Example Queries

What are the indications for taking selenium?

	Outcome name	Results during intervention	Overall RoB judgment
Asfour et al. (2006): Effect of high-dose sodium selenite therapy on polymorphonuclear leukocyte apoptosis in non-Hodgkin's lymphoma patients	Ejection fraction	After chemotherapy (8 days): significantly better cardiac ejection fraction in sodium selenite arm (mean(SD)= 63(6%)) vs. control arm (69(6%)); p <0.05	high risk
Asfour et al. (2006): Effect of high-dose sodium selenite therapy on polymorphonuclear leukocyte apoptosis in non-Hodgkin's lymphoma patients	Toxicity	After chemotherapy (8 days): significant less infections in sodium selenite arm (20%) compared to control arm (67%); p<0.05	high risk
Büntzel et al. (2010): Limited effects of selenium in the prevention of radiation-associated toxicities - results of a randomized study in head neck cancer patients	Toxicity	Maximum toxicity intervention vs. control arm: dysphagia 22.7% vs. 35.3%, ageusia 22.7% vs. 47.1%, xerostomia 22.7% vs. 23.5%, and stomatitis 36.4% vs. 23.5%; no significant differences; Significant mean difference between arms only for dysphagia at week 7: mean intervention arm 1.533 vs. control 2.167 (p=0.05)	some concerns
... further results

What are the side effects of cannabis?

