Large National Cohort Of Patients Research Articles

Determining the Risk Factors for Anastomotic Stricture Development after Esophageal Atresia Repair: Results from the Turkish Esophageal Atresia Registry.

Anastomotic stricture (AS) is the second most common complication after esophageal atresia (EA) repair. We aimed to evaluate the data in the Turkish Esophageal Atresia Registry to determine the risk factors for AS development after EA repair in a large national cohort of patients. The data between 2015 and 2021 were evaluated. Patients were enrolled into two groups according to the occurrence of AS. Patients with AS (AS group) and without AS (non-AS group) were compared according to demographic and operative features, postoperative intubation status, and postoperative complications, such as anastomotic leaks, fistula recanalization, and the presence of gastroesophageal reflux (GER). A multivariable logistic regression analysis was performed to define the risk factors for the development of AS after EA repair. Among the 713 cases, 144 patients (20.19%) were enrolled into the AS group and 569 (79.81%) in the non-AS group. The multivariable logistic regression showed that, being a term baby (odds ratio [OR]: 1.706; p = 0.006), having a birth weight over 2,500 g (OR: 1.72; p = 0.006), presence of GER (OR: 5.267; p < 0.001), or having a recurrent tracheoesophageal fistula (TEF, OR: 4.363; p = 0.006) were the risk factors for the development of AS. The results of our national registry demonstrate that 20% of EA patients developed AS within their first year of life. In patients with early primary anastomosis, birth weight greater than 2,500 g and presence of GER were risk factors for developing AS. When patients with delayed anastomosis were included, in addition to the previous risk factors, being a term baby, and having recurrent TEF also became risk factors. III.

Assessing Patterns of Continuous Glucose Monitoring Use and Metrics of Glycemic Control in Type 1 Diabetes and Type 2 Diabetes Patients in the Veterans Health Care System: Integrating Continuous Glucose Monitoring Device Data with Electronic Health Records Data.

Objective: To integrate long-term daily continuous glucose monitoring (CGM) device data with electronic health records (EHR) for patients with type 1 and type 2 diabetes (T1D and T2D) in the national Veterans Affairs Healthcare System to assess real-world patterns of CGM use and the reliability of EHR-based CGM information. Research Design and Methods: This observational study used Dexcom CGM device data linked with EHR (from 2015 to 2020) for a large national cohort of patients with diabetes. We tracked the initiation and consistency of CGM use, assessed concordance of CGM use and measures of glucose control between CGM device data and EHR records, and examined results by age, ethnicity, and diabetes type. Results: The time from pharmacy release of CGM to patients to initiation of uploading CGM data to Dexcom servers averaged 3 weeks but demonstrated wide variation among individuals; importantly, this delay decreased markedly over the later years. The average daily wear time of CGM exceeded 22 h over nearly 3 years of follow-up. Patterns of CGM use were generally consistent across age, race/ethnicity groups, and diabetes type. There was strong concordance between EHR-based estimates of CGM use and Dexcom CGM wear time and between estimates of glucose control from both sources. Conclusions: The study demonstrates our ability to reliably integrate CGM devices and EHR data to provide valuable insights into CGM use patterns. The results indicate in the real-world environment that CGM is worn consistently over many years for both patients with T1D and T2D within the Veterans Affairs Healthcare System and is similar across major race/ethnic groups and age-groups.

Arrhythmia Burden Among Adult PatientsWith Congenital Heart Disease: APopulation-Based Study.

A significant percentage of patients with congenital heart disease surviving into adulthood will develop arrhythmias. These arrhythmias are associated with an increased risk of adverse events and death. We aimed to assess arrhythmia prevalence, risk factors, and associated health care usage in a large national cohort of patients with adult congenital heart disease. Adults with a documented diagnosis of congenital heart disease, insured by Clalit and Maccabi health services between January 2007 and December 2011, were included. We assessed the associations between arrhythmia and subsequent hospitalization rates and death with mixed negative binomial and Cox proportional hazard models, respectively. Among 11 653 patients with adult congenital heart disease (median age, 47 years [interquartile range, 31-62]), 8.7% had a tachyarrhythmia at baseline, 1.5% had a conduction disturbance, and 0.5% had both. Among those without a baseline arrhythmia, 9.2% developed tachyarrhythmias, 0.9% developed a conduction disturbance, and 0.3% developed both during the study period. Compared with no arrhythmia (reference group), arrhythmia in the previous 6 months was associated with a higher multivariable adjusted hospitalization rate, 1.33-fold higher than the rate of the reference group (95% CI, 1.00-1.76) for ventricular arrhythmia, 1.27-fold higher (95% CI, 1.17-1.38) for atrial arrhythmias, and 1.33-fold higher (95% CI, 1.04-1.71) for atrioventricular block. Atrial tachyarrhythmias were associated with an adjusted mortality hazard ratio (HR) of 1.65 (95% CI, 1.44-2.94), and ventricular tachyarrhythmias with a >2-fold increase in mortality risk (HR, 2.06 [95% CI, 1.44-2.94]). Arrhythmias are significant comorbidities in the adult congenital heart disease population and have a significant impact on health care usage and survival.

