Hypertension Trends and Disparities Over 12 Years in a Large Health System: Leveraging the Electronic Health Records.

BACKGROUND: The digital transformation of medical data enables health systems to leverage real-world data from electronic health records to gain actionable insights for improving hypertension care. METHODS AND RESULTS: We performed a serial cross-sectional analysis of outpatients of a large regional health system from 2010 to 2021. Hypertension was defined by systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or recorded treatment with antihypertension medications. We evaluated 4 methods of using blood pressure measurements in the electronic health record to define hypertension. The primary outcomes were age-adjusted prevalence rates and age-adjusted control rates. Hypertension prevalence varied depending on the definition used, ranging from 36.5% to 50.9% initially and increasing over time by ≈5%, regardless of the definition used. Control rates ranged from 61.2% to 71.3% initially, increased during 2018 to 2019, and decreased during 2020 to 2021. The proportion of patients with a hypertension diagnosis ranged from 45.5% to 60.2% initially and improved during the study period. Non-Hispanic Black patients represented 25% of our regional population and consistently had higher prevalence rates, higher mean systolic and diastolic blood pressure, and lower control rates compared with other racial and ethnic groups. CONCLUSIONS: In a large regional health system, we leveraged the electronic health record to provide real-world insights. The findings largely reflected national trends but showed distinctive regional demographics and findings, with prevalence increasing, one-quarter of the patients not controlled, and marked disparities. This approach could be emulated by regional health systems seeking to improve hypertension care.

Use of Electronic Health Records to Characterize Patients with Uncontrolled Hypertension in Two Large Health System Networks.

Background: Improving hypertension control is a public health priority. However, consistent identification of uncontrolled hypertension using computable definitions in electronic health records (EHR) across health systems remains uncertain. Methods: In this retrospective cohort study, we applied two computable definitions to the EHR data to identify patients with controlled and uncontrolled hypertension and to evaluate differences in characteristics, treatment, and clinical outcomes between these patient populations. We included adult patients (≥ 18 years) with hypertension receiving ambulatory care within Yale-New Haven Health System (YNHHS; a large US health system) and OneFlorida Clinical Research Consortium (OneFlorida; a Clinical Research Network comprised of 16 health systems) between October 2015 and December 2018. We identified patients with controlled and uncontrolled hypertension based on either a single blood pressure (BP) measurement from a randomly selected visit or all BP measurements recorded between hypertension identification and the randomly selected visit). Results: Overall, 253,207 and 182,827 adults at YNHHS and OneFlorida were identified as having hypertension. Of these patients, 83.1% at YNHHS and 76.8% at OneFlorida were identified using ICD-10-CM codes, whereas 16.9% and 23.2%, respectively, were identified using elevated BP measurements (≥ 140/90 mmHg). Uncontrolled hypertension was observed among 32.5% and 43.7% of patients at YNHHS and OneFlorida, respectively. Uncontrolled hypertension was disproportionately higher among Black patients when compared with White patients (38.9% versus 31.5% in YNHHS; p < 0.001; 49.7% versus 41.2% in OneFlorida; p < 0.001). Medication prescription for hypertension management was more common in patients with uncontrolled hypertension when compared with those with controlled hypertension (overall treatment rate: 39.3% versus 37.3% in YNHHS; p = 0.04; 42.2% versus 34.8% in OneFlorida; p < 0.001). Patients with controlled and uncontrolled hypertension had similar rates of short-term (at 3 and 6 months) and long-term (at 12 and 24 months) clinical outcomes. The two computable definitions generated consistent results. Conclusions: Our findings illustrate the potential of leveraging EHR data, employing computable definitions, to conduct effective digital population surveillance in the realm of hypertension management.

Computational phenotypes for patients with opioid-related disorders presenting to the emergency department.

