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Governments around the world have acknowledged that urgent action is needed to conserve and restore ecological connectivity to help reverse the decline of biodiversity. In this study we tested the hypothesis that functional connectivity for multiple species can be estimated across Canada using a single, upstream connectivity model. We developed a movement cost layer with cost values assigned using expert opinion to anthropogenic land cover features and natural features based on their known and assumed effects on the movement of terrestrial, non-volant fauna. We used Circuitscape to conduct an omnidirectional connectivity analysis for terrestrial landscapes, in which the potential contribution of all landscape elements to connectivity were considered and where source and destination nodes were independent of land tenure. Our resulting map of mean current density provided a seamless estimate of movement probability at a 300 m resolution across Canada. We tested predictions in our map using a variety of independently collected wildlife data. We found that GPS data for individual caribou, wolves, moose, and elk that traveled longer distances in western Canada were all significantly correlated with areas of high current densities. The frequency of moose roadkill in New Brunswick was also positively associated with current density, but our map was not able to predict areas of high road mortality for herpetofauna in southern Ontario. The results demonstrate that an upstream modelling approach can be used to characterize functional connectivity for multiple species across a large study area. Our national connectivity map can help governments in Canada prioritize land management decisions to conserve and restore connectivity at both national and regional scales.

NMDA-induced superoxide production, which can lead to cell death at excessive levels, is widely believed to originate from mitochondria. Here, the authors find that, in both cultured neurons and mouse hippocampus, NADPH oxidase is actually the primary source of NMDA-induced superoxide production. Neuronal NMDA receptor (NMDAR) activation leads to the formation of superoxide, which normally acts in cell signaling. With extensive NMDAR activation, the resulting superoxide production leads to neuronal death. It is widely held that NMDA-induced superoxide production originates from the mitochondria, but definitive evidence for this is lacking. We evaluated the role of the cytoplasmic enzyme NADPH oxidase in NMDA-induced superoxide production. Neurons in culture and in mouse hippocampus responded to NMDA with a rapid increase in superoxide production, followed by neuronal death. These events were blocked by the NADPH oxidase inhibitor apocynin and in neurons lacking the p47 phox subunit, which is required for NADPH oxidase assembly. Superoxide production was also blocked by inhibiting the hexose monophosphate shunt, which regenerates the NADPH substrate, and by inhibiting protein kinase C zeta, which activates the NADPH oxidase complex. These findings identify NADPH oxidase as the primary source of NMDA-induced superoxide production.

In response to global declines in biodiversity, many global conservation prioritization schemes were developed to guide effective protected area establishment. Protected area coverage has grown dramatically since the introduction of several high-profile biodiversity prioritization schemes, but the impact of such schemes on protected area establishment has not been evaluated. We used matching methods and a Before-After Control-Impact causal analysis to evaluate the impact of two key prioritization schemes—Biodiversity Hotspots and Last of the Wild—representing examples of the reactive and proactive ends of the prioritization spectrum. We found that Last of the Wild had a positive impact on the rate of protection in its identified priority areas, but Biodiversity Hotspots did not. Because Biodiversity Hotspots are in or near human-dominated landscapes, this scheme may have been unable to overcome biases towards protecting areas with little human pressure. In contrast, Last of the Wild aligned with the tendency to protect areas far from high human use and thus with lower implementation costs, and so received greater uptake. Stronger links between large-scale prioritizations and more locally driven implementation of area-based conservation, as well as other forms of conservation action, are needed to overcome practical constraints and effectively protect biodiversity on an increasingly human-dominated planet.

ObjectivesThe objective of this systematic review was to examine the existing evidence base for the cost-effectiveness or cost-benefit of clinical quality registries (CQRs).DesignSystematic review and narrative synthesis.Data sourcesNine electronic bibliographic databases, including MEDLINE, EMBASE and CENTRAL, in the period from January 2000 to August 2019.Eligibility criteriaAny peer-reviewed published study or grey literature in English which had reported on an economic evaluation of one or more CQRs.Data extraction and synthesisData were screened, extracted and appraised by two independent reviewers. A narrative synthesis was performed around key attributes of each CQR and on key patient outcomes or changes to healthcare processes or utilisation. A narrative synthesis of the cost-effectiveness associated with CQRs was also conducted. The primary outcome was cost-effectiveness, in terms of the estimated incremental cost-effectiveness ratio (ICER), cost savings or return-on-investment (ROI) attributed to CQR implementation.ResultsThree studies and one government report met the inclusion criteria for the review. A study of the National Surgical Quality Improvement Programme (NSQIP) in the USA found that the cost-effectiveness of this registry improved over time, based on an ICER of US$8312 per postoperative event avoided. A separate study in Canada estimated the ROI to be US$3.43 per US$1.00 invested in the NSQIP. An evaluation of a post-splenectomy CQR in Australia estimated that registry cost-effectiveness improved from US$234 329 to US$18 358 per life year gained when considering the benefits accrued over the lifetime of the population. The government report evaluating five Australian CQRs estimated an overall return of 1.6–5.5 times the cost of investment.ConclusionsAvailable data indicate that CQRs can be cost-effective and can lead to significant returns on investment. It is clear that further studies that evaluate the economic and clinical impacts of CQRs are necessary.PROSPERO registration numberCRD42018116807.