Heart and Lung Dose as Predictors of Overall Survival in Patients With Locally Advanced Lung Cancer. A National Multicenter Study

IntroductionIt is an ongoing debate how much lung and heart irradiation impact overall survival (OS) after definitive radiotherapy for lung cancer. This study uses a large national cohort of patients with locally advanced NSCLC to investigate the association between OS and irradiation of lung and heart. MethodsTreatment plans were acquired from six Danish radiotherapy centers, and patient characteristics were obtained from national registries. A hybrid segmentation tool automatically delineated the heart and substructures. Dose-volume histograms for all structures were extracted and analyzed using principal component analyses (PCAs). Parameter selection for a multivariable Cox model for OS prediction was performed using cross-validation based on bootstrapping. ResultsThe population consisted of 644 patients with a median survival of 26 months (95% confidence interval [CI]: 24–29). The cross-validation selected two PCA variables to be included in the multivariable model. PCA1 represented irradiation of the heart and affected OS negatively (hazard ratio, 1.14; 95% CI: 1.04–1.26). PCA2 characterized the left-right balance (right atrium and left ventricle) irradiation, showing better survival for tumors near the right side (hazard ratio, 0.92; 95% CI: 0.84–1.00). Besides the two PCA variables, the multivariable model included age, sex, body-mass index, performance status, tumor dose, and tumor volume. ConclusionsBesides the classic noncardiac risk factors, lung and heart doses had a negative impact on survival, while it is suggested that the left side of the heart is a more radiation dose–sensitive region. The data indicate that overall heart irradiation should be reduced to improve the OS if possible.

Development of a Natural Language Processing System to Identify Clinical Documentation of Electronic Cigarette Use.

Electronic Nicotine Delivery Systems (ENDS) use has increased substantially in the United States since 2010. To date, there is limited evidence regarding the nature and extent of ENDS documentation in the clinical note. In this work we investigate the effectiveness of different approaches to identify a patient's documented ENDS use. We report on the development and validation of a natural language processing system to identify patients with explicit documentation of ENDS using a large national cohort of patients at the United States Department of Veterans Affairs.

Inpatient outcomes of blinatumomab use: A national inpatient sample analysis.

e19021 Background: Blinatumomab, a bispecific (CD3/CD19) T-cell engager, is indicated for the treatment of acute lymphoblastic leukemia (ALL). The initial portion of each cycle is administered in the inpatient setting for close monitoring for cytokine release syndrome and neurotoxicity. Real world data are lacking on the cost of hospitalization, length of stay (LOS), and mortality in inpatients treated with blinatumomab. The goal of this study was to analyze the clinical outcomes of inpatient blinatumomab administration utilizing a national database. Methods: The ICD-10 diagnosis and procedure codes were used to identify Blinatumomab admissions and related complications from the 2018 version of the Nationwide Inpatient Sample (NIS) database from the Healthcare Cost and Utilization Project (HCUP). Weighted analysis was used to calculate national estimates. Logistic regression analyses were used to examine predictors of hospital outcomes (in-hospital mortality, length of stay, and cost), with p &lt; 0.05 considered statistically significant. Data were analyzed using SAS v9.4 (SAS Institute, Cary, NC). Results: A total of 228 patients received inpatient blinatumomab in this cohort. Median age was 46 years old (IQR 26.8, 63.0) and 59.2% were males, 50.4% were white, and 47.4% had private insurance. The majority of patients received care at an urban teaching (96.1%) or large hospital (76.3%). The most relevant inpatient complications during hospitalization included hypotension (7.5%), pneumonia (6.1%), sepsis (9.2%), seizure (2.2%), neutropenia (6.1%), thrombocytopenia (14.0), tumor lysis syndrome (3.9%), and acute kidney injury (9.6%). Median LOS was 9.0 days (IQR 3.0-16.2) and median hospitalization charge was $114,936 USD (IQR 51,984.2-240,557.5). On multivariate regression analysis, dialysis (OR 1.67, 95% CI 1.05-2.65), blood product transfusion (OR 1.5, 95% CI 1.14-1.97), sepsis (OR 2.63, 95% CI 1.86-3.73), neutropenia (OR 1.86, 95% CI 1.23-2.81), and pancreatitis (OR 1.46, 95% CI 1.11-1.91) were all associated with longer LOS. Dialysis (OR 1.83, 95% CI 1.29-2.6), transfusions (OR 1.52, 95% CI 1.01-2.28), sepsis (OR 1.87, 95% CI 1.20-2.91) and neutropenia (OR 1.84, 95% 1.04-3.24) significantly increased the cost of hospitalization. Conclusions: In this cross-sectional study of a large national cohort of patients receiving inpatient blinatumomab, multiple blinatumomab associated toxicities led to increased LOS and cost of hospitalization.

