Effects of Vitamin D Supplementation on Disabling Foot Pain in Patients With Symptomatic Knee Osteoarthritis.

OBJECTIVE: The present study was undertaken to determine whether vitamin D supplementation or maintaining sufficient vitamin D level reduces foot pain over 2 years in patients with symptomatic knee osteoarthritis (OA). METHODS: A post hoc study was conducted from a randomized, double-blind, placebo-controlled trial named the Vitamin D Effect on Osteoarthritis (VIDEO) study. Symptomatic knee OA patients with serum 25-hydroxyvitamin D levels between 12.5 nmoles/liter and 60 nmoles/liter were included and randomly allocated to either monthly vitamin D3 or placebo treatment (1:1) for 2 years. Manchester Foot Pain and Disability Index (MFPDI) was used to evaluate foot pain and disabling foot pain was defined as at least 1 of the 10 functional limitation items (items 1-9 and 11) being documented as on "most/every day(s)" in the last month. A repeated-measures, mixed-effects model was used to analyze the change of MFPDI scores between groups adjusting for potential confounders. RESULTS: A total of 413 patients with a mean age of 63.2 years (49.7% males) were enrolled and 340 completed the study. The mean MFPDI score was 22.8 ± 7.3, with 23.7% of participants having disabling foot pain at baseline. There were significant differences in MFPDI scores change between groups over 2 years, with more improvements in the vitamin D group than in the placebo group (-0.03 versus 1.30; P = 0.013) and more improvement in those maintaining sufficient vitamin D levels (n = 226) than those who did not (n = 114) (-0.09 versus 2.19; P = 0.001). CONCLUSION: Vitamin D supplementation and maintenance of sufficient vitamin D levels may improve foot pain in those with knee OA.

Effect of vitamin D supplementation on pain and physical function in patients with knee osteoarthritis (OA): an OA Trial Bank protocol for a systematic review and individual patient data (IPD) meta-analysis.

INTRODUCTION: Observational data suggest that vitamin D deficiency is associated with the onset and progression of knee osteoarthritis (OA). However, randomised controlled trials (RCTs) to date investigating the efficacy of vitamin D supplementation in knee OA have reported conflicting results. Further research is needed to clarify the effects of vitamin D on patient-reported outcomes and determine whether there are patient subgroups who may benefit from the supplementation. The aim of this individual patient data (IPD) meta-analysis is to identify patient-level predictors of treatment response to vitamin D supplementation on pain and physical function. METHODS AND ANALYSIS: A systematic literature search will be conducted for RCTs of vitamin D supplementation on knee OA. Authors of original RCTs will be contacted to obtain the IPD. The primary outcomes will include long-term (≥12 months) pain and physical function. Secondary outcomes will include medium-term (≥6 months and <12 months) and short-term (<6 months) pain and physical function, as well as patient global assessment, quality of life and adverse events. Potential treatment effect modifiers to be examined in the subgroup analyses include age, gender, body mass index, baseline knee pain severity and physical function, baseline vitamin D level, radiographic stage, presence of bone marrow lesions on MRI, presence of clinical signs of local inflammation and concomitant depressive symptoms. Both one-step and two-step modelling methods will be used to determine the possible modifiable effect of each subgroup of interest. ETHICS AND DISSEMINATION: Research ethical or governance approval is exempt for this study as no new data are being collected. This study will be the first IPD meta-analysis to clarify the effect of vitamin D supplementation on clinical symptoms in different subgroups of patients with knee OA. The findings will be disseminated through peer-review publications and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42018107740.

Brief intervention on Smoking, Nutrition, Alcohol and Physical (SNAP) inactivity for smoking relapse prevention after release from smoke-free prisons: a study protocol for a multicentre, investigator-blinded, randomised controlled trial.

