Supplementary appendix

Transcription

1 Supplementary appendix This appendix formed part of the original submission and has been peer reviewed. We post it as supplied by the authors. Supplement to: Bolland MJ, Grey A, Gamble GD, Reid IR. The effect of vitamin D supplementation on skeletal, vascular, or cancer outcomes: a trial sequential meta-analysis. Lancet Diabetes Endocrinol 2014; published online Jan 24.

2 Appendix: Figure 1: Flow of trials Pubmed search (n=463) Trial-level meta-analysis (n=17) -MI/Stroke (n=4) -Cancer (n=3) -Fracture (n=4) -Mortality (n=6) Reports on vitamin D (n=3) RCTs retrieved -56 reports of 52 trials 12 excluded (see Table 1) RCTs eligible for inclusion -44 reports of 40 trials Page 1 of 4

3 Table1: Trials excluded from analyses and reasons for exclusion Trial Brohult Grove Larsen Campbell Sato Daly Law Moschonis Schleithoff Berggren Wejse Witham Reason for exclusion Population studied: rheumatoid arthritis Other co-intervention: fluoride plus calcium/vitamin D versus placebo. Cluster randomised controlled trial Other co-intervention: exercise plus vitamin D versus home safety programme versus social visits versus exercise plus vitamin D plus home safety programme Data inconsistencies- awaiting clarification from authors Agent: fortified dairy products Cluster randomised controlled trial Agent: fortified dairy products Population studied: congestive heart failure Other co-intervention: falls prevention programme plus calcium/vitamin D versus controls Population studied: tuberculosis Population studied: congestive heart failure References: 1. Brohult J, Jonson B. Effects of large doses of calciferol on patients with rheumatoid arthritis. A doubleblind clinical trial. Scand J Rheumatol 1973; 2: Grove O, Halver B. Relief of osteoporotic backache with fluoride, calcium, and calciferol. Acta Med Scand 1981; 209: Larsen ER, Mosekilde L, Foldspang A. Vitamin D and calcium supplementation prevents osteoporotic fractures in elderly community dwelling residents: a pragmatic population-based 3-year intervention study. J Bone Miner Res 2004; 19: Campbell AJ, Robertson MC, La Grow SJ, Kerse NM, Sanderson GF, Jacobs RJ, et al. Randomised controlled trial of prevention of falls in people aged > or =75 with severe visual impairment: the VIP trial. BMJ 2005; 331: Sato Y, Iwamoto J, Kanoko T, Satoh K. Low-dose vitamin D prevents muscular atrophy and reduces falls and hip fractures in women after stroke: a randomized controlled trial. Cerebrovasc Dis 2005; 20: Daly RM, Brown M, Bass S, Kukuljan S, Nowson C. Calcium- and vitamin D3-fortified milk reduces bone loss at clinically relevant skeletal sites in older men: a 2-year randomized controlled trial. J Bone Miner Res 2006; 21: Law M, Withers H, Morris J, Anderson F. Vitamin D supplementation and the prevention of fractures and falls: results of a randomised trial in elderly people in residential accommodation. Age Ageing 2006; 35: Moschonis G, Manios Y. Skeletal site-dependent response of bone mineral density and quantitative ultrasound parameters following a 12-month dietary intervention using dairy products fortified with calcium and vitamin D: the Postmenopausal Health Study. Br J Nutr 2006; 96: Schleithoff SS, Zittermann A, Tenderich G, Berthold HK, Stehle P, Koerfer R. Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: a double-blind, randomized, placebo-controlled trial. Am J Clin Nutr 2006; 83: Berggren M, Stenvall M, Olofsson B, Gustafson Y. Evaluation of a fall-prevention program in older people after femoral neck fracture: a one-year follow-up. Osteoporos Int 2008; 19: Wejse C, Gomes VF, Rabna P, Gustafson P, Aaby P, Lisse IM, et al. Vitamin D as supplementary treatment for tuberculosis: a double-blind, randomized, placebo-controlled trial. Am J Respir Crit Care Med 2009; 179: Witham MD, Crighton LJ, Gillespie ND, Struthers AD, McMurdo ME. The effects of vitamin D supplementation on physical function and quality of life in older patients with heart failure: a randomized controlled trial. Circ Heart Fail 2010; 3: Page 2 of 4

4 Table 2: Subgroup analyses of traditional meta-analysis by baseline and achieved 25OHD levels, and by duration of trial. Baseline 25OHD (nmol/l) Baseline/Achieved 25OHD (nmol/l) Duration of trial <50 50 Missing <50/<50 <50/ 50 50/ 50 Missing 2 years >2 years Myocardial infarction/ischaemic heart disease Studies Participants (N) 44, , ,866 RR (95% CI) 4 ( ) 0 ( ) 1.30 ( ) - 4 ( ) 0 ( ) 1.30 ( ) 1.90 ( ) 1 ( ) P (interaction) Stroke/Cerebrovascular disease Studies Participants (N) 42, , ,610 RR (95% CI) 0 ( ) 1.20 ( ) 5 ( ) - 0 ( ) 1.20 ( ) 5 ( ) 1.10 (6-2.17) 0 ( ) P (interaction) Cancer Studies Participants (N) 44, , ,865 RR (95% CI) 0.98 (0.92-4) 0.76 (0.38-5) 0.88 ( ) (0.92-4) 0.76 (0.38-5) 0.88 ( ) 0.20 (2-1.69) 0.99 (0.93-5) P (interaction) Total fracture Studies Participants (N) 55,640 10,194 10, ,287 10,194 10, ,497 RR (95% CI) 0.97 (0.90-6) 0.75 ( ) 0.87 ( ) 0.38 (0.14-5) 0.98 (0.91-6) 0.75 ( ) 0.87 ( ) 0.85 (0.70-4) 0.96 (0.89-4) P (interaction) Hip fracture- Vitamin D Studies Participants (N) 11, , ,290 RR (95% CI) 9 ( ) 0 (2-2.19) 1 ( ) 0.44 (7-2.93) 1.10 ( ) 0 (2-2.19) 1 ( ) 5 (0.73-3) 1.12 ( ) P (interaction) Hip fracture- calcium/vitamin D Studies Participants (N) 46, , ,395 RR (95% CI) 0.84 ( ) 0.36 (2-8.79) 0.73 ( ) 0.49 (3-7.70) 0.85 (0.72-0) 0.36 (2-8.79) 0.73 ( ) 0.64 (0.37-8) 0.85 ( ) P (interaction) Mortality Studies Participants (N) 57,843 12,180 11, ,488 12,180 11, ,215 RR (95% CI) 0.93 ( ) 0.98 ( ) 0.98 (0.93-4) 1.37 ( ) 0.93 ( ) 0.98 ( ) 0.98 (0.93-4) 0.96 (0.88-6) 0.96 (0.92-0) P (interaction) Abbreviations: 25OHD- 25- hydroxyvitamin D; RR- relative risk; CI confidence interval Page 3 of 4

5 Figure 2: Funnel Plots of Traditional Meta-analyses Funnel Plot of by Myocardial infarction P=6 Funnel Plot of by Total fracture P= Funnel Plot of by Stroke P=7 Funnel Plot of by Vitamin D Hip fracture P= Funnel Plot of by Cancer P=5 Funnel Plot of by Vitamin D/Calcium Hip fracture P= Funnel Plot of by Mortality P= P-values are for Egger s test. Page 4 of 4