A national service for delivering CD19 CAR-Tin large B-cell lymphoma - The UK real-world experience.

CD19 CAR-T have emerged as a new standard treatment for relapsed/refractory (r/r) large B-cell lymphoma (LBCL). CAR-T real-world (RW) outcomes published to date suggest significant variability across countries. We provide results of a large national cohort of patients intended to be treated with CAR-T in the UK. Consecutive patients with r/r LBCL approved for CAR-T by the National CAR-T Clinical Panel between December 2018 and November 2020 across all UK CAR-T centres were included. 404/432 patients were approved [292 axicabtagene ciloleucel (axi-cel), 112 tisagenlecleucel (tisa-cel)], 300 (74%) received the cells. 110/300 (38.3%) patients achieved complete remission (CR) at 6months (m). The overall response rate was 77% (52% CR) for axi-cel, 57% (44% CR) for tisa-cel. The 12-month progression-free survival was 41.8% (axi-cel) and 27.4% (tisa-cel). Median overall survival for the intention-to-treat population was 10.5m, 16.2m for infused patients. The incidence of grade ≥3 cytokine release syndrome and neurotoxicity were 7.6%/19.6% for axi-cel and 7.9%/3.9% for tisa-cel. This prospective RW population of CAR-T eligible patients offers important insights into the clinical benefit of CD19 CAR-T in LBCL in daily practice. Our results confirm long-term efficacy in patients receiving treatment similar to the pivotal trials, but highlight the significance of early CAR-T failure.

From the Editor’s Desk...

From the Editor’s Desk...

Revascularization in ischaemic heart failure with preserved ejection fraction: a nationwide cohort study.

Despite the common occurrence of coronary artery disease (CAD) and heart failure (HF) with preserved ejection fraction (HFpEF), there is limited evidence to guide revascularization. We investigated the long-term outcomes of coronary artery bypass grafting (CABG) in patients with HF and significant CAD across the spectrum of ejection fraction, using a large national cohort of patients from the Veteran Affairs (VA) Medical Centers in the US. Patients with HF were stratified into groups, HFpEF, HF with mid-range ejection fraction (HFmrEF), and HF with reduced ejection fraction (HFrEF) and compared to patients with no preoperative HF. We analysed 10 396 patients. Despite an increased hazard in the first year following revascularization, the long-term survival (median follow-up 6.6 years; interquartile range 3.7-10.1) of HFpEF post-CABG was similar to controls (hazard ratio 0.85, 95% confidence interval 0.68-1.06), but survival progressively declined with HFmrEF and HFrEF. Similar trends were seen with recurrent HF hospitalization with lower risk with baseline HFpEF (43.9 ± 6.9/100 patient-years) compared to HFmrEF (65.9 ± 3.8/100 patient-years) and HFrEF (93.4 ± 4.8/100 patient-years). Although HFpEF patients had lower mortality and HF hospitalization post-CABG compared to patients with a lower ejection fraction, they experienced the highest rates of future myocardial infarction. Although HFpEF patients with CAD have greater short-term risk post-CABG, their long-term survival is comparable to controls. However, they are at increased risk for HF hospitalizations and myocardial infarction. These data support the safety of CABG in HFpEF patients and suggest continuum of mortality risk for ischaemic HF when stratified by baseline ejection fraction before revascularization.