Background Clinical quality registries (CQRs) monitor compliance against optimal practice and provide feedback to the clinical community and wider stakeholder groups. Despite a number of CQRs having incorporated the patient perspective to support the evaluation of healthcare delivery, no recommendations for inclusion of patient-reported outcome measures (PROMs) in CQRs exist. The aim of this study was to develop a core set of recommendations for PROMs inclusion of in CQRs. Method An online two-round Delphi survey was performed among CQR data custodians, quality of life researchers, biostatisticians and clinicians largely recruited in Australia. A list of statements for the recommendations was identified from a literature and survey of the Australian registries conducted in 2019. The statements were grouped into the following domains: rationale, setting, ethics, instrument, administration, data management, statistical methods, and feedback and reporting. Eighteen experts were invited to participate, 11 agreed to undertake the first online survey (round 1). Of these, nine experts completed the online survey for round 2. Results From 117 statements presented to the Delphi panel in round 1, a total of 72 recommendations (55 from round 1 and 17 from round 2) with median importance (MI) ≥ 7 and disagreement index (DI) < 1 were proposed for inclusion into the final draft set and were reviewed by the project team. Recommendations were refined for clarity and to read as stand-alone statements. Ten overlapped conceptually and, therefore, were merged to reduce repetition. The final 62 recommendations were sent for review to the panel members for their feedback, which was incorporated into the final set. Conclusion This is the first study to develop preliminary recommendations for PROMs inclusion in CQRs. Recommendations for PROMs implementation are critically important for registries to assure meaningful PROMs data capture, use, interpretation, and reporting to improve health outcomes and healthcare value.

Registry randomised clinical trials (RRCTs) have the potential to provide pragmatic answers to important clinical questions. RRCTs can be embedded into large population-based registries or smaller single site registries to provide timely answers at a reduced cost compared with traditional randomised controlled trials. RRCTs can take a number of forms in addition to the traditional individual-level randomised trial, including parallel group trials, platform or adaptive trials, cluster randomised trials and cluster randomised stepped-wedge trials. From an implementation perspective, initially it is advantageous to embed RRCT into well-established registries as these have typically already overcome any issues with end point validation and adjudication. With advances in data linkage and data quality, RRCTs can play an important role in answering clinical questions in a pragmatic, cost-effective way.

Guidelines recommend trans-radial access (TRA) for all percutaneous coronary intervention (PCI). However, no randomized trials have shown a lower mortality when compared to the femoral approach in chronic coronary disease and femoral access may be preferred in certain situations. Consecutive eligible patients in a multi-center registry between 2014 – 2020 were included. Clinical characteristics and outcomes were compared between those who underwent radial versus femoral access. The main outcomes were major bleeding and 5-year mortality. Of the 6,158 patients included, 3,784 (61.4%) had TRA and 2,374 (38.6%) femoral access. TRA predominated from 2016. The femoral group had higher rates of diabetes mellitus, renal dysfunction and prior stroke. Trans-femoral procedures were more complex with higher rates of ACC/AHA type B2/C lesions, chronic total occlusions, left main PCI, use of adjuvants including rotational atherectomy, and lower procedural success rates. Major bleeding was higher in the femoral group (radial 0.4% vs femoral 0.8%, p = 0.039), however femoral access did not predict major bleeding (OR 1.68, 95% CI 0.74 to 3.82). There was no difference in 5-year mortality (radial 20.3% vs femoral 21%, p = 0.65). In conclusion, TRA predominates in contemporary PCI for CCD. The femoral group had higher procedural complexity and risk with a higher incidence of peri‑procedural major bleeding. Nonetheless, femoral access did not predict major bleeding and there was no difference in 5-year mortality as compared to TRA. In the absence of a contemporary randomized trial, the femoral approach appears reasonable if clinically preferred in patients with chronic coronary disease undergoing PCI. •No randomized studies have shown trans-radial access (TRA) lowers mortality as compared to the femoral approach in patients with chronic coronary disease (CCD) undergoing PCI.•Contemporary techniques in PCI including access have evolved which may improve outcomes.•In this study, although femoral access had a higher rate of major bleeding overall, the femoral approach was not an independent predictor of major bleeding and there was no difference compared to TRA after 2018 which may reflect improved safety of contemporary techniques.•There was no difference in 5-year mortality despite the femoral group having a higher risk profile and case complexity.•Contemporary femoral access appears safe and in the absence of a randomized controlled trial in patients with CCD, this study suggests femoral access is reasonable if clinically preferred. [Display omitted]

