{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T14:08:08Z","timestamp":1793196488700,"version":"4.5.0"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2022,3,19]],"date-time":"2022-03-19T00:00:00Z","timestamp":1647648000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,3,19]],"date-time":"2022-03-19T00:00:00Z","timestamp":1647648000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Updates Surg"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Multi-drug resistant organisms (MDR-Os) are emerging as a significant cause of surgical site infections (SSI), but clinical outcomes and risk factors associated to MDR-Os-SSI have been poorly investigated in general surgery. Aims were to investigate risk factors, clinical outcomes and costs of care of multi-drug resistant organisms (MDR-Os-SSI) in general surgery. From January 2018 to December 2019, all the consecutive, unselected patients affected by MDR-O SSI were prospectively evaluated. In the same period, patients with non-MDR-O SSI and without SSI, matched for clinical and surgical data were used as control groups. Risk factors for infection, clinical outcome, and costs of care were compared by univariate and multivariate analysis. Among 3494 patients operated on during the study period, 47 presented an MDR-O SSI. Two control groups of 47 patients with non-MDR-O SSI and without SSI were identified. MDR-Os SSI were caused by poly-microbial etiology, meanly related to Gram negative <jats:italic>Enterobacteriales<\/jats:italic>. MDR-Os-SSI were related to major postoperative complications. At univariate analysis, iterative surgery, open abdomen, intensive care, hospital stay, and use of aggressive and expensive therapies were associated to MDR-Os-SSI. At multivariate analysis, only iterative surgery and the need of total parenteral and immune-nutrition were significantly associated to MDR-Os-SSI. The extra-cost of MDR-Os-SSI treatment was 150% in comparison to uncomplicated patients. MDR-Os SSI seems to be associated with major postoperative complications and reoperative surgery, they are demanding in terms of clinical workload and costs of care, they are rare but increasing, and difficult to prevent with current strategies.<\/jats:p>","DOI":"10.1007\/s13304-022-01243-3","type":"journal-article","created":{"date-parts":[[2022,3,19]],"date-time":"2022-03-19T04:34:46Z","timestamp":1647664486000},"page":"1763-1771","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Surgical site infections caused by multi-drug resistant organisms: a case\u2013control study in general surgery"],"prefix":"10.1007","volume":"74","author":[{"given":"Diego","family":"Foschi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Al\u2019ona","family":"Yakushkina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Cammarata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Lamperti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Colombo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Rimoldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spinello","family":"Antinori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7168-441X","authenticated-orcid":false,"given":"Gianluca M.","family":"Sampietro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,19]]},"reference":[{"key":"1243_CR1","doi-asserted-by":"publisher","first-page":"1288","DOI":"10.1017\/ice.2016.174","volume":"37","author":"LM Weiner","year":"2016","unstructured":"Weiner LM, Webb AK, Limbago B et al (2016) Antimicrobial-resistant pathogens associated with healthcare-associated infections: summary of data reported to the national healthcare safety network at the Centers for Diseases Control and Prevention, 2011\u20132014. Infect Control Hosp Epidemiol 37:1288\u20131301","journal-title":"Infect Control Hosp Epidemiol"},{"key":"1243_CR2","unstructured":"ECDC (2014) Annual epidemiological report. Antibiotic resistance and healthcare-associated infections. http:\/\/www.ecdc.europa.eu"},{"key":"1243_CR3","doi-asserted-by":"publisher","first-page":"2224","DOI":"10.1111\/ajt.13893","volume":"16","author":"LC McDonald","year":"2016","unstructured":"McDonald LC (2016) Vital signs: preventing antibiotic-resistant infections in Hospitals United States, 2014. Am J Transplant 16:2224\u20132230","journal-title":"Am J Transplant"},{"key":"1243_CR4","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/S1473-3099(18)30605-4","volume":"19","author":"A Cassini","year":"2019","unstructured":"Cassini A, Diaz-Hogberg L, Plachouras D et al (2019) Attributable deaths and disability-adjusted life years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: a population-level modelling analysis. Lancet Infect Dis 19:56\u201366","journal-title":"Lancet Infect Dis"},{"key":"1243_CR5","unstructured":"CDC (2015) The five \u201cW\u201ds of the targeted assessment for prevention (TAP) strategy, Atlanta, GA: US