Automating and improving cardiovascular disease prediction using Machine learning and EMR data features from a regional healthcare system.

BACKGROUND: The ACC/AHA Pooled Cohort Equations (PCE) Risk Calculator is widely used in the US for primary prevention of atherosclerotic cardiovascular disease (ASCVD), but may under- or over-estimate risk in some populations. We therefore designed an automated, population-specific ASCVD risk calculator using machine-learning (ML) methods and electronic medical record (EMR) data, and compared its predictive power with that of the PCE calculator. METHODS AND FINDINGS: We collected data from 101,110 unique EMRs of living patients from January 1, 2009 to April 30, 2020. ML techniques were applied to patient datasets that included either only cross-sectional (CS) features, or CS combined with longitudinal (LT) features derived from vital statistics and laboratory values. We compared the utility of the models using a proposed new cost measure (Screened Cases Percentage @ Sensitivity level). All ML models tested achieved better predictive power than the PCE risk calculator. The random forest ML technique (RF) applied on the combination of CS and LT features (RF-LTC) produced the best area under curve (AUC) score of 0.902 (95% confidence interval (CI), 0.895-0.910). To detect 90% of all positive ASCVD cases, the best ML model required screening only 43% of patients, while the PCE risk calculator required screening 69% of patients. CONCLUSIONS: Prediction models built using ML techniques improved ASCVD prediction and reduced the number of screenings required to predict ASCVD when compared with the PCE calculator, alone. Combining LT and CS features in the ML models significantly improved ASCVD prediction compared with using CS features, alone.

Improving Familial Hypercholesterolemia Diagnosis Using an EMR-based Hybrid Diagnostic Model.

CONTEXT: Familial hypercholesterolemia (FH) confers a greatly increased risk for premature cardiovascular disease, but remains very underdiagnosed and undertreated in primary care populations. OBJECTIVE: We assessed whether using a hybrid model consisting of 2 existing FH diagnostic criteria coupled with electronic medical record (EMR) data would accurately identify patients with FH in a Midwest US metropolitan healthcare system. METHODS: We conducted a retrospective, records-based, cross-sectional study using datasets from unique EMRs of living patients. Using Structured Query Language to identify components of 2 currently approved FH diagnostic criteria, we created a hybrid model to identify individuals with FH. RESULTS: Of 264 264 records analyzed, between 794 and 1571 patients were identified as having FH based on the hybrid diagnostic model, with a prevalence of 1:300 to 1:160. These patients had a higher prevalence of premature coronary artery disease (CAD) (38-58%) than the general population (1.8%) and higher than those having a high CAD risk but no FH (10%). Although most patients were receiving lipid-lowering therapies (LLTs), only 50% were receiving guideline-recommended high-intensity LLT. CONCLUSION: Using the hybrid model, we identified FH with a higher clinical and genetic detection rate than using standard diagnostic criteria individually. Statin and other LLT use were suboptimal and below guideline recommendations. Because FH underdiagnosis and undertreatment are due partially to the challenges of implementing existing diagnostic criteria in a primary care setting, this hybrid model potentially can improve FH diagnosis and subsequent early access to appropriate treatment.

Lower-Intensity Statins Contributing to Gaps in Care for Patients With Primary Severe Hypercholesterolemia.