Statin exposure is associated with reduced development of acute-on-chronic liver failure in a Veterans Affairs cohort

There is a need to identify therapies that prevent the development of acute-on-chronic liver failure (ACLF) in patients with cirrhosis. This study sought to evaluate the association between statin exposure and the risk of developing ACLF in a large national cohort of patients with cirrhosis. We performed a retrospective cohort study of patients diagnosed with cirrhosis within the Veterans Health Administration from 2008 and 2018. Patients were stratified into 3 groups based on statin exposure (statin naïve, existing statin user, and new statin initiator). Cox proportional hazards regression models with inverse probability treatment weighting and marginal structural models were utilized to comprehensively address potential confounding in estimating the association between time-updated statin exposure and first occurrence of high-grade ACLF. The cohort included 84,963 patients, of whom 26.9% were on a statin at baseline. A total of 8,558 (10.1%) patients with cirrhosis were hospitalized with high-grade ACLF over a median follow-up time of 51.6 months (IQR 27.5-81.4). Time-updated statin use was associated with a significant reduction in the hazard of developing ACLF (hazard ratio [HR] 0.62, 95% CI 0.59-0.65, p <0.001). Increasing doses of statin were associated with progressively reduced hazard of developing ACLF (HR 0.75, 95% CI 0.66-0.86, p <0.001 for <20 mg vs. 0 mg of time-updated statin exposure, in simvastatin equivalents; HR 0.61, 95%, CI 0.58-0.64, p <0.001 for >20 mg vs. 0 mg statin exposure). Furthermore, every additional 5 months of statin exposure was associated with a 9% reduced hazard of high-grade ACLF (HR 0.91, 95% CI 0.90-0.92, p <0.001). In this large, retrospective, cohort study in patients with cirrhosis, statin use was significantly associated with reduced development of high-grade ACLF. Statin therapy has been shown to have numerous beneficial effects in patients with chronic liver disease. This study demonstrated a strong association between statin therapy and a reduced risk of acute-on-chronic liver failure development in patients with cirrhosis. The results of this study support the promising role that statins may play in future prevention of acute-on-chronic liver failure in patients with cirrhosis.

P043 Resource Utilization and Productivity Loss among Patients with Inflammatory Bowel Disease in Sweden: A Longitudinal Nationwide Population-based Study.

Crohn's disease (CD) and ulcerative colitis (UC) are the two most prevalent forms of inflammatory bowel disease (IBD) causing frequent diarrhea, rectal bleeding, fatigue, and abdominal pain. IBD may result in complications requiring hospitalizations and surgical procedure, hence IBD can negatively impact patients' quality of life, work productivity, and increase societal economic burden. Limited data exists assessing epidemiologic trends and population-level health outcomes among patients with IBD in Sweden. This study assessed the trends in annual incidence and prevalence of CD, annual inpatient and outpatient visits, employment status and sickness absence among adults with IBD in Sweden from 2001 to 2017. Data were acquired from four nationwide registers provided by the National Board of Health and Welfare in Sweden and linked through the unique personal identity number. Individuals aged ≥18 years with ≥2 primary diagnoses of CD (ICD-10 K50) or ≥2 primary diagnoses of UC (ICD-10 K51) from 01/01/2001 to 12/30/2017 were selected. Date of the first CD or UC diagnosis was designated as index date. All individuals were followed until death, lost to follow up or end of study. A total of 30,895 patients with CD and 50,415 with UC were included in the analysis, respectively. The mean follow-up for patients was 10.1 (±5.33) and 10.4 (±5.21) years for CD and UC. The mean (±SD) age among CD patients was 40.4 (±18.4) years and 42.6 (±18.2) years for UC. The most frequently observed comorbid condition was noninfective enteritis and colitis for patients with CD (24.2%) and UC (15.7%). The annual incidence of CD was 10 per 100,000 person-years in 2017, while the incidence of UC was 3 per 100,000 in 2017. 40.6% of CD patients and 30.8% of UC patients had ≥ 1 inpatient admission during 1-year post-index period, of which 53.5% and 51.2% had inpatient care lasting more than 1 week. Among patients with ≥ 1 outpatient services (CD: n = 30,675; UC: n = 50,183), 41.7% and 29.2% of patients had more than 5 visits during 1-year post-index period. Among patients who were eligible for employment and disability benefit analyses who had at least 1-year follow-up (CD: n = 23,731; UC: n = 39,391), 27.9% of CD patients and 23.1% of UC patients were not in employment; among those who were in employment (CD: n = 17,039; UC: n=30,302), 30% and 24.6% reported sickness absence within the calendar year after the index date, respectively. Findings from this study of a large national cohort of patients followed for many years demonstrates the significant epidemiological, clinical, and socioeconomic impact of patients with CD and UC. Further research is needed to understand underlying factors driving inpatient admissions among patients with IBD. With an increasing annual prevalence, IBD continues to impose a substantial public health burden to patients, their families and health care services.

