Molecular-derived risk of malignancy and the related positive call rate of indeterminate thyroid cytology diagnoses as quality metrics for individual cytopathologists.

BACKGROUND: Indeterminate thyroid cytopathology diagnoses represent differing degrees of risk that are corroborated by follow-up studies. However, traditional cytologic-histologic correlation may overestimate the risk of malignancy (ROM) because only a subset of cases undergo resection. Alternatively, some molecular tests provide probability of malignancy data to calculate the molecular-derived risk of malignancy (MDROM) and the positive call rate (PCR). The authors investigated MDROMs and PCRs of indeterminate diagnoses for individual cytopathologists as quality metrics. METHODS: This study was approved by the Department of Pathology Quality Improvement Program. Thyroid cytopathology diagnoses and ThyroSeq v3 results were retrieved for each cytopathologist for a 2-year period with at least 3 years of follow-up for the atypia of undetermined significance (AUS), follicular neoplasia (FN), and follicular neoplasia, oncocytic-type (ONC) cytopathologic diagnoses. MDROMs and PCRs were compared with reference ROMs and cytologic-histologic correlation outcomes. RESULTS: The overall MDROMs (and ranges for cytopathologists) for the AUS, FN, and ONC categories were 13.4% (range, 5.8%-20.8%), 28.1% (range, 22.1%-36.7%), and 27.0% (range, 19.5%-41.5%), respectively, and most individual cytopathologists' MDROMs were within reference ROM ranges. However, PCRs more effectively parsed the differences in cytopathologists' ROM performance. Although the overall PCRs were not significantly different across cytopathologists (p = .06), the AUS PCRs were quite different (p = .002). By cytologic-histologic correlation, six of 55 resected cases (10.9%) were falsely negative, and there were no false-positive cases. CONCLUSIONS: MDROMs and PCRs evaluate concordance with reference ROMs and with one another and provide individual feedback, which potentially facilitates quality improvement.

A Payer-Provider Partnership for Endocrine Targeted Automatic eConsults: Implementation and Early Impact on Diabetes and Cost Outcomes.

In the United States, many individuals with diabetes mellitus (DM) do not achieve treatment goals despite the availability of effective interventions. Provider clinical inertia is one cause of these unfavorable outcomes. Targeted automatic eConsults (TACos) are an emerging technology-based intervention with potential to address clinical inertia in primary care (PC). TACos prospectively identify at-risk patients and use unsolicited specialist recommendations to prompt treatment intensification. Through a payer-provider collaboration, a TACos intervention was piloted for adults with uncontrolled DM (HbA1c >8%) to understand impact on DM clinical inertia and outcomes. Clinical inertia was assessed by measuring whether a PC provider implemented recommended therapeutic changes. Six-month changes in HbA1c and health care costs per member per month were evaluated using an observational matched design and intention-to-treat (ITT) analysis. The analysis included 196 individuals who received a TACos between February 2021 and August 2021 (ITT group) matched to 392 controls based on clinical and demographic criteria. TACos recommendations were implemented 65% of the time. Median percent change in HbA1c was significantly greater for the ITT group versus controls (-10.9% vs. -10.2%; P = 0.0359). Median total costs were 7.9% lower in the ITT group (P = 0.0900). A per protocol analysis was done to examine effects between ITT group individuals with an implemented TACos recommendation (n = 126) and controls. Median percent change in HbA1c was significantly greater (-19.5% vs. -10.2%; P < 0.0001), but there was no difference in total costs (-7.9%; P = 0.1753). TACos may feasibly address clinical inertia in PC and improve HbA1c for uncontrolled DM.

Molecular Testing Predicts Incomplete Response to Initial Therapy in Differentiated Thyroid Carcinoma Without Lateral Neck or Distant Metastasis at Presentation: Retrospective Cohort Study.