Background Although severe hypercholesterolemia confers a 5-fold increased long-term risk for coronary artery disease, treatment guidelines may not be fully implemented, leading to underdiagnosis and suboptimal treatment. To further understand the clinical features and gaps in treatment approaches, we analyzed electronic medical record data from a midwestern US multidisciplinary healthcare system, between 2009 and 2020. Methods and Results We retrospectively assessed the prevalence, clinical presentation, and treatment characteristics of individuals currently treated with statin therapy having a low-density lipoprotein cholesterol (LDL-C) value that is either (1) an actual maximum electronic medical record-documented LDL-C ≥190 mg/dL (group 1, n=7542) or (2) an estimated pretreatment LDL-C ≥190 mg/dL (group 2, n=7710). Comorbidities and prescribed lipid-lowering therapies were assessed. Statistical analyses identified differences among individuals within and between groups. Of records analyzed (n=266 282), 7% met the definition for primary severe hypercholesterolemia. Group 1 had more comorbidities than group 2. More individuals in both groups were treated by primary care providers (49.8%-53.0%, 32.6%-36.4%) than by specialty providers (4.1%-5.5%, 2.1%-3.3%). High-intensity lipid-lowering therapy was prescribed less frequently for group 2 than for group 1, but moderate-intensity statins were prescribed more frequently for group 2 (65%) than for group 1 (52%). Conclusions Two percent of patients in our study population being treated with low- or moderate-intensity statins have an estimated LDL-C ≥190 mg/dL (indicating severe hypercholesterolemia), but receive less aggressive treatment than patients with a maximum measured LDL-C ≥190 mg/dL.

Prevalence and Characteristics of Patients With Primary Severe Hypercholesterolemia in a Multidisciplinary Healthcare System.

Severe hypercholesterolemia (SH) includes individuals with LDL-C ≥ 190 mg/dl, regardless of cause. These individuals have a fivefold increased long-term risk for coronary artery disease. Although systematic SH screening can trigger early treatment, current treatment guidelines may not be fully implemented or followed by patients. To further understand this treatment gap, we used electronic health record data to retrospectively assess SH prevalence, characteristics, and treatment in a midwest US healthcare system, between 2009 and 2020. Comorbidities, tobacco exposure, and prescribed lipid-lowering therapies were assessed. Statistical analyses were conducted to identify differences between individuals with primary SH (LDL-C ≥ 190 mg/dl, group 1) and those without primary SH (LDL-C < 190 mg/dl, group 2). Of 265,220 records analyzed, 7.4% met the definition for primary SH. These group 1 cases had more comorbidities than group 2 cases, including premature coronary artery disease (5.8% vs 2.7%). Results showed most individuals in group 1 were treated by primary care providers (43.2% to 45.7%), than by specialty providers (2.5% to 3.3%), and these primary care providers prescribed mainly moderate-intensity statins. Seventy-seven percent of group 1 individuals were treated with a statin, 27% were treated with a high-intensity statin, and 4% were treated with ezetimibe. Fewer young patients (< 40 years) were treated with statins (50% to 58.3%) than older patients (74.0% to 76.3%). Although use of general statins, high-intensity statins, and ezetimibe was higher in individuals with SH than those without SH, treatment remains below guideline recommendations, especially in younger individuals.

Translating U-500R Randomized Clinical Trial Evidence to the Practice Setting: A Diabetes Educator/Expert Prescriber Team Approach.

Purpose The purpose of this article is to provide recommendations to the diabetes educator/expert prescriber team for the use of human regular U-500 insulin (U-500R) in patients with severely insulin-resistant type 2 diabetes, including its initiation and titration, by utilizing dosing charts and teaching materials translated from a recent U-500R clinical trial. Conclusions Clinically relevant recommendations and teaching materials for the optimal use and management of U-500R in clinical practice are provided based on the efficacy and safety results of and lessons learned from the U-500R clinical trial by Hood et al, current standards of practice, and the authors' clinical expertise. This trial was the first robustly powered, randomized, titration-to-target trial to compare twice-daily and three-times-daily U-500R dosing regimens. Modifications were made to the initiation and titration dosing algorithms used in this trial to simplify dosing strategies for the clinical setting and align with current glycemic targets recommended by the American Diabetes Association. Leveraging the expertise, resources, and patient interactions of the diabetes educator who can provide diabetes self-management education and support in collaboration with the multidisciplinary diabetes team is strongly recommended to ensure patients treated with U-500R receive the timely and comprehensive care required to safely and effectively use this highly concentrated insulin.

PREDICTORS OF NONATTENDANCE AT AN ENDOCRINOLOGY OUTPATIENT CLINIC.