INTRODUCTION: Smoking remains the leading risk factor for disease burden and mortality worldwide. Heavy Smoking is often associated with poor Nutrition, Alcohol abuse and Physical inactivity (known as 'SNAP'). Australia's first prison smoking ban was introduced in the Northern Territory in July 2013. However, relapse to smoking after release from prison is normative. Holistic and cost-effective interventions are needed to maintain post-release abstinence to realise the potential public health impact of smoke-free prison policies. Rigorous, large-scale trials of innovative and scalable interventions are crucial to inform tobacco control policies in correctional settings. METHODS AND ANALYSIS: This multicentre, investigator-blinded, randomised parallel superiority trial will evaluate the effectiveness of a brief intervention on SNAP versus usual care in preventing smoking relapse among people released from smoke-free prisons in the Northern Territory, Australia. A maximum of 824 participants will be enrolled and randomly assigned to either SNAP intervention or usual care at a 1:1 ratio at baseline. The primary endpoint is self-reported continuous smoking abstinence three months after release from prison, verified by breath carbon monoxide test. Secondary endpoints include seven-day point prevalence abstinence, time to first cigarette, number of cigarettes smoked post release, Health Eating Index for Australian Adults, Alcohol Use Disorder Identification Test-Consumption and International Physical Activity Questionnaire scores. The primary endpoint will be analysed on an intention-to-treat basis using a simple log binomial regression model with multiple imputation for missing outcome data. A cost-effectiveness analysis of the brief intervention will be conducted subsequently. ETHICS AND DISSEMINATION: This study was approved by the University of New South Wales Human Research Ethics Committee (HREC), Menzies HREC and Central Australia HREC. Primary results of the trial and each of the secondary endpoints will be submitted for publication in a peer-review journal. TRIAL REGISTRATION NUMBER: ACTRN12617000217303; Pre-results.

Vitamin D supplementation and inflammatory and metabolic biomarkers in patients with knee osteoarthritis: post hoc analysis of a randomised controlled trial.

The aim of this study was to determine whether vitamin D supplementation and maintaining vitamin D sufficiency are associated with changes in inflammatory and metabolic biomarkers in patients with knee osteoarthritis (OA) and vitamin D deficiency. A total of 413 participants with symptomatic knee OA and vitamin D deficiency were enrolled in a randomised, placebo-controlled trial and received 1·25 mg vitamin D3 or placebo monthly for 24 months across two sites. In this post hoc analysis, 200 participants from one site (ninety-four from the placebo group and 106 from the vitamin D group; mean age 63·1 (sd 7·3) years, 53·3 % women) were randomly selected for measurement of serum levels of inflammatory and metabolic biomarkers at baseline and 24 months using immunoassays. In addition, participants were classified into two groups according to serum 25-hydroxyvitamin D (25(OH)D) levels at months 3 and 24: (1) not consistently sufficient (25(OH)D≤50 nmol/l at either month 3 or 24, n 61), and (2) consistently sufficient (25(OH)D>50 nmol/l at both months 3 and 24, n 139). Compared with placebo, vitamin D supplementation had no significant effect on change in serum high-sensitive C-reactive protein, IL-6, IL-8, IL-10, leptin, adiponectin, resistin, adipsin and apelin. Being consistently vitamin D sufficient over 2 years was also not associated with changes in these biomarkers compared with not being consistently sufficient. Vitamin D supplementation and maintaining vitamin D sufficiency did not alter serum levels of inflammatory and metabolic biomarkers over 2 years in knee OA patients who were vitamin D insufficient, suggesting that they may not affect systemic inflammation in knee OA patients.

Ganoderma lucidum (Reishi mushroom) for cancer treatment.

