Persistent racial disparities in postoperative management after tibia fracture fixation: A matched analysis of US medicaid beneficiaries.

INTRODUCTION: Racial and ethnic disparities in orthopaedic surgery are well documented. However, the extent to which these persist in fracture care is unknown. This study sought to assess racial disparities in the postoperative surgical and medical management of patients after diaphyseal tibia fracture fixation. METHODS: Patients with surgically treated tibial shaft fractures from October 1, 2015, to December 31, 2020, were identified in the MarketScan® Medicaid Database. Exclusion criteria included concurrent fractures or amputation. Outcomes included 2-year postoperative complications, reoperation rates, and filled prescriptions. Surgically-treated Black and White cohorts were propensity-score matched using nearest-neighbor matching on patient demographics, comorbidities, fracture pattern and severity, and fixation type. Chi-square tests and survival analyses (Kaplan-Meier and Cox proportional hazard models) were conducted. RESULTS: 5,472 patients were included, 2,209 Black and 3,263 White patients. After matching, 2,209 were retained in each cohort. No significant differences in complication rates were observed in the matched Black vs White cohorts. Rates of reoperation, however, were significantly lower in Black as compared to White patients (28.5 % vs. 35.5 % rate, risk difference = 7.0 % (95 % confidence interval (CI): 4.2 % to 9.7 %)). Implant removal was also significantly lower in Black (17.9 %) vs. White (25.1 %) patients (Risk difference = 7.2 %, (95 %CI: 4.8 % to 9.6 %)). The adjusted hazard ratio comparing the reoperation rate in Black versus White patients was 0.77 (95 %CI: 0.69-0.82, p < 0.0001). Significantly lower proportions of Black vs White patients filled at least one prescription for benzodiazepine, antidepressants, strong opiates, or antibiotics at every time point post-index. DISCUSSION: Fewer resources were used in post-operative management after surgical treatment of tibial shaft fractures for Black versus White Medicaid-insured patients. These results may be reflective of the undertreatment of complications after tibia fracture surgery for Black patients and highlight the need for further interventions to address racial disparities in trauma care.

Does radiofrequency ablation procedural data improve the accuracy of identifying atrial fibrillation recurrence?

Radiofrequency ablation (RFA) using the CARTO 3D mapping system is a common approach for pulmonary vein isolation to treat atrial fibrillation (AF). Linkage between CARTO procedural data and patients' electronical health records (EHR) provides an opportunity to identify the ablation-related parameters that would predict AF recurrence. The objective of this study is to assess the incremental accuracy of RFA procedural data to predict post-ablation AF recurrence using machine learning model. Procedural data generated during RFA procedure were downloaded from CARTONET and linked to deidentified Mercy Health EHR data. Data were divided into train (70%) and test (30%) data for model development and validation. Automate machine learning (AutoML) was used to predict 1 year AF recurrence, defined as a composite of repeat ablation, electrical cardioversion, and AF hospitalization. At first, AutoML model only included Patients' demographic and clinical characteristics. Second, an AutoML model with procedural variables and demographical/clinical variables was developed. Area under receiver operating characteristic curve (AUROC) and net reclassification improvement (NRI) were used to compare model performances using test data. Among 306 patients, 67 (21.9%) patients experienced 1-year AF recurrence. AUROC increased from 0.66 to 0.78 after adding procedural data in the AutoML model based on test data. For patients with AF recurrence, NRI was 32% for model with procedural data. Nine of 10 important predictive features were CARTO procedural data. From CARTO procedural data, patients with lower contact force in right inferior site, long ablation duration, and low number of left inferior and right roof lesions had a higher risk of AF recurrence. Patients with persistent AF were more likely to have AF recurrence. The machine learning model with procedural data better predicted 1-year AF recurrence than the model without procedural data. The model could be used for identification of patients with high risk of AF recurrence post ablation.

Predictive utility of the impedance drop on AF recurrence using digital intraprocedural data linked to electronic health record data.

