Association of Race and Ethnicity With Postoperative Gabapentinoid and Opioid Prescribing Trends for Older Adults.

BACKGROUND: Disparities in opioid prescribing by race/ethnicity have been described in many healthcare settings, with White patients being more likely to receive an opioid prescription than other races studied. As surgeons increase prescribing of nonopioid medications in response to the opioid epidemic, it is unknown whether postoperative prescribing disparities also exist for these medications, specifically gabapentinoids. METHODS: We conducted a retrospective cohort study using a 20% Medicare sample for 2013-2018. We included patients ≥66 years without prior gabapentinoid use who underwent one of 14 common surgical procedures. The primary outcome was the proportion of patients prescribed gabapentinoids at discharge among racial and ethnic groups. Secondary outcomes were days' supply of gabapentinoids, opioid prescribing at discharge, and oral morphine equivalent (OME) of opioid prescriptions. Trends over time were constructed by analyzing proportion of postoperative prescribing of gabapentinoids and opioids for each year. For trends by year by racial/ethnic groups, we ran a multivariable logistic regression with an interaction term of procedure year and racial/ethnic group. RESULTS: Of the 494,922 patients in the cohort (54% female, 86% White, 5% Black, 5% Hispanic, mean age 73.7 years), 3.7% received a new gabapentinoid prescription. Gabapentinoid prescribing increased over time for all groups and did not differ significantly among groups (P = 0.13). Opioid prescribing also increased, with higher proportion of prescribing to White patients than to Black and Hispanic patients in every year except 2014. CONCLUSIONS: We found no significant prescribing variation of gabapentinoids in the postoperative period between racial/ethnic groups. Importantly, we found that despite national attention to disparities in opioid prescribing, variation continues to persist in postoperative opioid prescribing, with a higher proportion of White patients being prescribed opioids, a difference that persisted over time.

Characterising the Aboriginal and Torres Strait Islander patient journey after a serious road traffic injury and barriers to access to compensation: a protocol.

INTRODUCTION: Road safety has been a long-enduring policy concern in Australia, with significant financial burden of road trauma and evident socioeconomic disparities. Transport injuries disproportionately impact individuals in remote areas, those in lower socioeconomic situations, and Aboriginal and Torres Strait Islander populations. There is a lack of insight into transport injuries in Aboriginal and Torres Strait Islander communities, absence of Indigenous perspective in published research and limited utilisation of linked data assets to address the inequity. Aim 1 is to determine the breadth, cost and causal factors of serious injury from road traffic crashes in South Australia (SA) and New South Wales (NSW) with a focus on injury prevention. Aim 2 is to identify enablers and barriers to compensation schemes for Aboriginal and Torres Strait Islander patients in SA and NSW. METHODS AND ANALYSIS: This study will be guided by an Aboriginal and Torres Strait Islander Governance Group, applying Knowledge Interface Methodology and Indigenous research principles to ensure Indigenous Data Sovereignty and incorporation of informed perspectives. A mixed-method approach will be undertaken to explore study aims including using big data assets and mapping patient journey. CONCLUSION: The results of this study will provide valuable insights for the development of focused injury prevention strategies and policies tailored to Aboriginal and Torres Strait Islander communities. By addressing the specific needs and challenges faced by these communities, the study aims to enhance road safety outcomes and promote equitable access to healthcare and compensation for affected individuals and their families.

Trends in the Use of Gabapentinoids and Opioids in the Postoperative Period Among Older Adults.