OBJECTIVE: We aimed to discover computationally-derived phenotypes of opioid-related patient presentations to the ED via clinical notes and structured electronic health record (EHR) data. METHODS: This was a retrospective study of ED visits from 2013-2020 across ten sites within a regional healthcare network. We derived phenotypes from visits for patients ≥18 years of age with at least one prior or current documentation of an opioid-related diagnosis. Natural language processing was used to extract clinical entities from notes, which were combined with structured data within the EHR to create a set of features. We performed latent dirichlet allocation to identify topics within these features. Groups of patient presentations with similar attributes were identified by cluster analysis. RESULTS: In total 82,577 ED visits met inclusion criteria. The 30 topics were discovered ranging from those related to substance use disorder, chronic conditions, mental health, and medical management. Clustering on these topics identified nine unique cohorts with one-year survivals ranging from 84.2-96.8%, rates of one-year ED returns from 9-34%, rates of one-year opioid event 10-17%, rates of medications for opioid use disorder from 17-43%, and a median Carlson comorbidity index of 2-8. Two cohorts of phenotypes were identified related to chronic substance use disorder, or acute overdose. CONCLUSIONS: Our results indicate distinct phenotypic clusters with varying patient-oriented outcomes which provide future targets better allocation of resources and therapeutics. This highlights the heterogeneity of the overall population, and the need to develop targeted interventions for each population.

Use of Electronic Health Records to Characterize Patients with Uncontrolled Hypertension in Two Large Health System Networks.

Background: Improving hypertension control is a public health priority. However, uncertainty remains regarding the optimal way to identify patients with uncontrolled hypertension using electronic health records (EHR) data. Methods: In this retrospective cohort study, we applied computable definitions to the EHR data to identify patients with controlled and uncontrolled hypertension and to evaluate differences in characteristics, treatment, and clinical outcomes between these patient populations. We included adult patients (≥18 years) with hypertension receiving ambulatory care within Yale-New Haven Health System (YNHHS; a large US health system) and OneFlorida Clinical Research Consortium (OneFlorida; a Clinical Research Network comprised of 16 health systems) between October 2015 and December 2018. We identified patients with controlled and uncontrolled hypertension based on either a single blood pressure (BP) measurement from a randomly selected visit or all BP measurements recorded between hypertension identification and the randomly selected visit). Results: Overall, 253,207 and 182,827 adults at YNHHS and OneFlorida were identified as having hypertension. Of these patients, 83.1% at YNHHS and 76.8% at OneFlorida were identified using ICD-10-CM codes, whereas 16.9% and 23.2%, respectively, were identified using elevated BP measurements (≥ 140/90 mmHg). Uncontrolled hypertension was observed among 32.5% and 43.7% of patients at YNHHS and OneFlorida, respectively. Uncontrolled hypertension was disproportionately higher among Black patients when compared with White patients (38.9% versus 31.5% in YNHHS; p<0.001; 49.7% versus 41.2% in OneFlorida; p<0.001). Medication prescription for hypertension management was more common in patients with uncontrolled hypertension when compared with those with controlled hypertension (overall treatment rate: 39.3% versus 37.3% in YNHHS; p=0.04; 42.2% versus 34.8% in OneFlorida; p<0.001). Patients with controlled and uncontrolled hypertension had similar rates of short-term (at 3 and 6 months) and long-term (at 12 and 24 months) clinical outcomes. The two computable definitions generated consistent results. Conclusions: Computable definitions can be successfully applied to health system EHR data to conduct population surveillance for hypertension and identify patients with uncontrolled hypertension who may benefit from additional treatment.

A Fracture From a Physical Exam: A Case Report of Osteogenesis Imperfecta and the Use of Fassier-Duval Rods.

Osteogenesis Imperfecta (OI) is a rare hereditary disorder that leads to fragile bone mineralization and is most often due to a genetic defect in type I collagen, the primary collagen subtype that comprises bone. Patients with OI suffer from a significant burden of fractures and bony deformities. It has been recognized in countries throughout the world and has a variable age and severity of presentation depending on the subtype of OI. Recognition of this disorder requires a high index of suspicion on the part of the clinician, as it can easily be mistaken for non-accidental trauma in children. The current approach to care for patients with this disorder comprises surgical care with intramedullary rod fixation, cyclic bisphosphonate therapy, and rehabilitation to maximize the patient's quality of life and function. This case report demonstrates the importance of considering OI in the differential diagnosis of a child presenting with recurrent fractures so that appropriate testing and treatment interventions can be implemented. The case presented here is that of a male patient with osteogenesis imperfecta who suffered from recurrent long bone fractures, including his femurs bilaterally. His index fracture occurred after a visit to the pediatric ER for an unrelated issue, where his mother claimed that the boy demonstrated pain in his affected leg shortly after the visit. There was a delay in his diagnosis, and the patient suffered multiple fractures before undergoing the insertion of Fassier-Duval rods bilaterally into his femurs to prevent further injury.

