Background: There is a paucity of real-world data on the treatments naturopathic doctors (NDs) use for supportive cancer care. We conducted an observational cohort study to comprehensively describe the treatments NDs with experience in cancer care recommend to their patients. Methods: Patients with advanced breast, colorectal, ovarian, or pancreatic cancer were recruited from 12 North American naturopathic clinics and followed for 2 to 3 years. Therapeutic recommendations were abstracted from clinic records. Results: 384 participants (154 breast, 112 colorectal, 71 ovarian, 47 pancreatic) were included in the analyses. The median number of ND visits was 5. The most common types of recommendations were natural health products (NHPs, 99% of participants), nutrition guidance (88%), and parenteral therapies (81%). Mental health (33%) and Traditional Chinese Medicine (29%) were least common. Participants were recommended a median of 11 NHPs throughout the study, with 430 unique products recommended across all participants. Nutrition guidance heavily favoured encouraging foods rather than discouraging them (83% vs. 17% of all dietary recommendations, respectively). Vitamin D, curcumin, intravenous vitamin C, increasing protein intake, and exercise were recommended to at least 50% of participants across each cancer type. Other common recommendations included melatonin, fish oil, Trametes versicolor, subcutaneous mistletoe, increasing vegetable intake, and eating behaviour changes. Recommendations were fairly uniform between cancer types, with the most variation seen in NHPs. Conclusion: NDs frequently recommend NHPs, nutrition guidance, and parenteral therapies for people with advanced cancer. The diversity of unique recommendations suggests individualized care, yet some commonly used treatments demonstrate a degree of consistency.

Background: Several traditional, complementary, and integrative therapies have been studied for their effect on cancer outcomes; however, few studies have evaluated naturopathic oncology in a real-world setting. We conducted an observational cohort study to evaluate whether consulting with a naturopathic doctor (ND) improves survival in people with advanced cancers. Methods: Participants with metastatic breast, metastatic colorectal, advanced ovarian, or advanced pancreatic cancer were recruited from 12 North American naturopathic clinics. The primary outcome was 5-year overall survival compared with a matched cohort from the Surveillance Epidemiology and End Results (SEER) registry. We additionally evaluated survival based on the number of ND visits and intravenous vitamin C (IVC), intravenous mistletoe, and hyperthermia treatments. Results: 400 participants were enrolled: 165 had breast cancer, 116 had colorectal cancer, 72 had ovarian cancer, and 47 had pancreatic cancer. A bootstrapped analysis showed no significant differences in 5-year survival compared with SEER (breast: median hazard ratio [HR] 1.10, 95% confidence interval [CI] 0.80–1.54; colorectal: median HR 0.95, 95% CI 0.68–1.31; ovarian: median HR 1.08, 95% CI 0.64–1.86; pancreatic: median HR 0.76, 95% CI 0.51–1.13). Higher survival odds were seen with increasing IVC treatments in breast cancer, and with increasing ND visits in all cancer types except ovarian. Conclusion: No survival benefits were seen in patients with advanced cancers who saw an ND compared with registry data. After controlling for survivorship bias, in general, the number of ND visits positively correlated with improved survival; however, the number of select naturopathic treatments did not. Findings should be interpreted with caution given study limitations.

This scoping review examines the role of digital solutions in active, participant-centered surveillance of adverse events following initial release of COVID-19 vaccines. The goals of this paper were to examine the existing literature surrounding digital solutions and technology used for active, participant centered, AEFI surveillance of novel COVID-19 vaccines approved by WHO. This paper also aimed to identify gaps in literature surrounding digital, active, participant centered AEFI surveillance systems and to identify and describe the core components of active, participant centered, digital surveillance systems being used for post-market AEFI surveillance of WHO approved COVID-19 vaccines, with a focus on the digital solutions and technology being used, the type of AEFI detected, and the populations under surveillance. The findings highlight the need for customized surveillance systems based on local contexts and the lessons learned to improve future vaccine monitoring and pandemic preparedness.

IntroductionCOVID-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 analysisThis 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 disseminationThis 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 numberNCT04780061.

Background: We aim to evaluate the safety and efficacy of mistletoe extract (ME) use during the oncological perioperative period. Methods: Details registered a priori on PROSPERO (CRD42018086168). Results: Seven RCTs (comprising 663 participants in nine reports) and three nonrandomized studies were included. In five RCTs, ME was evaluated as adjunctive care and the control group had no additional intervention, whereas in two RCTs, ME was compared head-to-head against common cancer treatments (i.e., etoposide or bacillus Calmette-Guérin) with the intervention groups not receiving standard care. Meta-analyses found no evidence for a difference between ME and no added therapy for mortality and recurrence (RR, 95% CI: 1.00, 0.79–1.27; and 1.03, 0.79–1.33, respectively). Two RCTs reported beneficial effects of ME on immune cells, specifically natural killer cells, in colorectal cancer, and one RCT reported quality of life improvement. Two RCTs reported ME discontinuations due to adverse events and grade 3/4 toxicities. Nevertheless, no safety signals were detected from these 10 studies. Quality appraisal revealed a substantial risk of bias. Conclusions: Preliminary data are encouraging for mistletoe extracts, particularly in the context of colorectal cancer. However, the evidence is limited by the number of studies, an evaluation of different outcomes, and methodological limitations. Further high-quality research is warranted.