Importance: In response to the opioid epidemic, recommendations from some pain societies have encouraged surgeons to embrace multimodal pain regimens with the intent of reducing opioid use in the postoperative period, including by prescribing gabapentinoids. Objective: To describe trends in postoperative prescribing of both gabapentinoids and opioids after a variety of surgical procedures by examining nationally representative Medicare data and further understand variation by procedure. Design, Setting, and Participants: This serial cross-sectional study of gabapentinoid prescribing from January 1, 2013, through December 31, 2018, used a 20% US Medicare sample. Gabapentinoid-naive patients 66 years or older undergoing 1 of 14 common noncataract surgical procedures performed in older adults were included. Data were analyzed from April 2022 to April 2023. Exposure: One of 14 common surgical procedures in older adults. Main Outcomes and Measures: Rate of postoperative prescribing of gabapentinoids and opioids, defined as a prescription filled between 7 days before the procedure and 7 days after discharge from surgery. Additionally, concomitant prescribing of gabapentinoids and opioids in the postoperative period was assessed. Results: The total study cohort included 494 922 patients with a mean (SD) age of 73.7 (5.9) years, 53.9% of whom were women and 86.0% of whom were White. A total of 18 095 patients (3.7%) received a new gabapentinoid prescription in the postoperative period. Of those receiving a new gabapentinoid prescription, 10 956 (60.5%) were women and 15 529 (85.8%) were White. After adjusting for age, sex, race and ethnicity, and procedure type in each year, the rate of new postoperative gabapentinoid prescribing increased from 2.3% (95% CI, 2.2%-2.4%) in 2014 to 5.2% (95% CI, 5.0%-5.4%) in 2018 (P < .001). While there was variation between procedure types, almost all procedures saw an increase in both gabapentinoid and opioid prescribing. In this same period, opioid prescribing increased from 56% (95% CI, 55%-56%) to 59% (95% CI, 58%-60%) (P < .001). Concomitant prescribing also increased from 1.6% (95% CI, 1.5%-1.7%) in 2014 to 4.1% (95% CI, 4.0%-4.3%) in 2018 (P < .001). Conclusions and Relevance: The findings of this cross-sectional study of Medicare beneficiaries suggest that new postoperative gabapentinoid prescribing increased without a subsequent downward trend in the proportion of patients receiving postoperative opioids and a near tripling of concurrent prescribing. Closer attention needs to be paid to postoperative prescribing for older adults, especially when using multiple types of medications, which can have adverse drug events.

Patient Perceptions of e-Visits: Qualitative Study of Older Adults to Inform Health System Implementation.

BACKGROUND: Electronic visits (e-visits) are billable, asynchronous patient-initiated messages that require at least five minutes of medical decision-making by a provider. Unequal use of patient portal tools like e-visits by certain patient populations may worsen health disparities. To date, no study has attempted to qualitatively assess perceptions of e-visits in older adults. OBJECTIVE: In this qualitative study, we aimed to understand patient perceptions of e-visits, including their perceived utility, barriers to use, and care implications, with a focus on vulnerable patient groups. METHODS: We conducted a qualitative study using in-depth structured individual interviews with patients from diverse backgrounds to assess their knowledge and perceptions surrounding e-visits as compared with unbilled portal messages and other visit types. We used content analysis to analyze interview data. RESULTS: We conducted 20 interviews, all in adults older than 65 years. We identified 4 overarching coding categories or themes. First, participants were generally accepting of the concept of e-visits and willing to try them. Second, nearly two-thirds of the participants voiced a preference for synchronous communication. Third, participants had specific concerns about the name "e-visit" and when to choose this type of visit in the patient portal. Fourth, some participants indicated discomfort using or accessing technology for e-visits. Financial barriers to the use of e-visits was not a common theme. CONCLUSIONS: Our findings suggest that older adults are generally accepting of the concept of e-visits, but uptake may be limited due to their preference for synchronous communication. We identified several opportunities to improve e-visit implementation.

Economic Evaluation of Nivolumab Versus Docetaxel for the Treatment of Advanced Squamous and Non-squamous Non-small Cell Lung Cancer After Prior Chemotherapy in China.

OBJECTIVE: To evaluate the economic value of nivolumab versus docetaxel for advanced non-small cell lung cancer (aNSCLC) treatment after platinum-based chemotherapy in adults without epidermal growth factor receptor/anaplastic lymphoma kinase aberrations in China. METHODS: Partitioned survival models evaluated lifetime costs and benefits of nivolumab versus docetaxel by squamous and non-squamous histologies from a Chinese healthcare payer perspective. Progression-free disease, progressed disease, and death health states were considered over a 20-year time horizon. Clinical data were derived from the CheckMate pivotal Phase III trials (ClinicalTrials.gov identifiers: NCT01642004, NCT01673867, NCT02613507); patient-level survival data were extrapolated using parametric functions. China-specific health state utilities, healthcare resource utilisation, and unit costs were applied. Sensitivity analyses explored uncertainty. RESULTS: Nivolumab resulted in extended survival (1.489 and 1.228 life-years [1.226 and 0.995 discounted]) and quality-adjusted survival benefits (1.034 and 0.833 quality-adjusted life-years) at additional costs of ¥214,353 (US$31,829) and ¥158,993 (US$23,608) versus docetaxel in squamous and non-squamous aNSCLC, respectively. Nivolumab was associated with higher acquisition costs, lower subsequent treatment costs, and lower adverse event management costs than docetaxel in both histologies. Drug acquisition costs, discount rate for outcomes, and average body weight were key model drivers. Stochastic results aligned with the deterministic results. CONCLUSIONS: Nivolumab yielded survival and quality-adjusted survival benefits at incremental cost versus docetaxel in aNSCLC. As a traditional healthcare payer perspective was applied, the true economic benefit of nivolumab may be underestimated as not all treatment benefits and costs of relevance to society were considered.

