Natural language processing for the assessment of cardiovascular disease comorbidities: The cardio-Canary comorbidity project.

OBJECTIVE: Accurate ascertainment of comorbidities is paramount in clinical research. While manual adjudication is labor-intensive and expensive, the adoption of electronic health records enables computational analysis of free-text documentation using natural language processing (NLP) tools. HYPOTHESIS: We sought to develop highly accurate NLP modules to assess for the presence of five key cardiovascular comorbidities in a large electronic health record system. METHODS: One-thousand clinical notes were randomly selected from a cardiovascular registry at Mass General Brigham. Trained physicians manually adjudicated these notes for the following five diagnostic comorbidities: hypertension, dyslipidemia, diabetes, coronary artery disease, and stroke/transient ischemic attack. Using the open-source Canary NLP system, five separate NLP modules were designed based on 800 "training-set" notes and validated on 200 "test-set" notes. RESULTS: Across the five NLP modules, the sentence-level and note-level sensitivity, specificity, and positive predictive value was always greater than 85% and was most often greater than 90%. Accuracy tended to be highest for conditions with greater diagnostic clarity (e.g. diabetes and hypertension) and slightly lower for conditions whose greater diagnostic challenges (e.g. myocardial infarction and embolic stroke) may lead to less definitive documentation. CONCLUSION: We designed five open-source and highly accurate NLP modules that can be used to assess for the presence of important cardiovascular comorbidities in free-text health records. These modules have been placed in the public domain and can be used for clinical research, trial recruitment and population management at any institution as well as serve as the basis for further development of cardiovascular NLP tools.

Association of Baseline Low-Density Lipoprotein Cholesterol and Percentage Low-Density Lipoprotein Cholesterol Reduction With Statins, Ezetimibe, and PCSK9 Inhibition.

IMPORTANCE: Low-density lipoprotein cholesterol (LDL-C) is an important modifiable risk factor for atherosclerotic cardiovascular disease. It is unclear whether the percentage LDL-C lowering with pharmacotherapies differs on the basis of baseline LDL-C levels. OBJECTIVE: To evaluate the association between baseline LDL-C levels and the percentage LDL-C reduction with a statin, ezetimibe, and a PCSK9 inhibitor. DESIGN, SETTING, AND PARTICIPANTS: This secondary exploratory study analyzed data from 3 randomized placebo-controlled clinical trials (Aggrastat to Zocor-Thrombolysis in Myocardial Infarction 21 [A to Z-TIMI 21], Improved Reduction of Outcomes: Vytorin Efficacy International Trial [IMPROVE-IT], and Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk [FOURIER]) of lipid-lowering therapies (statin, ezetimibe, and a PCSK9 inhibitor) and included participants with atherosclerotic cardiovascular disease. Analyses took place form April to October 2020. INTERVENTIONS: In A to Z-TIMI 21, 1:1 randomization to simvastatin, 40 mg, daily for 30 days followed by 80 mg daily thereafter vs placebo for 4 months followed by simvastatin, 20 mg, daily thereafter. In IMPROVE-IT, 1:1 randomization to ezetimibe, 10 mg, daily plus simvastatin, 40 mg, daily vs placebo plus simvastatin, 40 mg, daily. In FOURIER, 1:1 randomization to evolocumab, 140 mg, every 2 weeks or 420 mg monthly vs matching placebo. MAIN OUTCOMES AND MEASURES: The percentage LDL-C reduction at either 1 month (A to Z-TIMI 21, IMPROVE-IT) or 3 months (FOURIER) as a function of baseline LDL-C level. Data were modeled using a generalized linear regression model. RESULTS: A total of 3187 patients from A to Z-TIMI 21, 10 680 patients from IMPROVE-IT, and 25 847 patients from FOURIER were analyzed. There was a higher percentage reduction in LDL-C levels with evolocumab in patients with lower baseline LDL-C levels, ranging from 59.4% (95% CI, 59.1%-59.8%) in patients with a baseline LDL-C level of 130 mg/dL to 66.1% (95% CI, 65.6%-66.6%) in patients with a baseline LDL-C level of 70 mg/dL (P < .001). In contrast, across the same range of baseline LDL-C level, there was a more modest difference for simvastatin (44.6% [95% CI, 43.9%-45.2%] vs 47.8% [95% CI, 46.4%-49.2%]; P < .001) and minimal difference with ezetimibe (25.0% [95% CI, 23.3%-26.6%] vs 26.2% [95% CI, 24.2%-28.1%]; P = .007). CONCLUSIONS AND RELEVANCE: The percentage LDL-C reduction with statins, ezetimibe, and PCSK9 inhibition is not attenuated in patients starting with lower baseline LDL-C levels and is 6.6% greater for PCSK9 inhibition. These data are encouraging for the use of intensive LDL-C-lowering therapy even for patients with lower LDL-C levels.

Study of lipoprotein(a) and its impact on atherosclerotic cardiovascular disease: Design and rationale of the Mass General Brigham Lp(a) Registry.

Lipoprotein(a) [Lp(a)] is independently associated with atherosclerotic cardiovascular disease and calcific aortic valve stenosis. Elevated Lp(a) affects approximately one in five individuals and meaningfully contributes to the residual cardiovascular risk in individuals with otherwise well-controlled risk factors. With targeted therapies in the therapeutic pipeline, there is a need to further characterize the clinical phenotypes and outcomes of individuals with elevated levels of this unique biomarker. The Mass General Brigham Lp(a) Registry will be built from the longitudinal electronic health record of two large academic medical centers in Boston, Massachusetts, to develop a detailed cohort of patients who have had their Lp(a) measured. In combination with structured data sources, clinical documentation will be analyzed using natural language processing techniques to accurately characterize baseline characteristics. Important outcome measures including all-cause mortality, cardiovascular mortality, and cardiovascular events will be available for analysis. Approximately 30 000 patients who have had their Lp(a) tested within the Mass General Brigham system from January 2000 to July 2019 will be included in the registry. This large Lp(a) cohort will provide meaningful observational data regarding the differential risk associated with Lp(a) values and cardiovascular disease. With a new frontier of targeted Lp(a) therapies on the horizon, the Mass General Brigham Lp(a) Registry will help provide a deeper understanding of Lp(a)'s role in long term cardiovascular outcomes.

