence for an established etiology capable of causing brain death, two independent clinical confirmations of the absence of all brainstem reflexes and an apnea test, and exclude confounders that can mimic brain death. Numerous confounders can render the clinical neurological determination of death (NDD) virtually impossible. As such, clinicians must rely on additional ancillary testing.Methods/designWe will conduct a systematic review and a meta-analysis of ancillary testing for the neurological determination of death. The primary objective of this systematic review is to evaluate the accuracy of these ancillary tests compared to the three accepted reference standards: (1) clinical diagnosis, (2) four-vessel angiography and (3) radionuclide imaging. This objective will be investigated using two different populations with different baseline risks of brain death: comatose patients and patients with a neurological determination of death. We will search MEDLINE, EMBASE and the Cochrane Central databases for retrospective and prospective diagnostic test studies and interventional studies. We will report study characteristics and assess methodological quality using QUADAS-2, which is used to assess the quality of diagnostic tests. If pooling is appropriate, we will compute parameter estimates using a bivariate model to produce summary receiver operating curves, summary operating points (pooled sensitivity and specificity), and 95% confidence regions around the summary operating point. Clinical and methodological subgroup and sensitivity analyses will be performed to explore heterogeneity.DiscussionThe results of this project will provide a critical evidence base for the neurological determination of death. The results will help clinicians to select ancillary tests based on the best available evidence. Our systematic review will also identify the strengths and weaknesses in the current evidence for the use of ancillary tests in diagnosing brain death. It will serve as a foundation for further research and the development of prospective studies on currently used or novel techniques for NDD.Protocol registrationPROSPERO Registration Number: CRD42013005907

Successful Hepatitis C Antiviral Therapy Induces Remission of Type 2 Diabetes: A Case Report.

Patient: Male, 49 Final Diagnosis: Type 2 diabetes Symptoms: — Medication: — Clinical Procedure: — Specialty: Endocrinology and Metabolic Objective: Unusual clinical course Background: Type 2 diabetes is a well described extra-hepatic manifestation of hepatitis C infection (HCV). Eradication of HCV has led to improvements in insulin resistance but to date has not been shown to induce remission of diabetes. Case Report: We report a case of a 49-year-old man with HCV and a 2-year history of T2DM on oral agents. He was initially treated with peg-interferon/ribavirin (peg-IFN/rib) but did not achieve a HCV treatment response. Four years later he was retreated with peg-IFN/rib plus an HCV protease inhibitor (boceprevir). His HbA1c at the start of treatment was 7.9%. Antiviral response to HCV-therapy correlated with a significant improvement in glucose control without a change in diabetes therapy or improvement in adherence. He achieved a sustained virological response and within a year of completing antiviral therapy he no longer required medical therapy for diabetes. Two years after the completion of HCV treatment, the patient has maintained an HbA1c of 5.8% without any diabetes medications. Conclusions: This case provides evidence of the important relationship between HCV and diabetes and highlights the potential reversibility of glucose abnormalities with successful eradication of HCV. Increased awareness of this association may improve detection of undiagnosed HCV infection, identify patients with reversible causes of diabetes, guide therapeutic decisions for HCV treatment, and improve outcomes in patients with both diseases.

Using a Structured Discharge Letter Template to Improve Communication During the Transition from a Specialized Outpatient Diabetes Clinic to a Primary Care Physician.

OBJECTIVE Transition from specialists to primary care physicians is dependent on clear communication by means of a discharge letter. Primary care physicians have indicated that letters from specialists rarely contain the details they require. As part of a quality-improvement project to improve the transition from diabetes clinics to primary care physicians, a structured discharge letter template was developed to facilitate the dictation of useful letters by specialists. The objective was to evaluate the content and quality of discharge letters created using a structured discharge letter template as compared to letters completed without the template. METHODS Retrospective study of patients treated at the Ottawa Hospital and discharged from the outpatient diabetes clinic between November 1, 2009, and December 1, 2010. The letters were reviewed by 2 independent reviewers and were assessed for content, brevity, clarity, management plan, organization and quality. Word count, dictation and transcription times were also compared. RESULTS Letters completed using the structured discharge letter template were more comprehensive and more likely to contain guidelines on management for glycemic control (51.1% vs. 14.1%; p<0.001); cardiovascular risk factors (65.61% vs. 9.8%; p<0.001); diabetes complications (79.9% vs. 5.9%; p<0.001); and provided re-referral criteria (89.3% vs. 15.7%; p<0.001). Dictation time did not differ between formats. Transcription time (20:65 min vs. 13:45 min; p<0.01) and word count (502 words vs. 292 words; p<0.001) were higher with the template. CONCLUSIONS The use of a structured discharge letter template improved the content and quality of discharge letters dictated by specialists. Primary care physicians were more consistently provided with valued information and given criteria for re-referral.