Background: Local impedance drop in cardiac tissue during catheter ablation may be a valuable measure to guide atrial fibrillation (AF) ablation procedures for greater effectiveness. Objective: The study sought to assess whether local impedance drop during catheter ablation to treat AF predicts 1-year AF recurrence and what threshold of impedance drop is most predictive. Methods: We identified patients with AF undergoing catheter ablation in the Mercy healthcare system. We downloaded AF ablation procedural data recorded by the CARTO system from a cloud-based analytical tool (CARTONET) and linked them to individual patient electronic health records. Average impedance drops in anatomical region of right and left pulmonary veins were calculated. Effectiveness was measured by a composite outcome of repeat ablation, AF rehospitalization, direct current cardioversion, or initialization of a new antiarrhythmic drug post-blanking period. The association between impedance drop and 1-year AF recurrence was assessed by logistic regression adjusting for demographics, clinical, and ablation characteristics. Bootstrapping was used to determine the most predictive threshold for impedance drop based on the Youden index. Results: Among 242 patients, 23.6% (n = 57) experienced 1-year AF recurrence. Patients in the lower third vs upper third of average impedance drop had a 5.9-fold (95% confidence interval [CI] 1.81-21.8) higher risk of recurrence (37.0% vs 12.5%). The threshold of 7.2 Ω (95% CI 5.75-7.7 Ω) impedance drop best predicted AF recurrence, with sensitivity of 0.73 and positive predictive value of 0.33. Patients with impedance drop ≤7.2 Ω had 3.5-fold (95% CI 1.39-9.50) higher risk of recurrence than patients with impedance drop >7.2 Ω, and there was no statistical difference in adverse events between the 2 groups of patients. Sensitivity analysis on right and left wide antral circumferential ablation impedance drop was consistent. Conclusion: Average impedance drop is a strong predictor of clinical success in reducing AF recurrence but as a single criterion for predicting recurrence only reached 73% sensitivity and 33% positive predictive value.

Insurer costs of COVID-19 by disease severity and duration.

OBJECTIVES: To analyze US commercial insurance payments associated with COVID-19 as a function of severity and duration of disease. STUDY DESIGN: Retrospective database analysis. METHODS: Patients with COVID-19 between April 1, 2020, and June 30, 2021, in the Merative MarketScan Commercial database were identified and stratified as having asymptomatic, mild, moderate (with and without lower respiratory disease), or severe/critical (S/C) disease based on the severity of the acute COVID-19 infection. Duration of disease (DOD) was estimated for all patients. Patients with DOD longer than 12 weeks were defined as having post-COVID-19 condition (PCC). Outcomes were all-cause payments (ACP) and disease-specific payments (DSP) for the entire DOD. Variables included demographic and comorbidities at the time of acute disease. Adjusted payments by disease severity were estimated using generalized linear models (γ distribution with log link). RESULTS: A total of 738,339 patients were included (374,401 asymptomatic, 156,220 mild, 180,213 moderate, and 27,505 S/C cases). DSP increased from $217 (95% CI, $214-221) for asymptomatic cases to $2744 (95% CI, $2678-$2811) for moderate cases with lower respiratory disease and $28,250 (95% CI, $26,963-$29,538) for S/C cases. ACP increased from $505 (95% CI, $497-$512) for asymptomatic cases to $46,538 (95% CI, $44,096-$48,979) for S/C cases. The DSP and ACP further increased by $50,736 (95% CI, $45,337-$56,136) and $94,839 (95% CI, $88,029-$101,649), respectively, in S/C cases with PCC vs a DOD of fewer than 4 weeks. CONCLUSIONS: COVID-19 payments for S/C cases were more than 10-fold greater than those of moderate cases and further increased by nearly $95,000 in S/C cases with PCC vs a DOD of fewer than 4 weeks.

Risk of anastomotic leakage with two-row versus three-row manual circular staplers in colorectal anastomosis: a U.S. cohort study.

