Stent-Assisted Balloon-Induced Intimal Disruption and Relamination in Aortic Dissection Repair (STABILISE): A Meta-Analysis of Early Outcomes.

BACKGROUND: This meta-analysis aims to determine the early clinical outcomes and rate of complete false lumen obliteration associated with the stent-assisted balloon-induced intimal disruption and relamination in aortic dissection repair (STABILISE) technique in the management of aortic dissection. METHODS: Electronic databases searches were performed on PubMed, Embase, and the Cochrane Library to identify studies reporting early outcomes of the STABILISE technique. In addition, we retrospectively analyzed all patients treated with the STABILISE technique for aortic dissection at our institution. The case series data were pooled with relevant studies to perform a meta-analysis of proportions using random-effects models. RESULTS: One hundred and ninety two patients from 9 relevant studies were pooled with an additional 13 patients undergoing STABILISE at our institution over a 3-year period. Pooled in-hospital mortality rate was 6% [95% confidence interval (CI); 3%-10%, I2 = 0.00%] and the overall rate of intraoperative aortic rupture was 4% [95% CI; 2%-8%, I2 = 0.00%]. The rate of in-hospital reintervention was 8% [95% CI; 5%-14%, I2 = 13.37%]. Median follow-up ranged from 8 to 36 months. Pooled cumulative mortality at follow-up was 8% [95% CI; 4%-18%, I2 = 23.15%]. The overall rate of late reintervention was 11% [95% CI; 7%-17%, I2 = 0.00%]. Complete obliteration of the false lumen in the thoracic aorta was achieved in 93% of patients [95% CI; 84%-97%, I2 = 47.49%] and in the abdominal aorta in 86% of patients [95% CI; 79%-91%, I2 = 0.00%]. CONCLUSIONS: The STABILISE technique carries an acceptable operative safety profile with low in-hospital morbidity and mortality and excellent complete false lumen obliteration.

Diagnosis of Potomac horse fever (syn. equine neorickettsiosis) in 2 foals in southwestern Ontario.

Potomac horse fever (PHF) is characterized by fever, depression, anorexia, ileus, diarrhea, and occasionally, laminitis. The disease is caused by infection with Neorickettsia risticii and/or N. findlayensis. Equids of all ages may be affected; however, the condition has not been well-characterized in foals. This report describes clinical signs, laboratory findings, and treatment of 2 foals diagnosed with PHF in southwestern Ontario. Feces submitted for an equine PCR panel tested positive for Neorickettsia spp. and were subsequently confirmed to be N. risticii (Case 1) and N. findlayensis (Case 2). Both foals recovered following hospitalization and intensive care. Key clinical message: The purpose of this report is to make veterinarians aware that foals may develop PHF. During summer (July to September), when encountering foals in endemic areas with clinical signs compatible with PHF, veterinarians should consider PHF as a diagnostic rule-out. For confirmation of the diagnosis, blood and feces should be submitted for PCR testing for Neorickettsia spp.

Diagnostic de la fièvre équine du Potomac (syn. néorickettsiose équine) chez 2 poulains dans le sud-ouest de l'Ontario. La fièvre équine du Potomac (PHF) se caractérise par de la fièvre, une dépression, de l'anorexie, un iléus, de la diarrhée et, occasionnellement, une fourbure. La maladie est causée par une infection par Neorickettsia risticii et/ou N. findlayensis. Les équidés de tous âges peuvent être atteints; cependant, cette pathologie n'a pas été bien caractérisée chez les poulains. Ce rapport décrit les signes cliniques, les résultats de laboratoire et le traitement de 2 poulains diagnostiqués avec PHF dans le sud-ouest de l'Ontario. Les matières fécales soumises à un panel PCR équin se sont révélées positives pour Neorickettsia spp. et ont ensuite été confirmées comme étant positives pour N. risticii (cas 1) et N. findlayensis (cas 2). Les deux poulains se sont rétablis après une hospitalisation et des soins intensifs.Message clinique clé :Le but de ce rapport est de sensibiliser les vétérinaires au fait que les poulains peuvent développer une PHF. Pendant l'été (juillet à septembre), lorsqu'ils rencontrent des poulains dans des zones d'endémie présentant des signes cliniques compatibles avec le PHF, les vétérinaires doivent considérer le PHF comme une exclusion diagnostique. Pour confirmer le diagnostic, du sang et des selles doivent être soumis à un test PCR pour Neorickettsia spp.(Traduit par Dr Serge Messier).

