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OBJECTIVE: To describe changes in palliative care characteristics, utilisation and outcomes in Victoria during a period of enhanced public health management and a prolonged lockdown due to coronavirus disease 2019. METHODS: A national retrospective cohort study with palliative care service setting comparisons in Victoria and other mainland states was conducted. RESULTS: Analysis of 48 non-Victorian services (n=53,428 patients) and 20 Victorian services (n=31,125 patients) showed that for community services, patient volume, average length of stay, functional dependency and the proportion of admissions in a deteriorating phase increased during the lockdown in Victoria, yet little changed in comparator states. Regarding inpatient services, the management of family/carer problems remained constant in comparator states, yet substantial fluctuations in outcomes in Victoria were observed. CONCLUSIONS: As health systems adapt to changing circumstances during the pandemic, the ability to upscale community services is critical. Addressing the implications of shifting inpatient care to the community needs attention. IMPLICATIONS FOR PUBLIC HEALTH: Our study highlights the need to ensure community care providers are adequately considered within public health management responses. 'Joined up' policy and implementation across care settings are essential, especially as major barriers to infection control and increased utilisation may be evident in the community during the coronavirus disease 2019 pandemic.
Subject(s)
COVID-19 , Community Health Services , Palliative Care , Humans , Communicable Disease Control , COVID-19/epidemiology , Public Health , Retrospective Studies , Health Policy , PandemicsABSTRACT
Background. There is a continued need for therapeutics for the treatment of COVID-19, including intramuscular (IM) agents, which will enable broader use across a variety of healthcare delivery settings. Methods. COMET-PEAK (NCT04779879) is a 3-part study evaluating the safety, tolerability, pharmacokinetics (Part A), and viral pharmacodynamics (PD) of sotrovimab as treatment in adults >= 18 years with early mild/moderate COVID-19. In Parts B and C, the safety, tolerability and viral PD of sotrovimab administered as a 500 mg intravenous (IV) infusion or as a 500 mg or 250 mg IM injection, respectively, was evaluated. The primary objective for Parts B and C was to compare the virologic response of sotrovimab IM to IV, with an endpoint of mean area under the curve (AUC) of SARS-CoV-2 viral load as measured by qRT-PCR from Day 1 to Day 8 (AUCD1-8) in nasopharyngeal swabs and predefined 90% confidence interval (CI) limits of 0.5-2.0 indicating equivalence. Results. A total of 167 and 157 participants were enrolled in Part B and C, respectively, from February-July 2021. The median age of participants was 47 and 42 years in Part B and C, respectively, and ~50% had >= 1 risk factor for progression to severe disease. The viral load at baseline and through Day 29 of follow-up for each arm is shown in Table 1 and Figure 1. The primary objective was met for both study parts: the ratio of the least square geometric mean viral load AUC(D1-8) of sotrovimab IM vs IV was 1.04 (90% CI, 0.98, 1.09) and 1.02 (90% CI, 0.94, 1.11), for Part B and C, respectively. Through Day 29 of follow-up, the most common adverse event was injection site reactions (ISRs) in the IM arms. A total of 10 (12%) participants in the 500 mg IM group and 4 (5%) participants in the 250 mg IM group experienced an ISR, all Grade 1. Serious adverse events were uncommon, and related to COVID-19 progression, including one death in the 250 mg IM arm (Table 2). ISRs aside, there were few treatment-related AEs (2/84 IV, 1/82 IM) in Part B, none serious. Conclusion. IM administration of sotrovimab 500 mg and 250 mg each demonstrated equivalence to 500 mg sotrovimab IV in viral load assessments. Overall, there were no treatment-related serious AEs and sotrovimab was well tolerated. An 500 mg IM formulation will allow for expanded treatment potential with sotrovimab.
ABSTRACT
Background. Sotrovimab is a human monoclonal antibody targeting a conserved region of the SARS-CoV-2 spike (S) protein. COMET-PEAK was a 3-part, phase 2 study that evaluated intravenous (500 mg) and intramuscular (500 mg and 250 mg) administration of sotrovimab in outpatients (n=353) with mild-to-moderate COVID-19. We assessed amino acid substitutions in the SARS-CoV-2 S protein and circulating variants of concern/interest (VOC/VOI) in COMET-PEAK participants (enrolled Feb-July 2021). Methods. Mid-turbinate (Part A) or nasopharyngeal (Part B/C) samples were obtained from all participants at Baseline and Post-Baseline visits. Next generation sequencing of the SARS-CoV-2 S gene was conducted using Illumina MiSeq with a >=5% allelic frequency cut-off for samples with a viral load above 3.0 log10 copies/mL. Baseline, post-baseline and treatment-emergent (TE) substitutions were assessed, and prevalence of VOC/VOI was evaluated. Phenotypic analyses of epitope substitutions were conducted using a pseudotyped virus assay. Results. In total, 282/353 participants had sequencing results for >=1 visit (253 baseline, 248 post-baseline), and 219 had paired baseline and post-baseline sequences;among these, 149 (68%) had TE substitutions in the S protein (26 [12%] in the epitope). E340K was the predominant TE substitution in the epitope (15 [7%]). Across all arms 92/245 (38%) experienced virologic rebound, 8 of whom (Part A: 2;Part B: 2;Part C: 4) had TE substitutions in the epitope;none had evidence of clinical progression to severe disease. Prevalence of VOC/VOI or single amino acid substitutions of concern was 94% (266/282);the most frequent were Alpha (Part A: 8/16 [50%];Part B: 75/128 [59%]) and Delta (Part C: 99/122 [81%]). Of 7 participants with evidence of clinical progression, none had S protein substitutions in the epitope and all hadVOC/VOI (3Alpha, 3 Delta, 1 Gamma). Sotrovimab effectively neutralized most epitope substitutions tested in vitro;P337L and E340A/K/V conferred significantly reduced susceptibility. Conclusion. There was no evidence that sotrovimab epitope substitutions were associated with clinical progression or virologic rebound. These data are consistent with those from the COMET-ICE study.
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Background: Australia is experiencing ever more frequent weather/environmental challenges, including extreme heatwaves and bushfires. There are no proven interventions to reduce seasonal challenges to the cardiovascular health of vulnerable individuals. The REsilience to Seasonal ILlness and Increased Emergency admissioNs CarE (RESILIENCE) Trial will test the hypothesis that an individually-tailored intervention program will reduce re-hospitalisation risk and mortality in vulnerable individuals. Methods: We will recruit 300 medical patients admitted to the Austin Hospital (Melbourne, Australia), with chronic heart disease and multimorbidity and randomise (1:1) to standard care or the RESILIENCE program (RP). Applying a COVID-19 adapted protocol, the RP group will have their bio-behavioural profile and home environment assessed to determine their vulnerability to seasonal events. An individualised case-management program, including virtual clinic review with a nurse and physician, will be applied to promote seasonal resilience. The primary endpoint is all-cause days alive out of hospital during 12-month follow-up. Trial registered at ClinicalTrials.gov NCT04614428. Results: To date, 27 patients have been recruited and randomised. The mean age was 76±9 years and 11 (40%) were female. The most common comorbidities were hypertension (76 %), coronary artery disease (52 %), heart failure (52 %) and chronic kidney disease (52 %). Ten patients (37 %) have had a post-discharge home visit by the RP nurse and 5 (18 %) have attended the clinic. Conclusion: Recruitment is ongoing, and in the absence of further COVID-19 related lockdowns, all patients will be recruited over the next 12 months. Funding: MRFF-Keeping Australians Out of Hospital Grant