PURPOSES: To compare the risk of anastomotic leak (AL) between Ethicon manual circular staplers (two-row) versus Medtronic EEA™ circular stapler with Tri-Staple™ technology (three-row) and between Medtronic EEA™ circular stapler with DST™ Series technology (two-row) versus Tri-Staple™ technology. METHODS: A retrospective cohort study was conducted in adult patients who underwent a left-sided colorectal surgery 2019-2022 in U.S. Premier Healthcare Database to assess the risk of AL within 30 days post-index procedure. The study devices were Ethicon manual circular staplers, Medtronic EEA™ circular stapler with DST™ technology, and Medtronic EEA™ circular stapler with Tri-Staple™ technology. RESULTS: Across 447 hospitals, the cumulative incidences (95% confidence intervals [CI]) of AL within 30 days post-index procedure were 7.78% (6.91-8.74%) among 8337 patients in the Ethicon manual circular stapler cohort, 7.54% (6.87-8.27%) among 7928 patients in the Medtronic EEA™ circular stapler with DST™ technology cohort, and 8.19% (6.57-10.07%) among 1306 patients in the Medtronic EEA™ circular stapler with Tri-Staple™ technology cohort. Comparative analyses revealed no difference comparing Ethicon manual circular staplers with Medtronic EEA™ circular staplers with Tri-Staple™ technology (risk ratio [RR], 0.72; 95% CI, 0.52-1.01) or comparing Medtronic EEA™ circular staplers with DST™ technology to Tri-Staple™ technology (RR, 0.75; 95% CI, 0.53-1.06). CONCLUSION: In this analysis of a large cohort of patients undergoing a left-sided colorectal surgery from a U.S. hospital database, the risk of AL observed with manual two-row circular staplers was similar to that seen with three-row devices. This study affirms the safety of manual two-row circular staplers in colorectal anastomosis.

Health care costs of COVID-19 vs influenza and pneumonia.

OBJECTIVES: To estimate payments for the treatment of COVID-19 compared with that of influenza or viral pneumonia (IP), from the perspective of the US payer. STUDY DESIGN: Retrospective cohort analysis. METHODS: Patients with COVID-19 during the period from October 1, 2020, to February 1, 2021, or IP during the period from October 1, 2018, to February 1, 2019, in the IBM MarketScan databases were identified. The index was defined as the date of the first COVID-19 or IP diagnosis. Patients with COVID-19 were stratified by severity. Variables for all patients included demographics and comorbidities at the time of index and duration of disease. IP and COVID-19 cohorts were matched using propensity scores, and inflation-adjusted all-cause payments (ACP), and disease-specific payments (DSP) for IP vs COVID-19 were estimated using generalized linear models. RESULTS: Matched cohorts included 6332 Medicare (female, 58.5%; mean [SD] age, 75.3 [7.6] years), and 397,532 commercially insured patients (female, 57.6%; mean [SD] age, 34.7 [16.7] years). ACP and DSP were significantly higher in the COVID-19 cohort vs IP cohort. Payments for severe/critical COVID-19 were significantly greater than those for IP, with adjusted marginal incremental DSP and ACP of $24,852 (95% CI, $21,573-$28,132) and $50,325 (95% CI, $43,932-$56,718), respectively. IP was significantly less expensive than moderate COVID-19 for commercial payers but not Medicare. IP was more expensive than mild COVID-19 for all payers. CONCLUSIONS: Payments associated with severe/critical COVID-19 significantly exceeded those associated with IP. For Medicare, IP was more expensive than mild or moderate COVID-19. For commercial payers, IP was less expensive than moderate COVID-19 but more expensive than mild COVID-19.

Race and Ethnic and Sex Differences in Rhythm Control Treatment of Incident Atrial Fibrillation.

Background: Atrial fibrillation (AF) is associated with considerable morbidity and mortality. Timely management and treatment is critical in alleviating AF disease burden. Variation in treatment by race and ethnic and sex could lead to inequities in health outcomes. Objective: To identify racial and ethnic and sex differences in rhythm treatment for patients with incident AF. Methods: Using 2010-2019 Optum Clinformatics database, an administrative claims data for commercially insured patients in the United States (US), incident AF patients ≥20 years old who were continuously enrolled 12-months pre- and post-index diagnosis were identified. Rhythm control treatment (ablation, antiarrhythmic drugs [AAD], and cardioversion) for AF were compared by patient race and ethnicity (Asian, Hispanic, Black vs White) and sex (female vs male). Multivariable regression analysis was used to examine the relationship of race and ethnicity and sex with rhythm control AF treatment. Results: A total of 77,932 patients were identified with incident AF. Black and Hispanic female patients had the highest CHA2DS2VASc scores (4.3 ± 1.8) and Elixhauser scores (4.1 ± 2.8 and 4.0 ± 6.7), respectively. Black males were less likely to receive AAD treatment (adjusted odds ratio [aOR] 0.87; 95% confidence interval [CI], 0.79-0.96) or ablation (aOR, 0.72; 95% CI, 0.58-0.90). Compared to White males, all groups had lower likelihood of receiving cardioversion with Asian females having the lowest [aOR, 0.48; 95% CI, (0.37-0.63)]. Conclusion: Black patients were less likely to receive pharmacologic and procedural rhythm control therapies. Further research is needed to understand the drivers of undertreatment among racial and ethnic groups and females with AF.