OBJECTIVE: To identify predictors potentially contributing to patients' nonattendance or to same-day cancellation of scheduled appointments at an adult endocrinology office practice. METHODS: A retrospective, records-based, cross-sectional study was conducted using data from 9,305 electronic medical records of patients presenting at a U.S. metropolitan adult endocrinology clinic in 2013. Statistical analyses included multivariate regression, calculated odds ratios, and posttest probabilities. RESULTS: Of 29,178 total patient visits analyzed, 68% were attended by patients. Of total scheduled appointments, 7% resulted in nonattendance and 5% in same-day cancellation. The most significant predictors of nonatten-dance were a previous history of nonattendance (P<.001), uncontrolled diabetes (P<.001), and new patients to the practice (P<.001). Long lead-time to appointment (P = .001), younger age (P<.001), and certain insurance carriers (P<.001) also were significant predictors. CONCLUSION: Specific predictors of nonattendance at scheduled appointments were identified using statistical analysis of electronic medical record data. Previous history of nonattendance and having uncontrolled diabetes (especially in patients newly referred to the practice) are among these significant predictors. Identifying specific predictors for nonattendance enables targeted strategies to be developed. ABBREVIATIONS: APRN = Advanced Practice Registered Nurse CI = confidence interval DM = diabetes mellitus EMR = electronic medical record HbA1c = glycated hemoglobin NS = no-show OR = odds ratio SDC = same-day cancellation.

A systematic review of IT for diabetes self-management: are we there yet?

BACKGROUND: Recent advances in information technology (IT) coupled with the increased ubiquitous nature of information technology (IT) present unique opportunities for improving diabetes self-management. The objective of this paper is to determine, in a systematic review, how IT has been used to improve self-management for adults with Type 1 and Type 2 diabetes. METHODS: The review covers articles extracted from relevant databases using search terms related information technology and diabetes self-management published after 1970 until August 2012. Additional articles were extracted using the citation map in Web of Science. Articles representing original research describing the use of IT as an enabler for self-management tasks performed by the patient are included in the final analysis. RESULTS: Overall, 74% of studies showed some form of added benefit, 13% articles showed no-significant value provided by IT, and 13% of articles did not clearly define the added benefit due to IT. Information technologies used included the Internet (47%), cellular phones (32%), telemedicine (12%), and decision support techniques (9%). Limitations and research gaps identified include usability, real-time feedback, integration with provider electronic medical record (EMR), as well as analytics and decision support capabilities. CONCLUSION: There is a distinct need for more comprehensive interventions, in which several technologies are integrated in order to be able to manage chronic conditions such as diabetes. Such IT interventions should be theoretically founded and should rely on principles of user-centered and socio-technical design in its planning, design and implementation. Moreover, the effectiveness of self-management systems should be assessed along multiple dimensions: motivation for self-management, long-term adherence, cost, adoption, satisfaction and outcomes as a final result.

Mobile applications for diabetes self-management: status and potential.

BACKGROUND: Advancements in smartphone technology coupled with the proliferation of data connectivity has resulted in increased interest and unprecedented growth in mobile applications for diabetes self-management. The objective of this article is to determine, in a systematic review, whether diabetes applications have been helping patients with type 1 or type 2 diabetes self-manage their condition and to identify issues necessary for large-scale adoption of such interventions. METHODS: The review covers commercial applications available on the Apple App Store (as a representative of commercially available applications) and articles published in relevant databases covering a period from January 1995 to August 2012. The review included all applications supporting any diabetes self-management task where the patient is the primary actor. RESULTS: Available applications support self-management tasks such as physical exercise, insulin dosage or medication, blood glucose testing, and diet. Other support tasks considered include decision support, notification/alert, tagging of input data, and integration with social media. The review points to the potential for mobile applications to have a positive impact on diabetes self-management. Analysis indicates that application usage is associated with improved attitudes favorable to diabetes self-management. Limitations of the applications include lack of personalized feedback; usability issues, particularly the ease of data entry; and integration with patients and electronic health records. CONCLUSIONS: Research into the adoption and use of user-centered and sociotechnical design principles is needed to improve usability, perceived usefulness, and, ultimately, adoption of the technology. Proliferation and efficacy of interventions involving mobile applications will benefit from a holistic approach that takes into account patients' expectations and providers' needs.