Clinical trials have shown that radial access percutaneous coronary intervention (PCI) is associated with improved patient outcomes compared to femoral artery access. However, few studies have evaluated the cost-effectiveness of radial access PCI. This analysis sought to evaluate the cost-effectiveness of transradial versus transfemoral access PCI for patients with acute coronary syndrome (ACS) using data from the Minimizing Adverse Hemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox (MATRIX) trial. A decision analytic Markov model was constructed from an Australian health care perspective with a 2 year time horizon. The model simulated recurrent cardiovascular disease and death post PCI among a hypothetical cohort of 1000 individuals with ACS. Population and efficacy data were based on the MATRIX trial. Cost and utility data were drawn from published sources. Over a 2-year time horizon, radial access was predicted to save 12 (discounted) quality adjusted life years (QALYs) compared with femoral access PCI. Cost savings (discounted) amounted to AUD $51,305. Hence from a health economic point of view, radial access PCI was dominant over femoral access PCI. Sensitivity analyses supported the robustness of these findings. Radial access PCI is likely to be associated with both better outcomes and lower costs compared to femoral access PCI over 2 years post procedure. In conclusion, these findings support radial access being the preferred approach in PCI for ACS.

Measuring patient reported outcomes can improve the quality and effectiveness of healthcare interventions. The aim of this study was to identify the final set of items that can be included in a patient-reported outcome measure to assess recovery of patients following percutaneous coronary interventions. A consecutive sample of 200 patients registered in the Victorian Cardiac Outcomes Registry participated in a telephone survey 30 days following their percutaneous cardiac procedure. Rasch analysis was used to select the best set of items to form a concise and psychometrically sound patient-reported outcome measure. Key measurement properties assessed included overall fit to the Rasch measurement model, unidimensionality, response formats (thresholds), targeting, internal consistency and measurement invariance. Five items were identified as being reliable and valid measures of patient-reported outcomes: pain or discomfort, shortness of breath, confidence in performing usual activities, feeling unhappy and having trouble sleeping. Data showed overall fit to a Rasch model of expected item functioning (χ2 16.99; p = 0.07) and all items demonstrated unidimensionality (t-test less than 0.05 threshold value). Internal consistency was acceptable (equivalent Cronbach's α 0.65) given there are only five items, but there was a ceiling effect (mean logit score -1.24) with compromised score precision for patients with better recovery. We identified a succinct set of items that can be used in a patient-reported outcome measure following percutaneous coronary interventions. This patient-report outcome measure has good structural validity and acceptable internal consistency. While further psychometric evaluations are recommended, the items identified capture the patient's perspective of their recovery following a percutaneous coronary intervention.

Patients with acute coronary syndrome (ACS)-related cardiogenic shock (CS) with or without concomitant CA may have disparate prognoses. We compared clinical characteristics and outcomes of patients with CS secondary to ACS with and without cardiac arrest (CA). Between 2014 and 2020, 1,573 patients with ACS-related CS with or without CA who underwent percutaneous coronary intervention enrolled in a multicenter Australian registry were analyzed. Primary outcome was 30-day major adverse cardiovascular and cerebrovascular events (MACCE) (composite of mortality, myocardial infarction, stent thrombosis, target vessel revascularization and stroke). Long-term mortality was obtained through linkage to the National Death Index. Compared with the no-CA group (n = 769, 49%), the CA group (n = 804, 51%) was younger (62 vs 69 years, p <0.001) and had fewer comorbidities. Patients with CA more frequently had ST-elevation myocardial infarction (92% vs 86%), occluded left anterior descending artery (43% vs 33%), and severe preprocedural renal impairment (49% vs 42%) (all p <0.001). CA increased risk of 30-day MACCE by 45% (odds ratio 1.45, 95% confidence interval 1.05 to 2.00, p = 0.024) after adjustment. CA group had higher 30-day MACCE (55% vs 42%, p <0.001) and mortality (52% vs 37%, p <0.001). Three-year survival was lower for CA compared with no-CA patients (43% vs 52%, p <0.001). In Cox regression, CS with CA was associated with a trend toward greater long-term mortality hazard (hazard ratio 1.19, 95% confidence interval 1.00 to 1.41, p = 0.055). In conclusion, concomitant CA among patients with ACS-related CS conferred a particularly heightened short-term risk with a diminishing legacy effect over time for mortality. CS survivors continue to exhibit high sustained long-term mortality hazard regardless of CA status.