	Side Effects / Interactions
Côté et al. (2016): Improving Quality of Life With Nabilone During Radiotherapy Treatments for Head and Neck Cancers: A Randomized Double-Blind Placebo-Controlled Trial	No differences for sleepiness (p=0.32), anxiety (p=0.92) and xerostomia (p=0.83) No differences for sleepiness (p=0.32), anxiety (p=0.92) and xerostomia (p=0.83)
Fallon et al. (2017) I: Sativex oromucosal spray as adjunctive therapy in advanced cancer patients with chronic pain unalleviated by optimized opioid therapy: two double-blind, randomized, placebo-controlled phase 3 studies	Overall 68% at least one event; assessed as probably intervention-associated with frequency ≥ 5%: Total n=64 (32.2%), of which somnolence n=18 (9%), dizziness n=15 (7.5%), nausea n=10 (5%) 2 severe side effects associated with intervention: 1x constipation (with 360mg/day morphine equivalents), 1x moderate disorientation and somnolence on day 4 (with 2.5 daily sprays of Sativex) None of the deaths related to intervention Overall 64% at least one event; assessed as probably intervention-associated with frequency ≥ 5%: Total n=41 (20.7%), of which somnolence n=6 (3%), dizziness n=6 (3%), nausea n=8 (4%) 2 severe side effects associated with intervention: 1x constipation (with 360mg/day morphine equivalents), 1x moderate disorientation and somnolence on day 4 (with 2.5 daily sprays of Sativex) None of the deaths related to intervention
Fallon et al. (2017) II: Sativex oromucosal spray as adjunctive therapy in advanced cancer patients with chronic pain unalleviated by optimized opioid therapy: two double-blind, randomized, placebo-controlled phase 3 studies	Part A Overall 60% at least one event, assessed as probably intervention-associated with frequency ≥ 5%: Total n=128, 31.7%, somnolence (n=42, 10.4%), nausea (n=21, 5.2%) and dizziness (n=21, 5.2%) Part B Overall 72% at least one event; assessed as probably intervention-associated with frequency ≥ 5%: Total n=16, 15.5%; somnolence (n=6, 5.8%) More than twice as many patients in Sativex arm discontinued study due to side effects (n=14, 13.6% vs. n=6, 5.8%); no statistical comparison given) None of the deaths related to intervention Part A Overall 60% at least one event, assessed as probably intervention-associated with frequency ≥ 5%: Total n=128, 31.7%, somnolence (n=42, 10.4%), nausea (n=21, 5.2%) and dizziness (n=21, 5.2%) Part B Overall 62% at least one event; assessed as probably intervention-associated with frequency ≥ 5%: Total n=12, 11.7%; somnolence n=0
Grimison et al. (2020): Oral THC:CBD cannabis extract for refractory chemotherapy-induced nausea and vomiting: a randomised, placebo-controlled, phase II crossover trial	Moderate or severe cannabinoid-related side effects in intervention arm and placebo arm (31% vs. 7%, p=0.002): Significant differences for sedation (19% vs. 4%, p=0.002) and dizziness (10% vs. 1%, p=0.03) No differences for disorientation (p=0.5) and anxiety (p=1.00) No cannabinoid-related serious adverse events reported 83% of the participants preferred cannabis over placebo and 15% had a preference for placebo (p<0.001) Moderate or severe cannabinoid-related side effects in intervention arm and placebo arm (31% vs. 7%, p=0.002): Significant differences for sedation (19% vs. 4%, p=0.002) and dizziness (10% vs. 1%, p=0.03) No differences for disorientation (p=0.5) and anxiety (p=1.00) No cannabinoid-related serious adverse events reported 83% of the participants preferred cannabis over placebo and 15% had a preference for placebo (p<0.001)
Jatoi et al. (2002): Dronabinol Versus Megestrol Acetate Versus Combination Therapy for Cancer-Associated Anorexia: A North Central Cancer Treatment Group Study	Impotence in 18 % of men; vomiting; fluid retention; confused thinking; drowsiness; loss of coordination; inappropriate behavior Impotence in 4% of men; vomiting; fluid retention; confused thinking; drowsiness; loss of coordination; inappropriate behavior Impotence in 14% of men; vomiting; fluid retention; confused thinking; drowsiness; loss of coordination; inappropriate behavior
