Transforming nursing assessment in acute hospitals: A cluster randomised controlled trial of an evidence-based nursing core assessment (the ENCORE trial).

BACKGROUND: Patient safety is threatened when early signs of clinical deterioration are missed or not acted upon. This research began as a clinical-academic partnership established around a shared concern of nursing physical assessment practices on general wards and delayed recognition of clinical deterioration. The outcome was the development of a complex intervention facilitated at the ward level for proactive nursing surveillance. METHODS: The evidence-based nursing core assessment (ENCORE) trial was a pragmatic cluster-randomised controlled trial. We hypothesised that ward intervention would reduce the incidence of patient rescue events (medical emergency team activations) and serious adverse events. We randomised 29 general wards in a 1:2 allocation, across 5 Australian hospitals to intervention (n = 10) and usual care wards (n = 19). Skilled facilitation over 12 months enabled practitioner-led, ward-level practice change for proactive nursing surveillance. The primary outcome was the rate of medical emergency team activations and secondary outcomes were unplanned intensive care unit admissions, on-ward resuscitations, and unexpected deaths. Outcomes were prospectively collected for 6 months following the initial 6 months of implementation. Analysis was at the patient level using generalised linear mixed models to account for clustering by ward. RESULTS: We analysed 29,385 patient admissions to intervention (n = 11,792) and control (n = 17,593) wards. Adjusted models for overall effects suggested the intervention increased the rate of medical emergency team activations (adjusted incidence rate ratio 1.314; 95 % confidence interval 0.975, 1.773), although the confidence interval was compatible with a marginal decrease to a substantial increase in rate. Confidence intervals for secondary outcomes included a range of plausible effects from benefit to harm. However, considerable heterogeneity was observed in intervention effects by patient comorbidity. Among patients with few comorbid conditions in the intervention arm there was a lower medical emergency team activation rate and decreased odds of unexpected death. Among patients with multimorbidity in the intervention arm there were higher rates of medical emergency team activation and intensive care unit admissions. CONCLUSION: Trial outcomes have refined our assumptions about the impact of the ENCORE intervention. The intervention appears to have protective effects for patients with low complexity where frontline teams can respond locally. It also appears to have redistributed medical emergency team activations and unplanned intensive care unit admissions, mobilising higher rates of rescue for patients with multimorbidity. TRIAL REGISTRATION NUMBER: ACTRN12618001903279 (Date of registration: 22/11/2018; First participant recruited: 01/02/2019).

Changes in and correlates of Australian public attitudes toward illicit drug use.

INTRODUCTION: The present study explores Australian public support for more lenient treatment of persons found in possession of small amounts of illegal drugs for personal use. METHODS: Data for the study are drawn from the 2013, 2016 and 2019 National Drug Strategy Household Surveys. Bivariate associations were tested using χ2 tests corrected for survey design. Multivariate analyses of public support for legalisation and imprisonment involved logistic regression. Multivariate analyses of public preferences for various responses to those found in possession of illicit drugs involved the use of multinomial regression. RESULTS: Support for legalising personal use of three drugs (cannabis, ecstasy and cocaine) has risen significantly since 2013 but remained stable (and low) for two (heroin and methamphetamine). Support for no action, a caution or a warning has grown for those found in possession of cannabis, ecstasy and heroin for personal use but not for those found in possession of methamphetamine. There is, however, more support for responding to this group with treatment, education or a small fine than there is for imprisonment. DISCUSSION AND CONCLUSION: There is strong support for legalising use of cannabis. There is little support for legalising use of ecstasy and cocaine but growing public support for a less punitive approach to those who use these drugs. There is little public support for a change in the current approach to heroin and methamphetamine.

The Australian ready-to-drink beverages tax missed its target age group.

BACKGROUND: During 2008 and 2009, the Australian Government increased the tax on ready-to-drink alcoholic beverages by 70% to discourage drinking among adolescents. METHODS: To evaluate the tax, we use the difference-in-difference and comparative interrupted time series estimators, where age is used to define the control and treatment groups. This methodology is applied to the Household Income and Labour Dynamics in Australia survey. RESULTS: We show that the tax did not affect the alcohol consumption of those aged under 25 (the tax targeted age group) but substantially reduced drinking among those aged 25-69, reducing their average daily consumption of standard drinks by 8.9% from 2010 to 2018. CONCLUSION: The age group under 25 did not respond to the tax likely because of product substitution. Alcohol price policy may need to acknowledge complex substitute/complement relationships between beverages and consider a floor price on alcohol or a uniform volumetric tax per standard drink.

Randomized double-blind clinical trial comparing safety and efficacy of the biosimilar BCD-022 with reference trastuzumab.