Associations Between Alcohol Use and Liver-Related Outcomes in a Large National Cohort of Patients With Cirrhosis.

Alcohol use can cause hepatic necroinflammation and worsening portal hypertension in patients with cirrhosis. We aimed to evaluate the associations between degree of alcohol use and clinical liver‐related outcomes according to etiology of cirrhosis. In this retrospective cohort analysis, 44,349 U.S. veterans with cirrhosis from alcohol‐associated liver disease (ALD), chronic hepatitis C virus (HCV) infection, or nonalcoholic fatty liver disease were identified who completed the Alcohol Use Disorders Identification Test Consumption questionnaire in 2012. Based on this score, level of alcohol use was categorized as none, low level, or unhealthy. Multivariable Cox proportional hazards regression was used to assess for associations between alcohol use and mortality, cirrhosis decompensation (new ascites, encephalopathy, or variceal bleeding), and hepatocellular carcinoma (HCC). At baseline, 36.4% of patients endorsed alcohol use and 17.1% had unhealthy alcohol use. During a mean 4.9 years of follow‐up, 25,806 (57.9%) patients died, 9,409 (21.4%) developed a new decompensation, and 4,733 (11.1%) developed HCC. In patients with ALD‐cirrhosis and HCV‐cirrhosis, unhealthy alcohol use, compared with no alcohol use, was associated with higher risks of mortality (adjusted hazard ratio [aHR] = 1.13, 95% confidence interval [CI] = 1.07‐1.19 and aHR = 1.14, 95% CI = 1.08‐1.20, respectively) and decompensation (aHR = 1.18, 95% CI = 1.07‐1.30 and aHR = 1.08, 95% CI = 1.00‐1.16, respectively). Alcohol use was not associated with HCC, regardless of cirrhosis etiology. Conclusion: Unhealthy alcohol use was common in patients with cirrhosis and was associated with higher risks of mortality and cirrhosis decompensation in patients with HCV‐cirrhosis and ALD‐cirrhosis. Therefore, health care providers should make every effort to help patients achieve abstinence. The lack of association between alcohol use and HCC merits further investigation.

Real-World Diagnosis and Treatment of Diabetic Kidney Disease.

People with type2 diabetes mellitus (T2DM) and diabetic kidney disease (DKD) have increased morbidity and mortality risk. Angiotensin-converting enzyme inhibitors (ACEi) or angiotensinII receptor blockers (ARB) are recommended to slow kidney function decline in DKD. This representative, real-world data analysis of patients with T2DM was performed to detect onset of DKD and determine methods and timing of DKD diagnosis and time to initiation of ACEi/ARB therapy. Patients diagnosed with T2DM before January1, 2016 who developed DKD between January1, 2017 and June30, 2019 were identified from a longitudinal ambulatory electronic health record (EHR) dataset (Veradigm Inc). Each record was analyzed using the CLinical INTelligence engine (CLINT™, HealthPals, Inc.) to identify delays and gaps in diagnosing DKD. DKD was diagnosed through two reduced estimated glomerular filtration rate (eGFR; < 60mL/min/1.73m2) measurements at least 90days apart, a single elevated urine albumin-to-creatinine ratio (UACR; > 30mg/g) measurement, or ICD-9/10 diagnosis codes for DKD and/or albuminuria. Time to diagnose (TTD), time to treat (TTT), and diagnosis to treatment time were assessed. Of 6,499,409 patients with T2DM before January 2016, 245,978 developed DKD between January1, 2017 and June30, 2019. In this DKD cohort, ca. 50% were first identified through EHR diagnosis and ca. 50% by UACR or eGFR lab-based diagnosis. In patients who had UACR/eGFR assessed, more than 90% exhibited DKD-level results on the first diagnostic test. Average TTD after eGFR labs was 2years; average TTT with ACEi/ARB was 6-9months after DKD lab evidence. The majority of patients who developed DKD received ACEi/ARB therapy 6-7months after diagnosis. In a contemporary, large national cohort of patients with T2DM, progression to DKD was common but likely underrepresented. The low rate of DKD-screening labs, along with sizable delays in diagnosis of DKD and initiation of ACEi/ARB therapy, indicates that many patients who progress to DKD are not being properly treated.