Racial and Health Insurance Differences in Patient Outcomes After Surgical Treatment for Cauda Equina Syndrome: A United States Retrospective Hospital Claims Database Analysis.

STUDY DESIGN: Retrospective database evaluation. OBJECTIVES: To study the association between race, health care insurance, mortality, postoperative visits, and reoperation within a hospital setting in patients with cauda equina syndrome (CES) undergoing surgical intervention. SUMMARY OF BACKGROUND DATA: CES can lead to permanent neurological deficits if the diagnosis is missed or delayed. Evidence of racial or insurance disparities in CES is sparse. MATERIALS AND METHODS: Patients with CES undergoing surgery from 2000 to 2021 were identified from the Premier Health care Database. Six-month postoperative visits and 12-month reoperations within the hospital were compared by race ( i.e ., White, Black, or Other [Asian, Hispanic, or other]) and insurance ( i.e. , Commercial, Medicaid, Medicare, or Other) using Cox proportional hazard regressions; covariates were used in the regression models to control for confounding. Likelihood ratio tests were used to compare model fit. RESULTS: Among 25,024 patients, most were White (76.3%), followed by Other race (15.4% [ 8.8% Asian, 7.3% Hispanic, and 83.9% other]) and Black (8.3%). Models with race and insurance combined provided the best fit for estimating the risk of visits to any setting of care and reoperations. White Medicaid patients had the strongest association with a higher risk of 6-month visits to any setting of care versus White patients with commercial insurance (HR: 1.36 (1.26,1.47)). Being Black with Medicare had a strong association with a higher risk of 12-month reoperations versus White commercial patients (HR: 1.43 (1.10,1.85)). Having Medicaid versus Commercial insurance was strongly associated with a higher risk of complication-related (HR: 1.36 (1.21, 1.52)) and ER visits (HR: 2.26 (2.02,2.51)). Medicaid had a significantly higher risk of mortality compared with Commercial patients (HR: 3.19 (1.41,7.20)). CONCLUSIONS: Visits to any setting of care, complication-related, ER visits, reoperation, or mortality within the hospital setting after CES surgical treatment varied by race and insurance. Insurance type had a stronger association with the outcomes than race. LEVEL OF EVIDENCE: Level-III.

Impact of a digital surgical workflow including Digital Device Briefing Tool on morbidity and mortality in a patient population undergoing primary stapled colorectal anastomosis for benign or malignant colorectal disease: protocol for a multicentre prospective cohort study.

INTRODUCTION: With growing emphasis on surgical safety, it appears fundamental to assess the safety of colorectal resection involving primary stapled anastomosis. Surgical stapling devices can considerably foster patient safety in colorectal surgery, but their misuse or malfunction encompass a unique risk of postoperative complications. The Digital Device Briefing Tool (DDBT) is a digital cognitive aid developed to enhance safe use of the Ethicon circular stapling device during colorectal resection. The purpose of this study is to evaluate how a digital operative workflow, including DDBT, compared with routine surgical care, affects morbidity and mortality in patients undergoing left-sided colorectal resection with primary stapled colorectal anastomosis for colorectal cancer or benign disease. METHODS AND ANALYSIS: A multicentre, prospective cohort study will be conducted at five certified academic colorectal centres in Germany. It compares a non-digital with a Johnson & Johnson digital solution (Surgical Process Institute Deutschland (SPI))-guided operative workflow in patients undergoing left hemicolectomy, sigmoidectomy, anterior rectal resection and Hartmann reversal procedure. The sample size is set at 528 cases in total, divided into 3 groups (a non-digital and two SPI-guided workflow cohorts, with and without DDBT) in a ratio of 1:1:1, with 176 patients each. The primary endpoint is a composite outcome comprising the overall rate of surgical complications, including death, during hospitalisation and within the first 30 days after colorectal resection. Secondary endpoints include operating time, length of hospital stay and 30-day hospital readmission rate. ETHICS AND DISSEMINATION: This study will be performed in line with the Declaration of Helsinki. The ethics committee of the Charité-University Medicine Berlin, Germany, approved the study (No: 22-0277-EA2/060/22). Study Investigators will obtain written informed consent from each patient before a patient may participate in this study. The study results will be submitted to an international peer-reviewed journal. TRIAL REGISTRATION NUMBER: DRKS00029682.