Minnesota Data Sharing May Be Model For Near-Real-Time Tracking Of Drug Overdose Hospital And ED Trends.

The drug overdose epidemic in the US necessitates detailed and timely data to inform public health responses. In this article we describe how an electronic health record (EHR) data-sharing collaboration across health systems in Minnesota that was developed in response to the COVID-19 pandemic was adapted to monitor trends in substance use-related hospital and emergency department (ED) visits. We found large increases in methamphetamine- and opioid-involved hospital and ED visits. Throughout the study period, Native American, Black, and multiple-race people experienced the highest rates of drug-involved hospital and ED visits. Monitoring drug-involved health care use through EHR data has the potential to help public health officials detect trends in near real time before mortality spikes and may also inform early intervention. The use of EHR data also allows for detailed monitoring of the impact of the drug overdose epidemic across racial and ethnic groups.

Pediatric and Adult Brain Death/Death by Neurologic Criteria Consensus Guideline.

BACKGROUND AND OBJECTIVES: The purpose of this guideline is to update the 2010 American Academy of Neurology (AAN) brain death/death by neurologic criteria (BD/DNC) guideline for adults and the 2011 American Academy of Pediatrics, Child Neurology Society, and Society of Critical Care Medicine guideline for infants and children and to clarify the BD/DNC determination process by integrating guidance for adults and children into a single guideline. Updates in this guideline include guidance related to conducting the BD/DNC evaluation in the context of extracorporeal membrane oxygenation, targeted temperature management, and primary infratentorial injury. METHODS: A panel of experts from multiple medical societies developed BD/DNC recommendations. Because of the lack of high-quality evidence on the subject, a novel, evidence-informed formal consensus process was used. This process relied on the panel experts' review and detailed knowledge of the literature surrounding BD/DNC to guide the development of preliminary recommendations. Recommendations were formulated and voted on, using a modified Delphi process, according to the 2017 AAN Clinical Practice Guideline Process Manual. MAJOR RECOMMENDATIONS: Eighty-five recommendations were developed on the following: (1) general principles for the BD/DNC evaluation, (2) qualifications to perform BD/DNC evaluations, (3) prerequisites for BD/DNC determination, (4) components of the BD/DNC neurologic examination, (5) apnea testing as part of the BD/DNC evaluation, (6) ancillary testing as part of the BD/DNC evaluation, and (7) special considerations for BD/DNC determination.

Evaluation of a viral transcriptome Next Generation Sequencing assay as an alternative to animal assays for viral safety testing of cell substrates.

The viral safety of biological products is ensured by tests throughout the production chain, and, for certain products, by steps in the manufacturing process enabling the elimination or inactivation of viruses. Current testing programs include sample inoculation in animals and embryonic eggs. Following the 3Rs principles of replacement, reduction, and refinement of animal-use methods, such techniques are intended to be replaced not only for ethical reasons but also because of their inherent technical limitations, their long turnaround times, and their limits in virus detection. Therefore, we have compared the limit and range of sensitivity of in vivo tests used for viral testing of cells with a transcriptomic assay based on Next Generation Sequencing (NGS). Cell cultures were infected with a panel of nine (9) viruses, among them only five (5) were detected, with variable sensitivity, by in vivo tests. The transcriptomic assay was able to detect one (1) infected cell among 103 to 107 non-infected cells for all viruses assessed, including those not detected by the conventional in vivo tests. Here we show that NGS extends the breath of detection of viral contaminants compared to traditional testing. Collectively, these results support the replacement of the conventional in vivo tests by an NGS-based transcriptomic assay for virus safety testing of cell substrates.

Prenatal care coordination, racial and socioeconomic inequities, and pre- and post-operative outcomes in hypoplastic left heart syndrome.

OBJECTIVE: We sought to identify associations between prenatal care coordination (PNC) and outcomes in hypoplastic left heart syndrome (HLHS). STUDY DESIGN: We hypothesized that suboptimal PNC is associated with worse pre-operative status. HLHS patients from 2016 through 2019 were identified using a multicenter registry. Optimal PNC was defined as (1) a completed interdisciplinary conference and (2) closed-loop communication with the obstetric team. Associations between PNC and outcomes were identified. RESULTS: Of 1441 patients, 1242 (86%) had prenatal diagnosis. Among those with a prenatal diagnosis, PNC was achieved in only 845 (68%). Suboptimal PNC was associated with adverse events (50% vs 40%, p < 0.001), inotrope need (19% vs 13%, p = 0.007), mechanical ventilation (22% vs 16%, p = 0.016), and parenteral feeding (60% vs 46%, p < 0.001). African-American race and non-commercial insurance were associated with a lower likelihood of optimal PNC (p = 0.006 and p < 0.001, respectively). CONCLUSION: Improving PNC and overcoming racial and socioeconomic barriers are important targets to improve HLHS perinatal care.

