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The Cochrane Collaboration. Available: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.cochrane-handbook.org\" xlink:type=\"simple\">http:\/\/www.cochrane-handbook.org<\/ext-link>. Accessed 20 October 2013."},{"key":"ref9","doi-asserted-by":"crossref","first-page":"264","DOI":"10.7326\/0003-4819-151-4-200908180-00135","article-title":"Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement","volume":"151","author":"D Moher","year":"2009","journal-title":"Ann Intern Med"},{"key":"ref10","unstructured":"Wells GA, Shea B, O&apos;Connell D, Peterson P, Welch V, <etal>et al<\/etal>.. (2010) The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa: Ottawa Hospital Research Institute. Available: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.ohri.ca\/programs\/clinical_epidemiology\/oxford.htm\" xlink:type=\"simple\">http:\/\/www.ohri.ca\/programs\/clinical_epidemiology\/oxford.htm<\/ext-link>. 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and risk of vitamin B-12 deficiency: randomised placebo controlled trial","volume":"340","author":"J de Jager","year":"2010","journal-title":"Br Med J"},{"key":"ref17","first-page":"46","article-title":"Association of low vitamin B<sub>12<\/sub> level and ischemic heart disease in diabetes patients","volume":"26","author":"RN Kulambil Padinjakara","year":"2009","journal-title":"Diabetic Medicine"},{"key":"ref18","first-page":"245","article-title":"Metformin-associated upregulation in methylmalonic acid levels correlates with clinical deterioration in patients with diabetic peripheral neuropathy","volume":"14","author":"C Toth","year":"2009","journal-title":"Journal of the Peripheral Nervous System"},{"key":"ref19","first-page":"S352","article-title":"The high prevalence of malnutrition and unnecessary drug therapy in very old diabetic patients","volume":"52","author":"UM Vischer","year":"2009","journal-title":"Diabetologia"},{"key":"ref20","first-page":"215","article-title":"The impact 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