Dietary supplements to reduce symptom severity and duration in people with SARS-CoV-2: a double-blind randomised controlled trial.

BACKGROUND: COVID-19 has caused morbidity, hospitalisation and mortality worldwide. Despite effective vaccines, there is still a need for effective treatments, especially for people in the community. Dietary supplements have long been used to treat respiratory infections, and preliminary evidence indicates some may be effective in people with COVID-19. We sought to evaluate whether a combination of vitamin C, vitamin D3, vitamin K2 and zinc could improve overall health and decrease symptom burden in outpatients diagnosed with COVID-19. METHODS: Participants were randomised to receive either vitamin C (6 g), vitamin D3 (1000 units), vitamin K2 (240 µg) and zinc acetate (75 mg) or placebo daily for 21 days and were followed for 12 weeks. An additional loading dose of 50 000 units vitamin D3 (or placebo) was given on day one. The primary outcome was participant-reported overall health using the EuroQol Visual Assessment Scale summed over 21 days. Secondary outcomes included health status, symptom severity, symptom duration, delayed return to usual health, frequency of hospitalisation and mortality. RESULTS: 90 patients (46 control, 44 treatment) were randomised. The study was stopped prematurely due to insufficient capacity for recruitment. The mean difference (control-treatment) in cumulative overall health was -37.4 (95% CI -157.2 to 82.3), p=0.53 on a scale of 0-2100. No clinically or statistically significant differences were seen in any secondary outcomes. INTERPRETATION: In this double-blind, placebo-controlled, randomised trial of outpatients diagnosed with COVID-19, the dietary supplements vitamin C, vitamin D3, vitamin K2 and zinc acetate showed no clinically or statistically significant effects on the documented measures of health compared with a placebo when given for 21 days. Termination due to feasibility limited our ability to demonstrate the efficacy of these supplements for COVID-19. Further research is needed to determine clinical utility. TRIAL REGISTRATION NUMBER: NCT04780061.

A survey of multidisciplinary healthcare providers utilizing the KNOWintegrativeoncology.org educational platform.

BACKGROUND: Although the vast majority of cancer patients use natural health products (NHPs), 59% of oncology healthcare providers (HCP) report not receiving any education on NHPs. KNOWintegrativeoncology.org (KNOW) is a web-based educational platform that provides up-to-date evidence on NHPs used in cancer care with a user-friendly interface. KNOW is a database of human studies systematically gathered from MEDLINE and EMBASE. We surveyed HCPs before and after accessing KNOW to identify their information needs regarding NHPs in cancer care, their preferred way to receive information, barriers they face accessing NHP information, and to obtain feedback on the website. METHODS: Recruitment was done through Beaumont Health Systems, the Society for Integrative Oncology, and the Andrew Weil Centre for Integrative Medicine, University of Arizona. HCPs who consented completed an initial survey and then a follow-up survey after being given access to KNOW for 4-6 weeks. Participants were required to access KNOW at least three times before completion of the follow-up survey. RESULTS: A total of 65 participants completed the initial survey, with 60% (n = 39) from the conventional medical community, 33% (n = 21) from the integrative medicine community, and 7% (n = 5) from the research community. The majority of participants (82%; n = 53) preferred educational websites to email updates, podcasts/webinars, in-house experts, PubMed searches and smartphone apps. The most common barriers identified to accessing information on NHPs were time, accessibility at point-of-care, and credibility of sources. A high number of participants were lost to follow up, with 18 participants demographically representative of the initial sample of 65 completing the follow-up survey. Half (n = 9) of participants stated accessing the KNOW website changed their clinical practice. Close to 90% (n = 16) reported they would recommend KNOW to a colleague. CONCLUSION: Oncology HCPs reported preferring to use, and already relying on, numerous web-based educational platforms to gather information on NHPs, with time, accessibility, and credibility being common barriers to obtaining information. Our study findings highlight the promise of the KNOW web-based educational platform in reducing barriers to accessing up-to-date information on NHPs in busy cancer care settings.