Addressing discrepancies in estimates of road traffic deaths and injuries in Ethiopia.

BACKGROUND: There are large discrepancies between official statistics of traffic injuries in African countries and estimates from the Global Burden of Disease (GBD) study and WHO's Global Status Reports on Road Safety (GSRRS). We sought to assess the magnitude of the discrepancy in Ethiopia, its implications and how it can be addressed. METHODS: We systematically searched for nationally representative epidemiological data sources for road traffic injuries and vehicle ownership in Ethiopia and compared estimates with those from GBD and GSRRS. FINDINGS: GBD and GSRRS estimates vary substantially across revisions and across projects. GSRRS-2018 estimates of deaths (27 326 in 2016) are more than three times GBD-2019 estimates (8718), and these estimates have non-overlapping uncertainty ranges. GSRRS estimates align well with the 2016 Demographic and Health Survey (DHS-2016; 27 838 deaths, 95th CI: 15 938 to 39 738). Official statistics are much lower (5118 deaths in 2018) than all estimates. GBD-2019 estimates of serious non-fatal injuries are consistent with DHS-2016 estimates (106 050 injuries, 95th CI: 81 728 to 130 372) and older estimates from the 2003 World Health Survey. Data from five surveys confirm that vehicle ownership levels in Ethiopia are much lower than in other countries in the region. INTERPRETATION: Inclusion of data from national health surveys in GBD and GSRRS can help reduce discrepancies in estimates of deaths and support their use in highlighting under-reporting in official statistics and advocating for better prioritisation of road safety in the national policy agenda. GBD methods for estimating serious non-fatal injuries should be strengthened to allow monitoring progress towards Sustainable Development Goal target 3.6.

Prolonged use of newly prescribed gabapentin after surgery.

BACKGROUND: Surgeons have made substantial efforts to decrease postoperative opioid prescribing, largely because it can lead to prolonged use. These efforts include adoption of non-opioid pain medication including gabapentin. Like opioids, gabapentin use may be prolonged, increasing the risk of altered mental status and even overdose and death when taken concurrently with opioids. However, little is known about postoperative prolonged use of gabapentin in older adults. METHODS: We merged a 20% sample of Medicare Carrier, MedPAR and Outpatient Files with Part D for 2013-2018. We included patients >65 years old without prior gabapentinoid use who underwent common non-cataract surgical procedures. We defined new postoperative gabapentin as fills for 7 days before surgery until 7 days after discharge. We excluded patients whose discharge disposition was hospice or death. The primary outcome was prolonged use of gabapentin, defined as a fill>90 days after discharge. To identify risk factors for prolonged use, we constructed logistic regression models, adjusted for procedure and patient characteristics, length of stay, disposition location, and care complexity. RESULTS: Overall, 17,970 patients (3% of all eligible patients) had a new prescription for gabapentin after surgery. Of these, the mean age was 73 years old and 62% were female. The most common procedures were total knee (45%) and total hip (21%) replacements. Prolonged use occurred in 22%. Those with prolonged use were more likely to be women (64% vs. 61%), be non-White (14% vs. 12%), have concurrent prolonged opioid use (44% vs. 18%), and have undergone emergency surgery (8% vs. 4%). On multivariable analysis, being female, having a higher Charlson comorbidity score, having an opioid prescription at discharge and at >90 days and having a higher care complexity were associated with prolonged use of gabapentin. CONCLUSIONS: More than one-fifth of older adults prescribed gabapentin postoperatively filled a prescription >90 days after discharge, especially among patients with more comorbidities and concurrent prolonged opioid use, increasing the risk of adverse drug events and polypharmacy.

Addressing the challenges of conducting community-engaged research during COVID-19: Rapid development and evaluation of a COVID-19 Research Patient and Community Advisory Board (PCAB).