A Multifaceted Evaluation of a COVID-19 Contact Tracing Program in King County, Washington.

CONTEXT: Despite the massive scale of COVID-19 case investigation and contact tracing (CI/CT) programs operating worldwide, the evidence supporting the intervention's public health impact is limited. OBJECTIVE: To evaluate the Public Health-Seattle & King County (PHSKC) CI/CT program, including its reach, timeliness, effect on isolation and quarantine (I&Q) adherence, and potential to mitigate pandemic-related hardships. DESIGN: This program evaluation used descriptive statistics to analyze surveillance records, case and contact interviews, referral records, and survey data provided by a sample of cases who had recently ended isolation. SETTING: The PHSKC is one of the largest governmental local health departments in the United States. It serves more than 2.2 million people who reside in Seattle and 38 other municipalities. PARTICIPANTS: King County residents who were diagnosed with COVID-19 between July 2020 and June 2021. INTERVENTION: The PHSKC integrated COVID-19 CI/CT with prevention education and service provision. RESULTS: The PHSKC CI/CT team interviewed 42 900 cases (82% of cases eligible for CI/CT), a mean of 6.1 days after symptom onset and 3.4 days after SARS-CoV-2 testing. Cases disclosed the names and addresses of 10 817 unique worksites (mean = 0.8/interview) and 11 432 other recently visited locations (mean = 0.5/interview) and provided contact information for 62 987 household members (mean = 2.7/interview) and 14 398 nonhousehold contacts (mean = 0.3/interview). The CI/CT team helped arrange COVID-19 testing for 5650 contacts, facilitated grocery delivery for 7253 households, and referred 9127 households for financial assistance. End of I&Q Survey participants (n = 304, 54% of sampled) reported self-notifying an average of 4 nonhousehold contacts and 69% agreed that the information and referrals provided by the CI/CT team helped them stay in isolation. CONCLUSIONS: In the 12-month evaluation period, CI/CT reached 42 611 households and identified thousands of exposure venues. The timing of CI/CT relative to infectiousness and difficulty eliciting nonhousehold contacts may have attenuated the intervention's effect. Through promotion of I&Q guidance and services, CI/CT can help mitigate pandemic-related hardships.

Functional susceptibility of tropical forests to climate change.

Tropical forests are some of the most biodiverse ecosystems in the world, yet their functioning is threatened by anthropogenic disturbances and climate change. Global actions to conserve tropical forests could be enhanced by having local knowledge on the forests' functional diversity and functional redundancy as proxies for their capacity to respond to global environmental change. Here we create estimates of plant functional diversity and redundancy across the tropics by combining a dataset of 16 morphological, chemical and photosynthetic plant traits sampled from 2,461 individual trees from 74 sites distributed across four continents together with local climate data for the past half century. Our findings suggest a strong link between climate and functional diversity and redundancy with the three trait groups responding similarly across the tropics and climate gradient. We show that drier tropical forests are overall less functionally diverse than wetter forests and that functional redundancy declines with increasing soil water and vapour pressure deficits. Areas with high functional diversity and high functional redundancy tend to better maintain ecosystem functioning, such as aboveground biomass, after extreme weather events. Our predictions suggest that the lower functional diversity and lower functional redundancy of drier tropical forests, in comparison with wetter forests, may leave them more at risk of shifting towards alternative states in face of further declines in water availability across tropical regions.

IDEAL-D Framework for Device Innovation: A Consensus Statement on the Preclinical Stage.

OBJECTIVE: To extend the IDEAL framework for device innovation, IDEAL-D, to include the preclinical stage of development (stage 0). BACKGROUND: In previous work, the IDEAL collaboration has proposed frameworks for new surgical techniques and complex therapeutic technologies, the central tenet being that development and evaluation can and should proceed together in an ordered and logical manner that balances innovation and safety. METHODS: Following agreement at the IDEAL Collaboration Council, a multidisciplinary working group was formed comprising 12 representatives from healthcare, academia, industry, and a patient advocate. The group conducted a series of discussions following the principles used in the development of the original IDEAL framework. Importantly, IDEAL aims for maximal transparency, optimal validity in the evaluation of primary effects, and minimization of potential risk to patients or others. The proposals were subjected to further review and editing by members of the IDEAL Council before a final consensus version was adopted. RESULTS: In considering which studies are required before a first-in-human study, we have: (1) classified devices according to what they do and the risks they carry, (2) classified studies according to what they show about the device, and (3) made recommendations based on the principle that the more invasive and high risk a device is, the greater proof required of their safety and effectiveness before progression to clinical studies (stage 1). CONCLUSIONS: The proposed recommendations for preclinical evaluation of medical devices represent a proportionate and pragmatic approach that balances the de-risking of first-in-human translational studies against the benefits of rapid translation of new devices into clinical practice.