Angiolymphoid Hyperplasia with Eosinophilia in a Patient With Coccidioidomycosis.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare nodular mass that has not commonly been reported in the literature in association with coccidioidomycosis (CM). Coccidioidomycosis has other known skin manifestations including erythema nodosum and interstitial granulomatous dermatitis. Pulmonary CM is the most common form of the disease and the most common cause of CM-associated rash. This is an important clinical consideration for patients with ALHE who reside in CM-endemic areas, which notably include the southwestern region of the United States, Mexico, and South America. We report the case of an ALHE lesion that resolved following treatment for CM.

Congenital self-healing reticulohistiocytosis: An atypical presentation acquired in a 10-month-old.

Congenital self-healing reticulohistiocytosis of Hashimoto and Pritzker (CSHR) is a rare, benign form of Langerhans Cell Histiocytosis (LCH) that presents at birth and involutes by 6 months of age. We present an atypical case of CSHR with the first onset at 7 months of age, treated with surgical excision.

Is intensive care unit mortality a valid survival outcome measure related to critical illness?

RATIONALE: Use of death as an outcome of intensive care unit (ICU) admission may be biased by differential discharge decisions. OBJECTIVE: To determine the validity of ICU survival status as an outcome measure of all cause case-fatality. METHODS: A retrospective cohort of first admissions among adults to four ICUs in North Brisbane, Australia was assembled. Death in ICU (censored at discharge or 30 days) was compared with 30-day overall case-fatality. RESULTS: The 30-day overall case-fatality was 8.1% (2436/29,939). One thousand six hundred and thirty-one deaths occurred within the ICU stay and 576 subsequent during hospital post-ICU discharge within 30-days; ICU and hospital case-fatality rates were 5.4% and 7.4%, respectively. An additional 229 patients died after hospital separation within 30 days of ICU admission of which 110 (48.0%) were transferred to another acute care hospital, 80 (34.9%) discharged home, and 39 (17.0%) transferred to an aged care/chronic care/rehabilitation facility. Patients who died after ICU discharge were older, had higher APACHE III scores, were more likely to be elective surgical patients, and were less likely to be out of state residents or managed in a tertiary referral hospital. Limiting determination of case-fatality to ICU information alone would correctly detect 95% (780/821) of all-cause mortality at day 3, 90% (1093/1213) at day 5, 75% (1524/2019) at day 15, 72% (1592/2244) at day 21, and 67% (1631/2436) at day 30 of follow-up. CONCLUSIONS: Use of ICU case-fatality significantly underestimates the true burden and biases assessment of determinants of critical illness-related mortality in our region.

Almost One-Third of Large Sessile Serrated Polyps Are Missed on CT Colonography.

BACKGROUND: Nearly one-third of colorectal cancers (CRC) arise via the serrated pathway. CT colonography (CTC) is a CRC screening examination. Endoscopic detection of sessile serrated polyps (SSPs) varies widely; it is unknown whether CTC effectively detects SSPs. The aim of this study is to determine whether CTC detects SSPs at an institution that performs a large volume of CTC. METHODS: We conducted a search of pathology records to identify serrated polyps (SPs) from 2005 to 2012. We extracted demographic data from the electronic health records (EHRs) of subjects with an SSP and examined endoscopy reports for location and size of each SSP. We identified subjects with a CTC within 1 year prior to the colonoscopy that found an SSP, and determined if the CTC identified the SSP. RESULTS: Our search found 3978 subjects with SP over the 7-year period. Seven hundred thirty-two subjects had at least 1 SSP. Eightytwo subjects had CTC done within 1 year prior to the colonoscopy that identified SSP. Seventy-nine subjects' polyps were identified on CTC. CT colonography was done an average of 38 ± 54 days prior to colonoscopy. One hundred fifteen SSPs were identified endoscopically. A total of 48.7% of all SSPs were identified via CTC; larger SSPs were more likely to be seen on CTC (P < .001), and 69.6% of SSPs larger than 10 mm were found via CTC. Proximal SSPs were more often identified than distal SSPs (P = .005). CONCLUSION: Given the miss rate for SSPs on CTC, endoscopists should be vigilant about examining the proximal colon in subjects referred after CTC, even if the imaging does not reveal a proximal polyp.