Introduction: We created a COVID-19 Research Patient and Community Advisory Board (PCAB) to provide patient and community input into clinical and translational research studies. The purpose of this article is to describe the PCAB creation, implementation, and evaluation. Methods: We identified PCAB members who had participated in previous stakeholder engaged activities at our institution and invited their participation. We created a systematic consultation process where researchers could submit plain language research summaries and questions for the PCAB. A facilitated 1-hour virtual consultation was then held where PCAB members provided feedback. We assessed satisfaction of PCAB members and researchers who received consultations using surveys. We also reviewed video recordings of PCAB consultations and reflections from team meetings to identify key lessons learned. Results: Twenty-seven PCAB members took part in 23 consultation sessions. Twenty-two completed an evaluation survey (81% response rate). Most members agreed or strongly agreed their opinions were valued (86%), it was a productive use of time (86%) and were satisfied (86%). Nineteen researchers completed an evaluation survey (83% response rate). Researchers reported positive experiences of working with the PCAB. Additional insights include limited funding in COVID-19 research for equitable community engagement, deficiencies in researcher communication skills, and a lack of cultural humility incorporated into study activities. Conclusions: PCAB members provided recommendations that maximized the patient-centeredness and health equity focus of COVID-19 research. The detailed description of the process of developing, implementing, and evaluating our PCAB can be used as a template for others wishing to replicate this engagement model.

Estimates of road traffic deaths in Tanzania.

INTRODUCTION: There is considerable uncertainty in estimates of traffic deaths in many sub-Saharan African countries, with the Global Burden of Disease (GBD) and the Global Status Report on Road Safety (GSRRS) reporting widely differing estimates. As a case study, we reviewed and compared estimates for Tanzania. METHODS: We estimated the incidence of traffic deaths and vehicle ownership in Tanzania from nationally representative surveys. We compared findings with GBD and GSRRS estimates. RESULTS: Traffic death estimates based on the 2012 census (9382 deaths; 95% CI: 7565 to 11 199) and the 2011-2014 Sample Vital Registration with Verbal Autopsy (8778; 95% CI: 7631 to 9925) were consistent with each other and were about halfway between GBD (5 608; 95% UI: 4506 to 7014) and WHO (16 252; 95% CI: 13 130 to 19 374) estimates and more than twice official statistics (3885 deaths in 2013). Surveys and vehicle registrations data show that motorcycles have increased rapidly since 2007 and now comprise 66% of vehicles. However, these trends are not reflected in GBD estimates of motorcycles in the country, likely resulting in an underestimation of motorcyclist deaths. CONCLUSION: Reducing discrepancies between GBD and GSRRS estimates and demonstrating consistency with local epidemiological data will increase the legitimacy of such estimates among national stakeholders. GBD, which is the only project that models the road-user distribution of traffic deaths in all countries, likely severely underestimates motorcycle deaths in countries where there has been a recent increase in motorcycles. Addressing police under-reporting and strengthening surveillance capacity in Tanzania will allow a better understanding of the road safety problem and better targeting of interventions.

Comparing estimates of road traffic deaths and non-fatal road traffic injuries in Cambodia.

INTRODUCTION: Timely, accurate and detailed information about traffic injuries are essential for managing national road safety programmes. However, there is considerable under-reporting in official statistics of many low and middle-income countries (LMICs) and large discrepancies between estimates from the Global Burden of Disease (GBD) study and WHO's Global Health Estimates (GHE). We compared all sources of epidemiological information on traffic injuries in Cambodia to guide efforts to improve traffic injury statistics. METHODS: We estimated the incidence of traffic deaths and injuries and household ownership of motor vehicles in Cambodia from nationally representative surveys and censuses. We compared findings with GDB and GHE estimates. RESULTS: We identified seven sources for estimating traffic deaths and three for non-fatal injuries that are not included as data sources in GBD and GHE models. These sources and models suggest a fairly consistent estimate of approximately 3100 deaths annually, about 50% higher than official statistics, likely because most hospital deaths are not recorded. Surveys strongly suggest that the vehicle fleet is dominated by motorcycles, which is not consistent with GBD estimates that suggest similar numbers of motorcyclist and vehicle occupant deaths. Estimates of non-fatal injuries from health surveys were about 7.5 times official statistics and 1.5 times GBD estimates. CONCLUSION: Including local epidemiological data sources from LMICs can help reduce uncertainty in estimates from global statistical models and build trust in estimates among local stakeholders. Such analysis should be used as a benchmark to assess and strengthen the completeness of reporting of the national surveillance system.

Late Gadolinium Enhancement Cardiovascular Magnetic Resonance Assessment of Substrate for Ventricular Tachycardia With Hemodynamic Compromise.