As the global incidence of multiple myeloma (MM) increases, the identification of modifiable risk factors for disease prevention becomes paramount. Maintaining optimal vitamin D status is a candidate for prevention efforts, based on pre-clinical evidence of a possible role in disease activity and progression. A structured scoping review was performed to identify and describe human-level research regarding the association between vitamin D and MM risk and/or prognosis. Searches of three databases (OVID-Medline, OVID-Embase, and OVID-Cochrane Library) yielded 15 included publications. Vitamin D deficiency is fairly common among patients with MM, with 42.3% of participants in the studies identified as having a vitamin D deficiency. No included publication reported on vitamin D status and the risk of developing or being newly diagnosed with MM. Possible associations with vitamin D that warrant future exploration include the incident staging of MM disease, the occurrence of peripheral neuropathy, and survival/prognosis. Vitamin D receptor (VDR) polymorphisms associated with MM also warrant further investigation. Overall, this scoping review was effective in mapping the research regarding vitamin D and MM and may help support new hypotheses to better describe this association and to better address identified knowledge gaps in the literature.

BACKGROUND:Elderly long-term care residents (ELTCRs) face considerable burden of infection, especially evident during the COVID-19 pandemic. The nutritional status of the host can influence susceptibility to infection by altering immune system integrity, therefore, nutrition-based interventions may be a viable complement to existing infection prevention measures. OBJECTIVE:This scoping review sought to identify nutritional interventions and factors that have the strongest evidence to benefit ELTCRs, and thus best poised for rigorous clinical trial evaluation and subsequent implementation. METHODS:A database search of OVID-Medline, OVID-Embase, and Web of Science was performed from 2011 to 2021 to identify nutritional intervention studies which attribute to changes in infection in contemporary ELTCR settings. Articles were screened in duplicate and data extraction completed by a single reviewer, while a second reviewer verified the data which was fitted to identify evidence for nutritional interventions related to reducing rates of infection among ELTCRs. RESULTS:The search identified 1018 studies, of which 11 (nine clinical trials and two observational cohort studies) satisfied screening criteria. Interventions that significantly reduced risk of infection included whey protein (any infection), Black Chokeberry (urinary tract infection), and vitamin D (acute respiratory tract infection, skin and soft tissue infection). Both zinc and a dedicated meal-plan significantly improved lymphocyte parameters. Vitamin D deficiency was associated with the development of respiratory tract infections. Probiotic and soy-based protein interventions did not significantly affect risk of infection or lymphocyte parameters, respectively. CONCLUSION:The current scoping review was effective in identifying the use of nutrition-based interventions for infection prevention among ELTCRs. In this study, some nutrition-based interventions were observed to significantly influence the risk of infection among ELTCRs. Nutritional interventions such as vitamin D (preventing deficiency/insufficiency), Black Chokeberry juice, zinc gluconate, whey protein, and varied and nutrient dense meal plans may be suitable for future rigorous clinical trial evaluation.