Obesity and type 2 diabetes mellitus in South Dakota: focused insight into prevalence, physiology and treatment.

Type 2 diabetes mellitus is one of the significant comorbidities of obesity. This review addresses the prevalence of obesity and diabetes mellitus nationally and in South Dakota. It elaborates on some of the mechanisms of association of obesity with diabetes mellitus, including effects related to adipokines, lipotoxicity, vitamin D deficiency and apolipoprotein C1. This review addresses the prevention and treatment of diabetes mellitus in the obese population through life style changes, medications and/or surgery. Future directions in the management of diabetes are explored in the obese population.

Value of hemoglobin A1c in diagnosing diabetes mellitus within a chronic disease management system illustrated by the receiver operating characteristic curve.

OBJECTIVE: To develop a receiver operating characteristic (ROC) curve of glycosylated hemoglobin (HbA1c) for diagnosing diabetes mellitus within a chronic disease management system. METHODS: A case-control study including medical records from January 1, 1997, to December 31, 2005, was conducted at the Sioux Falls Veterans Affairs Medical Center. Medical records for the case group (patients with diabetes) were selected based on 1 of 3 criteria: International Classification of Diseases, Ninth Revision, Clinical Modification or Current Procedural Terminology codes specific for type 1 and type 2 diabetes; patients' use of medications (oral hypoglycemic agents, antidiabetes agents, or insulin); or results from random blood or plasma glucose tests (at least 2 measurements of blood glucose > or = 200 mg/dL). Records for the control group were selected based on patients having HbA1c measured, but not meeting the above diagnostic criteria for diabetes during the study period. Records for cases and controls were randomly frequency-matched, one-to-one. The control group was randomly divided into 5 sets of an equal number of records. Five sets of an equal number of cases were then randomly selected from the total number of cases. Each test data set included 1 case group and 1 control group, resulting in 5 independent data sets. RESULTS: In total, 5040 patient records met the case definition in the diabetes registry. Records of 15 patients who were prescribed metformin only, but did not meet any other case criteria, were reviewed and excluded after determining the patients were not diabetic. The control group consisted of 5 sets of 616 records each (totaling 3080 records), and the case group consisted of 5 sets of 616 records each (totaling 3080 records). Thus, each of the 5 independent data sets of 1 case group and 1 control group contained 1232 records. The case group was predominantly composed of white men (mean age, 69 years; mean body mass index, 31 kg/m2). Demographic data were similar for control patients. The ROC curve revealed that a HbA1c > or = 6.3% (mean + 1 SD) offered the most accurate cutoff value for diagnosing type 2 diabetes mellitus, with the following statistical values: C statistic, 0.78; sensitivity, 70%; specificity, 85%; and positive likelihood ratio, 4.6 (95% confidence interval, 4.2-5.0). CONCLUSION: A HbA1c value > or = 6.3% may be a useful benchmark for diagnosing diabetes mellitus within a chronic disease management system and may be a useful tool for monitoring high-risk populations.

Osteodystrophy in celiac disease: ultimate complications and possible treatment.

Hypovitaminosis D and its consequences are significant complications in the course of untreated celiac disease (CD). We report a case that illustrates the natural evolution of osteomalacia in an adult patient with untreated CD and his response to vitamin D supplementation. In patients with complicated CD and hypovitaminosis D, vitamin D-2 replacement in high enough doses is important to improving functional performance and for the treatment of osteomalacia.

Case report: 66 year-old man with recurrent pneumonias and sinusitis.