Background: Molecular testing (MT) is emerging as a potential prognostic factor that can be available before treatment of differentiated thyroid carcinoma begins. Among patients eligible for either lobectomy or total thyroidectomy as their initial therapy, our study aims were to assess (1) if conventionally available preoperative factors are associated with incomplete response to initial therapy, and (2) if MT results can be a surrogate for the ATA Risk Stratification System (RSS) to estimate risk of recurrence. Methods: The data of consecutive thyroid cancer patients without preoperative lateral neck disease or distant metastasis who underwent index thyroidectomy between November 1, 2017 and October 31, 2021 were reviewed. Logistic regression models including preoperative variables such as MT and/or the postoperatively available RSS were constructed to predict disease recurrence, either structural or biochemical. Model discrimination using the c-statistic and goodness-of-fit test were compared. Results: Among 945 patients studied, 50 (5.2%) recurred with 18-month median follow-up. Recurrences were detected in 17 (2.9%), 20 (6.7%), and 13 (22.8%) patients with RSS-low, -intermediate, and -high cancers, respectively (p < 0.001). In multivariable analysis, only tumor size was associated with recurrence (odds ratio [OR] 1.3, 95% confidence interval [CI] 1.1-1.5). In a different model analyzing 440 (46.6%) patients with available MT results, recurrence was associated with both larger tumor size (OR 1.4 [95% CI 1.1-1.8]) and MT results (p < 0.001). Including MT improved the c-statistic by 27%, which was statistically no different than the model incorporating only the RSS (p = 0.15). Conclusions: Disease recurrence was observed across all ATA RSS categories in short-term follow-up, and tumor size was the only conventional preoperative factor associated with recurrence. When MT results were incorporated, they not only improved predictive ability beyond tumor size alone, but also yielded similar ability as the gold standard ATA RSS. Thus, MT results might aid the development of novel preoperative risk stratification algorithms.

A thyroid EIF1AX story: how clinical, cytologic, and molecular surveillance led to appropriate management.

INTRODUCTION: Indeterminate thyroid cytology diagnoses are associated with intermediate risks of malignancy. Application of molecular testing (MT) to indeterminate specimens provides additional diagnostic and prognostic information. While a positive or suspicious MT result may prompt surgery, a negative MT result is associated with a low probability of cancer or noninvasive follicular thyroid neoplasm with papillary-like nuclear features and approximates that of a benign cytology diagnosis. Furthermore, ThyroSeq v3 MT has a "currently negative" result for findings with the probability of cancer or noninvasive follicular thyroid neoplasm with papillary-like nuclear feature that is slightly greater than that for the negative ThyroSeq v3 MT result but less than 10%, suggesting active surveillance. In this report, we discuss a case of a patient for whom clinical, cytologic, and molecular surveillance led to timely surgery and management. CLINICAL DETAILS: A 53-year-old man with a thyroid isthmus nodule had a fine-needle aspiration cytology diagnosis of atypia of undetermined significance and a subsequent ThyroSeq v3 MT, which revealed an EIF1AX mutation and a "currently negative" MT result. Surveillance with additional fine-needle aspiration samples demonstrated concerning genomic alterations (fluctuating EIF1AX allelic frequency and a non-V600E BRAF mutation), culminating in the conversion to a positive MT result 3 years later. Resection revealed an encapsulated noninvasive, oncocytic solid subtype of papillary thyroid carcinoma with increased mitotic activity. CONCLUSION: The case is notable for clinical, cytologic, and molecular surveillance demonstrating sequential pathologic alterations in an indeterminate thyroid nodule with EIF1AX mutation, leading to timely resection of the neoplasm before invasion manifested.

Association of comprehensive thyroid cancer molecular profiling with tumor phenotype and cancer-specific outcomes.