Structure-function relationships explain CTCF zinc finger mutation phenotypes in cancer.

CCCTC-binding factor (CTCF) plays fundamental roles in transcriptional regulation and chromatin architecture maintenance. CTCF is also a tumour suppressor frequently mutated in cancer, however, the structural and functional impact of mutations have not been examined. We performed molecular and structural characterisation of five cancer-specific CTCF missense zinc finger (ZF) mutations occurring within key intra- and inter-ZF residues. Functional characterisation of CTCF ZF mutations revealed a complete (L309P, R339W, R377H) or intermediate (R339Q) abrogation as well as an enhancement (G420D) of the anti-proliferative effects of CTCF. DNA binding at select sites was disrupted and transcriptional regulatory activities abrogated. Molecular docking and molecular dynamics confirmed that mutations in residues specifically contacting DNA bases or backbone exhibited loss of DNA binding. However, R339Q and G420D were stabilised by the formation of new primary DNA bonds, contributing to gain-of-function. Our data confirm that a spectrum of loss-, change- and gain-of-function impacts on CTCF zinc fingers are observed in cell growth regulation and gene regulatory activities. Hence, diverse cellular phenotypes of mutant CTCF are clearly explained by examining structure-function relationships.

Inhibition of the ubiquitin-proteasome system by an NQO1-activatable compound.

Malignant cells display an increased sensitivity towards drugs that reduce the function of the ubiquitin-proteasome system (UPS), which is the primary proteolytic system for destruction of aberrant proteins. Here, we report on the discovery of the bioactivatable compound CBK77, which causes an irreversible collapse of the UPS, accompanied by a general accumulation of ubiquitylated proteins and caspase-dependent cell death. CBK77 caused accumulation of ubiquitin-dependent, but not ubiquitin-independent, reporter substrates of the UPS, suggesting a selective effect on ubiquitin-dependent proteolysis. In a genome-wide CRISPR interference screen, we identified the redox enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1) as a critical mediator of CBK77 activity, and further demonstrated its role as the compound bioactivator. Through affinity-based proteomics, we found that CBK77 covalently interacts with ubiquitin. In vitro experiments showed that CBK77-treated ubiquitin conjugates were less susceptible to disassembly by deubiquitylating enzymes. In vivo efficacy of CBK77 was validated by reduced growth of NQO1-proficient human adenocarcinoma cells in nude mice treated with CBK77. This first-in-class NQO1-activatable UPS inhibitor suggests that it may be possible to exploit the intracellular environment in malignant cells for leveraging the impact of compounds that impair the UPS.

Overutilization of surgical resection for benign colorectal polyps: analysis from a tertiary care center.

Background and study aims Adequate removal of precancerous polyps is an independent factor in colorectal cancer prevention. Despite advances in polypectomy techniques, there is an increasing rate of surgery for benign polyps. We assessed whether surgical resection is properly utilized for benign colorectal polyps. Patients and methods We identified 144 patients with surgical resection for benign colorectal polyps. Polyp location, size and the indication for and type of surgery were obtained. For the purposes of this analysis, we assumed that gastroenterologists should assess polyp size accurately, endoscopically resect polyps < 2 cm, and treat incompletely excised polyps on follow-up. Results A total of 118 patients (82 %) were referred to surgery without attempted endoscopic removal. In 26 (22 %) of 118, the macroscopic polyp size was < 2 cm (23 in right, 3 in the left colon) and 18 (15 %; 14 in the right, four in the left colon) were found to have had size overestimation during endoscopy. Twenty-two (15 %) of 144 underwent surgical resection for incomplete endoscopic resection of adenomas (16 in the right, 6 in the left colon); 12 (54.5 %) had a residual polyp size of < 2 cm (10 in the right colon; 2 in the left colon). In-hospital mortality was 0.7 % and morbidity was 20.1 %. Conclusions Of the patients, 41 % could have potentially avoided surgical intervention (37 polyps < 2 cm and/or size overestimations precluding endoscopic polypectomy and 22 incomplete resections). When including polyps with size ≥ 2 to < 4 cm, the percentage of patients with avoidable surgery reached 80 %. This confirms the need to develop standardized quality metrics for endoscopic polypectomies and for better overall training of endoscopists performing these procedures. Given the risks of surgery, referral to an experienced gastroenterologist should be considered as a first step.