A current myth is that Cystic Fibrosis (CF) is a disease of childhood. However, among adults with CF, 64% are between the ages of 18 and 29 years of age; 25% are between 30 and 39 years of age; 10% are between 40 and 49 years old; and 2% are 50 years of age. We report a case of a 66 year-old male with newly diagnosed cystic fibrosis after a history of recurrent pneumonias and sinusitis, with acute exacerbation of Chronic Obstructive Pulmonary Disease (COPD). Physicians must maintain a high index of suspicion to make the diagnosis of cystic fibrosis in elderly presenting with COPD exacerbation and recurrent pneumonias and sinusitis.

Obesity is associated with bronchial hyper-responsiveness in women.

The study's objective was to compare the bronchial hyper-responsiveness (BHR) between those with normal and increased weight and evaluate if the association was sex-specific. In this cross-sectional review of methacholine challenge test results of 1,141 adults for evaluation of respiratory symptoms, logistic regression analysis was conducted to adjust for covariates. When compared to normal weight, overweight or obese women showed a higher prevalence of symptomatic BHR with odds ratios of 1.63 (95% C.I. 1.16-2.29). This association was not seen in men, with a significant sex-specific interaction. This study shows a sex-specific association between symptomatic BHR and overweight or obese status.

Recurrent hypercalcemia due to ectopic production of parathyroid hormone-related protein and intact parathyroid hormone in a single patient with multiple malignancies.

OBJECTIVE: To report a case of recurrent hypercalcemia due to ectopic production of parathyroid hormone (PTH) and parathyroid hormone-related protein (PTH-rP) from transitional cell carcinoma of the urinary bladder. METHODS: We present clinical, laboratory, and pathologic findings in a 73-year-old man with recurrent hypercalcemia. Results of serum calcium, PTH, PTH-rP and immunostaining of tumors for PTH and PTH-rP over 9 years are presented. RESULTS: In 1990 this patient was diagnosed with primary hyperparathyroidism, which was cured by resection of a parathyroid adenoma in the neck. Hypercalcemia recurred in 1992, and he was found to have squamous cell carcinoma of the right lung. PTH-rP levels were not measured, but the resected tumor immunostained positive for the presence of PTH-rP. The patient subsequently remained normocalcemic until 1996, when the plasma calcium and PTH levels increased again. Surgical exploration of the neck revealed no parathyroid adenoma. Elevated plasma levels of calcium and PTH persisted after surgery. In 1998 the patient was diagnosed with stage IV invasive transitional cell carcinoma (TCC) of the urinary bladder and underwent radical cystectomy. The tumor tissue was not immunoreactive to PTH-rP. A year later, plasma levels of PTH and PTH-rP increased, but surgical re-exploration of the neck again revealed no parathyroid adenoma. CT scanning identified a large retroperitoneal mass, and a CT-guided biopsy of the mass showed metastatic, poorly differentiated TCC immunopositive for PTH and PTH-rP. CONCLUSION: This is the first report of ectopic production of PTH from metastatic TCC of the urinary bladder coexisting with PTH-rP mediated hypercalcemia.

In vivo preservation of steroid specificity in CWR22 xenografts having a mutated androgen receptor.

BACKGROUND: In vitro studies of CWR22 tumor cells lack steroid specificity. We sought to determine if CWR22 xenografts also lack steroid specificity. METHODS: We injected castrated nude mice with CWR22 tumor cells (6 x 10(6) cells) and implanted Alzet osmotic pumps that delivered approximately 1 mg steroid/kg body weight/day. RESULTS: Serum PSA levels were detectable in intact mice and castrated mice treated with testosterone (T), but not in those treated with estradiol (E(2)), progesterone (P), or flutamide (F). T maintained mean tumor weight similar to that in intact mice (P = NS). We observed no tumors in castrated mice or mice treated with E(2), P, or F, and tumor histology was consistent with weights. CONCLUSIONS: The mutation of the androgen receptor (H874Y) that occurs in the CWR22 xenograft model of human prostate cancer does not significantly affect in vivo steroid specificity for E(2), P, or F.