Treatment of Extensively Drug-Resistant (XDR) Acinetobacter in US Veterans’ Affairs (VA) Medical Centers

Background: Infections caused by Acinetobacter spp are often healthcare acquired and associated with high mortality. Extensively drug-resistant (XDR) Acinetobacter are nonsusceptible to at least 1 agent in all but 2 or fewer antibiotic classes. Few of the new antibiotics targeting multidrug-resistant gram-negative bacteria are effective against XDR Acinetobacter. Recent national guidelines for treatment of resistant gram-negative infections do not include Acinetobacter, leaving a knowledge gap in best practices. Methods: This retrospective cohort study included microbiology, clinical, and pharmacy data from all patients hospitalized between 2012 and 2018 at any Veterans’ Affairs medical center who had cultures that grew XDR Acinetobacter spp. Bivariate unadjusted analyses compared clinical outcomes by monotherapy versus combination therapy. Using mixed-effects ordinal logistic regression, propensity score–adjusted models accounting for severity of illness and other variables associated with treatment were fit to compare outcomes. Results: Of 11,546 patients with 15,364 cultures that grew Acinetobacter spp, 408 patients (3.5%) had 666 cultures (4.3%) with XDR Acinetobacter. Moreover, 276 of these patients (67.6%) had gram-negative targeted antibiotic treatment within −2 to +5 days from the culture. Furthermore, 118 patients (42.8%) received monotherapy, most commonly piperacillin-tazobactam (n = 54, 45.7%) or an anti-Pseudomonas cephalosporin (n = 21, 17.8%). Also, 158 (57.2%) patients received combination therapy, most commonly a carbapenem (n = 93, 58.9%) and/or polymyxin (n = 68, 43.0%). Moreover, 41 patients (25.9%) received both a carbapenem and polymyxin. In both unadjusted and adjusted analyses, there were no significant differences in the odds of 30-day mortality (aOR, 1.43; 95% CI, 0.86–2.38) or 1-year mortality (aOR, 1.04; 95% CI, 0.68–1.60) between combination therapy and monotherapy groups. Among 264 patients (96%) whose cultures occurred during an inpatient or long-term care admission, unadjusted analyses showed increased odds of in-hospital mortality (OR, 1.89; 95% CI, 1.08–3.29) and longer postculture length of stay in the combination therapy group: median, 23 days (IQR, 11–57) versus 14 days (IQR, 7–32) (P = .02). However, with propensity score adjustment, these associations were no longer significant. Furthermore, there was no significant difference in odds of 90-day readmission between groups in either unadjusted or adjusted analyses (aOR, 1.20; 95% CI, 0.74–1.95). Conclusions: In this large national cohort of patients with XDR Acinetobacter cultures, more patients received combination therapy than monotherapy, and carbapenems and polymyxins were the most-used classes. However, there were no significant differences in outcomes between patients receiving combination therapy and monotherapy, suggesting lack of clinical benefit to the common practice of treating XDR Acinetobacter infections with multiple antibiotics. Further research is needed to determine optimal treatment strategies for this pathogen.Funding: NoDisclosures: None

Abstract 14778: Watchman Associated With Lower Risk of Stroke and Mortality in Patients With Atrial Fibrillation and Difficulties Taking Anticoagulation

Introduction: Watchman has been increasingly used in AF patients who have difficulties taking anticoagulation, but the RCTs only compared Watchman to warfarin. There was also a signal of increased ischemic stroke with Watchman in comparison to warfarin in RCTs, which made some clinicians question the fundamental premise that Watchman can reduce stroke. We aimed to compare Watchman to no anticoagulation in a large national cohort of patients in the US. Methods: We identified AF patients treated with Watchman (N=7,309) or no anticoagulation (N=1,234,543) between 2015-2017 from the OptumLabs Data Warehouse, which is the first to link private insurance, Medicare Advantage, and Medicare Fee-for-Service records at patient level longitudinally. One-to-one propensity score matching was used to balance patients on demographics and medical history. The primary outcomes were ischemic stroke or systemic embolism (hereafter referred to as stroke) and major bleeding. Secondary outcomes included all-cause mortality and intracranial bleeding. Results: In the unmatched cohort, the mean age was 76.6±6.4 yr in the Watchman group and 76.6 ±8.5 yr in the no anticoagulation group, but Watchman patients were more likely to have a history of bleeding (44.9% vs 13.7%) and intracranial bleeding (9.5% vs 2.6%). After matching, the two groups were similar on 18 baseline characteristics. Watchman was associated with a lower risk of stroke and mortality, but a higher risk of major bleeding and a similar risk of intracranial bleeding. The associations were largely consistent across subgroups, including those with relative contraindications to anticoagulation (Figure). Conclusions: In AF patients who had difficulties taking anticoagulation, Watchman offers an alternative approach to reduce stroke and mortality. The results provide important evidence to inform clinical decision making in the absence of RCTs, since 40% of AF patients in routine practice are not on anticoagulation.