BACKGROUND: Molecular testing improves the diagnostic accuracy of thyroid cancer. Whether specific molecular testing results are associated with tumor phenotype or provide prognostic information needs further delineation. METHODS: Consecutive thyroid cancer patients after index thyroidectomy with ThyroSeq version 3 (Rye Brook, NY) molecular testing obtained on preoperative fine-needle aspiration or thyroidectomy specimens from patients with thyroid cancer were categorized into 3 molecular risk groups based on detected mutations, fusions, copy number alterations, and/or gene expression alterations and correlated with histopathology and recurrence, defined as biochemical or structural. RESULTS: Of 578 patients, 49.9%, 37.5%, and 12.6% had molecular risk group-low, molecular risk group-intermediate, and molecular risk group-high cancers, respectively. With a median 19-month follow-up, 9.1% patients recurred. Compared with molecular risk group-low, molecular risk group-intermediate cancers were diagnosed in younger patients and more often had microscopic extrathyroidal extension, involved margins, and nodal disease. Compared with molecular risk group-intermediate, molecular risk group-high cancers were diagnosed in older patients and more often had gross extrathyroidal extension and vascular invasion. In multivariable analysis, recurrence was more likely in molecular risk group-high cancers than in molecular risk group-intermediate (hazard ratio = 4.0; 95% confidence interval, 1.9-8.6; P < .001) and more likely in molecular risk group-intermediate than in molecular risk group-low (hazard ratio = 5.0; 95% confidence interval, 2.0-12.5; P < .001). CONCLUSION: Using modern comprehensive genotyping, the genetic profile of thyroid cancers can be categorized into 3 novel molecular risk groups that were associated with histopathologic phenotype and recurrence in short-term follow-up.

Clinicopathologic Characteristics and Postsurgical Follow-Up of Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features in the Postnomenclature Revision Era.

Background: Noninvasive encapsulated follicular variant papillary thyroid carcinoma (EFVPTC) was reclassified as "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP) in 2016. Most existing studies that examined outcomes included patients managed as EFVPTC and only retrospectively reclassified as NIFTP. This is the first study to evaluate the clinicopathologic, molecular, and surveillance characteristics of patients diagnosed with NIFTP at the time of surgery and managed based on this diagnosis. Methods: We performed a retrospective cohort study of consecutive cases diagnosed as NIFTP from June 2016 to October 2021 identified from electronic medical records at a large tertiary care institution. Patients with coexisting low-risk thyroid cancers ≥1.0 cm in size or any size aggressive histology were excluded, and review of demographic, clinical, imaging, cytologic, and molecular genetic data was performed. Initial care was delivered according to existing clinical guidelines, with a consensus institutional plan for five-year follow-up after surgery. Results: Among 79 patients with 84 nodules diagnosed as NIFTP after surgery, 83.5% (66/79) were women and the mean age was 51 years (range, 21-84). Mean NIFTP size was 2.4 cm (range 0.15-8.0). On ultrasound, the majority of nodules were categorized as thyroid imaging, reporting and data system TI-RADS 3 (55.3%, 42/76), and TI-RADS 4 (36.8%, 28/76). On cytology, they were typically diagnosed as Bethesda III (69.1%, 47/68) or Bethesda IV (23.5%, 16/68). Molecular testing was performed on 62 nodules, and molecular alterations were found in 93.5% (58/62). The most common alterations identified in NIFTP were RAS mutation (75.4%, 43/57), THADA fusion (12.3%, 7/57), and BRAFK601E mutation (7.0%, 4/57). Fifty-two (65.8%) patients underwent lobectomy and 27 (34.2%) total thyroidectomy, and no patient received completion thyroidectomy. Twenty-one patients (26.5%) had coexisting papillary or follicular microcarcinoma. None of the patients received radioiodine ablation. On a mean follow-up of 28.5 months (range, 6-69 months), no structural or biochemical recurrences were observed. Conclusions: In this large cohort of patients with NIFTP diagnosed at the time of surgery and managed typically by lobectomy with no radioiodine ablation, no evidence of tumor recurrence was identified on a limited follow-up. This finding supports indolent clinical course of NIFTP.

Performance of a Multigene Genomic Classifier in Thyroid Nodules with Suspicious for Malignancy Cytology.