Using real-world data from health systems to evaluate the safety and effectiveness of a catheter to treat ischemic ventricular tachycardia.

BACKGROUND: The ThermoCool STSF catheter is used for ablation of ischemic ventricular tachycardia (VT) in routine clinical practice, although outcomes have not been studied and the catheter does not have Food and Drug Administration (FDA) approval for this indication. We used real-world health system data to evaluate its safety and effectiveness for this indication. METHODS: Among patients undergoing ischemic VT ablation with the ThermoCool STSF catheter pooled across two health systems (Mercy Health and Mayo Clinic), the primary safety composite outcome of death, thromboembolic events, and procedural complications within 7 days was compared to a performance goal of 15%, which is twice the expected proportion of the primary composite safety outcome based on prior studies. The exploratory effectiveness outcome of rehospitalization for VT or heart failure or repeat VT ablation at up to 1 year was averaged across health systems among patients treated with the ThermoCool STSF vs. ST catheters. RESULTS: Seventy total patients received ablation for ischemic VT using the ThermoCool STSF catheter. The primary safety composite outcome occurred in 3/70 (4.3%; 90% CI, 1.2-10.7%) patients, meeting the pre-specified performance goal, p = 0.0045. At 1 year, the effectiveness outcome risk difference (STSF-ST) at Mercy was - 0.4% (90% CI: - 25.2%, 24.3%) and at Mayo Clinic was 12.6% (90% CI: - 13.0%, 38.4%); the average risk difference across both institutions was 5.8% (90% CI: - 12.0, 23.7). CONCLUSIONS: The ThermoCool STSF catheter was safe and appeared effective for ischemic VT ablation, supporting continued use of the catheter and informing possible FDA label expansion. Health system data hold promise for real-world safety and effectiveness evaluation of cardiovascular devices.

Frequent and unpredictable changes in COVID-19 policies and restrictions reduce the accuracy of model forecasts.

Between June and August 2020, an agent-based model was used to project rates of COVID-19 infection incidence and cases diagnosed as positive from 15 September to 31 October 2020 for 72 geographic settings. Five scenarios were modelled: a baseline scenario where no future changes were made to existing restrictions, and four scenarios representing small or moderate changes in restrictions at two intervals. Post hoc, upper and lower bounds for number of diagnosed Covid-19 cases were compared with actual data collected during the prediction window. A regression analysis with 17 covariates was performed to determine correlates of accurate projections. It was found that the actual data fell within the lower and upper bounds in 27 settings and out of bounds in 45 settings. The only statistically significant predictor of actual data within the predicted bounds was correct assumptions about future policy changes (OR 15.04; 95% CI 2.20-208.70; p = 0.016). Frequent changes in restrictions implemented by governments, which the modelling team was not always able to predict, in part explains why the majority of model projections were inaccurate compared with actual outcomes and supports revision of projections when policies are changed as well as the importance of modelling teams collaborating with policy experts.

Integrating real-world data to assess cardiac ablation device outcomes in a multicenter study using the OMOP common data model for regulatory decisions: implementation and evaluation.

The objective of this study is to describe application of the Observational Medical Outcomes Partnership (OMOP) common data model (CDM) to support medical device real-world evaluation in a National Evaluation System for health Technology Coordinating Center (NESTcc) Test-Case involving 2 healthcare systems, Mercy Health and Mayo Clinic. CDM implementation was coordinated across 2 healthcare systems with multiple hospitals to aggregate both medical device data from supply chain databases and patient outcomes and covariates from electronic health record data. Several data quality assurance (QA) analyses were implemented on the OMOP CDM to validate the data extraction, transformation, and load (ETL) process. OMOP CDM-based data of relevant patient encounters were successfully established to support studies for FDA regulatory submissions. QA analyses verified that the data transformation was robust between data sources and OMOP CDM. Our efforts provided useful insights in real-world data integration using OMOP CDM for medical device evaluation coordinated across multiple healthcare systems.

Comparison of Clinical Outcomes of Gripping Surface Technology Staple Reloads versus Standard Staple Reloads Used with Manual Linear Surgical Staplers.

