Katherine L. Modzelewski’s research while affiliated with University of Massachusetts Chan Medical School and other places

Importance Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been shown to have benefits when used in patients with heart failure. The comparative outcomes of SGLT2 inhibitors relative to each other has not been well defined and may impact medication selection. Objective To determine the comparative outcomes of empagliflozin and dapagliflozin on reducing the composite of all-cause mortality and hospitalizations in patients with heart failure. Design, Setting, and Participants This multicenter retrospective cohort study included patients with heart failure from August 18, 2021, and December 6, 2022, in the TriNetX Research Collaborative, a centralized database of deidentified electronic medical record data from a network of 81 health care organizations. Eligible patients had a diagnosis of heart failure, had never received an SGLT2 inhibitor previously, and were newly started on empagliflozin or dapagliflozin. Patients were followed up for 1 year. Exposure Initiation of dapagliflozin or empagliflozin. Main Outcomes and Measures The primary outcome was the time to the composite of all-cause mortality or hospitalization between study days 1 to 365. Kaplan-Meier analyses, hazard ratios (HRs), and 95% CIs were used to assess the primary outcome. Results Among 744 914 eligible patients, 28 075 began empagliflozin (15 976 [56.9%]) or dapagliflozin (12 099 [43.1%]). After nearest-neighbor matching for demographics, diagnoses, and medication use, there were 11 077 patients in each group. Of patients who received empagliflozin, 9247 (57.9%) were male, 3130 (19.6%) were Black individuals, and 9576 (59.9%) were White individuals. Similarly, of those who received dapagliflozin, 7439 (61.5%) were male, 2445 (20.2%) were Black individuals, and 7131 (58.9%) were White individuals. Patients receiving empagliflozin were less likely to experience the composite of all-cause mortality or hospitalization compared with those initiated on dapagliflozin (3545 [32.2%] vs 3828 [34.8%] events; HR, 0.90 [95% CI, 0.86-0.94]) in the year following SGLT2 inhibitor initiation and less likely to be hospitalized (HR, 0.90 [95% CI, 0.86-0.94]). All-cause mortality did not differ between exposure groups (HR, 0.91 [95% CI, 0.82-1.00]). There was no difference in mean hemoglobin A 1c or adverse events between groups. Conclusions and Relevance In this cohort study, patients who initiated empagliflozin were less likely to experience the composite of all-cause mortality or hospitalization compared with patients who started dapagliflozin. Additional studies are needed to confirm these finding.

Type 1 and type 2 diabetes account for up to 90% of all cases of diabetes. However, the remaining “atypical” cases, while rare, appear frequently enough that every practitioner should be aware of them. Some forms of diabetes, distinct from type 1 or type 2 diabetes, are caused by single gene mutations. In addition to monogenic diabetes, other atypical causes of diabetes include: genetic defects in insulin action; diseases of the exocrine pancreas; and endocrinopathies. Atypical Diabetes is divided into three parts, each exploring distinct categories of atypical diabetes, and each part includes case studies that illustrate the clinical challenges presented by different forms of atypical diabetes. This book is a comprehensive resource for the successful diagnosis and treatment of these rare, but significant, forms of diabetes.

Importance: Thyroid storm is the most severe form of thyrotoxicosis, with high mortality, and is treated with propylthiouracil and methimazole. Some guidelines recommend propylthiouracil over methimazole, although the difference in outcomes associated with each treatment is unclear. Objective: To compare outcomes associated with use of propylthiouracil vs methimazole for the treatment of thyroid storm. Design, setting, and participants: This comparative effectiveness study comprised a large, multicenter, US-based cohort from the Premier Healthcare Database between January 1, 2016, and December 31, 2020. It included 1383 adult patients admitted to intensive or intermediate care units with a diagnosis of thyroid storm per International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes and treated with either propylthiouracil or methimazole. Analyses were conducted from July 2022 to February 2023. Exposure: Patients received either propylthiouracil or methimazole for treatment of thyroid storm. Exposure was assigned based on the initial thionamide administered. Main outcomes and measures: The primary outcome was the adjusted risk difference of in-hospital death or discharge to hospice between patients treated with propylthiouracil and those treated with methimazole, assessed by targeted maximum likelihood estimation. Results: A total of 1383 patients (656 [47.4%] treated with propylthiouracil; mean [SD] age, 45 [16] years; 473 women [72.1%]; and 727 [52.6%] treated with methimazole; mean [SD] age, 45 [16] years; 520 women [71.5%]) were included in the study. The standardized mean difference for age was 0.056, and the standardized mean difference for sex was 0.013. The primary composite outcome occurred in 7.4% of of patients (102 of 1383; 95% CI, 6.0%-8.8%). A total of 8.5% (56 of 656; 95% CI, 6.4%-10.7%) of patients who initiated propylthiouracil and 6.3% (46 of 727; 95% CI, 4.6%-8.1%) who initiated methimazole died in the hospital (adjusted risk difference, 0.6% [95% CI, -1.8% to 3.0%]; P = .64). There were no significant differences in duration of organ support, total hospitalization costs, or rates of adverse events between the 2 treatment groups. Conclusion and relevance: In this comparative effectiveness study of a multicenter cohort of adult patients with thyroid storm, no significant differences were found in mortality or adverse events in patients who were treated with propylthiouracil or methimazole. Thus, current guidelines recommending propylthiouracil over methimazole for treatment of thyroid storm may merit reevaluation.

