Effect of treatment of clinical seizures vs electrographic seizures in full-term and near-term neonates : a randomized clinical trial

Importance: Seizures in the neonatal period are associated with increased mortality and morbidity. Bedside amplitude-integrated electroencephalography (aEEG) has facilitated the detection of electrographic seizures; however, whether these seizures should be treated remains uncertain. Objective: To determine if the active management of electrographic and clinical seizures in encephalopathic term or near-term neonates improves survival free of severe disability at 2 years of age compared with only treating clinically detected seizures. Design, Setting, and Participants: This randomized clinical trial was conducted in tertiary newborn intensive care units recruited from 2012 to 2016 and followed up until 2 years of age. Participants included neonates with encephalopathy at 35 weeks’ gestation or more and younger than 48 hours old. Data analysis was completed in April 2021. Interventions: Randomization was to an electrographic seizure group (ESG) in which seizures detected on aEEG were treated in addition to clinical seizures or a clinical seizure group (CSG) in which only seizures detected clinically were treated. Main Outcomes and Measures: Primary outcome was death or severe disability at 2 years, defined as scores in any developmental domain more than 2 SD below the Australian mean assessed with Bayley Scales of Neonate and Toddler Development, 3rd ed (BSID-III), or the presence of cerebral palsy, blindness, or deafness. Secondary outcomes included magnetic resonance imaging brain injury score at 5 to 14 days, time to full suck feeds, and individual domain scores on BSID-III at 2 years. Results: Of 212 randomized neonates, the mean (SD) gestational age was 39.2 (1.7) weeks and 122 (58%) were male; 152 (72%) had moderate to severe hypoxic-ischemic encephalopathy (HIE) and 147 (84%) had electrographic seizures. A total of 86 neonates were included in the ESG group and 86 were included in the CSG group. Ten of 86 (9%) neonates in the ESG and 4 of 86 (4%) in the CSG died before the 2-year assessment. The odds of the primary outcome were not significantly different in the ESG group compared with the CSG group (ESG, 38 of 86 [44%] vs CSG, 27 of 86 [31%]; odds ratio [OR], 1.83; 95% CI, 0.96 to 3.49; P = .14). There was also no significant difference in those with HIE (OR, 1.77; 95% CI, 0.84 to 3.73; P = .26). There was evidence that cognitive outcomes were worse in the ESG (mean [SD] scores, ESG: 97.4 [17.7] vs CSG: 103.8 [17.3]; mean difference, −6.5 [95% CI, −1.2 to −11.8]; P = .01). There was little evidence of a difference in secondary outcomes, including time to suck feeds, seizure burden, or brain injury score. Conclusions and Relevance: Treating electrographic and clinical seizures with currently used anticonvulsants did not significantly reduce the rate of death or disability at 2 years in a heterogeneous group of neonates with seizures

Better Regional Ocean Observing Through Cross-National Cooperation: A Case Study From the Northeast Pacific

The ocean knows no political borders. Ocean processes, like summertime wind-driven upwelling, stretch thousands of kilometers along the Northeast Pacific (NEP) coast. This upwelling drives marine ecosystem productivity and is modulated by weather systems and seasonal to interdecadal ocean-atmosphere variability. Major ocean currents in the NEP transport water properties such as heat, fresh water, nutrients, dissolved oxygen, pCO2, and pH close to the shore. The eastward North Pacific Current bifurcates offshore in the NEP, delivering open-ocean signals south into the California Current and north into the Gulf of Alaska. There is a large and growing number of NEP ocean observing elements operated by government agencies, Native American Tribes, First Nations groups, not-for-profit organizations, and private entities. Observing elements include moored and mobile platforms, shipboard repeat cruises, as well as land-based and estuarine stations. A wide range of multidisciplinary ocean sensors are deployed to track, for example, upwelling, downwelling, ocean productivity, harmful algal blooms, ocean acidification and hypoxia, seismic activity and tsunami wave propagation. Data delivery to shore and observatory controls are done through satellite and cell phone communication, and via seafloor cables. Remote sensing from satellites and land-based coastal radar provide broader spatial coverage, while numerical circulation and biogeochemical modeling complement ocean observing efforts. Models span from the deep ocean into the inland Salish Sea and estuaries. NEP ocean observing systems are used to understand regional processes and, together with numerical models, provide ocean forecasts. By sharing data, experiences and lessons learned, the regional ocean observatory is better than the sum of its parts

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

Modeling intermittent cycling performance in hypoxia using the critical power concept