Purpose: Linear surgical staplers reduce rates of surgical adverse events (bleeding, leaks, infections) compared to manual sutures thereby reducing patient risks, surgeon workflow disruption, and healthcare costs. However, further improvements are needed. Ethicon Gripping Surface Technology (GST) reloads, tested and approved by regulatory authorities in combination with powered staplers, may reduce surgical risks through improved tissue grip. While manual staplers are used in some regions due to affordability, clinical data on GST reloads used with manual staplers are unavailable. This study compared surgical adverse event rates of manual staplers with GST vs standard reloads. These data may be used for label changes in China and Latin America. Patients and Methods: Patients undergoing general or thoracic surgery between October 1, 2015 and August 31, 2021 using ECHELON FLEX™ manual staplers with GST or standard reloads were identified from the Premier Healthcare Database. GST reloads were compared to standard reloads for non-inferiority in bleeding and anastomotic leak for general surgery. Secondary outcomes included sepsis for general surgery, and bleeding and prolonged air leak for thoracic surgery. Covariate balancing was performed using stable balancing weights. Results: The general and thoracic surgery cohorts contained 4571 (GST: 2780; standard: 1791) and 814 (GST: 514; standard: 300) patients, respectively. GST reloads were non-inferior to standard reloads for bleeding and anastomotic leak (adjusted cumulative incidence ratio: 1.02 [90% CI: 0.71, 1.45] and 1.03 [90% CI: 0.72, 1.46], respectively) for general surgery. Compared with standard reloads, GST reloads had a similar incidence of sepsis (2.2% vs 2.1%) for general surgery and lower incidences of bleeding (9.5% vs 16.0%) and prolonged air leak (12.6% vs 14.0%,) for thoracic surgery. Conclusion: GST reloads, compared to standard reloads, used with ECHELON FLEX™ manual staplers had comparable perioperative bleeding and anastomotic leak for general surgery, and lower incidences of safety events for thoracic surgery.

Evaluation of intervertebral body implant performance using active surveillance of electronic health records.

Objectives: To assess the feasibility of using electronic health record (EHR) derived clinical data within an active surveillance setting to evaluate the safety of a novel intervertebral body implant (IVBI) stabilization device. Design: Retrospective, longitudinal observational cohort study comparing clinical outcomes for patients seen through 1 year following spinal fusion surgery. Setting: Lahey Health network, which includes academic tertiary hospitals, outpatient clinics, and independent provider offices in the New England region of the USA. Participants: All spine surgery patients aged 18 or older who underwent thoracic or lumbar spinal arthrodesis surgeries were included. Main outcome measures: The clinical outcomes of patients treated with the CONCORDE Bullet (CB) interbody spine system (DePuy) between April 2015 and December 2018 were compared with those patients receiving alternative spine stabilization interbody device implants. The primary endpoint was reoperation rate at 1 year, with secondary endpoints including the requirement for blood transfusion during index hospitalization, 1 year rate of any cause hospitalization, 1 year rate of surgical site infection, and mortality at 1 year. Results: Among the 606 patients undergoing thoracic or lumbar spinal fusion surgery during the study period, 136 received only the CB. In comparison with patients who did not receive the CB, no significant differences were found in the rate of reoperation at 1 year or the rates of secondary safety outcomes. Conclusions: Data derived from the EHR can be successfully leveraged to assess the safety of IVBI devices, in this case demonstrating no significant differences in the rates of risk-adjusted safety endpoints between patients undergoing spinal surgery with the CB as compared with alternative spinal implants.

Safety and Effectiveness of a Catheter With Contact Force and 6-Hole Irrigation for Ablation of Persistent Atrial Fibrillation in Routine Clinical Practice.