Background: Molecular testing is increasingly used to refine the probability of cancer and assess recurrence risk in thyroid nodules with Bethesda III/IV fine needle aspiration (FNA) cytology. However, limited data exist for Bethesda V (suspicious for malignancy [SFM]) samples. This study evaluated the performance of ThyroSeq v3 (TSv3) in thyroid nodules with SFM cytology. Methods: In this single-institution retrospective cohort study, consecutive thyroid FNA samples diagnosed as SFM with TSv3 testing and known surgical outcome were identified. Clinical, pathology, and molecular findings were reviewed. The TSv3 Cancer Risk Classifier was used to determine molecular risk groups (MRGs). For test-negative cases diagnosed as cancer/noninvasive follicular thyroid neoplasm with papillary-like nuclear features, TSv3 was performed on the resected tumors. Results: Among 128 SFM samples studied, 100 (78.1%) were TSv3 positive, and 28 (21.9%) were negative. The cancer prevalence on surgery was 82.8%. Among test-positive samples, 95% were malignant and 5% benign. Among test-negative samples, 17 (60.7%) were benign and 11 (39.3%) malignant. Overall, TSv3 had a sensitivity of 89.6% (confidence interval; CI 82.4-94.1) and a specificity of 77.3% (CI 56.6-89.9). For a cancer prevalence of 50-75% expected in SFM cytology by the Bethesda system, the negative predictive value was expected to range from 71.2% to 88.1% and the positive predictive value from 79.8% to 92.2%. Among test-positive nodules, 20% were MRG-Low (mostly RAS-like alterations), 66% MRG-Intermediate (mostly BRAF-like alterations), and 14% MRG-High. Among patients with cancer, 65 (61.3%) were American Thyroid Association low risk, 25 (23.6%) intermediate risk, and 6 (5.7%) high risk. During the mean follow-up of 51.2 months (range: <1 to 470 months), 12 (13.0%) patients had disease recurrence, which was more common in MRG-High (54.6%) compared with MRG-Intermediate (9.5%) and MRG-Low (0%) cancers (p < 0.001). Upon reexamining tumors with false-negative results, half of evaluable cases had alterations likely missed due to limiting FNA sampling, and the remainder represented low-risk tumors. Potentially targetable alterations were identified in 10 samples. Conclusions: In this large series of SFM thyroid nodules, TSv3 further improved cancer prediction and detected RAS-like, BRAF-like, high-risk, and potentially targetable alterations, all of which may inform more optimal patient management. MRGs were associated with recurrence-free survival, offering potential preoperative cancer risk stratification.

Clinicopathological features and outcomes of thyroid nodules with EIF1AX mutations.

EIF1AX gene mutations are reported in both benign and malignant thyroid tumors, with unclear outcomes when detected preoperatively. The aim of this study was to determine the features and outcomes of thyroid nodules with various types of mutation identified in cytologic (fine-needle aspiration) samples on preoperative ThyroSeq testing and with surgical outcomes. In this single-institution retrospective study of 31 consecutive patients, 77% were female and nodule size ranged from 1.5 to 9.4 cm with widely varying cytologic and TI-RADS ultrasound categorizations. Among two main mutational hotspots, 55% were located in exon 2 and 45% at the intron 5/exon 6 splice site. On histology, 45% of -positive nodules were cancer/noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) including 19% encapsulated follicular variant papillary thyroid carcinoma, 10% follicular carcinoma, 10% anaplastic carcinoma (ATC), and 7% NIFTP. Almost half (48%) of patients had one or more coexisting mutations, most frequently RAS. The prevalence of cancer/NIFTP was 80% for mutation with coexisting molecular alteration vs 13% with an isolated mutation (P = 0.0002). Cancer probability was associated with mutation type and was 64% for splice-site mutation and 29% for non-splice mutation (P = 0.075). All 3 nodules with EIF1AX+RAS+TERT+TP53 mutations were ATC. In summary, in this study, all nodules with an isolated non-splice mutation were benign, one-third of those with an isolated splice mutation were cancer, and most nodules with coexisting with RAS or other alterations were malignant. These findings suggest that clinical management decisions for patients with EIF1AX-mutant nodules should consider both the type of mutation and its co-occurrence with other genetic alterations.