The Association of COVID-19 With Acute Kidney Injury Independent of Severity of Illness: A Multicenter Cohort Study.

RATIONALE & OBJECTIVE: Although coronavirus disease 2019 (COVID-19) has been associated with acute kidney injury (AKI), it is unclear whether this association is independent of traditional risk factors such as hypotension, nephrotoxin exposure, and inflammation. We tested the independent association of COVID-19 with AKI. STUDY DESIGN: Multicenter, observational, cohort study. SETTING & PARTICIPANTS: Patients admitted to 1 of 6 hospitals within the Yale New Haven Health System between March 10, 2020, and August 31, 2020, with results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing via polymerase chain reaction of a nasopharyngeal sample. EXPOSURE: Positive test for SARS-CoV-2. OUTCOME: AKI by KDIGO (Kidney Disease: Improving Global Outcomes) criteria. ANALYTICAL APPROACH: Evaluated the association of COVID-19 with AKI after controlling for time-invariant factors at admission (eg, demographic characteristics, comorbidities) and time-varying factors updated continuously during hospitalization (eg, vital signs, medications, laboratory results, respiratory failure) using time-updated Cox proportional hazard models. RESULTS: Of the 22,122 patients hospitalized, 2,600 tested positive and 19,522 tested negative for SARS-CoV-2. Compared with patients who tested negative, patients with COVID-19 had more AKI (30.6% vs 18.2%; absolute risk difference, 12.5% [95% CI, 10.6%-14.3%]) and dialysis-requiring AKI (8.5% vs 3.6%) and lower rates of recovery from AKI (58% vs 69.8%). Compared with patients without COVID-19, patients with COVID-19 had higher inflammatory marker levels (C-reactive protein, ferritin) and greater use of vasopressors and diuretic agents. Compared with patients without COVID-19, patients with COVID-19 had a higher rate of AKI in univariable analysis (hazard ratio, 1.84 [95% CI, 1.73-1.95]). In a fully adjusted model controlling for demographic variables, comorbidities, vital signs, medications, and laboratory results, COVID-19 remained associated with a high rate of AKI (adjusted hazard ratio, 1.40 [95% CI, 1.29-1.53]). LIMITATIONS: Possibility of residual confounding. CONCLUSIONS: COVID-19 is associated with high rates of AKI not fully explained by adjustment for known risk factors. This suggests the presence of mechanisms of AKI not accounted for in this analysis, which may include a direct effect of COVID-19 on the kidney or other unmeasured mediators. Future studies should evaluate the possible unique pathways by which COVID-19 may cause AKI.

References Values for Left Atrial Volumes, Emptying Fractions, Strains, and Strain Rates and Their Determinants by Age, Gender, and Ethnicity: The Multiethnic Study of Atherosclerosis (MESA).