Impact of screening for metabolic syndrome on the evaluation of obese living kidney donors.

BACKGROUND: We report our experience with metabolic syndrome screening for obese living kidney donor candidates to mitigate the long-term risk of CKD. METHODS: We retrospectively reviewed 814 obese (BMI≥30) and 993 nonobese living kidney donor evaluations over 12 years. Using logistic regression, we explored interactions between social/clinical variables and candidate acceptance before and after policy implementation. RESULTS: Obese donor candidate acceptance decreased after metabolic syndrome screening began (56.3%, 46.3%, p < 0.01), while nonobese candidate acceptance remained similar (59.6%, 59.2%, p = 0.59). Adjusting for age, gender, race, BMI, and number of prior evaluations, acceptance of obese candidates decreased significantly more than nonobese (p = 0.025). In candidates without metabolic syndrome, there was no significant change in how age, sex, race, or BMI affected a donor candidate's probability of acceptance. CONCLUSION: Metabolic syndrome screening is a simple stratification tool for centers with liberal absolute BMI cut-offs to exclude potentially higher-risk obese candidates.

Incidental Anatomic Finding of Celiacomesenteric Trunk Associated with 'Nutcracker Phenomenon,' or Compression of the Left Renal Vein.

BACKGROUND Celiacomesenteric trunk (CMT) is a very rare anatomic finding in which the celiac artery and the superior mesenteric artery (SMA) originate from the abdominal aorta through a common trunk. Clinical associations with CMT include arterial aneurysm, thrombosis, and celiac artery compression. However, an association between CMT and abdominal venous congestion caused by left renal vein compression, or 'nutcracker phenomenon,' has not been previously reported. CASE REPORT A 91-year-old woman, who died from a cerebrovascular accident (CVA), underwent a cadaveric examination at our medical school. On examination of the abdomen, there was an incidental finding of CMT. The arterial and venous diameters were measured, and vascular histopathology was undertaken. The vascular anatomy was consistent with CMT type 1-b. Nutcracker phenomenon (NCP) (left renal vein compression) was seen anatomically as dilatation and engorgement of the left renal vein, relative to the right renal vein (10.77±0.13 mm vs. 4.49±0.56 mm, respectively), and dilatation and engorgement of the left ovarian vein, relative to the right ovarian vein (4.37±0.15 mm vs. 1.06±0.09 mm, respectively) with left ovarian varicocele. The aortoceliac angle (ACA) and the aortomesenteric angle (AMA) approached zero degrees. CONCLUSIONS We have described a rare anatomic finding of CMT that created an acute AMA and NCP. Awareness of this rare association between CMT and NCP by clinicians, vascular surgeons, and radiologists may be of value in the future evaluation and surgical management of patients who present clinically with 'nutcracker syndrome.'

Prescription Opioid Use among Opioid-Naive Women Undergoing Immediate Breast Reconstruction.

BACKGROUND: Cancer patients may be particularly vulnerable to the deleterious effects of prolonged opioid use. The authors explored the factors that influence postoperative opioid prescription fills among women following postmastectomy reconstruction. METHODS: Using the Truven Health MarketScan Research Databases, the authors identified a cohort of 4113 opioid-naive patients undergoing mastectomy and immediate breast reconstruction between January of 2010 and August of 2014. Outcomes included average daily oral morphine equivalents and the incidence of prolonged opioid fills (between 90 and 120 days after surgery). Using multivariable regression, the authors examined the effect of patient demographic characteristics, reconstructive technique, comorbid medical and psychiatric conditions, and postoperative complications on outcome variables. RESULTS: In this cohort, 90 percent of patients filled opioid prescriptions perioperatively, and 10 percent continued to fill prescriptions beyond 3 months after surgery. Patients with depression were more likely to fill prescriptions of higher average daily oral morphine equivalents (74.2 mg versus 58.3 mg; p < 0.01), and patients with anxiety were more likely to fill opioids for prolonged periods (13.4 percent versus 9.1 percent; p < 0.01). Patients undergoing autologous free flap reconstruction were less likely to fill prescriptions for a prolonged period following surgery (5.9 percent versus 10.2 percent; p < 0.001). CONCLUSIONS: Prescription opioid fills are common following breast reconstruction, and 10 percent of all patients continue to fill opioid prescriptions beyond 3 months after surgery. Prolonged fills are influenced by both patient factors and surgical procedure, and attention should be directed toward identifying opioid alternatives when possible. CLINCAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Challenges in imaging in preclinical rheumatoid arthritis.

There exists a preclinical phase to the disease progression of rheumatoid arthritis, in which there is evidence of autoimmunity but no overt clinical arthritis. Identifying patients in this phase would allow for early treatment, to potentially halt manifestation of the disease. Imaging, because it is noninvasive, provides an appealing alternative to gold-standard synovial biopsies for identification of these preclinical patients. Ultrasonography, magnetic resonance imaging, and positron emission tomography all have their advantages and disadvantages as imaging modalities in this regard. Further research into alternative imaging modalities with larger cohorts is required to determine the most effective technique.