Scalable Approach to Consumer Wearable Postmarket Surveillance: Development and Validation Study.

Background: With the capability to render prediagnoses, consumer wearables have the potential to affect subsequent diagnoses and the level of care in the health care delivery setting. Despite this, postmarket surveillance of consumer wearables has been hindered by the lack of codified terms in electronic health records (EHRs) to capture wearable use. Objective: We sought to develop a weak supervision-based approach to demonstrate the feasibility and efficacy of EHR-based postmarket surveillance on consumer wearables that render atrial fibrillation (AF) prediagnoses. Methods: We applied data programming, where labeling heuristics are expressed as code-based labeling functions, to detect incidents of AF prediagnoses. A labeler model was then derived from the predictions of the labeling functions using the Snorkel framework. The labeler model was applied to clinical notes to probabilistically label them, and the labeled notes were then used as a training set to fine-tune a classifier called Clinical-Longformer. The resulting classifier identified patients with an AF prediagnosis. A retrospective cohort study was conducted, where the baseline characteristics and subsequent care patterns of patients identified by the classifier were compared against those who did not receive a prediagnosis. Results: The labeler model derived from the labeling functions showed high accuracy (0.92; F1-score=0.77) on the training set. The classifier trained on the probabilistically labeled notes accurately identified patients with an AF prediagnosis (0.95; F1-score=0.83). The cohort study conducted using the constructed system carried enough statistical power to verify the key findings of the Apple Heart Study, which enrolled a much larger number of participants, where patients who received a prediagnosis tended to be older, male, and White with higher CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes, stroke, vascular disease, age 65-74 years, sex category) scores (P<.001). We also made a novel discovery that patients with a prediagnosis were more likely to use anticoagulants (525/1037, 50.63% vs 5936/16,560, 35.85%) and have an eventual AF diagnosis (305/1037, 29.41% vs 262/16,560, 1.58%). At the index diagnosis, the existence of a prediagnosis did not distinguish patients based on clinical characteristics, but did correlate with anticoagulant prescription (P=.004 for apixaban and P=.01 for rivaroxaban). Conclusions: Our work establishes the feasibility and efficacy of an EHR-based surveillance system for consumer wearables that render AF prediagnoses. Further work is necessary to generalize these findings for patient populations at other sites.

Direct Oral Anticoagulant Adherence of Patients With Atrial Fibrillation Transitioned from Warfarin.

Background Reduced time in international normalized ratio therapeutic range (TTR) limits warfarin safety and effectiveness. In patients switched from warfarin to direct oral anticoagulants (DOACs), patient factors associated with low TTR could also increase risk of DOAC nonadherence. We investigated the relationship between warfarin TTR and DOAC adherence in warfarin-treated patients with atrial fibrillation switched to DOAC. Methods and Results Using data from the Veterans Health Administration, we identified patients with atrial fibrillation switched from warfarin to DOAC (switchers) or treated with warfarin alone (non-switchers). Logistic regression was used to evaluate association between warfarin TTR and DOAC adherence. We analyzed 128 605 patients (age, 71±9; 1.6% women; CHA2DS2-VASc 3.5±1.6); 32 377 switchers and 96 228 non-switchers. In 8016 switchers with international normalized ratio data to calculate 180-day TTR before switch, TTR was low (median 0.45; IQR, 0.26-0.64). Patients with TTR <0.5 were more likely to be switched to DOAC (odds ratio [OR],1.68 [95% CI,1.62-1.74], P<0.0001), as were those with TTR <0.6 or TTR <0.7. Proportion of days covered ≥0.8 was achieved by 76% of switchers at 365 days. In low-TTR individuals, proportion of days covered ≥0.8 was achieved by 70%, 72%, and 73% of switchers with TTR <0.5, 0.6, and 0.7, respectively. After multivariable adjustment, TTR <0.5 decreased odds of achieving 365-day proportion of days covered ≥0.8 (OR, 0.49; 0.43-0.57, P<0.0001), with similar relationships for TTR <0.6 and TTR <0.7. In non-switchers with TTR <0.5, long-term TTR remained low. Conclusions In patients with atrial fibrillation switched from warfarin to DOAC, most achieved adequate DOAC adherence despite low pre-switch TTRs. However, TTR trajectories remained low in non-switchers. Patients with low warfarin TTR more consistently achieved treatment targets after switching to DOACs, although adherence-oriented interventions may be beneficial.