BACKGROUND: BCD-022 is a trastuzumab biosimilar which was shown to be equivalent to reference trastuzumab in a wide panel of physicochemical studies as well as preclinical studies in vitro and in vivo. International multicenter phase III clinical trial was conducted to comparatively assess efficacy and safety of BCD-022 and reference trastuzumab in combination with paclitaxel used as the therapy of metastatic HER2(+) breast cancer. Pharmacokinetics and immunogenicity were also studied. METHODS: Patients with no previous treatment for metastatic HER2(+) breast cancer were randomly assigned 1:1 to BCD-022 or reference trastuzumab and were treated with trastuzumab + paclitaxel. Therapy continued for 6 cycles of therapy (every 3 weeks), until progression of the disease or unbearable toxicity. Primary study endpoint was overall response rate. Study goal was to prove equivalent efficacy of BCD-022 and reference trastuzumab. Equivalence margins for 95% CI for difference in overall response rates were set at [- 20%; 20%]. RESULTS: In total 225 patients were enrolled into the study, 115 in BCD-022 arm and 110 in reference trastuzumab arm. Overall response rate was 49.6% in BCD-022 arm and 43.6% in reference trastuzumab arm. Limits of 95% CI for difference of overall response rates between arms were [(- 8.05)-19.89%], thus, they lied within predetermined equivalence margins [- 20%; 20%]. Profile of adverse events was similar between groups (any AEs were reported in 93.81% of patients in BCD-022 arm and 94.55% of patients in reference arm). No unexpected adverse reactions were reported throughout the study. No statistically significant differences regarding antibody occurrence rate (either BAb or NAb) was found between BCD-022 (n = 3; 2.65%) and comparator (n = 4; 3.64%). Both drug products are characterized with low occurrence rate and short life of anti-trastuzumab antibodies. Pharmacokinetics assessment after 1st and 6th study drug injection also demonstrated equivalent PK parameters by all outcome measures: AUC0-504, Сmах, Тmax, T1/2. Analysis of Ctrough did not reveal any significant inter-group differences as well. CONCLUSIONS: Thus, results of this study have demonstrated therapeutic equivalence of trastuzumab biosimilar BCD-022 and referent trastuzumab drug. TRIAL REGISTRATION: The trial was registered with ClinicalTrials.gov (Study Number NCT01764022 ). The date of registration was January 9, 2013.

Rituximab biosimilar and reference rituximab in patients with previously untreated advanced follicular lymphoma (ASSIST-FL): primary results from a confirmatory phase 3, double-blind, randomised, controlled study.

BACKGROUND: GP2013 is a rituximab biosimilar developed to stringent development guidelines, including non-clinical and preclinical investigations and clinical trials in rheumatoid arthritis and follicular lymphoma. We aimed to compare the efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of GP2013 plus cyclophosphamide, vincristine, and prednisone (GP2013-CVP) with rituximab-CVP (R-CVP) in patients with follicular lymphoma. METHODS: In this phase 3, multinational, double-blind, randomised, controlled trial, adults (aged 18 years or older) with previously untreated, advanced stage (Ann Arbor stage III or IV) follicular lymphoma of WHO histological grades 1, 2, or 3a were randomly assigned (1:1) using interactive response technology to eight cycles of GP2013-CVP or R-CVP (combination phase), followed by monotherapy maintenance in responders for a 2-year period. Randomisation was stratified by Follicular Lymphoma International Prognostic Index risk group and geographic region. The primary endpoint was comparability in overall response, with equivalence concluded if the entire 95% CI was within a margin of -12% to 12%. The primary endpoint was analysed using the per-protocol set, which included all patients who received at least one (partial or complete) dose of investigational treatment and who did not have any major protocol deviations. The trial is registered with ClinicalTrials.gov, number NCT01419665, and is ongoing. FINDINGS: Between Dec 1, 2011, and Jan 15, 2015, 858 patients were screened for eligibility. 314 patients were randomly assigned to GP2013, of whom 312 were given GP2013, and 315 were assigned to reference rituximab. Median follow-up was 11·6 months (IQR 5·8-18·2) for the primary analysis. The primary endpoint, equivalence of overall response, was met (271 [87%] of 311 patients with GP2013 and 274 [88%] of 313 patients with reference rituximab achieved an overall response; difference -0·40% [95% CI -5·94 to 5·14]). Occurrence of adverse events and serious adverse events was similar between the treatment groups (289 [93%] of 312 patients in the GP2013-CVP group had an adverse event and 71 [23%] of 312 patients had a serious adverse event; 288 [91%] of 315 patients in the R-CVP group had an adverse event and 63 [20%] had a serious adverse event). The most common adverse event was neutropenia (80 [26%] of 312 patients in the GP2013-CVP group and 93 [30%] of 315 patients in the R-CVP group in the combination phase and 23 [10%] of 231 patients in the GP2013-CVP group and 13 [6%] of 231 patients in the R-CVP group in the maintenance phase). The most common grade 3 or 4 adverse event during the combination and maintenance phase was neutropenia (55 [18%] of 312 patients in the GP2013-CVP group and 65 [21%] of 315 patients in the R-CVP group in the combination phase and 17 [7%] of 231 patients in the GP2013-CVP group and nine [4%] of 231 patients in the R-CVP group in the maintenance phase). The occurrence of anti-drug antibodies was similar in the treatment groups (five [2%] of 268 patients in the GP2013-CVP; three [1%] in the R-CVP group). INTERPRETATION: Our results show that GP2013 represents a viable rituximab biosimilar candidate for patients with previously untreated advanced follicular lymphoma. The introduction of biosimilars provides additional therapeutic options with potential to increase access to effective and life-saving biological therapies such as rituximab. FUNDING: Hexal.