BACKGROUND: Ganoderma lucidum is a natural medicine that is widely used and recommended by Asian physicians and naturopaths for its supporting effects on immune system. Laboratory research and a handful of preclinical trials have suggested that G. lucidum carries promising anticancer and immunomodulatory properties. The popularity of taking G. lucidum as an alternative medicine has been increasing in cancer patients. However, there is no systematic review that has been conducted to evaluate the actual benefits of G. lucidum in cancer treatment. OBJECTIVES: To evaluate the clinical effects of G. lucidum on long-term survival, tumour response, host immune functions and quality of life in cancer patients, as well as adverse events associated with its use. SEARCH METHODS: We searched an extensive set of databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, NIH, AMED, CBM, CNKI, CMCC and VIP Information/Chinese Scientific Journals Database was searched for randomised controlled trials (RCTs) in October 2011. Other strategies used were scanning the references of articles retrieved, handsearching of the International Journal of Medicinal Mushrooms and contact with herbal medicine experts and manufacturers of G. lucidum. For this update we updated the searches in February 2016. SELECTION CRITERIA: To be eligible for being included in this review, studies had to be RCTs comparing the efficacy of G. lucidum medications to active or placebo control in patients with cancer that had been diagnosed by pathology. All types and stages of cancer were eligible for inclusion. Trials were not restricted on the basis of language. DATA COLLECTION AND ANALYSIS: Five RCTs met the inclusion criteria and were included in this review. Two independent review authors assessed the methodological quality of individual trials. Common primary outcomes were tumour response evaluated according to the World Health Organization (WHO) criteria, immune function parameters such as natural killer (NK)-cell activity and T-lymphocyte co-receptor subsets, and quality of life measured by the Karnofsky scale score. No trial had recorded long-term survival rates. Associated adverse events were reported in one study. A meta-analysis was performed to pool available data from the primary trials. Results were gauged using relative risks (RR) and standard mean differences (SMD) for dichotomous and continuous data respectively, with a 95% confidence interval (CI). MAIN RESULTS: The methodological quality of primary studies was generally unsatisfying and the results were reported inadequately in many aspects. Additional information was not available from primary trialists. The meta-analysis results showed that patients who had been given G. lucidum alongside with chemo/radiotherapy were more likely to respond positively compared to chemo/radiotherapy alone (RR 1.50; 95% CI 0.90 to 2.51, P = 0.02). G. lucidum treatment alone did not demonstrate the same regression rate as that seen in combined therapy. The results for host immune function indicators suggested that G. lucidum simultaneously increases the percentage of CD3, CD4 and CD8 by 3.91% (95% CI 1.92% to 5.90%, P < 0.01), 3.05% (95% CI 1.00% to 5.11%, P < 0.01) and 2.02% (95% CI 0.21% to 3.84%, P = 0.03), respectively. In addition, leukocyte, NK-cell activity and CD4/CD8 ratio were marginally elevated. Four studies showed that patients in the G. lucidum group had relatively improved quality of life in comparison to controls. One study recorded minimal side effects, including nausea and insomnia. No significant haematological or hepatological toxicity was reported. AUTHORS' CONCLUSIONS: Our review did not find sufficient evidence to justify the use of G. lucidum as a first-line treatment for cancer. It remains uncertain whether G. lucidum helps prolong long-term cancer survival. However, G. lucidum could be administered as an alternative adjunct to conventional treatment in consideration of its potential of enhancing tumour response and stimulating host immunity. G. lucidum was generally well tolerated by most participants with only a scattered number of minor adverse events. No major toxicity was observed across the studies. Although there were few reports of harmful effect of G. lucidum, the use of its extract should be judicious, especially after thorough consideration of cost-benefit and patient preference. Future studies should put emphasis on the improvement in methodological quality and further clinical research on the effect of G. lucidum on cancer long-term survival are needed. An update to this review will be performed every two years.

Effect of Vitamin D Supplementation on Tibial Cartilage Volume and Knee Pain Among Patients With Symptomatic Knee Osteoarthritis: A Randomized Clinical Trial.

IMPORTANCE: Observational studies suggest that vitamin D supplementation is associated with benefits for knee osteoarthritis, but current trial evidence is contradictory. OBJECTIVE: To compare the effects of vitamin D supplementation vs placebo on knee pain and knee cartilage volume in patients with symptomatic knee osteoarthritis and low vitamin D levels. DESIGN, SETTING, AND PARTICIPANTS: A multicenter randomized, double-blind, placebo-controlled clinical trial in Tasmania and Victoria, Australia. Participants with symptomatic knee osteoarthritis and low 25-hydroxyvitamin D (12.5-60 nmol/L) were enrolled from June 2010 to December 2011. The trial was completed in December 2013. INTERVENTIONS: Participants were randomly assigned to receive monthly treatment with oral vitamin D3 (50,000 IU; n = 209) or an identical placebo (n = 204) for 2 years. MAIN OUTCOMES AND MEASURES: Primary outcomes were change in tibial cartilage volume (assessed using magnetic resonance imaging [MRI]) and change in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score (0 [no pain] to 500 [worst pain]) from baseline to month 24. Secondary outcomes were cartilage defects and bone marrow lesions (assessed using MRI). RESULTS: Of 413 enrolled participants (mean age, 63.2 years; 50% women), 340 (82.3%) completed the study. The level of 25-hydroxyvitamin D increased more in the vitamin D group (40.6 nmol/L) than in the placebo group (6.7 nmol/L) (P < .001) over 2 years. There were no significant differences in annual change of tibial cartilage volume or WOMAC pain score. There were no significant differences in change of tibiofemoral cartilage defects or change in tibiofemoral bone marrow lesions. Adverse events (≥ 1 per patient) occurred in 56 participants in the vitamin D group and in 37 participants in the placebo group (P = .04). [table: see text]. CONCLUSIONS AND RELEVANCE: Among patients with symptomatic knee osteoarthritis and low serum 25-hydroxyvitamin D levels, vitamin D supplementation, compared with placebo, did not result in significant differences in change in MRI-measured tibial cartilage volume or WOMAC knee pain score over 2 years. These findings do not support the use of vitamin D supplementation for preventing tibial cartilage loss or improving WOMAC knee pain in patients with knee osteoarthritis. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01176344; anzctr.org.au Identifier: ACTRN12610000495022.

