Randomized controlled trial (RCT) of symptom screening with targeted early palliative care (STEP) versus usual care in patients with advanced cancer

Background: To direct limited specialized palliative care resources to patients in greatest need, we developed STEP (Symptom screening with Targeted Early Palliative care). STEP entails symptom screening (ESAS-r) at each oncology clinic visit and triggered alerts (for moderate-high physical and psychological symptoms) to a nurse who calls the patient to offer a palliative care clinic (PCC) visit. We conducted a phase III RCT to assess the impact of STEP versus usual care on quality of life and other patient-reported outcomes (PROs). Methods: Adults with advanced cancer were recruited from medical oncology clinics at the Princess Margaret Cancer Centre, Toronto, Canada. Consenting patients with oncologist-assessed ECOG 0-2 and estimated survival of 6-36 months were enrolled and block randomized (stratified by tumour site and symptom severity) to STEP or usual care. Participants completed measures of quality of life (FACT-G7), depression (PHQ-9), symptom control (ESASr-CS), and satisfaction with care (FAMCARE-P16) at baseline, 2, 4 and 6 months. The primary outcome was FACT-G7 at 6 months, with a planned sample size of 261/arm. Results: From 8/2019 to 3/2020, 69 patients were enrolled: 33 randomized to STEP and 36 to usual care. The trial was then halted permanently due to the COVID-19 pandemic, owing to substantial changes to elements of STEP (shift to virtual symptom screening and palliative care) and usual care (shift to virtual oncology care). Median age was 64 years (range 25-87) and 62% (43/69) were women;study arms were balanced at baseline except gender, with more women randomized to STEP. Within the STEP arm, 20 (61%) participants triggered a nurse's call to offer a PCC visit, of whom 13 attended the clinic at least once. All outcomes tended to be better in the STEP arm compared to usual care, particularly depression and satisfaction with care at 6 months;however, results were not statistically significant (Table). Conclusions: STEP holds promise for improving quality of life and other PROs in patients with advanced cancer and effectively directing early palliative care towards those who need it most. In response to the pandemic, an online version of STEP has been developed and a further trial is in progress.

Antiviral activity of natural phenolic compounds in complex at an allosteric site of SARS-CoV-2 papain-like protease.

SARS-CoV-2 papain-like protease (PLpro) covers multiple functions. Beside the cysteine-protease activity, facilitating cleavage of the viral polypeptide chain, PLpro has the additional and vital function of removing ubiquitin and ISG15 (Interferon-stimulated gene 15) from host-cell proteins to support coronaviruses in evading the host's innate immune responses. We identified three phenolic compounds bound to PLpro, preventing essential molecular interactions to ISG15 by screening a natural compound library. The compounds identified by X-ray screening and complexed to PLpro demonstrate clear inhibition of PLpro in a deISGylation activity assay. Two compounds exhibit distinct antiviral activity in Vero cell line assays and one inhibited a cytopathic effect in non-cytotoxic concentration ranges. In the context of increasing PLpro mutations in the evolving new variants of SARS-CoV-2, the natural compounds we identified may also reinstate the antiviral immune response processes of the host that are down-regulated in COVID-19 infections.

SYMPTOM SCREENING WITH TARGETED EARLY PALLIATIVE CARE (STEP) VERSUS USUAL CARE FOR PATIENTS WITH ADVANCED CANCER: A RANDOMIZED CONTROLLED TRIAL

Introduction To direct scant specialized palliative care (PC) resources to patients in greatest need, we developed the STEP intervention (Symptom screening with Targeted Early Palliative care). STEP entails symptom screening with ESAS-r at each oncology visit and triggered alerts (for moderatehigh symptoms) to a nurse who calls the patient to offer a PC clinic visit. Methods Consenting adults with advanced cancer, ECOG 0-2, attending medical oncology clinics at the Princess Margaret Cancer Centre, were randomized to STEP or usual care. Participants completed quality of life (FACTG7), depression (PHQ-9), symptom control (ESASr-CS), and satisfaction with care (FAMCARE-P16) measures at baseline, 2, 4, and 6 months. The primary outcome was FACT-G7 at 6 months. Results From August 2019 to March 2020, 33 patients were randomized to STEP and 36 to usual care. The trial was subsequently permanently halted due to the COVID-19 pandemic. Groups were balanced at baseline except gender, with more females in the STEP arm (Table 1). In the STEP arm, 20 participants triggered a nurse 's call, of whom 13 had ≥1 PC clinic visit. At 6 months, all outcomes tended to be better in the STEP arm compared to usual care, particularly depression and satisfaction with care;however, results were not statistically significant (Table 2, Figure 1). Conclusions STEP holds promise for improving outcomes in patients with advanced cancer. An online version (eSTEP) is being developed in response to the COVID-19 pandemic.

Improving medication reconciliation in ambulatory cancer care

Background: Adverse drug events are common in ambulatory oncology where care spans multiple providers and medication documentation is often poor. We undertook a QI project with the aim of having 30% of patients have a best possible medication history (BPMH) or medication reconciliation (MedRec) documented within 30 days of starting systemic therapy. Methods: An Electronic Medical record-Integrated Tool (EMITT) was developed to facilitate documentation. 2 Plan-Do-Study-Act (PDSA) cycles have been completed to date;PDSA 1 consisted of piloting EMITT in 3 clinics run by physician champions. PDSA 2 which consisted of expanding pharmacy support and addition of a 4 clinic was impacted by care changes related to COVID. The proportion of patients with BPMH/MedRec documented in EMITT was calculated monthly for each period (PDSA 1, PDSA 2 pre-COVID and PDSA 2 post-COVID). The balancing measure of time to complete an entry was evaluated through a time motion study. Results: Between 9/9/2019 and 31/5/2020, 9.4% (233/2488) of patients had BPMH/MedRec completed;Table shows proportion of patients by month. BPMH and MedRec were most frequently performed by pharmacists followed by pharmacy students and nurses. On average, it took 5.5 minutes to complete an entry (n = 10;median number of medications per patient = 12.3). Conclusions:BPMH was documented more often than MedRec. While some usage was sustained, the changes to care as a result of COVID-19 negatively impacted ambulatory medication reconciliation. Future PDSA cycles will involve engaging patients in MedRec and extending EMITT to all ambulatory cancer clinics where medication management is a major component of care.