Detection and Response to an HIV Cluster: People Living Homeless and Using Drugs in Seattle, Washington.

INTRODUCTION: The HIV epidemic in King County, Washington has traditionally been highly concentrated among men who have sex with men, and incidence has gradually declined over 2 decades. In 2018, King County experienced a geographically concentrated outbreak of HIV among heterosexual people who inject drugs. METHODS: Data sources to describe the 2018 outbreak and King County's response were partner services interview data, HIV case reports, syringe service program client surveys, hospital data, and data from a rapid needs assessment of homeless individuals and people who inject drugs. In 2020, the authors examined the impact of delays in molecular sequence analyses and cluster member size thresholds, for identifying genetically similar clusters, on the timing of outbreak identification. RESULTS: In 2018, the health department identified a North Seattle cluster, growing to 30 people with related HIV infections diagnosed in 2008-2019. In total, 70% of cluster members were female, 77% were people who inject drugs, 87% were homeless, and 27% reported exchanging sex. Intervention activities included a rapid needs assessment, 2,485 HIV screening tests in a jail and other outreach settings, provision of 87,488 clean syringes in the outbreak area, and public communications. A lower cluster size threshold and more rapid receipt and analyses of data would have identified this outbreak 4-16 months earlier. CONCLUSIONS: This outbreak shows the vulnerability of people who inject drugs to HIV infection, even in areas with robust syringe service programs and declining HIV epidemics. Although molecular HIV surveillance did not identify this outbreak, it may have done so with a lower threshold for defining clusters and more rapid receipt and analyses of HIV genetic sequences.

High aboveground carbon stock of African tropical montane forests.

Tropical forests store 40-50 per cent of terrestrial vegetation carbon1. However, spatial variations in aboveground live tree biomass carbon (AGC) stocks remain poorly understood, in particular in tropical montane forests2. Owing to climatic and soil changes with increasing elevation3, AGC stocks are lower in tropical montane forests compared with lowland forests2. Here we assemble and analyse a dataset of structurally intact old-growth forests (AfriMont) spanning 44 montane sites in 12 African countries. We find that montane sites in the AfriMont plot network have a mean AGC stock of 149.4 megagrams of carbon per hectare (95% confidence interval 137.1-164.2), which is comparable to lowland forests in the African Tropical Rainforest Observation Network4 and about 70 per cent and 32 per cent higher than averages from plot networks in montane2,5,6 and lowland7 forests in the Neotropics, respectively. Notably, our results are two-thirds higher than the Intergovernmental Panel on Climate Change default values for these forests in Africa8. We find that the low stem density and high abundance of large trees of African lowland forests4 is mirrored in the montane forests sampled. This carbon store is endangered: we estimate that 0.8 million hectares of old-growth African montane forest have been lost since 2000. We provide country-specific montane forest AGC stock estimates modelled from our plot network to help to guide forest conservation and reforestation interventions. Our findings highlight the need for conserving these biodiverse9,10 and carbon-rich ecosystems.

Resistance of African tropical forests to an extreme climate anomaly.

The responses of tropical forests to environmental change are critical uncertainties in predicting the future impacts of climate change. The positive phase of the 2015-2016 El Niño Southern Oscillation resulted in unprecedented heat and low precipitation in the tropics with substantial impacts on the global carbon cycle. The role of African tropical forests is uncertain as their responses to short-term drought and temperature anomalies have yet to be determined using on-the-ground measurements. African tropical forests may be particularly sensitive because they exist in relatively dry conditions compared with Amazonian or Asian forests, or they may be more resistant because of an abundance of drought-adapted species. Here, we report responses of structurally intact old-growth lowland tropical forests inventoried within the African Tropical Rainforest Observatory Network (AfriTRON). We use 100 long-term inventory plots from six countries each measured at least twice prior to and once following the 2015-2016 El Niño event. These plots experienced the highest temperatures and driest conditions on record. The record temperature did not significantly reduce carbon gains from tree growth or significantly increase carbon losses from tree mortality, but the record drought did significantly decrease net carbon uptake. Overall, the long-term biomass increase of these forests was reduced due to the El Niño event, but these plots remained a live biomass carbon sink (0.51 ± 0.40 Mg C ha-1 y-1) despite extreme environmental conditions. Our analyses, while limited to African tropical forests, suggest they may be more resistant to climatic extremes than Amazonian and Asian forests.