Importance: The ThermoCool SmartTouch catheter (ablation catheter with contact force and 6-hole irrigation [CF-I6]) is approved by the US Food and Drug Administration (FDA) for paroxysmal atrial fibrillation (AF) ablation and used in routine clinical practice for persistent AF ablation, although clinical outcomes for this indication are unknown. There is a need to understand whether data from routine clinical practice can be used to conduct regulatory-grade evaluations and support label expansions. Objective: To use health system data to compare the safety and effectiveness of the CF-I6 catheter for persistent AF ablation with the ThermoCool SmartTouch SurroundFlow catheter (ablation catheter with contact force and 56-hole irrigation [CF-I56]), which is approved by the FDA for this indication. Design, Setting, and Participants: This retrospective, comparative-effectiveness cohort study included patients undergoing catheter ablation for persistent AF at Mercy Health or Mayo Clinic from January 1, 2014, to April 30, 2021, with up to a 1-year follow-up using electronic health record data. Exposures: Use of the CF-I6 or CF-I56 catheter. Main Outcomes and Measures: The primary safety outcome was a composite of death, thromboembolic events, and procedural complications within 7 to 90 days. The exploratory effectiveness outcome was a composite of AF-related hospitalization events after a 90-day blanking period. Propensity score weighting was used to balance baseline covariates. Risk differences were estimated between catheter groups and averaged across the 2 health care systems, testing for noninferiority of the CF-I6 vs the CF-I56 catheter with respect to the safety outcome using 2-sided 90% CIs. Results: Overall, 1450 patients (1034 [71.3%] male; 1397 [96.3%] White) underwent catheter ablation for persistent AF, including 949 at Mercy Health (186 CF-I6 and 763 CF-I56; mean [SD] age, 64.9 [9.2] years) and 501 at Mayo Clinic (337 CF-I6 and 164 CF-I56; mean [SD] age, 63.7 [9.5] years). A total of 798 (55.0%) had been treated with class I or III antiarrhythmic drugs before ablation. The safety outcome (CF-I6 - CF-I56) was similar at both Mercy Health (1.3%; 90% CI, -2.1% to 4.6%) and Mayo Clinic (-3.8%; 90% CI, -11.4% to 3.7%); the mean difference was noninferior, with a mean of 0.5% (90% CI, -2.6% to 3.5%; P < .001). The effectiveness was similar at 12 months between the 2 catheter groups (mean risk difference, -1.8%; 90% CI, -7.3% to 3.7%). Conclusions and Relevance: In this cohort study, the CF-I6 catheter met the prespecified noninferiority safety criterion for persistent AF ablation compared with the CF-I56 catheter, and effectiveness was similar. This study demonstrates the ability of electronic health care system data to enable safety and effectiveness evaluations of medical devices.

Site-specific cancer risk following cobalt exposure via orthopedic implants or in occupational settings: A systematic review and meta-analysis.

In 2020, the European Commission up-classified metal cobalt as Class 1B Carcinogen (presumed to have carcinogenic potential) based primarily on data from rodent inhalation carcinogenicity studies. This up-classification requires an assessment under the Medical Device Regulations of cobalt cancer risk from medical devices. We performed a systematic review and meta-analysis to evaluate site-specific cancer risks with cobalt exposure from either total joint replacement (TJR) or occupational exposure (OC). Results were stratified by exposure type (OC or TJR), exposure level (metal-on-metal (MoM) or non-MoM), follow-up duration (latency period: <5, 5-10 or >10 years), and cancer incidence or mortality (detection bias assessment). From 30 studies (653,104 subjects, average 14.5 years follow-up), the association between TJR/OC and cancer risk was null for 22 of 27 cancer sites, negative for 3 sites, and positive for prostate cancer and myeloma. Significant heterogeneity and large estimate ranges were observed for many cancer sites. No significant increase in estimates was observed by exposure level or follow-up duration. The current evidence, including weak associations, heterogeneity across studies and no increased association with exposure level or follow-up duration, is insufficient to conclude that there exists an increased risk for people exposed to cobalt in TJR/OC of developing site-specific cancers.

Challenges of evaluating and modelling vaccination in emerging infectious diseases.

Outbreaks of emerging pathogens pose unique methodological and practical challenges for the design, implementation, and evaluation of vaccine efficacy trials. Lessons learned from COVID-19 highlight the need for innovative and flexible study design and application to quickly identify promising candidate vaccines. Trial design strategies should be tailored to the dynamics of the specific pathogen, location of the outbreak, and vaccine prototypes, within the regional socioeconomic constraints. Mathematical and statistical models can assist investigators in designing infectious disease clinical trials. We introduce key challenges for planning, evaluating, and modelling vaccine efficacy trials for emerging pathogens.

Carcinogenic assessment of cobalt-containing alloys in medical devices or cobalt in occupational settings: A systematic review and meta-analysis of overall cancer risk from published epidemiologic studies.