Multiphase Computed Tomographic Enterography: Diagnostic Yield and Efficacy in Patients With Suspected Small Bowel Bleeding.

OBJECTIVE: To estimate the diagnostic yield and efficacy of multiphase computed tomographic enterography (mpCTE) for suspected small bowel bleeding in routine clinical practice. PATIENTS AND METHODS: All mpCTEs performed between January 1, 2006, and December 31, 2014, for suspected small bowel bleeding were included and classified by a gastroenterologist and an abdominal radiologist. The reference standard for a definitive diagnosis was balloon-assisted enteroscopic, angiographic, surgical, or pathologic results. Overall and lesion-specific diagnostic yield (DY), sensitivity, and positive predictive value were calculated. The relationship of mpCTE diagnosis and continued bleeding or iron supplementation was examined using logistic regression in patients with at least 1 year of follow-up. RESULTS: We identified 1087 patients who had an initial mpCTE indication of small bowel bleeding. The overall DY was 31.6% (344 of 1087 patients; 95% CI, 29.0%-35.0%), higher for an indication of small bowel bleeding that was overt or occult with heme-positive stool vs occult with only iron-deficiency anemia (DY, 35.0% [170 of 486] and 35.3% [66 of 187] vs 26.1% [108 of 414]; P=.004 and P=.02, respectively). The highest sensitivity and positive predictive value were for small bowel masses (90.2% [55 of 61] and 98.2% [55 of 56], respectively). Higher risk of future bleeding and iron supplementation was seen with a negative result on mpCTE (odds ratio [OR], 1.91; 95% CI, 1.28-2.86), lack of surgical intervention (OR, 4.37; 95% CI, 2.31-8.29), or discrepant balloon-assisted enteroscopic findings (OR, 2.50; 95% CI, 1.03-6.09). CONCLUSION: Multiphase computed tomographic enterography has a higher rate of detection in patients with overt bleeding or heme-positive stool. The procedure provides actionable targets for further intervention and leads to substantially reduced rates of rebleeding in long-term follow-up.

Yield of the RYR2 Genetic Test in Suspected Catecholaminergic Polymorphic Ventricular Tachycardia and Implications for Test Interpretation.

BACKGROUND: Pathogenic RYR2 variants account for ≈60% of clinically definite cases of catecholaminergic polymorphic ventricular tachycardia. However, the rate of rare benign RYR2 variants identified in the general population remains a challenge for genetic test interpretation. Therefore, we examined the results of the RYR2 genetic test among patients referred for commercial genetic testing and examined factors impacting variant interpretability. METHODS: Frequency and location comparisons were made for RYR2 variants identified among 1355 total patients of varying clinical certainty and 60 706 Exome Aggregation Consortium controls. The impact of the clinical phenotype on the yield of RYR2 variants was examined. Six in silico tools were assessed using patient- and control-derived variants. RESULTS: A total of 18.2% (218/1200) of patients referred for commercial testing hosted rare RYR2 variants, statistically less than the 59% (46/78) yield among clinically definite cases, resulting in a much higher potential genetic false discovery rate among referrals considering the 3.2% background rate of rare, benign RYR2 variants. Exclusion of clearly putative pathogenic variants further complicates the interpretation of the next novel RYR2 variant. Exonic/topologic analyses revealed overrepresentation of patient variants in exons covering only one third of the protein. In silico tools largely failed to show evidence toward enhancement of variant interpretation. CONCLUSIONS: Current expert recommendations have resulted in increased use of RYR2 genetic testing in patients with questionable clinical phenotypes. Using the largest to date catecholaminergic polymorphic ventricular tachycardia patient versus control comparison, this study highlights important variables in the interpretation of variants to overcome the 3.2% background rate that confounds RYR2 variant interpretation.

Sudden cardiac death and late arrhythmias after the Fontan operation.