Background: The majority of data regarding tissue substrate for post myocardial infarction (MI) VT has been collected during hemodynamically tolerated VT, which may be distinct from the substrate responsible for VT with hemodynamic compromise (VT-HC). This study aimed to characterize tissue at diastolic locations of VT-HC in a porcine model. Methods: Late Gadolinium Enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging was performed in eight pigs with healed antero-septal infarcts. Seven pigs underwent electrophysiology study with venous arterial-extra corporeal membrane oxygenation (VA-ECMO) support. Tissue thickness, scar and heterogeneous tissue (HT) transmurality were calculated at the location of the diastolic electrograms of mapped VT-HC. Results: Diastolic locations had median scar transmurality of 33.1% and a median HT transmurality 7.6%. Diastolic activation was found within areas of non-transmural scar in 80.1% of cases. Tissue activated during the diastolic component of VT circuits was thinner than healthy tissue (median thickness: 5.5 mm vs. 8.2 mm healthy tissue, p < 0.0001) and closer to HT (median distance diastolic tissue: 2.8 mm vs. 11.4 mm healthy tissue, p < 0.0001). Non-scarred regions with diastolic activation were closer to steep gradients in thickness than non-scarred locations with normal EGMs (diastolic locations distance = 1.19 mm vs. 9.67 mm for non-diastolic locations, p < 0.0001). Sites activated late in diastole were closest to steep gradients in tissue thickness. Conclusions: Non-transmural scar, mildly decreased tissue thickness, and steep gradients in tissue thickness represent the structural characteristics of the diastolic component of reentrant circuits in VT-HC in this porcine model and could form the basis for imaging criteria to define ablation targets in future trials.

Advocacy in action: Medical student reflections of an experiential curriculum.

INTRODUCTION: Patient advocacy is a core value in medical education. Although students learn about social determinants of health (SDH) in the pre-clinical years, applying this knowledge to patients during clerkship rotations is not prioritized. Physicians must be equipped to address social factors that affect health and recognize their roles as patient advocates to improve care and promote health equity. We created an experience-based learning curriculum called Advocacy in Action (AiA) to promote the development and application of health advocacy knowledge and skills during an Internal Medicine (IM) clerkship rotation. METHODS: Sixty-six students completed a mandatory curriculum, including an introductory workshop on SDH and patient advocacy using tools for communication, counselling and collaboration skills. They then actively participated in patient advocacy activities, wrote about their experience and joined a small group debriefing about it. Forty-nine written reflections were reviewed for analysis of the impact of this curriculum on student perspectives. RESULTS: Written reflections had prominent themes surrounding advocacy skills development, meaningful personal experiences, interprofessional dynamics in patient advocacy and discovery of barriers to optimal patient care. DISCUSSION: AiA is a novel method to apply classroom knowledge of SDH to the clinical setting in order to incorporate advocacy in daily patient care. Students learned about communication with patients, working with interprofessional team members to create better health outcomes and empathy/compassion from this curriculum. It is important to utilize experiential models of individual patient-level advocacy during clerkships so that students can continuously reflect on and integrate advocacy into their future careers.

Economic evaluation of nivolumab combined with ipilimumab in the first-line treatment of advanced melanoma in Japan.

AIMS: The objective of this study was to evaluate the cost-effectiveness of nivolumab in combination with ipilimumab (nivo + ipi) compared to current therapeutic alternatives in first-line treatment of patients with advanced melanoma from the Japanese national healthcare payer perspective using 48-month survival data from the CheckMate 067 Phase III trial. MATERIALS AND METHODS: A three-state partitioned survival model was developed from projections of overall survival (OS) and progression-free survival (PFS) to estimate accrued quality-adjusted survival and costs over a 30-year time horizon. The analysis included nivo + ipi, nivolumab, and ipilimumab monotherapies (the three treatments included in CheckMate 067). Drug acquisition, administration, disease management, subsequent therapy, and adverse event (AE) costs were obtained via published sources and expert input (solicited via Delphi panel). AE frequencies were collected from the Checkmate 067 trial. Utility weights were estimated from the Checkmate 067 trial, based on Japanese tariffs. Results were presented as incremental cost-utility ratios (ICURs, cost per quality-adjusted life-year (QALY)). RESULTS: Nivo + ipi had the greatest estimated survival among the three competing treatments, followed by nivolumab monotherapy accruing the second greatest survival. The incremental cost-effectiveness of nivo + ipi was ¥778,000 per QALY vs. nivolumab and ¥1,584,000 per QALY vs. ipilimumab. The results indicate that nivo + ipi is cost-effective in Japan when compared to a threshold of ¥7,500,000 per QALY. This finding was found to be generally robust to sensitivity and scenario analyses. LIMITATIONS: Limitations include uncertainty in long-term survival extrapolations and lack of Japan-specific clinical data. CONCLUSIONS: This analysis indicates that adding ipilimumab to nivolumab therapy represents a cost-effective new treatment option for patients with unresectable malignant melanoma in Japan.