Ganoderma lucidum (Reishi mushroom) for cancer treatment.

BACKGROUND: Ganoderma lucidum is a natural medicine that is widely used and recommended by Asian physicians and naturopaths for its supporting effects on immune system. Laboratory research and a handful of preclinical trials have suggested that G. lucidum carries promising anticancer and immunomodulatory properties. The popularity of taking G. lucidum as an alternative medicine has been increasing in cancer patients. However, there is no systematic review that has been conducted to evaluate the actual benefits of G. lucidum in cancer treatment. OBJECTIVES: To evaluate the clinical effects of G. lucidum on long-term survival, tumour response, host immune functions and quality of life in cancer patients, as well as adverse events associated with its use. SEARCH METHODS: The authors ran an extensive set of databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, NIH, AMED, CBM, CNKI, CMCC and VIP Information/Chinese Scientific Journals Database was searched for randomised controlled trials (RCTs) in October 2011. Other strategies used were scanning the references of articles retrieved, handsearching of the International Journal of Medicinal Mushrooms and contact with herbal medicine experts and manufacturers of G. lucidum. SELECTION CRITERIA: To be eligible for being included in this review, studies had to be RCTs comparing the efficacy of G. lucidum medications to active or placebo control in patients with cancer that had been diagnosed by pathology. All types and stages of cancer were eligible for inclusion. Trials were not restricted on the basis of language. DATA COLLECTION AND ANALYSIS: Five RCTs met the inclusion criteria and were included in this review. Two independent review authors were assigned to assess the methodological quality of individual trials. Common primary outcomes were tumour response evaluated according to the World Health Organization (WHO) criteria, immune function parameters such as natural killer (NK)-cell activity and T-lymphocyte co-receptor subsets, and quality of life measured by the Karnofsky scale score. No trial had recorded long-term survival rates. Associated adverse events were reported in one study. A meta-analysis was performed to pool available data from the primary trials. Results were gauged using relative risks (RR) and standard mean differences (SMD) for dichotomous and continuous data respectively, with a 95% confidence interval (CI). MAIN RESULTS: The methodological quality of primary studies was generally unsatisfying and the results were reported inadequately in many aspects. Additional information was not available from primary trialists. The meta-analysis results showed that patients who had been given G. lucidum alongside with chemo/radiotherapy were more likely to respond positively compared to chemo/radiotherapy alone (RR 1.50; 95% CI 0.90 to 2.51, P = 0.02). G. lucidum treatment alone did not demonstrate the same regression rate as that seen in combined therapy. The results for host immune function indicators suggested that G. lucidum simultaneously increases the percentage of CD3, CD4 and CD8 by 3.91% (95% CI 1.92% to 5.90%, P < 0.01), 3.05% (95% CI 1.00% to 5.11%, P < 0.01) and 2.02% (95% CI 0.21% to 3.84%, P = 0.03), respectively. In addition, leukocyte, NK-cell activity and CD4/CD8 ratio were marginally elevated. Four studies showed that patients in the G. lucidum group had relatively improved quality of life in comparison to controls. One study recorded minimal side effects, including nausea and insomnia. No significant haematological or hepatological toxicity was reported. AUTHORS' CONCLUSIONS: Our review did not find sufficient evidence to justify the use of G. lucidum as a first-line treatment for cancer. It remains uncertain whether G. lucidum helps prolong long-term cancer survival. However, G. lucidum could be administered as an alternative adjunct to conventional treatment in consideration of its potential of enhancing tumour response and stimulating host immunity. G. lucidum was generally well tolerated by most participants with only a scattered number of minor adverse events. No major toxicity was observed across the studies. Although there were few reports of harmful effect of G. lucidum, the use of its extract should be judicious, especially after thorough consideration of cost-benefit and patient preference. Future studies should put emphasis on the improvement in methodological quality and further clinical research on the effect of G. lucidum on cancer long-term survival are needed. An update to this review will be performed every two years.