In 2020, the European Commission up-classified pure cobalt metal to a Category 1B hazard, based primarily on data from rodent inhalation carcinogenicity studies of metallic cobalt. The European Commission review did not evaluate cobalt-containing alloys in medical devices, which have very different properties vs. pure cobalt metal and did not include a systematic epidemiologic review. We performed a systematic review and meta-analysis of published, peer-reviewed epidemiologic studies evaluating the association between overall cancer risk and exposure to orthopedic implants containing cobalt alloys or cobalt particulates in occupational settings. Study-specific estimates were pooled using random-effects models. Analyses included 20 papers on orthopedic implants and 10 occupational cohort papers (~1 million individuals). The meta-analysis summary estimates (95% confidence intervals) for overall cancer risk were 1.00 (0.96-1.04) overall and 0.97 (0.94-1.00) among high-quality studies. Results were also similar in analyses stratified by type of exposure/data sources (occupational cohort, implant registry or database), comparators (general or implant population), cancer incidence or mortality, follow-up duration (latency period), and study precision. In conclusion, meta-analysis found no association between exposure to orthopedic implants containing cobalt alloys or cobalt particulates in occupational settings and overall cancer risk, including an analysis of studies directly comparing metal-on-metal vs. non-metal-on-metal implants.

An integrated benefit-risk assessment of cobalt-containing alloys used in medical devices: Implications for regulatory requirements in the European Union.

In 2017, the European Union (EU) Committee for Risk Assessment (RAC) recommended the classification of metallic cobalt (Co) as Category 1B with respect to its carcinogenic and reproductive hazard potential and Category 2 for mutagenicity but did not evaluate the relevance of these classifications for patients exposed to Co-containing alloys (CoCA) used in medical devices. CoCA are inherently different materials from Co metal from a toxicological perspective and thus require a separate assessment. CoCA are biocompatible materials with a unique combination of properties including strength, durability, and a long history of safe use that make them uniquely suited for use in a wide-range of medical devices. Assessments were performed on relevant preclinical and clinical carcinogenicity and reproductive toxicity data for Co and CoCA to meet the requirements under the EU Medical Device Regulation triggered by the ECHA re-classification (adopted in October 2019 under the 14th Adaptation to Technical Progress to CLP) and to address their relevance to patient safety. The objective of this review is to present an integrated overview of these assessments, a benefit-risk assessment and an examination of potential alternative materials. The data support the conclusion that the exposure to CoCA in medical devices via clinically relevant routes does not represent a hazard for carcinogenicity or reproductive toxicity. Additionally, the risk for the adverse effects that are known to occur with elevated Co concentrations (e.g., cardiomyopathy) are very low for CoCA implant devices (infrequent reports often reflecting a unique catastrophic failure event out of millions of patients) and negligible for CoCA non-implant devices (not measurable/no case reports). In conclusion, the favorable benefit-risk profile also in relation to possible alternatives presented herein strongly support continued use of CoCA in medical devices.

Feasibility of capturing real-world data from health information technology systems at multiple centers to assess cardiac ablation device outcomes: A fit-for-purpose informatics analysis report.

OBJECTIVE: The study sought to conduct an informatics analysis on the National Evaluation System for Health Technology Coordinating Center test case of cardiac ablation catheters and to demonstrate the role of informatics approaches in the feasibility assessment of capturing real-world data using unique device identifiers (UDIs) that are fit for purpose for label extensions for 2 cardiac ablation catheters from the electronic health records and other health information technology systems in a multicenter evaluation. MATERIALS AND METHODS: We focused on data capture and transformation and data quality maturity model specified in the National Evaluation System for Health Technology Coordinating Center data quality framework. The informatics analysis included 4 elements: the use of UDIs for identifying device exposure data, the use of standardized codes for defining computable phenotypes, the use of natural language processing for capturing unstructured data elements from clinical data systems, and the use of common data models for standardizing data collection and analyses. RESULTS: We found that, with the UDI implementation at 3 health systems, the target device exposure data could be effectively identified, particularly for brand-specific devices. Computable phenotypes for study outcomes could be defined using codes; however, ablation registries, natural language processing tools, and chart reviews were required for validating data quality of the phenotypes. The common data model implementation status varied across sites. The maturity level of the key informatics technologies was highly aligned with the data quality maturity model. CONCLUSIONS: We demonstrated that the informatics approaches can be feasibly used to capture safety and effectiveness outcomes in real-world data for use in medical device studies supporting label extensions.