Hyperglycemic crisis (HC) has been reported in patients with COVID-19 infection, but there is little data about HC following COVID-19 vaccination, with 10 patients described to date. We performed a retrospective observational study examining the correlation between COVID-19 vaccination and HC in adult patients admitted from 1/1/21-7/1/21 at our institution. There were 91 admissions for HC during the study period. Forty-one were admissions for diabetic ketoacidosis (DKA) in patients with type 1 diabetes (T1D) , 2 of which also had hyperglycemic hyperosmolar state (HHS) . In patients with type 2 diabetes (T2D) , there were 49 admissions for DKA, 6 of which also had HHS, and 1 admission for HHS alone. In patients with T1D, 17 admissions occurred following COVID-19 vaccination, ranging from <24 hours to more than 3 months after, including 1 new diagnosis of T1D. All cases had a trigger of insulin omission or other medical illness, including 7 with admission for COVID-19 infection. In patients with T2D, 20 DKA or overlap admissions and 1 HHS admission occurred following COVID-19 vaccination, ranging from 1 to 40 days after. Six of these patients had no clear trigger of medical illness or insulin omission, 3 of which were new diagnoses of T2D. Two were following the first vaccination and 4 following the second vaccination. Hemoglobin A1c at admission was >11% in all 6 of these patients. Among patients with T1D, there were no cases of HC that appeared to be attributable to COVID-19 vaccination. In patients with T2D, while there were six cases following vaccination with no other clear trigger, the degree of hemoglobin A1C elevation at the time of admission was suggestive of longer duration of poor glycemic control. Three of these cases did have acute symptom onset following vaccination within one week of presentation, so it is possible that HC was provoked by vaccination in these patients. While it is not clear that COVID vaccination leads to HC in T1D, it may be an acute trigger for HC in patients with T2D who have poor underlying glycemic control. Large scale population studies are needed to better assess rates of HC following COVID-19 vaccination. Disclosure K. L. Modzelewski: None. S. Alexanian: None.

Background There is urgent need for safe, effective, and easily implementable treatments that reduce the progression of respiratory failure in COVID-19. Despite increased adoption during the pandemic, the effectiveness of prone positioning on respiratory failure progression among non-intubated patients is unclear. Research Question What is the effectiveness of smartphone-guided self-prone positioning recommendations and instructions compared to usual care to reduce progression of respiratory failure among non-intubated patients with COVID-19? Study Design and Methods APPEX-19 is a multicenter randomized clinical trial that randomized non-intubated adults with COVID-19 on <6 L/minute supplemental oxygen to receive a smartphone-guided self-prone positioning intervention or usual care. The primary outcome was the composite of respiratory deterioration (an increase in supplemental oxygen requirement) or intensive care unit transfer. Using a Bayesian statistical approach, we calculated the posterior probability of superiority within each treatment arm (superiority threshold 95%). Results The trial was stopped early for slow enrollment. A total of 293 participants were included in the modified intention to treat analysis (159 self-prone positioning intervention and 134 usual care). Among participants who self-reported body positioning (n=139; 70 intervention; 69 usual care), 71.4% in the intervention arm and 59.4% in the usual care arm attempted prone positioning. Thirty-one participants (posterior mean 24.7%, 95% credible interval 18.6-31.4%) receiving usual care and 32 participants (posterior mean 22.1%, 95% credible interval 16.6-28.1%) receiving the self-prone positioning intervention experienced the primary outcome; the posterior probability of superiority for the self-prone positioning intervention was 72.1%, less than the 95% threshold for superiority. Adverse events occurred in 26.9% of participants in the usual care arm and 11.9% of participants in the intervention arm. Interpretation Among non-intubated patients with COVID-19, smartphone-guided self-prone positioning recommendations and instructions did not promote strong adherence to prone positioning.