OBJECTIVES: We sought to examine the incidence and predictors of arrhythmias and sudden cardiac death (SCD) after Fontan operation. BACKGROUND: Arrhythmias and SCD have been reported following operations for congenital heart disease, but the incidence and risk factors have not been well defined in patients after a Fontan operation. METHODS: We reviewed records of all patients who had a Fontan operation from 1973 to 2012 (n = 1052) at our institution. A questionnaire was mailed to patients who were not known to be deceased at the initiation of the study. Late arrhythmias were classified as bradyarrhythmias or tachyarrhythmias requiring treatment >30 days after operation. RESULTS: We included 996/1052 (95%) patients with no arrhythmia diagnosis prior to Fontan. Overall 10-, 20-, and 30-year freedom from arrhythmias was 71%, 42%, and 24%, respectively. Of 864 patients who survived >30 days after Fontan, 304 (35%) had atrial flutter, 161 (19%) had atrial fibrillation, 108 (13%) had atrial tachycardia, 37 (4%) had reentrant supraventricular tachycardia, 40 (5%) had ventricular tachycardia, and 113 (13%) had sinus node dysfunction. Predictors of late arrhythmias included an atriopulmonary Fontan, age at operation (>16 years) or atrial arrhythmias postoperatively. During follow-up, 52/1052 (5%) patients had SCD, with 51 having documentation available; 8 patients died suddenly within 30 days and the remaining 43 had an average time to SCD of 6.9 ± 6.7 years (median was 3.8 years). Arrhythmias were documented in 28/43 (65%) patients prior to SCD. Predictors of SCD included atrioventricular valve replacement and post-bypass Fontan pressures >20 mm Hg; preoperative sinus rhythm was protective. CONCLUSIONS: Arrhythmias and SCD are significant concerns among Fontan patients and specific risk factors may warrant closer follow-up and earlier consideration for therapy.

40-Year Follow-Up After the Fontan Operation: Long-Term Outcomes of 1,052 Patients.

BACKGROUND: There are limited long-term, single-cohort, follow-up studies available about patients after the Fontan operation. OBJECTIVES: This study sought to determine the long-term outcome of all patients who had a Fontan operation at the Mayo Clinic. METHODS: Records of all patients who had a modified Fontan operation between 1973 and 2012 were reviewed. A follow-up questionnaire was mailed to all patients alive at the time of the study. RESULTS: Overall, 10-, 20-, and 30-year survival for 1,052 patients was 74%, 61%, and 43%, respectively. Factors associated with decreased overall or late survival in multivariate analysis included pre-operative diuretic use, longer cardiopulmonary bypass time, operation prior to 1991, atrioventricular valve (AVV) replacement at the time of Fontan operation, elevated post-bypass Fontan (>20 mm Hg) or left atrial (>13 mm Hg) pressures, prolonged chest tube drainage (>21 days), post-operative ventricular arrhythmias, renal insufficiency, and development of protein-losing enteropathy (PLE). Pre-operative and intraoperative sinus rhythm were associated with improved survival. Long-term survival was similar for patients regardless of ventricular morphology. The most common reoperations were pacemaker insertion/revision in 212 patients (20%), Fontan revision/conversion in 117 patients (11%), and AVV repair/replacement in 66 patients (5%). Clinically significant late atrial or ventricular arrhythmias occurred in 468 patients (44%). Ninety-five patients (9%) developed PLE, and 5-, 10-, and 20-year survival after diagnosis of PLE was 50%, 35%, and 19%, respectively. CONCLUSIONS: As the surgical techniques for the Fontan operation have changed over the last 40 years, survival has improved. However, development of PLE and arrhythmias and the need for reoperation during long-term follow-up pose significant management challenges.

Forequarter amputation for recurrent breast cancer.

INTRODUCTION: Localized excision combined with radiation and chemotherapy represents the current standard of care for recurrent breast cancer. However, in certain conditions a forequarter amputation may be employed for these patients. PRESENTATION OF CASE: We present a patient with recurrent breast cancer who had a complicated treatment history including multiple courses of chemotherapy, radiation, and local surgical excision. With diminishing treatment options, she opted for a forequarter amputation in an attempt to limit the spread of cancer. DISCUSSION: In our patient the forequarter amputation was utilized as a last resort to slow disease progression after she had failed multiple rounds of chemotherapy and received maximal radiation. Unfortunately, while she had symptomatic relief in the short-term, she had cutaneous recurrence of metastatic adenocarcinoma within 2 months of the procedure. In comparing this case with other reported forequarter amputations, patients with non-metastatic disease showed a mean survival of approximately two years. Furthermore, among patients who had significant pain prior to surgery, all patients reported pain relief, indicating a significant palliative benefit. This seems to indicate that our patient's unfortunate outcome was anomalous compared to that of most patients undergoing forequarter amputation for recurrent breast cancer. CONCLUSION: Forequarter amputation can be judiciously used for patients with recurrent or metastatic breast cancer. Patients with recurrent disease without evidence of distant metastases may be considered for curative amputation, while others may receive palliative benefit; disappointingly our patient achieved neither of these outcomes. In the long term, these patients may still have significant psychological problems.