Australian health care providers' views on opt-out HIV testing

Background: Opt-out HIV testing is a novel concept in Australia. In the opt-out approach, health care providers (HCPs) routinely test patients for HIV unless they explicitly decline or defer. Opt-out HIV testing is only performed with the patients' consent, but pre-test counselling is abbreviated. Australian national testing guidelines do not currently recommend opt-out HIV testing for the general population. Non-traditional approaches to HIV testing (such as opt-out) could identify HIV infections and facilitate earlier treatment, which is particularly important now that HIV is a chronic, manageable disease. Our aim was to explore HCPs' attitudes toward opt-out HIV testing in an Australian context, to further understanding of its acceptability and feasibility. Methods: In this qualitative study, we used purposeful sampling to recruit HCPs who were likely to have experience with HIV testing in Western Australia. We interviewed them using a semi-structured guide and used content analysis as per Graneheim to code the data. Codes were then merged into subcategories and finally themes that unified the underlying concepts. We refined these themes through discussion among the research team. Results: Twenty four HCPs participated. Eleven participants had a questioning attitude toward opt-out HIV testing, while eleven favoured the approach. The remaining two participants had more nuanced perspectives that incorporated some characteristics of the questioning and favouring attitudes. Participants' views about opt-out HIV testing largely fell into two contrasting themes: normalisation and routinisation versus exceptionalism; and a need for proof versus openness to new approaches. Conclusion: Most HCPs in this study had dichotomous attitudes toward opt-out HIV testing, reflecting contrasting analytical styles. While some HCPs viewed it favourably, with the perceived benefits outweighing the perceived costs, others preferred to have evidence of efficacy and cost-effectiveness

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Heterogeneous treatment effects of therapeutic-dose heparin in patients hospitalized for COVID-19

Importance Randomized clinical trials (RCTs) of therapeutic-dose heparin in patients hospitalized with COVID-19 produced conflicting results, possibly due to heterogeneity of treatment effect (HTE) across individuals. Better understanding of HTE could facilitate individualized clinical decision-making. Objective To evaluate HTE of therapeutic-dose heparin for patients hospitalized for COVID-19 and to compare approaches to assessing HTE. Design, Setting, and Participants Exploratory analysis of a multiplatform adaptive RCT of therapeutic-dose heparin vs usual care pharmacologic thromboprophylaxis in 3320 patients hospitalized for COVID-19 enrolled in North America, South America, Europe, Asia, and Australia between April 2020 and January 2021. Heterogeneity of treatment effect was assessed 3 ways: using (1) conventional subgroup analyses of baseline characteristics, (2) a multivariable outcome prediction model (risk-based approach), and (3) a multivariable causal forest model (effect-based approach). Analyses primarily used bayesian statistics, consistent with the original trial. Exposures Participants were randomized to therapeutic-dose heparin or usual care pharmacologic thromboprophylaxis. Main Outcomes and Measures Organ support–free days, assigning a value of −1 to those who died in the hospital and the number of days free of cardiovascular or respiratory organ support up to day 21 for those who survived to hospital discharge; and hospital survival. Results Baseline demographic characteristics were similar between patients randomized to therapeutic-dose heparin or usual care (median age, 60 years; 38% female; 32% known non-White race; 45% Hispanic). In the overall multiplatform RCT population, therapeutic-dose heparin was not associated with an increase in organ support–free days (median value for the posterior distribution of the OR, 1.05; 95% credible interval, 0.91-1.22). In conventional subgroup analyses, the effect of therapeutic-dose heparin on organ support–free days differed between patients requiring organ support at baseline or not (median OR, 0.85 vs 1.30; posterior probability of difference in OR, 99.8%), between females and males (median OR, 0.87 vs 1.16; posterior probability of difference in OR, 96.4%), and between patients with lower body mass index (BMI 90% for all comparisons). In risk-based analysis, patients at lowest risk of poor outcome had the highest propensity for benefit from heparin (lowest risk decile: posterior probability of OR >1, 92%) while those at highest risk were most likely to be harmed (highest risk decile: posterior probability of OR <1, 87%). In effect-based analysis, a subset of patients identified at high risk of harm (P = .05 for difference in treatment effect) tended to have high BMI and were more likely to require organ support at baseline. Conclusions and Relevance Among patients hospitalized for COVID-19, the effect of therapeutic-dose heparin was heterogeneous. In all 3 approaches to assessing HTE, heparin was more likely to be beneficial in those who were less severely ill at presentation or had lower BMI and more likely to be harmful in sicker patients and those with higher BMI. The findings illustrate the importance of considering HTE in the design and analysis of RCTs. Trial Registration ClinicalTrials.gov Identifiers: NCT02735707, NCT04505774, NCT04359277, NCT0437258