Background Despite increases in continuous glucose monitor (CGM) and insulin pump use in adults with diabetes, there is room for expansion. Technology adoption may be influenced by the training environment and fellowship education. However, little is known about adult endocrinology trainee comfort with, understanding of, or methods by which trainees receive education about diabetes technology. Methods Mixed methods, sequential explanatory evaluation using survey and semi-structured interviews of endocrinology trainees and fellowship leadership in Accreditation Council for Graduate Medical Education (ACGME)-accredited adult endocrinology fellowship programs to assess trainee and leadership comfort with, perceived knowledge of, and current methods for diabetes technology education. Results Seventy-seven respondents completed the survey. The majority of training programs have curricula for training on insulin pumps (74%) and CGM (75.3%); 52% of fellows felt curricula are adequate. First- and second-year fellows were more comfortable with CGM than insulin pump use. Only half of third-year fellows felt comfortable with starting insulin pump therapy or recommending insulin dose adjustments based on CGM rate of change arrows. Qualitative interviews identified the importance of both direct instruction and experiential learning in diabetes technology education. Conclusions Almost half of trainees feel that curricula for learning to use and manage insulin pumps and CGM are inadequate and feel uncomfortable with critical aspects of technology use, demonstrating the need for increased attention to trainee education in the use of diabetes technology. Based on a better understanding of current and preferred methods for instruction, this study provides direction for future development of initiatives to improve fellow education in this field.

Background: Continuous Glucose Monitoring (CGM) has been increasingly shown to be beneficial in patients with both type 1 and type 2 diabetes using insulin. Despite this, challenges remain in obtaining coverage for these devices. We sought to define the process of initiation of CGM and better understand factors associated with successful initiation. Methods: A single-center retrospective cohort study of 271 patients seen over a three-year period from 2017-2020 in the adult endocrinology clinic at Boston Medical Center who were prescribed CGM was performed. The primary outcome was time to CGM initiation. Secondary outcomes included factors associated with initiation and continued use of CGMs and glycemic control. Results: Obtaining CGM through prescription benefit was significantly faster than through durable medical equipment companies (78 days vs. 152 days, p<0.0001). Factors associated with initiation of CGM were younger age, private insurance, and education with a clinical diabetes educator. Identifying as Black or Hispanic was significantly associated with decreased initiation of CGM. Glycemic control as represented by hemoglobin A1C improved in patients initiated on CGM from 9.06% to 8.22% (p<0.001). Conclusion: Prescribing CGM as a pharmacy benefit significantly reduces the time to initiation, but on average still takes several months, delaying potentially life-saving care for patients living with diabetes. Barriers to CGM initiation must be addressed to ensure timely delivery of optimal care to our patients.

Over millennia, sharing the practical experience of one physician with others has been a proven way of disseminating best practices of the time with esteemed colleagues and teaching new generations of doctors. This selfless and generous sharing of knowledge is the cornerstone of teaching medical students and residents at the bedside and in classrooms, at local grand rounds and national conferences. The best way of acquiring clinical skills is to observe experienced physicians and to follow their example. Thus, learning from colleagues’ experience is a time-tested learning process. This book sets out to accomplish exactly that—to facilitate the learning process by sharing unusual and interesting cases with a great number of readers. We are fully aware that the readers may have had or currently have similar cases in their own practice and have selected similar or different approaches to their cases. Regardless, good clinicians always learn from others, always sharpen their own thought process, and always improve their acumen and skills.

Background Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are potentially life-threatening complications of diabetes. Many hospitals have developed protocols to guide the management of these conditions and align with best practices. One of the main complications encountered in the treatment of hyperglycemic crises is hypoglycemia. Methods At our institution, we undertook a review of our insulin infusion titration protocol, rates of hypoglycemia, and time to clinical resolution for patients with hyperglycemic crises. A multidisciplinary team performed a literature review and analyzed baseline hospital data with the existing protocol. With the input of multiple stakeholders, several changes were made to the titration algorithm over multiple PDSA cycles to refine the protocol. Effectiveness and safety of the protocol, as well as fidelity with the protocol, were assessed after each PDSA cycle. Results After the initial cycle, chart review showed a reduction in hypoglycemia rates of more than 50% in patients treated with the new protocol without any increase in time to resolution of DKA. A second version of the protocol was implemented to improve usability, and improvement in hypoglycemia was maintained. Conclusion Despite the fact that the initial protocol had been developed based on best practice recommendations, rates of hypoglycemia were initially high. Critical assessment of pitfalls in management allowed changes to the protocol that significantly and sustainably reduced hypoglycemia.