Carpal tunnel syndrome in acromegaly: a nationwide study.

Carpal tunnel syndrome (CTS) is common in patients with acromegaly, with a reported prevalence of 19-64%. We studied CTS in a large national cohort of patients with acromegaly and the temporal relationship between the two diagnoses. Retrospective, nationwide, cohort study including patients diagnosed with acromegaly in Sweden, 2005-2017, identified in the Swedish Healthcare Registries. CTS (diagnosis and surgery in specialised healthcare) was analysed from 8.5 years before the diagnosis of acromegaly until death or end of the study. Standardised incidence ratios (SIRs) with 95% CIs were calculated for CTS with the Swedish population as reference. The analysis included 556 patients with acromegaly (50% women) diagnosed at mean (s.d.) age 50.1 (15.0) years. During the study period, 48 patients were diagnosed with CTS and 41 patients underwent at least one CTS surgery. In the latter group, 35 (85%) were operated for CTS before the acromegaly diagnosis; mean interval (range) 2.2 (0.3-8.5) years and the SIR for having CTS surgery before the diagnosis of acromegaly was 6.6 (4.8-8.9). Women with acromegaly had a higher risk for CTS than men (hazard ratio: 2.5, 95% CI: 1.3-4.7). Patients with acromegaly had a 6-fold higher incidence for CTS surgery before the diagnosis of acromegaly compared with the general population. The majority of patients with both diagnoses were diagnosed with CTS prior to acromegaly. Increased awareness of signs of acromegaly in patients with CTS might help to shorten the diagnostic delay in acromegaly, especially in women.

Effects of Metformin Exposure on Survival in a Large National Cohort of Patients With Diabetes and Cirrhosis

Type II diabetes mellitus worsens the prognosis of cirrhosis. Multiple medications including metformin and statins often are co-administered to manage patients with diabetes. The aim of this study was to assess the impact of metformin exposure on mortality, hepatic decompensation, and hepatocellular carcinoma in individuals with diabetes and cirrhosis, controlling for multiple concomitant exposures. We performed a retrospective cohort study of patients with cirrhosis diagnosed between January 1, 2008, through June 30, 2016, in the Veterans Health administration. Marginal structural models and propensity-matching approaches were implemented to quantify the treatment effect of metformin in patients with pre-existing diabetes with or without prior metformin exposure. Among 74,984 patients with cirrhosis, diabetes mellitus was present before the diagnosis of cirrhosis in 53.8%, and was diagnosed during follow-up evaluation in 4.8%. Before the diagnosis of cirrhosis, 11,114 patients had active utilization of metformin. In these patients, metformin, statin, and angiotensinogen-converting enzyme inhibitor/angiotensin-2-receptor blocker exposure were associated independently with reduced mortality (metformin hazard ratio, 0.68; 95% CI, 0.61-0.75); metformin was not associated with reduced hepatocellular carcinoma or hepatic decompensation after adjustment for concomitant statin exposure. For patients with diabetes before a diagnosis of cirrhosis but no prior metformin exposure, metformin similarly was associated with reduced mortality (hazard ratio, 0.72; 95% CI, 0.35-0.97), but not with reduced hepatocellular carcinoma or hepatic decompensation. Metformin use in patients with cirrhosis and diabetes appears safe and is associated independently with reduced overall, but not liver-related, mortality, hepatocellular carcinoma, or decompensation after adjusting for concomitant statin and angiotensinogen-converting enzyme inhibitor/angiotensin-2-receptor blocker exposure.