Johnson et al. (2010): Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain	Intervention-associated events in n=106 (60%): drowsiness, dizziness, nausea, confusion, vomiting, hypotension, hypercalcemia, increased gamma GT Most side effects were mild/moderate; no statistical comparisons given; one case of syncope probably related to THC; other events not associated with intervention Intervention-associated events in n=106 (60%): drowsiness, dizziness, nausea, confusion, vomiting, hypotension, hypercalcemia, increased gamma GT; Most side effects were mild/moderate; no statistical comparisons given; one case of syncope probably related to THC; other events not associated with intervention NI
Lichtmann et al. (2018): Results of a Double-Blind, Randomized, Placebo-Controlled Study of Nabiximols Oromucosal Spray as an Adjunctive Therapy in Advanced Cancer Patients with Chronic Uncontrolled Pain	Most frequently nausea (n=17) and dizziness (n=15); 1 case of disorientation and 1 case of visual hallucinations Most frequently nausea (n=10) and dizziness (n=5); 1 case of vomiting
Portenoy et al. (2012): Nabiximols for Opioid-Treated Cancer Patients With Poorly-Controlled Chronic Pain: A Randomized, Placebo-Controlled, Graded-Dose Trial	Cognitive functions: negative effect of nabiximols (no values given); nausea and vomiting; dizziness; drowsiness; disorientation; anorexia, constipation; dry mouth; anemia; diarrhea; dysgeusia headache; asthenia hallucinations; reduced appetite; fatigue; pain; insomnia; stomatitis; weight loss Cognitive functions: negative effect of nabiximols (no values given); nausea and vomiting; dizziness; drowsiness; disorientation; anorexia, constipation; dry mouth; anemia; diarrhea; dysgeusia headache; asthenia hallucinations; reduced appetite; fatigue; pain; insomnia; stomatitis; weight loss Cognitive functions: negative effect of nabiximols (no values given); nausea and vomiting; dizziness; drowsiness; disorientation; anorexia, constipation; dry mouth; anemia; diarrhea; dysgeusia headache; asthenia hallucinations; reduced appetite; fatigue; pain; insomnia; stomatitis weight loss NI
Strasser et al. (2006): Comparison of orally administered cannabis extract and delta-9-tetrahydrocannabinol in treating patients with cancer-related anorexia-cachexia syndrome: a multicenter, phase III, randomized, double-blind, placebo-controlled (…)	Total adverse events: n=197, of which possibly intervention-associated n=45 and likely intervention-associated n=7 Temporary or permanent dose reduction was necessary for 30 patients Adverse events that occurred more than 10 times were: Nausea/vomiting (n=21), fatigue (n=14), pain (n=17), anemia (n=14), dizziness (n=11), dyspnea (n=7), diarrhea (n=7), obstipation (n=7), vertigo (n not reported); no differences in frequencies between arm Of all side effects n=101 were mild, n=71 moderate, n=24 severe (mainly dizziness, nausea/vomiting, dyspnea) 33 very severe side effects such as dyspnoea, tumor progression, vomiting, deterioration of general well-being, death, pain, fever, diarrhoea, exsiccation; 6 of which were life-threatening, 27 required hospitalization Total adverse events: n=238, of which possibly intervention-associated n=28 and likely intervention-associated n=9 Temporary or permanent dose reduction was necessary for 34 patients Adverse events that occurred more than 10 times were: Nausea/vomiting (n=23), fatigue (n=16), pain (n=11), anemia (n=9), dizziness (n=9), dyspnea (n=9), diarrhea (n=6), obstipation (n=6), vertigo (n not reported); no differences in frequencies between arms Of all side effects n=104 were mild, n=113 moderate, n=21 severe (mainly dizziness, nausea/vomiting, dyspnea) 32 very severe side effects such as dyspnoea, tumor progression, vomiting, deterioration of general well-being, death, pain, fever, diarrhoea, exsiccation; 6 of which were life-threatening, 25 required hospitalization Total adverse events: n=91, of which possibly intervention-associated n=17 and likely intervention-associated n=4 Temporary or permanent dose reduction was necessary for 14 patients Adverse events that occurred more than 10 times were: Nausea/vomiting (n=11), fatigue (n=4), pain (n=5), anemia (n=6), dizziness (n=7), dyspnea (n=2), diarrhea (n=2), obstipation (n=2), vertigo (n not reported); no differences in frequencies between arms Of all side effects n=36 were mild, n=43 moderate, n=12 severe (mainly dizziness, nausea/vomiting, dyspnea) 17 very severe side effects such as dyspnoea, tumor progression, vomiting, deterioration of general well-being, death, pain, fever, diarrhoea, exsiccation; 1 of which were life-threatening, 16 required hospitalization