Timing of chronic obstructive pulmonary disease diagnosis in lung cancer prognosis: a clinical and genomic-based study.

BACKGROUND: A two-phase study (clinical and genomic-based) was conducted to evaluate the effect of timing of chronic obstructive pulmonary disease (COPD) diagnosis on lung cancer outcomes. METHODS: The prognostic influence of COPD was investigated in a clinical cohort of 1,986 patients who received surgery for stage I lung cancer; 823 (41.4%) of them also had COPD, including 549 (27.6%) incidental COPD (diagnosed within 6-months of lung cancer diagnosis) and 274 (13.8%) prior COPD (>6 months before lung cancer diagnosis). The genomic variations were analyzed from another cohort of 1,549 patients for association with 384 lung cancer-related single nucleotide polymorphisms (SNPs). RESULTS: Older age (≥70 years), smokers, and respiratory symptoms were independent predictors of incidental COPD in lung cancer (all P<0.05). Similar to prior COPD, incidental COPD increased postoperative complications and worsened quality-of-life related to dyspnea (both P<0.05). Multivariate Cox regression analysis showed lung cancer survival decreased significantly in incidental COPD (HR, 1.30; 95% CI, 1.02-1.66), but not in prior COPD (HR, 1.15; 95% CI, 0.87-1.52). Among prior COPD, median survival showed a trend for being better in those with fewer exacerbations (0-1 vs. ≥2 exacerbation/year; 6.1 vs. 4.1 years; P=0.10). The SNP-based analysis identified ADCY2:rs52827085 was significantly associated with risk of incidental COPD (OR, 1.76; 95% CI, 1.30-2.38) and NRXN1:rs1356888 associated with prior COPD complicated with lung cancer (OR, 1.73; 95% CI, 1.29-2.33). CONCLUSIONS: Different long-term survival and genomic variants were observed between lung cancer patients with incidental and with prior COPD, suggesting timing of COPD diagnosis should be considered in lung cancer clinical management and mechanistic research.

Implementation of a data accuracy plan to improve data extraction yield in the Axon Registry®.

OBJECTIVE: To conduct a data quality improvement project to improve the quality measure data mapping and to measure key phrase logic in the Axon Registry.® METHODS: Prior validation analysis of the Axon Registry identified 2 main areas for remediation: methodology for mapping data from electronic health record (EHR) into the registry clinical data record (CDR) and key phrase logic for each measure. Practice groups participating in Axon Registry and 6 Axon Registry quality measures were selected for intervention. Mapping of measure elements and measure performances for each of the selected measures and practices were reviewed before intervention. The Data Accuracy Plan (DAP) was performed, and documentation data and visit data counts and data yield after intervention were calculated and analyzed. RESULTS: Documentation data and visit data counts and data yield increased for all 6 quality measures and all practices in the DAP. Increase in documentation data count ranged from 815 to 15,782 occurrences, while visit data count increase ranged from 519 to 16,383 visits. Average data yield range was 7.22% to 33.46% before intervention and increased to a range from 15.34% to 74.40% after intervention. CONCLUSION: There was substantial improvement in the accuracy of data extraction for quality measure elements after intervention to improve methodology for mapping EHR data into CDR and key phrase logic. Implementation of changes and continued review of data mapping and data dictionary are important to ensure accurate measure performance and to improve reliability and validity of Axon Registry data.

Long-term thermal sensitivity of Earth's tropical forests.

The sensitivity of tropical forest carbon to climate is a key uncertainty in predicting global climate change. Although short-term drying and warming are known to affect forests, it is unknown if such effects translate into long-term responses. Here, we analyze 590 permanent plots measured across the tropics to derive the equilibrium climate controls on forest carbon. Maximum temperature is the most important predictor of aboveground biomass (-9.1 megagrams of carbon per hectare per degree Celsius), primarily by reducing woody productivity, and has a greater impact per °C in the hottest forests (>32.2°C). Our results nevertheless reveal greater thermal resilience than observations of short-term variation imply. To realize the long-term climate adaptation potential of tropical forests requires both protecting them and stabilizing Earth's climate.