Radioactive Seed Versus Wire-Guided Localization for Ductal Carcinoma in Situ of the Breast: Comparable Resection Margins

BackgroundThere are currently two widely used methods for preoperative localization of ductal carcinoma in situ (DCIS) of the breast: wire-guided localization (WGL) and radioactive seed localization (RSL). Several studies compared these localization techniques in small cohorts.ObjectiveThe aim of this study was to compare the surgical resection margin status between RSL and WGL in a large national cohort of patients with DCIS.Patients and MethodsWe included patients from the Dutch Pathology Registry who underwent breast-conserving surgery for DCIS by either RSL (n = 1851) or WGL (n = 2187) between 2009 and 2019. Several clinicopathological characteristics were compared between these two groups, including resection margin status and number of re-excisions.ResultsPatients undergoing RSL were younger (p = 0.014) and were more often diagnosed with a large DCIS (p = 0.013), high grade DCIS (p < 0.001) and comedonecrosis (p < 0.001) compared with patients undergoing WGL. There was no significant difference in resection margin status between both groups (p = 0.089) and the number of re-excisions (p = 0.429). However, in case of re-excision, patients in the RSL group were more often treated with breast-conserving surgery (p = 0.029).ConclusionIn this large national cohort study of patients with DCIS, we demonstrated that there was no difference in resection margin status between both procedures, or in the number of re-excisions, but patients in the RSL group were more often treated with breast-conserving therapy in case of a re-excision.

Characterization and genotype-phenotype correlation of patients with Fanconi anemia in a multi-ethnic population.

Fanconi anemia (FA), an inherited bone marrow failure (BMF) syndrome, caused by mutations in DNA repair genes, is characterized by congenital anomalies, aplastic anemia, high risk of malignancies and extreme sensitivity to alkylating agents. We aimed to study the clinical presentation, molecular diagnosis and genotype-phenotype correlation among patients with FA from the Israeli inherited BMF registry. Overall, 111 patients of Arab (57%) and Jewish (43%) descent were followed for a median of 15 years (range: 0.1-49); 63% were offspring of consanguineous parents. One-hundred patients (90%) had at least one congenital anomaly; over 80% of the patients developed bone marrow failure; 53% underwent hematopoietic stem-cell transplantation; 33% of the patients developed cancer; no significant association was found between hematopoietic stem-cell transplant and solid tumor development. Nearly 95% of the patients tested had confirmed mutations in the Fanconi genes FANCA (67%), FANCC (13%), FANCG (14%), FANCJ (3%) and FANCD1 (2%), including twenty novel mutations. Patients with FANCA mutations developed cancer at a significantly older age compared to patients with mutations in other Fanconi genes (mean 18.5 and 5.2 years, respectively, P=0.001); however, the overall survival did not depend on the causative gene. We hereby describe a large national cohort of patients with FA, the vast majority genetically diagnosed. Our results suggest an older age for cancer development in patients with FANCA mutations and no increased incidence of solid tumors following hematopoietic stem-cell transplant. Further studies are needed to guide individual treatment and follow-up programs.

Natalizumab-associated progressive multifocal leukoencephalopathy in Germany.

To evaluate characteristics relevant to diagnosis of JC polyomavirus-associated progressive multifocal leukoencephalopathy (PML), and PML risk stratification in a large national cohort of patients with multiple sclerosis during therapy with natalizumab. Analysis of 292 adverse drug reaction forms on suspected cases of PML reported to the German national competent authority until July 2017. Patients not fulfilling PML diagnostic criteria or with insufficient information available were excluded. Of the 142 confirmed patients with PML, 72.3% (95% confidence interval [CI] 64.4%-79.1%) were women, and the median age was 43 years (range 19-69). Of these patients, 7.7% (95% CI 4.3%-13.5%) were clinically asymptomatic at time of PML diagnosis. PML was fatal in 9.1% (95% CI 5.3%-15.1%) of the patients. Infratentorial lesions on imaging were reported in 40% (95% CI 32.0%-48.6%) of the patients. JC polyomavirus DNA in CSF was undetectable at time of first analysis in 23.8% (95% CI 17.3%-31.9%) of the patients. Three patients tested negative for anti-JC polyomavirus antibodies within 6 to 18 months before PML diagnosis, with seroconversion confirmed 5.5 months, 7 months (in a post hoc analysis only), or at time of PML diagnosis. JC polyomavirus DNA detection in CSF has limited sensitivity in early PML, and clinical and imaging presentation may be atypical. Thus, critical revision of current PML diagnostic criteria is warranted. Negative anti-JC polyomavirus antibodies in sera do not preclude the later development of PML. This emphasizes the need for close and regular serologic, imaging, and clinical monitoring in patients treated with natalizumab.