Dietary supplements to reduce symptom severity and duration in people with SARS-CoV-2: study protocol for a randomised, double-blind, placebo controlled clinical trial.

INTRODUCTION: COVID-19 has caused morbidity, hospitalisations and deaths worldwide. Despite four approved vaccines for COVID-19 in Canada, there is still a need for effective treatments, especially for people in the community. Vaccine efficacy is not 100% and long-term efficacy is still unknown. Furthermore, there are challenges to herd immunity including vaccine hesitancy and underlying conditions preventing vaccination. We aim to explore if the nutrients vitamin C, vitamin D, vitamin K2 and zinc are an effective treatment option for outpatients diagnosed with COVID-19. The primary outcome is the difference in participant-reported overall health; secondary outcomes include the effect on health status, symptom severity and duration, frequency and length of hospitalisations and mortality. METHODS AND ANALYSIS: This study is a two-arm, parallel-group, double-blind, placebo-controlled, phase III randomised controlled trial. 200 patients will be recruited remotely from COVID-19 test centres in Ottawa, Canada associated with The Ottawa Hospital. Overall health will be measured using the EuroQol Visual Assessment Scale; health status will be measured using the EuroQol 5-dimension 5-level questionnaire; symptom severity and duration will be measured using an independently developed questionnaire; analyses will use an area under the curve approach and compare mean scores using unadjusted t tests. Study data will be recorded on electronic case report forms using the Research Electronic Data Capture platform. An independent data safety and monitoring board will perform ongoing review of the study for feasibility and safety. ETHICS AND DISSEMINATION: This study has received ethical approval from the research ethics boards of the Canadian College of Naturopathic Medicine and the Ottawa Health Sciences Network, as well as regulatory approval from the Therapeutic Products Directorate and Natural and Non-Prescription Health Products Directorate of Health Canada. Results will be published in a peer-reviewed scientific journal with open access. TRIAL REGISTRATION NUMBER: NCT04780061.

Evolution of Process and Outcome Measures during an Enhanced Recovery after Thoracic Surgery Program.

BACKGROUND: A time course analysis was undertaken to evaluate how perioperative process-of-care and outcome measures evolved after implementation of an enhanced recovery after thoracic surgery (ERATS) program. METHODS: Outcome and process-of-care measures were compared between patients undergoing major elective thoracic surgery during a 9-month pre-ERATS implementation period to those at 1-3, 4-6, and 7-9 months post-ERATS implementation. Outcome measures included length of stay, the 30-day readmission rate, 30-day emergency department visits, and minor and major adverse events. Process measures included first time to activity, out-of-bed, ambulation, fluid diet, diet as tolerated, as well as removal of the first and last chest tube, epidural, patient-controlled analgesia, and Foley and intravenous catheters. RESULTS: In total, 704 patients (352 pre-ERATS, 352 post-ERATS) were included. Mobilization-related process measures, including time to first activity (16.5 vs. 6.8 hours, p<0.001), out-of-bed (17.6 vs. 8.9 hours, p<0.001), and ambulation (32.4 vs. 25.4 hours, p=0.04) saw statistically significant improvements by 1-3 months post-ERATS implementation compared to pre-ERATS. Time to Foley removal improved by 4-6 months post-ERATS (19.5 vs. 18.2 hours, p=0.003). Outcome measures, including the 30-day readmission rate and emergency department visits, steadily decreased post-ERATS. By 7-9 months post-ERATS, both minor (18.2% vs. 7.9%, p=0.009) and major (13.6% vs. 4.4%, p=0.007) adverse events demonstrated statistically significant improvements. Length of stay trended towards improvement from 6.2 days pre-ERATS to 4.8 days by 7-9 months post-ERATS (p=0.06). CONCLUSION: The adoption of ERATS led to improvements in multiple process-of-care measures, which may collectively and gradually achieve optimization of clinical outcomes.