Additive treatment considerations in COVID‐19—The clinician’s perspective on extracorporeal adjunctive purification techniques

The aim of this document was to inform the scientific community of sparse preliminary results regarding advanced supportive therapies and technology-driven systems in addition to highlighting the benefits and possibilities of performing concise research during challenging times. Advanced organ support for lung and heart offers the possibility to buy the time needed for recovery. However, remaining a bridging strategy, extracorporeal life support cannot act as the ultimate treatment for the underlying COVID-19 disease. Appropriate patient selection criteria addressed by experts and scientific organizations, such as Extracorporeal Life Support Organization and World Health Organization, may provide significant help in the difficult decision-making and to reduce mortality in patients with profound respiratory and/or cardiac failure due to COVID-19. Severe, systemic cytokine-mediated inflammation associated with the SARS-CoV-2 has also been described. Effects of crosstalk between coagulation and inflammatory pathways appear to significantly affect disease progression and lead to poor outcomes. Multiple therapeutic strategies, including antibody therapies (such as Tocilizumab, Sarilumab, Siltuximab), therapeutic plasma exchange (TPE), and blood purification techniques for direct removal of cytokines, including filtration, dialysis (diffusion), and adsorption are available. Further, we believe, that research should be facilitated and promoted, particularly under the guidance of recognized scientific societies or expert-based multicenter investigation, with rapid communication of critical and relevant information to enhance better appraisal of patient profiles, complications, and treatment modalities.</p

An Open-Label, Dose-Response Study of CM4620-Injectable Emulsion in Emergency Department Patients With Acute Pancreatitis

Study Objectives: Hyperactivation of Calcium Release-Activated Calcium (CRAC) channels results in excessive Ca2+ influx in acinar cells and plays a pivotal role in cellular injury and the progression of acute pancreatitis. Our purpose was to evaluate the efficacy of CM4620-IE, a potent selective CRAC channel inhibitor, to improve outcomes in ED patients with acute pancreatitis. Methods: This was a 2 phase, open-label, multicenter, placebo controlled dose-response pilot study enrolling patients with acute pancreatitis (AP), who met SIRS criteria, and who had a room air SpO2 \u3c96% (NCT03401190). Patients were randomized in a 3:1 fashion to CM4620-IE or placebo, in all phases. In phase 1, patients received 1.0 mg/kg on day 1 and 1.4 mg/kg on Days 2-4. In phase 2, females had the same dose of CM4620-IE as in the 1st phase, and males received 2.08 mg/kg of CM4620-IE on Days 1-2, and 1.6 mg/kg on Days 3-4. Patients were discharged after meeting local criteria, potentially before completion of study drug. All patients had pancreatic CT imaging before randomization and again at the earliest of days 5-7 or discharge. CTs, read by a central reader blinded to therapy, were graded as severe AP (SAP), moderately SAP (MSAP), or mild AP (MAP) using the CT severity index (CTSI) scoring system. All patients had daily dietary assessments, and tolerating a solid diet was defined as eating \u3e50% of a solid meal. Results: Of 21 patients, 14 received CM4620-IE and 7 placebo. Five females and 3 males received low dose and 6 males received the high dose CM4620-IE. In both phases, all CM4620-IE patients received a median of 3 doses. The median age, baseline SpO2, number of patients with \u3e2 SIRS criteria, and percent of patients with MSAP or SAP on the initial CT were comparable between CM4620-IE and placebo. The results are presented in Table 1. No serious adverse events were reported as being drug-related. Conclusion: CM4620-IE was well tolerated, was not associated with an increase in serious adverse events and had multiple efficacy signals that warrant further clinical development and a larger Phase 2b/3 study