Sex differences in glycemic measures, complications, discharge disposition, and postdischarge emergency room visits and readmission among non-critically ill, hospitalized patients with diabetes.

INTRODUCTION: The purpose of this prospective observational cohort study was to examine sex differences in glycemic measures, diabetes-related complications, and rates of postdischarge emergency room (ER) visits and hospital readmissions in non-critically ill, hospitalized patients with diabetes. RESEARCH DESIGN AND METHODS: Demographic data including age, body mass index, race, blood pressure, reason for admission, diabetes medications at admission and discharge, diabetes-related complications, laboratory data (hematocrit, creatinine, hemoglobin A1c, point-of-care blood glucose measures), length of stay (LOS), and discharge disposition were collected. Patients were followed for 90 days following hospital discharge to obtain information regarding ER visits and readmissions. RESULTS: 120 men and 100 women consented to participate in this study. There were no sex differences in patient demographics, diabetes duration or complications, or LOS. No differences were observed in the percentage of men and women with an ER visit or hospital readmission within 30 (39% vs 33%, p=0.40) or 90 (60% vs 49%, p=0.12) days of hospital discharge. More men than women experienced hypoglycemia prior to discharge (18% vs 8%, p=0.026). More women were discharged to skilled nursing facilities (p=0.007). CONCLUSIONS: This study demonstrates that men and women hospitalized with an underlying diagnosis of diabetes have similar preadmission glycemic measures, diabetes duration, and prevalence of diabetes complications. More men experienced hypoglycemia prior to discharge. Women were less likely to be discharged to home. Approximately 50% of men and women had ER visits or readmissions within 90 days of hospital discharge. TRIAL REGISTRATION NUMBER: NCT03279627.

Flash glucose monitoring in type 2 diabetes managed with basal insulin in the USA: a retrospective real-world chart review study and meta-analysis.

INTRODUCTION: Evidence supporting use of continuous glucose monitoring in type 2 diabetes treated with basal insulin is unclear. This real-world study aimed to assess the impact on glycated hemoglobin (HbA1c) of flash glucose monitoring use in adults with type 2 diabetes managed with basal insulin. RESEARCH DESIGN AND METHODS: Medical records were reviewed for adult individuals with type 2 diabetes using basal insulin for ≥1 year with or without additional antihyperglycemic medication, HbA1c 8.0%-12.0% prior to FreeStyle Libre Flash Glucose Monitoring use for ≥90 days and an HbA1c measurement recorded between 90 and 194 days after device use. Exclusion criteria included utilization of bolus insulin. Meta-analysis data are from the current study (USA) and a similar Canadian cohort. RESULTS: Medical record analysis (n=100) from 8 USA study sites showed significant HbA1c decrease of 1.4%±1.3%, from 9.4%±1.0% at baseline to 8.0%±1.2% after device use, p<0.0001 (mean±SD).Meta-analysis of medical records from USA and Canada sites (n=191) showed HbA1c significantly decreased by 1.1%±0.14% (mean±SE), from baseline 9.2%±1.0% to 8.1%±1.1%, p≤0.0001, with moderate to high heterogeneity between sites (Q=43.9, I2=74.9, p<0.0001) explained by differences in baseline HbA1c between sites.The HbA1c improvement in both groups was observed by age group, body mass index, duration of insulin use and sex at birth. CONCLUSIONS: In a real-world retrospective USA study and a meta-analysis of a larger USA and Canada cohort, HbA1c significantly reduced in basal insulin-treated type 2 diabetes, without bolus insulin initiation and following the commencement of flash glucose monitoring technology.

Can TP53-mutant follicular adenoma be a precursor of anaplastic thyroid carcinoma?