The Association Between Fault Attribution and Work Participation After Road Traffic Injury: A Registry-Based Observational Study.

Purpose To characterise associations between fault attribution and work participation and capacity after road traffic injury. Methods People aged 15-65 years, working pre-injury, without serious brain injury, who survived to 12 months after road traffic injury were included from two Victorian trauma registries (n = 2942). Fault profiles from linked compensation claims were defined as no other at fault, another at fault, denied another at fault, claimed another at fault, and unknown. Claimant reports in the denied and claimed another at fault groups contradicted police reports. Patients reported work capacity (Glasgow outcome scale-extended) and return to work (RTW) at 6, 12 and 24 months post-injury (early and sustained RTW, delayed RTW (≥ 12 months), failed RTW attempts, no RTW attempts). Analyses adjusted for demographic, clinical and injury covariates. Results The risk of not returning to work was higher if another was at fault [adjusted relative risk ratio (aRRR) = 1.67, 95% confidence interval (CI) 1.29, 2.17] or was claimed to be at fault (aRRR = 1.58, 95% CI 1.04, 2.41), and lower for those who denied that another was at fault (aRRR = 0.51, 95% CI 0.29, 0.91), compared to cases with no other at fault. Similarly, people had higher odds of work capacity limitations if another was at fault (12m: AOR = 1.49, 95% CI 1.24, 1.80; 24m: 1.63, 95% CI 1.35, 1.97) or was claimed to be at fault (12m: AOR = 1.54, 95% CI 1.16, 2.05; 24m: AOR = 1.80, 95% CI 1.34, 2.41), and lower odds if they denied another was at fault (6m: AOR = 0.67, 95% CI 0.48, 0.95), compared to cases with no other at fault. Conclusion Targeted interventions are needed to support work participation in people at risk of poor RTW post-injury. While interventions targeting fault and justice-related attributions are currently lacking, these may be beneficial for people who believe that another caused their injury.

Pulmonary vein encirclement using an Ablation Index-guided point-by-point workflow: cardiovascular magnetic resonance assessment of left atrial scar formation.

AIMS: A point-by-point workflow for pulmonary vein isolation (PVI) targeting pre-defined Ablation Index values (a composite of contact force, time, and power) and minimizing interlesion distance may optimize the creation of contiguous ablation lesions whilst minimizing scar formation. We aimed to compare ablation scar formation in patients undergoing PVI using this workflow to patients undergoing a continuous catheter drag workflow. METHODS AND RESULTS: Post-ablation cardiovascular magnetic resonance imaging was performed in patients undergoing 1st-time PVI using a parameter-guided point-by-point workflow (n = 26). Total left atrial scar burden and the width and continuity of the pulmonary vein encirclement were determined on analysis of atrial late gadolinium enhancement sequences. Comparison was made with a cohort of patients (n = 20) undergoing PVI using continuous drag lesions. Mean post-ablation scar burden and scar width were significantly lower in the point-by-point group than in the control group (6.6 ± 6.8% vs. 9.6 ± 5.0%, P = 0.03 and 7.9 ± 3.6 mm vs. 10.7 ± 2.3 mm, P = 0.003). More complete bilateral pulmonary vein encirclements were seen in the point-by-point group (P = 0.038). All patients achieved acute PVI. CONCLUSION: Pulmonary vein isolation using a point-by-point workflow is feasible and results in a lower scar burden and scar width with more complete pulmonary vein encirclements than a conventional drag lesion approach.

A comprehensive multi-index cardiac magnetic resonance-guided assessment of atrial fibrillation substrate prior to ablation: Prediction of long-term outcomes.