Background: Branched-chain amino acids (BCAAs; leucine, isoleucine, and valine) are essential amino acids involved in immune responses, and may have roles in protein malnutrition and sarcopenia. Furthermore, certain liver diseases have been associated with a decreased Fischer’s ratio (BCAAs to aromatic amino acids; phenylalanine, tyrosine, and tryptophan). We aimed to evaluate the safety and efficacy of BCAAs use in patients with cancer undergoing surgery. Methods: MEDLINE, Embase, and CENTRAL were searched (inception to July 24, 2020) for randomized controlled trials (RCTs) and comparative observational studies in English evaluating BCAAs (alone or in combinations) during the oncological peri-operative period. Study selection, data extraction, and quality appraisal were done in duplicate. RCT risk-of-bias was appraised using Cochrane Risk-of-Bias tool, and observational studies’ quality assessment was conducted with Newcastle-Ottawa Scale. Meta-analyses were conducted when appropriate. Results: 20 articles were included comprising 13 RCTs and 6 observational cohort studies in 7 reports and 2019 total participants overall. Among 13 RCTs, 77% involved liver cancer. Methodological study quality scored substantial risk-of-bias across most RCTs. Meta-analysis of RCTs found a 38% decreased risk of post-operative infections in BCAAs group compared to controls (RR = 0.62; 95% CI = 0.44 to 0.87; P = .006; number of RCTs, k = 6; total sample size, N = 389; I2 = 0%). BCAAs were also found to be beneficial for ascites (RR = 0.55; 95% CI = 0.35 to 0.86; P = .008; k = 4; N = 296; I2 = 0%), body weight (MD = 3.24 kg; 95% CI = 0.44 to 6.04; P = .02; k = 3; N = 196; I2 = 24%), and hospitalization length (MD = −2.07 days; 95% CI = −3.97 to −0.17; P = .03; k = 5; N = 362; I2 = 59%). No differences were found between BCAAs and controls for mortality, recurrence, other post-operative complications (liver failure, edema, pleural effusion), blood loss, quality of life, ammonia level, and prothrombin time. No serious adverse events were related to BCAAs; however, serious adverse events were reported due to intravenous catheters. No safety concerns from observational studies were identified. Conclusions: Branched-chain amino acids during the oncological surgical period demonstrated promise in reducing important post-operative morbidity from infections and ascites compared to controls. Blinded, placebo-controlled confirmatory trials of higher methodological quality are warranted, especially using oral, short-term BCAAs-enriched supplements within the context of recent ERAS programs. PROSPERO registration: CRD42018086168.

Introduction: Hyperthermia (HT) in cancer management refers to the external application of heat to raise intratumoural temperature to between 39°C and 45°C. Locoregional hyperthermia (LRHT) is the most used and studied type of HT in cancer care. A literature search was conducted to produce a monograph to help clinicians and patients make informed choices in considering the application of this therapy. Methods: A search was performed in Medline and Cochrane library for LRHT and cancer in May 2020. Eligible studies were English-language clinical studies reporting on efficacy, quality of life (QoL), safety, or feasibility. Additional cursory literature scoping was performed to identify missing papers and background information. Papers were independently screened by two reviewers. Following development of a full monograph, a condensed version suitable for publication was created and is presented here. Results: A total of 980 articles were identified and 166 met inclusion criteria. Most were single-arm or observational. However, among the 166, there were 7 systematic reviews (including 37 RCTs) and 18 additional RCTs identified. Several mechanisms of action have been proposed for HT in cancer care including physiological changes, direct cytotoxic effects, chemosensitization and radiosensitization, and immune modulation. Locoregional HT is used primarily as an adjunct to chemotherapy and radiotherapy due to its possible synergistic effects. Various studies demonstrated improved outcomes for patients treated with LRHT and chemo-and/or-radiotherapy. The best evidence for improved disease control and survival is seen for breast cancer (locally recurrent), cervical cancer, esophageal and gastric cancers, head and neck squamous cell carcinoma, and high-risk soft tissue sarcoma. Research related to quality of life (QoL) is limited and often focuses on pain. Hyperthermia with modern technology and treatment planning is generally well tolerated; the most common side effects are discomfort, mild pain, local erythema, skin burns, and, less commonly, subcutaneous burns. Trial heterogeneity and methodological concerns limit the strength of conclusions. Conclusions: Locoregional HT is a promising adjunct treatment to chemotherapy and radiotherapy for a variety of cancer types. To determine in what situations this therapy could be best applied, more high-quality well-controlled studies are needed.

Background: Objectives were to evaluate probiotics safety and efficacy in oncological surgery. Methods: Systematic review methodology guided by Cochrane, PRISMA, SWiM, and CIOMS. Protocol registered on PROSPERO (CRD42018086168). Results: 36 RCTs (on 3305 participants) and 6 nonrandomized/observational studies were included, mainly on digestive system cancers. There was evidence of a beneficial effect on preventing infections, with 70% of RCTs' (21/30) direction of effect favoring probiotics. However, five RCTs (17%) favored controls for infections, including one trial with RR 1.57 (95% CI: 0.79, 3.12). One RCT that changed (balanced) its antibiotics protocol after enrolling some participants had mortality risk RR 3.55 (95% CI: 0.77, 16.47; 7/64 vs. 2/65 deaths). The RCT identified with the most promising results overall administered an oral formulation of Lactobacillus acidophilus LA-5 + Lactobacillus plantarum + Bifidobacterium lactis BB-12 + Saccharomyces boulardii. Methodological quality appraisals revealed an overall substantial risk-of-bias, with only five RCTs judged as low risk-of-bias. Conclusions: This large evidence synthesis found encouraging results from most formulations, though this was contrasted by potential harms from a few others, thus validating the literature that "probiotics" are not homogeneous microorganisms. Given microbiome developments and infections morbidity, further high-quality research is warranted using those promising probiotics identified herein.

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.