Mutations of the TP53 tumor suppressor gene are highly prevalent in thyroid anaplastic carcinomas (AC) but are also reported in some well-differentiated cancers and even in benign adenomas. The natural history of TP53-mutant adenomas and whether they may represent a precursor for well-differentiated cancer or AC is largely unknown. Similarly, the frequency of TP53 mutations in thyroid nodules found on routine molecular analysis of fine-needle aspiration (FNA) samples is not established. A database on 44,510 FNA samples from thyroid nodules with predominantly indeterminate cytology tested using ThyroSeq v3 was reviewed to identify TP53-mutant cases and analyze their genetic profile and available clinicopathological findings. Among 260 (0.6%) selected thyroid nodules, 36 had an isolated TP53 mutation and 224 carried a combination of TP53 with other genetic alterations. No significant difference was observed between these groups with respect to patient age, gender, nodule size, and spectrum of TP53 mutations. Histopathologically, 86% of the resected nodules with isolated TP53 mutations were benign (mostly adenomas), whereas 82% of nodules carrying TP53 mutations co-occurring with other alterations were cancers (P = 0.001), including de-differentiated AC. TP53-mutant benign tumors and well-differentiated cancers often had scattered single neoplastic cells with bizarre nuclei resembling those comprising AC. Our study demonstrates that a small but distinct proportion of thyroid nodules carry a TP53 mutation, either as a single genetic event or in combination with other alterations. While the latter is mostly cancers prone to dedifferentiation, there is at least a theoretical possibility that TP53-mutated adenomas may represent a precursor for such cancers, including AC.

Patient Understanding of Discharge Instructions for Home Diabetes Self-Management and Risk for Hospital Readmission and Emergency Department Visits.

OBJECTIVE: The primary objective of this study was to examine the patient comprehension of diabetes self-management instructions provided at hospital discharge as an associated risk of readmission. METHODS: Noncritically ill patients with diabetes completed patient comprehension questionnaires (PCQ) within 48 hours of discharge. PCQ scores were compared among patients with and without readmission or emergency department (ED) visits at 30 and 90 days. Glycemic measures 48 hours preceding discharge were investigated. Diabetes Early Readmission Risk Indicators (DERRIs) were calculated for each patient. RESULTS: Of 128 patients who completed the PCQ, scores were similar among those with 30-day (n = 31) and 90-day (n = 54) readmission compared with no readmission (n = 72) (79.9 ± 14.4 vs 80.4 ± 15.6 vs 82.3 ± 16.4, respectively) or ED visits. Clarification of discharge information was provided for 47 patients. PCQ scores of 100% were achieved in 14% of those with and 86% without readmission at 30 days (P = .108). Of predischarge glycemic measures, glycemic variability was negatively associated with PCQ scores (P = .035). DERRIs were significantly higher among patients readmitted at 90 days but not 30 days. CONCLUSION: These results demonstrate similar PCQ scores between patients with and those without readmission or ED visits despite the need for corrective information in many patients. Measures of glycemic variability were associated with PCQ scores but not readmission risk. This study validates DERRI as a predictor for readmission at 90 days.

Risk assessment for distant metastasis in differentiated thyroid cancer using molecular profiling: A matched case-control study.

BACKGROUND: Risk stratification for patients with differentiated thyroid cancer (DTC) is based primarily on pathologic tumor characteristics. Accurate preoperative prognostication could allow for more informed initial surgical recommendations, particularly among patients at a higher risk for distant metastasis (DM). The objective of this study was to characterize the genetic profile of DTC with DM and to validate a molecular-based risk stratification. METHODS: A case-control study design was used to analyze patients who had DTC with DM (n = 62) and a propensity matched cohort of patients who had DTC without DM after at least 5 years of follow-up using the ThyroSeq version 3 targeted next-generation sequencing assay. The results were classified into high-risk, intermediate-risk, and low-risk of aggressive disease. RESULTS: Most patients who had DTC with DM (66%) had a late-hit mutation in TERT, TP53, or PIK3CA. After propensity matching by age, tumor size, and sex, the high-risk molecular profile had strong association with DM (high-risk vs intermediate-risk: odds ratio, 25.1; 95% CI, 3.07-204.4; P < .001; high-risk vs low-risk: odds ratio, 122.5; 95% CI, 14.5-1038.4; P < .001). Overall, molecular risk categories were associated with DM risk, with a concordance index of 0.836 (95% CI, 0.759-0.913), which remained consistent after internal validation. Within the range of 5% to 10% of DM observed in DTC, the expected probability of DM would be 0.2% to 0.4% for the low-risk molecular profile, 4.7% to 9.4% for the intermediate-risk molecular profile, and 19.3% to 33.5% for the high-risk molecular profile. CONCLUSIONS: In this matched case-control study, genetic profiling using an available molecular assay provided accurate and robust risk stratification for DM in patients with DTC. The availability of preoperative prognostication may allow tailoring treatment for patients with DTC.

Diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome: review of acute decompensated diabetes in adult patients.

Diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome (HHS) are life threatening complications that occur in patients with diabetes. In addition to timely identification of the precipitating cause, the first step in acute management of these disorders includes aggressive administration of intravenous fluids with appropriate replacement of electrolytes (primarily potassium). In patients with diabetic ketoacidosis, this is always followed by administration of insulin, usually via an intravenous insulin infusion that is continued until resolution of ketonemia, but potentially via the subcutaneous route in mild cases. Careful monitoring by experienced physicians is needed during treatment for diabetic ketoacidosis and HHS. Common pitfalls in management include premature termination of intravenous insulin therapy and insufficient timing or dosing of subcutaneous insulin before discontinuation of intravenous insulin. This review covers recommendations for acute management of diabetic ketoacidosis and HHS, the complications associated with these disorders, and methods for preventing recurrence. It also discusses why many patients who present with these disorders are at high risk for hospital readmissions, early morbidity, and mortality well beyond the acute presentation.

Use of an electronic health record to identify prevalent and incident cardiovascular disease in type 2 diabetes according to treatment strategy.

BACKGROUND: The increasing use of electronic health records (EHRs) in clinical practice offers the potential to investigate cardiovascular outcomes over time in patients with type 2 diabetes (T2D). OBJECTIVE: To develop a methodology for identifying prevalent and incident cardiovascular disease (CVD) in patients with T2D who are candidates for therapeutic intensification of glucose-lowering therapy. METHODS: Patients with glycated hemoglobin (HbA1c) ≥7% (53 mmol/mol) while receiving 1-2 oral diabetes medications (ODMs) were identified from an EHR (2005-2011) and grouped according to intensification with insulin (INS) (n=372), a different class of ODM (n=833), a glucagon-like peptide receptor 1 agonist (GLP-1RA) (n=59), or no additional therapy (NAT) (n=2017). Baseline prevalence of CVD was defined by documented International Classification of Diseases Ninth Edition (ICD-9) codes for coronary artery disease, cerebrovascular disease, or other CVD with first HbA1c ≥7% (53 mmol/mol). Incident CVD was defined as a new ICD-9 code different from existing codes over 4 years of follow-up. ICD-9 codes were validated by a chart review in a subset of patients. RESULTS: Sensitivity of ICD-9 codes for CVD ranged from 0.83 to 0.89 and specificity from 0.90 to 0.96. Baseline prevalent (INS vs ODM vs GLP-1RA vs NAT: 65% vs 39% vs 54% vs 59%, p<0.001) and incident CVD (Kaplan-Meier estimates: 58%, 31%, 52%, and 54%, p=0.002) were greater in INS group after controlling for differences in baseline HbA1c (9.2±2.0% vs 8.3±1.2% vs 8.2±1.3% vs 7.7±1.1% (77 vs 67 vs 66 vs 61 mmol/mol), p<0.001) and creatinine (1.15±0.96 vs 1.10±0.36 vs 1.01±0.35 vs 1.07±0.45 mg/dL, p=0.001). CONCLUSIONS: An EHR can be an effective method for identifying prevalent and incident CVD in patients with T2D.