INTRODUCTION: Multiple cardiac magnetic resonance (CMR)-derived indices of atrial fibrillation (AF) substrate have been shown in isolation to predict long-term outcome following catheter ablation. Left atrial (LA) fibrosis, LA volume, LA ejection fraction (EF), left ventricular ejection fraction (LVEF), LA shape (sphericity) and pulmonary vein anatomy have all been shown to correlate with late AF recurrence. This study aimed to validate and assess the relative contribution of multiple indices in a long-term single-center study. METHODS AND RESULTS: Eighty-nine patients (53% paroxysmal AF, 73% male) underwent comprehensive CMR study before first-time AF ablation (median follow-up 726 days [IQR: 418-1010 days]). The 3D late gadolinium-enhanced acquisition (1.5T, 1.3 × 1.3 × 2 mm) was quantified for fibrosis; LA volume and sphericity were assessed on manual segmentation at atrial diastole; LAEF and LVEF were quantified on multislice cine imaging. AF recurred in 43 patients (48%) overall (31 at 1 year). In the recurrence group, LA fibrosis was higher (42% vs 29%; hazard ratio [HR]: 1.032; P = .002), left atrial ejection fraction (LAEF) lower (25% vs 34%; HR: 0.063; P = .016) and LVEF lower (57% vs 63%; HR: 0.011; P = .008). LA volume (135 vs 124 mL) and sphericity (0.819 vs 0.822) were similar. Multivariate Cox regression analysis was adjusted for age and sex (Model 1), additionally AF type (Model 2) and combined (Model 3). In Models 1 and 2, LA fibrosis, LAEF, and LVEF were independently associated with outcome, but only LA fibrosis was independent in Model 3 (HR: 1.021; P = .022). CONCLUSIONS: LAEF, LVEF, and LA fibrosis differed significantly in the AF recurrence cohort. However, on combined multivariate analysis only LA fibrosis remained independently associated with outcome.

Evaluation of a real-time magnetic resonance imaging-guided electrophysiology system for structural and electrophysiological ventricular tachycardia substrate assessment.

AIMS: Potential advantages of real-time magnetic resonance imaging (MRI)-guided electrophysiology (MR-EP) include contemporaneous three-dimensional substrate assessment at the time of intervention, improved procedural guidance, and ablation lesion assessment. We evaluated a novel real-time MR-EP system to perform endocardial voltage mapping and assessment of delayed conduction in a porcine ischaemia-reperfusion model. METHODS AND RESULTS: Sites of low voltage and slow conduction identified using the system were registered and compared to regions of late gadolinium enhancement (LGE) on MRI. The Sorensen-Dice similarity coefficient (DSC) between LGE scar maps and voltage maps was computed on a nodal basis. A total of 445 electrograms were recorded in sinus rhythm (range: 30-186) using the MR-EP system including 138 electrograms from LGE regions. Pacing captured at 103 sites; 47 (45.6%) sites had a stimulus-to-QRS (S-QRS) delay of ≥40 ms. Using conventional (0.5-1.5 mV) bipolar voltage thresholds, the sensitivity and specificity of voltage mapping using the MR-EP system to identify MR-derived LGE was 57% and 96%, respectively. Voltage mapping had a better predictive ability in detecting LGE compared to S-QRS measurements using this system (area under curve: 0.907 vs. 0.840). Using an electrical threshold of 1.5 mV to define abnormal myocardium, the total DSC, scar DSC, and normal myocardium DSC between voltage maps and LGE scar maps was 79.0 ± 6.0%, 35.0 ± 10.1%, and 90.4 ± 8.6%, respectively. CONCLUSION: Low-voltage zones and regions of delayed conduction determined using a real-time MR-EP system are moderately associated with LGE areas identified on MRI.

The value of ablation parameter indices for predicting mature atrial scar formation in humans: An in vivo assessment using cardiac magnetic resonance imaging.

INTRODUCTION: The VisiTag module (CARTO3) provides an objective assessment of radiofrequency (RF) ablation parameters. This study aimed to determine the predictive value and optimal VisiTag threshold settings for prediction of gaps in mature atrial scar, as assessed non-invasively using cardiac magnetic resonance (CMR) imaging. METHODS: Twenty-four subjects (11 paroxysmal atrial fibrillation) underwent first-time RF ablation with operators blinded to VisiTag data. Three-dimensional late gadolinium enhancement (LGE) CMR scans were performed at 3 months (1.3 × 1.3 × 4 mm3 ). A survey of UK operators defined the standard VisiTag settings ("Force," 8 g; "Time," 10 seconds; "Percentage Time," 50%; "Range," 3 mm; "Impedance" and "Temperature" "off"). Each ablation procedure was exported 27 times, varying single VisiTag parameters from default values. The presence of gaps in VisiTag markers (18 sectors) was assessed for each export and compared with gaps in CMR enhancement. RESULTS: At default settings, VisiTag gaps were specific (97.5%) but less sensitive (50.4%) for CMR gaps. Sensitivity improved at higher thresholds (89.2% at 20 g, 85.6% at 30 seconds, 88.5% impedance 10 Ω, 92.8% temperature 42°C), but with a lower positive predictive value (PPV) (42.3%, 42.7%, 41.1%, and 37.7%, respectively, vs 90.9% at baseline). "Force" thresholds demonstrated stable PPV from 2 to 8 g (P = 0.24), but a rapid fall at forces more than 10 g. The binomial logistic regression model explained 41.7% of gaps; χ 2 (4), 148; P < 0.0001, correctly classifying 82% of cases (specificity 94.9%, sensitivity 56.8%). CONCLUSION: Gaps in VisiTags predict gaps in CMR LGE enhancement with high specificity at default settings. Sensitivity may be improved using more stringent thresholds but at the potential cost of unnecessary ablation, particularly when a force more than 10 g is stipulated.