PURPOSE: This study investigated the efficacy of an intermittent critical power model, termed the &quot;work-balance&quot; (W\u27BAL) model, during high-intensity exercise in hypoxia. METHODS: Eleven trained, male cyclists (mean &plusmn; SD; age 27 &plusmn; 6.6 yr, V[Combining Dot Above]O2peak 4.79 &plusmn; 0.56 L.min) completed a maximal ramp test and a 3 min &quot;all-out&quot; test to determine critical power (CP) and work performed above CP (W\u27). On another day an intermittent exercise test to task failure was performed. All procedures were performed in normoxia (NORM) and hypoxia (HYPO; FiO2 &asymp; 0.155) in a single-blind, randomized and counter-balanced experimental design. The W\u27BAL model was used to calculate the minimum W\u27 (W\u27BALmin) achieved during the intermittent test. W\u27BALmin in HYPO was also calculated using CP + W\u27 derived in NORM (N+H). RESULTS: In HYPO there was an 18% decrease in V[Combining Dot Above]O2peak (4.79 &plusmn; 0.56 vs 3.93 &plusmn; 0.47 L.min ; P&lt;0.001) and a 9% decrease in CP (347 &plusmn; 45 vs 316 &plusmn; 46 W; P&lt;0.001). No significant change for W\u27 occurred (13.4 &plusmn; 3.9 vs 13.7 &plusmn; 4.9 kJ; P=0.69; NORM vs HYPO). The change in V[Combining Dot Above]O2peak was significantly correlated with the change in CP (r = 0.72; P=0.01). There was no difference between NORM and HYPO for W\u27BALmin (1.1 &plusmn; 0.9 kJ vs 1.2 &plusmn; 0.6 kJ). The N+H analysis grossly overestimated W\u27BALmin (7.8 &plusmn; 3.4 kJ) compared with HYPO (P&lt;0.001). CONCLUSION: The W\u27BAL model produced similar results in hypoxia and normoxia, but only when model parameters were determined under the same environmental conditions as the performance task. Application of the W\u27BAL model at altitude requires a modification of the model, or that CP and W\u27 are measured at altitude

Adoption and use of guidelines for whiplash: an audit of insurer and health professional practice in New South Wales, Australia

Abstract Background In Australia, the New South Wales (NSW) State Insurance Regulatory Authority has been continuously developing and implementing clinical practice guidelines to address the health and economic burden from whiplash associated disorders (WAD). Despite this, it is uncertain the extent to which the guidelines are followed. This study aimed to determine insurer and health professional compliance with recommendations of the 2014 NSW clinical practice guidelines for the management of acute WAD; and explore factors related to adherence. Methods This was an observational study involving an audit of 288 randomly-selected claimant files from 4 insurance providers in NSW, Australia between March and October 2016. Data extracted included demographic, claim and injury details, use of health services, and insurer and health professional practices related to the guidelines. Analyses involved descriptive statistics and correlation analysis. Results Median time for general practitioner medical consultation was 4 days post-injury and 25 days for physical treatment (e.g. physiotherapy). Rates of x-ray investigations were low (21.5%) and most patients (90%) were given active treatments in line with the guideline recommendations. The frequency of other practices recommended by the guidelines suggested lower guideline adherence in some areas such as; using the Quebec Task Force classification (19.9%); not using specialised imaging for WAD grades I and II (e.g. MRI, 45.8%); not using routine passive treatments (e.g. manual therapy, 94.0%); and assessing risk of non-recovery using relevant prognostic tools (e.g. Neck Disability Index, 12.8%). Over half of the claimants (59.0%) were referred to other professionals at 9–12 weeks post-injury, among which 31.2% were to psychologists and 68.8% to specialists (surgical specialists, 43.6%; WAD specialists, 20.5%). Legal representation and lodgment of full claim were associated with increased number of medical visits and imaging (ρ 0.23 to 0.3; p < 0.01). Conclusion There is evidence of positive uptake of some guideline recommendations by insurers and health professionals; however, there are practices that are not compliant and might lead to poor health outcomes and greater treatment cost. Organisational, regulatory and professional implementation strategies may be considered to change practice, improve scheme performance and ultimately improve outcomes for people with WAD

Additional file 1: of Adoption and use of guidelines for whiplash: an audit of insurer and health professional practice in New South Wales, Australia

Appendix 1. Insurer and health professional data collected based on recommendations of the guidelines. Appendix 2. Quebec Task Force classification of grades of WAD. Appendix 3. Flow diagram of claimant files included in the study. (DOCX 37 kb