Does selenium help with mucositis?

	Results after intervention	Overall RoB judgment
Jahangard-Rafsanjani et al. (2013): The efficacy of selenium in prevention of oral mucositis in patients undergoing hematopoietic SCT: a randomized clinical trial	NA No difference between selenium arm (26.92±6.26 days) and placebo arm (25.81±4.33 days); p=0.38 Overall: No difference between the arms; p= 0.35 No difference between the arms; p= 0.69 Overall: No difference between arms for increase in serum creatinine; p=0.31 or increase in aspartate aminotransferase and alanine transaminase: p=0.62 Significant difference in mean serum selenium level between two arms at 14 days after transplantation (8.34 mcg/dL in the selenium arm vs 7.36 mcg/dL in the placebo arm), p=0.018 Overall: Cumulative incidence (grade 1-4) comparable in both selenium arm (83.8%) and placebo arm (81.1%); p=0.76; grade 3-4 mucositis significantly lower in selenium arm (10.8%) compared to placebo arm (35.1%); p=0.013 (grade 4: 2x in placebo arm, 0x in selenium arm) Mean duration comparable (p=0.048), only duration of objective mucositis from grade 2 to 4 and back was significantly shorter in the selenium arm (3.6±1.84 days) than in the placebo arm (5.3±2.2 days); p=0.014 NA	some concerns some concerns some concerns some concerns some concerns some concerns high risk some concerns
Laali et al. (2020): Effect of Selenium on Incidence and Severity of Mucositis during Radiotherapy in Patients with Head and Neck Cancer	At the end of radiation (after 7 weeks) there was no difference in the mean serum selenium level between the selenium arm and placebo arm (p=0.24) Based on the selenium level before radiation, developing severe oral mucositis was statistically significant postponed in patients who had selenium levels ≥ 65 mcg/L (p=0.04) After 7 weeks no significant differences between the selenium arm and the placebo arm for: mean duration of oral mucositis (grade 1–4) (p=0.27) onset of oral mucosits (p =0.31) recovery (day after radiation completion (p=0.80) cumulative incidence of oral mucusitis (grade 1–4) (p=0.79) Severe oral mucositis (grade 3 or 4) was seen in 25 patients in the selenium arm and in 20 patients in the placebo arm. Addition: Development of oral mucositis in patients with selenium levels >65 mcg/l significantly delayed from baseline (p=0.04, no further explanation given)	NA high risk
Mix et al. (2015): Randomized phase II trial of selenomethionine as a modulator of efficacy and toxicity of chemoradiation in squamous cell carcinoma of the head and neck	Overall: No significant differences between arms (grade 3 intervention arm 2x, placebo arm 3x, no grade 4) Only one patient from the intervention arm did not reach CR and died After 12 months: No significant differences between arms After 12 months: No significant differences between arms No significant difference for week 6-8 post-treatment and Follow-up within a year Overall: Hearing dysfunction n=1 each in the intervention arm and placebo arm; elevated creatinine n=1 in the placebo arm; myelosuppression: anemia in the placebo arm n=1; leukopenia in the intervention arm n=3 and placebo arm n=2; dermatitis in the intervention arm n=2; dry mouth in the placebo arm n=2; dysgeusia in the intervention arm n=2, placebo arm n=1; odyno-/dysphagia in the intervention arm n=1, placebo arm n=2; oral/throat pain in the placebo arm n=2; mucus/sputum intervention arm n=3, placebo arm n=1	some concerns low risk low risk low risk some concerns some concerns

What is the optimal dosage of cannabis for the treatment of nausea?

	Outcome name	Dosage and regime
Côté et al. (2016): Improving Quality of Life With Nabilone During Radiotherapy Treatments for Head and Neck Cancers: A Randomized Double-Blind Placebo-Controlled Trial	Pain Weight Appetite Nausea Unspecified effects Toxicity Quality of life	0.5 mg nabilone tablets (from Valeant Canada) once a day before radiotherapy in the first week twice a day in the second week third week until end of radiotherapy: adjusted by radiation oncologist up to maximal 4 tablets Placebo tablets once a day before radiotherapy in the first week twice a day in the second week third week until end of radiotherapy: adjusted by radiation oncologist up to maximal 4 tablets
Johnson et al. (2010): Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain	Pain Pain Sleep Nausea Cognitive functioning Cognitive functioning Appetite Quality of life Pain	THC:CBD via oral spray (self-applied by patient, one dose 2.7mg THC and 2.5mg CBD) Week 1: dose finding Week 2: stable dose, maximum of 8 sprays every 3 hours and 48 sprays in 24 hours: dose was determined by patients themselves THC extract via oral spray (2.7 mg), dosage variable; Week 1: dose finding Week 2: stable dose, maximum of 8 sprays every 3 hours and 48 sprays in 24 hours: dose was determined by patients themselves NI
Strasser et al. (2006): Comparison of orally administered cannabis extract and delta-9-tetrahydrocannabinol in treating patients with cancer-related anorexia-cachexia syndrome: a multicenter, phase III, randomized, double-blind, placebo-controlled (…)	Appetite Quality of life Mood/Affect Nausea Anorexia/Cachexia Toxicity Functionality Weight	2.5mg THC orally, 2x a day, preferably taken before lunch and dinner/at bedtime 2,5mg THC + 1mg cannabidiol, 2x a day, preferably taken before lunch and dinner/at bedtime 2x a day, preferably taken before lunch and dinner/at bedtime