Adjuvant melatonin for the prevention of recurrence and mortality following lung cancer resection (AMPLCaRe): A randomized placebo controlled clinical trial.

BACKGROUND: Despite curative intent resection in patients with non-small cell lung cancer (NSCLC), recurrence leading to mortality remains too common. Melatonin has shown promise for the treatment of patients with lung cancer; however, its effect following cancer resection has not been studied. We evaluated if melatonin taken after complete resection reduces lung cancer recurrence and mortality, or impacts quality of life (QOL), symptomatology or immune function. METHODS: Participants received melatonin (20 mg) or placebo nightly for one year following surgical resection of primary NSCLC. The primary outcome was two-year disease-free survival (DFS). Secondary outcomes included five-year DFS, adverse events, QOL, fatigue, sleep, depression, anxiety, pain, and biomarkers assessing for immune function/inflammation. This study is registered at https://clinicaltrials.gov NCT00668707. FINDINGS: 709 patients across eight centres were randomized to melatonin (n = 356) versus placebo (n = 353). At two years, melatonin showed a relative risk of 1·01 (95% CI 0·83-1·22), p = 0·94 for DFS. At five years, melatonin showed a hazard ratio of 0·97 (95% CI 0·86-1·09), p = 0·84 for DFS. When stratified by cancer stage (I/II and III/IV), a hazard reduction of 25% (HR 0·75, 95% CI 0·61-0·92, p = 0·005) in five-year DFS was seen for participants in the treatment arm with advanced cancer (stage III/IV). No meaningful differences were seen in any other outcomes. INTERPRETATION: Adjuvant melatonin following resection of NSCLC does not affect DFS for patients with resected early stage NSCLC, yet may increase DFS in patients with late stage disease. Further study is needed to confirm this positive result. No beneficial effects were seen in QOL, symptoms, or immune function. FUNDING: This study was funded by the Lotte and John Hecht Memorial Foundation and the Gateway for Cancer Research Foundation.

A Prospective Outcomes Pilot Evaluation of Inspire Now: A Program for People with Lung Cancer.

BACKGROUND: Lung cancer is the leading cause of cancer mortality in Canada, yet patients are often under-supported. A six-week program called Inspire Now, created to address unmet supportive care needs, was evaluated in this study. Feasibility and preliminary outcomes were assessed in order to inform future changes to the program. OBJECTIVES: (1) Assess the feasibility of the program and its evaluation; (2) pilot the collection of patient-reported outcomes; (3) identify outcomes that may be positively influenced; and (4) inform program modifications. METHODS: Participants were recruited from the first session of Inspire Now for an observational pilot study. The primary outcome was feasibility. Secondary outcomes included within-person changes in Functional Assessment of Cancer Therapy - Lung (FACT-L) and Measure Yourself Concerns and Wellbeing (MYCaW), and program satisfaction and qualitative experiences of participants and facilitators through internally-developed questionnaires and semi-structured interviews. Analysis was primarily descriptive, within person changes in FACT-L and MYCaW were analyzed using the Wilcoxon signed-rank test and qualitative data was assessed for common themes. RESULTS: The program and its evaluation were feasible; 8 of 9 (89%) participants consented to the study, median attendance was 6 of 6 sessions (IQR 4.5-6), and questionnaire completion was 100% at baseline and 75% at follow-up. There were clinically meaningful improvements in MYCaW concern 1 (-1.2, 95% CI -2.0 to -0.4) and overall wellbeing (-0.9, 95% CI -2.1 to 0.4). Seven of eight FACT-L sub-sections trended toward improvement, with absolute changes ranging from -1.7 to 10.8%. Participant feedback was overwhelmingly positive; group support and social interactions were highly valued. CONCLUSIONS: The group intervention for people with lung cancer was feasible to both run and evaluate. Participants responded positively to the program. Findings will inform changes to future sessions and an analysis of multiple sessions is planned.