RATIONALE AND OBJECTIVES: Left Atrial (LA) adverse remodeling is an important predictor of morbidity and mortality in several cardiovascular (CV) diseases. Our goals were to quantify and provide reference ranges for LA structure and function using feature tracking cine cardiac magnetic resonance. MATERIALS AND METHODS: 2526 participants of the Multiethnic Study of Atherosclerosis study who had feature tracking cine cardiac magnetic resonance derived LA data and were free of atrial fibrillation/flutter and prior CV events at year five follow-up examination (2010-2012) were included in this study. LA phasic indexed volumes: maximum (LAVi max), minimum (LAVi min), and preatrial contraction (LAVi preA); LA empty fractions: total, passive, and active (LAtEF, LApEF, and LAaEF); LA longitudinal strain: maximum and preatrial contraction (S max and S preA); and LA longitudinal strain rate: systolic (SR max) and early/late diastolic (SR e and SR a) were measured. Age, gender, and race/ethnicity-specific reference ranges were identified. Also, reference values in a select subgroup of healthy participants free of traditional CV risk factors at the time of exam date were reported. RESULTS: The mean ± SD for LAVi max, LAVi min, LAVi preA, S max, SR e, and SR a were in the 45-65-year-old participants: (33.8 ± 10 mL/m2), (14.5 ± 6.4 mL/m2), (24.8 ± 8.2 mL/m2), (34.6 ± 13.8 %), (-1.4 ± 0.7 s-1), (-2.1 ± 1 s-1) and in the ≥ 65-year-old participants: (35 ± 11.5 mL/m2), (16.6 ± 8.3 mL/m2), (27.6 ± 9.9 mL/m2), (31.2 ± 14.3 %), (-1 ± 0.6 s-1), (-2.1 ± 1 s-1) respectively. Younger individuals had Powered by Editorial Manager and ProduXion Manager from Aries Systems Corporation smaller LA volumes and better LA function compared to their older counterparts. Similar findings were observed in Chinese-Americans as compared to Whites. CONCLUSION: This study provides reference values of LA structure and function parameters from a healthy multiethnic community-based population aged 53-94 years evaluated by FTMRI.

Low Risk of Progression of Barrett's Esophagus to Neoplasia in Women.

BACKGROUND AND AIMS: Men are at a higher risk for Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC), but little is known about BE progression to dysplasia and EAC in women. We performed a retrospective, multicenter cohort study to assess risk of BE progression to dysplasia and EAC in women compared with men. We also investigated comorbidities, medication use, and endoscopic features that contribute to sex differences in risk of BE progression. METHODS: We collected data from large cohort of patients with BE seen at 6 centers in the United States and Europe, followed for a median 5.7 years. We obtained demographic information (age, sex, ethnicity), clinical history (tobacco use, body mass index, comorbidities), endoscopy results (procedure date, BE segment length), and histopathology findings. Neoplasia was graded as low-grade dysplasia, high-grade dysplasia (HGD), or EAC. Rates of disease progression between women and men were compared using χ2 analysis and the Student t test. Multivariable logistic regression was used to assess the association between sex and disease progression after adjusting for possible confounding variables. RESULTS: Of the total 4263 patients in the cohort, 2145 met the inclusion criteria, including 324 (15%) women. There was a total of 34 (1.6%) incident EACs, with an overall annual incidence of 0.3% (95% confidence interval: 0.2%-0.4%). We found significant differences between women and men in annual incidence rates of EAC (0.05% for women vs. 0.3% in men; P=0.04) and in the combined endpoint of HGD or EAC (0.1% for women vs. 1.1% for men; P<0.001). Female gender was an independent predictor for reduced progression to HGD or EAC when rates of progression were adjusted for body mass index, smoking history, race, use of aspirin, nonsteroidal anti-inflammatory drugs, proton-pump inhibitors, or statins, hypertriglyceridemia, BE length, and histology findings at baseline (hazard ratio: 0.11; 95% confidence interval: 0.03-0.45; P=0.002). CONCLUSIONS: In a multicenter study of men versus women with BE, we found a significantly lower risk of disease progression to cancer and HGD in women. The extremely low risk of EAC in women with BE (0.05%/y) indicates that surveillance endoscopy may not be necessary for this subgroup of patients with BE.

Colon Cancer Metastatic to the Pancreas Presenting as of Diabetic Ketoacidosis.

Most of the malignant pancreatic lesions are primary pancreatic tumors with only a small percentage due to metastases. Pancreatic malignancies often present with symptoms such as jaundice and weight loss. Less commonly, new-onset diabetes mellitus has been seen in the setting of pancreatic adenocarcinomas. Although colon cancer commonly presents with metastatic disease, it typically spreads to the liver, lung, and peritoneum. We present a rare case of colon cancer metastatic to the pancreas presenting as diabetic ketoacidosis.