Validating injury burden estimates using population birth cohorts and longitudinal cohort studies of injury outcomes: the VIBES-Junior study protocol.

INTRODUCTION: Traumatic injury is a leading contributor to the global disease burden in children and adolescents, but methods used to estimate burden do not account for differences in patterns of injury and recovery between children and adults. A lack of empirical data on postinjury disability in children has limited capacity to derive valid disability weights and describe the long-term individual and societal impacts of injury in the early part of life. The aim of this study is to establish valid estimates of the burden of non-fatal injury in children and adolescents. METHODS AND ANALYSIS: Five longitudinal studies of paediatric injury survivors <18 years at the time of injury (Australia, Canada, UK and USA) and two whole-of-population linked administrative data paediatric studies (Australia and Wales) will be analysed over a 3-year period commencing 2018. Meta-analysis of deidentified patient-level data (n≈2,600) from five injury-specific longitudinal studies (Victorian State Trauma Registry; Victorian Orthopaedic Trauma Outcomes Registry; UK Burden of Injury; British Columbia Children's Hospital Longitudinal Injury Outcomes; Children's Health After Injury) and >1 million children from two whole-of-population cohorts (South Australian Early Childhood Data Project and Wales Electronic Cohort for Children). Systematic analysis of pooled injury-specific cohort data using a variety of statistical techniques, and parallel analysis of whole-of-population cohorts, will be used to develop estimated disability weights for years lost due to disability, establish appropriate injury classifications and explore factors influencing recovery. ETHICS AND DISSEMINATION: The project was approved by the Monash University Human Research Ethics Committee project number 12 311. Results of this study will be submitted for publication in internationally peer-reviewed journals. The findings from this project have the capacity to improve the validity of paediatric injury burden measurements in future local and global burden of disease studies.

Simultaneous Assessment In Vitro of Transporter and Metabolic Processes in Hepatic Drug Clearance: Use of a Media Loss Approach.

Hepatocyte drug depletion-time assays are well established for determination of metabolic clearance in vitro. The present study focuses on the refinement and evaluation of a "media loss" assay, an adaptation of the conventional depletion assay involving centrifugation of hepatocytes prior to sampling, allowing estimation of uptake in addition to metabolism. Using experimental procedures consistent with a high throughput, a selection of 12 compounds with a range of uptake and metabolism characteristics (atorvastatin, cerivastatin, clarithromycin, erythromycin, indinavir, pitavastatin, repaglinide, rosuvastatin, saquinavir, and valsartan, with two control compounds-midazolam and tolbutamide) were investigated in the presence and absence of the cytochrome P450 inhibitor 1-aminobenzotriazole and organic anion transporter protein inhibitor rifamycin SV in rat hepatocytes. Data were generated simultaneously for a given drug, and provided, through the use of a mechanistic cell model, clearance terms characterizing metabolism, active and passive uptake, together with intracellular binding and partitioning parameters. Results were largely consistent with the particular drug characteristics, with active uptake, passive diffusion, and metabolic clearances ranging between 0.4 and 777, 3 and 383, and 2 and 236 µl/min per milligram protein, respectively. The same experiments provided total and unbound drug cellular partition coefficients ranging between 3.8 and 254 and 2.3 and 8.3, respectively, and intracellular unbound fractions between 0.014 and 0.263. Following in vitro-in vivo extrapolation, the lowest prediction bias was noted using uptake clearance, compared with metabolic clearance or apparent clearance from the media loss assay alone. This approach allows rapid and comprehensive characterization of hepatocyte drug disposition valuable for prediction of hepatic processes in vivo.