Improving Glycemic Control in Adults and Children With Type 1 Diabetes With the Use of Smartphone-Based Mobile Applications: A Systematic Review

OBJECTIVES Management of type 1 diabetes is often challenging. Smartphone mobile applications (apps) may provide additional support and help to improve glycemic control and clinical outcomes. The objectives of this study were to examine the literature evaluating the use of mobile apps (stand-alone and text messaging/feedback) in type 1 diabetes and to review top-rated mobile apps applicable to type 1 diabetes. METHODS Medline, Cochrane and Embase databases were systematically searched to identify studies published from inception to February 2018. Top-rated relevant apps from Google Play Store and Apple App Store were reviewed in July 2017. RESULTS The literature search yielded 3,462 studies. Of these studies, 9 evaluated the stand-alone apps; 3 showed significant improvement in glycated hemoglobin (A1C) levels (0.5%, p<0.05, 0.57%, p<0.05, and 0.58%, p=0.02); 3 demonstrated improved adherence to glucose monitoring; and 1 study demonstrated a reduction in hypoglycemic events (glucose<3.0 mmol/L) in 6 of 10 participants who completed the study. Also, 5 studies evaluated a mobile app plus text-messaging/feedback system. Only 1 showed a significant reduction in severe hypoglycemic events (mobile app+text, IQR 0.33, 95% CI 0.17 to 0.63; vs. control, IQR 2.29, 95% CI 1.80 to 2.91), while another single study demonstrated a reduction in median glycated hemoglobin levels (0.3%; p<0.001). Most top-rated mobile apps logged parameters relevant to diabetes management, and some provided graphic analysis and set reminders. CONCLUSIONS This study highlights the need for larger and longer studies to explore the efficacy of apps to optimize outcomes in type 1 diabetes, the populations that would benefit most from these tools and the resources needed to support mobile apps plus text-messaging/feedback systems.

Antibiotic exposure and risk of weight gain and obesity: protocol for a systematic review

BackgroundThe prevalence of obesity is increasing worldwide, and there is growing interest in better delineating the role of the human gut microbiome in this phenomenon. Obesity-specific gut microbiome features have been observed in both human and animal studies, and these variations appear to play a causative role in increasing body weight. There is evidence that antibiotics can modify the composition and diversity of the gut microbiome and that this may contribute to body weight changes. The primary objective of the proposed systematic review is to evaluate and synthesize the existing evidence evaluating the possible association between antibiotic use, weight gain, and obesity.MethodsA comprehensive search of the MEDLINE and EMBASE databases will be performed. Both randomized and non-randomized studies (excluding case reports) in neonates, children, adults, and pregnant women will be included. The exposure of interest is antibiotics of any type, duration, and route given for any indication. All included studies must have a comparator group. The primary outcomes are the development of overweight and obesity. Secondary outcomes are percent weight-change from baseline and change in body mass index or waist circumference. Additional secondary outcomes in pregnant women are gestational weight gain, postpartum weight retention, offspring birth weight, childhood weight, and obesity. Risk of bias of included trials will be performed. Two reviewers will screen and perform data extraction independently.DiscussionThis systematic review will summarize the existing evidence evaluating the association between antibiotic use, weight gain, and obesity and facilitate the identification of important gaps and uncertainties in the literature.Systematic review registrationPROSPERO CRD42017069177

Pituitary hyperplasia: a complication of the pseudomalabsorption of thyroxine

Objective “The pseudomalabsorption of thyroxine” has been used to describe patients with hypothyroidism who fail to comply with their treatment. We describe a unique case of a 32-year-old with hypothyroidism who developed pituitary hyperplasia and hyperprolactinemia secondary to the pseudomalabsorption of thyroxine. Investigations and treatment After baseline thyroid-function tests were performed, the patient was administered levothyroxine 0.5 mg under the supervision of a registered nurse. Thyroid function testing was repeated at 30, 60, 120, and 180 minutes. Arrangements were made for further daily supervised loading of levothyroxine 0.1 mg. Results With the administration of 0.5 mg levothyroxine, free thyroxine levels increased by 120 minutes, and with daily supervised dosing of 0.1 mg there was normalization of the thyroid hormone levels and a reduction of thyroid-stimulating hormone levels. Maintenance of thyroid-stimulating hormone < 15 mU/L for 2 weeks led to a reduction in prolactin levels and regression in the size of the pituitary on magnetic resonance imaging. Conclusion If left untreated, these patients face significant morbidity and are at risk of developing pituitary hyperplasia, complications from an increase in pituitary size, hyperprolactinemia, and potentially myxedema coma. Recognizing pituitary hyperplasia and hyperprolactinemia as a complication from the pseudomalabsorption of levothyroxine may prevent the potential of a misdiagnosis of a prolactinoma leading to unnecessary investigations and inappropriate treatment. Patient awareness of this serious complication and the rapid, demonstrable resolution with adequate thyroid hormone replacement may provide motivation to comply with supervised dosing of levothyroxine. It has also been suggested that supervised treatment enables the individual to maintain their patient status, which may be in part the motivation behind this disorder.