Department of Health and Human Services. CDC. http:\/\/www.cdc.gov\/hai\/prevent\/tap.html"},{"key":"1243_CR6","doi-asserted-by":"publisher","first-page":"1433","DOI":"10.1086\/345476","volume":"36","author":"SE Cosgrove","year":"2003","unstructured":"Cosgrove SE, Carmeli Y (2003) The impact of antimicrobial resistance on health and economic outcomes. CID 36:1433\u20131437","journal-title":"CID"},{"key":"1243_CR7","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1038\/nrmicro1614","volume":"5","author":"GD Wright","year":"2007","unstructured":"Wright GD (2007) The antibiotic resistoma nexus of chemical and genetic diversity. Nat Rev Microbiol 5:175\u2013186","journal-title":"Nat Rev Microbiol"},{"key":"1243_CR8","doi-asserted-by":"publisher","first-page":"902","DOI":"10.1111\/j.1469-0691.2009.03027.x","volume":"16","author":"S Nseir","year":"2010","unstructured":"Nseir S, Grailles G, Soury-Lavergne A et al (2010) Accuracy of American Thoracic Society\/Infectious Diseases Society of America criteria in predicting infection or colonization with multidrug-resistant bacteria at intensive-care unit admission. Clin Microbiol Infect 16:902\u2013908","journal-title":"Clin Microbiol Infect"},{"key":"1243_CR9","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1089\/mdr.2018.0279","volume":"25","author":"L Sun","year":"2019","unstructured":"Sun L, Liu S, Wang J, Wang L (2019) Analysis of risk factors for multiantibiotic-resistant infections among surgical patients at a Children\u2019s hospital. Microb Drug Resist 25:297\u2013303","journal-title":"Microb Drug Resist"},{"key":"1243_CR10","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1111\/j.1469-0691.2011.03570.x","volume":"18","author":"AP Magiorakos","year":"2012","unstructured":"Magiorakos AP, Srinivasan A, Carag RB et al (2012) Multidrug-resistant, extensively drug-resistant and pan drug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 18:268\u2013281","journal-title":"Clin Microbiol Infect"},{"key":"1243_CR11","doi-asserted-by":"publisher","first-page":"2107","DOI":"10.1097\/TP.0000000000001356","volume":"100","author":"JA Viehman","year":"2016","unstructured":"Viehman JA, Clancy CJ, Clarke L et al (2016) Surgical site infections after liver transplantation: emergence of multidrug-resistant bacteria and implications for prophylaxis and treatment strategies. Transplantation 100:2107\u20132114","journal-title":"Transplantation"},{"key":"1243_CR12","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.1016\/j.surg.2017.12.031","volume":"163","author":"G Sugawara","year":"2018","unstructured":"Sugawara G, Yokoyama Y, Ebata T et al (2018) Preoperative biliary colonization\/infection caused by multidrug-resistant (MDR) pathogens in patients undergoing major hepatectomy with extrahepatic bile duct resection. Surgery 163:1106\u20131113","journal-title":"Surgery"},{"key":"1243_CR13","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1016\/j.jiac.2018.05.007","volume":"24","author":"Y Takahashi","year":"2018","unstructured":"Takahashi Y, Takesue Y, Frejiwara M et al (2018) Risk factors for surgical site infection after major hepatobiliary surgery and pancreatic surgery. J Infect Chemother 24:739\u2013743","journal-title":"J Infect Chemother"},{"key":"1243_CR14","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1016\/j.surg.2018.09.011","volume":"165","author":"S Sano","year":"2019","unstructured":"Sano S, Sugiura T, Kawamura I et al (2019) Third-generation cephalosporin for antimicrobial prophylaxis in pancreatoduodenectomy in patients with internal preoperative biliary drainage. Surgery 165:559\u2013564","journal-title":"Surgery"},{"key":"1243_CR15","doi-asserted-by":"publisher","first-page":"916","DOI":"10.1016\/j.ajic.2019.01.020","volume":"47","author":"MF Golzarri","year":"2019","unstructured":"Golzarri MF, Sanchez JS, Cornejo-Juarez P et al (2019) Colonization by fecal extended-spectrum \u03b2-lactamase-producing Enterobacteriaceae and surgical site infections in patients with cancer undergoing gastrointestinal and gynecological surgery. Am J Infect Control 47:916\u2013921","journal-title":"Am J Infect Control"},{"key":"1243_CR16","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1016\/j.ajic.2017.02.023","volume":"45","author":"JC Hernaiz-Leonardo","year":"2017","unstructured":"Hernaiz-Leonardo JC, Golzarri MF, Cornejo-Juarez P et al (2017) Microbiology of surgical site infections in patients with cancer: a 7-year review. Am J Infect Cont 45:761\u2013766","journal-title":"Am J Infect Cont"},{"key":"1243_CR17","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/j.jhin.2004.01.003","volume":"56","author":"C Dobbin","year":"2004","unstructured":"Dobbin C, Maley M, Harkness J et al (2004) The impact of pan-resistant bacterial pathogens on survival after lung transplantation in cystic fibrosis: results from a single large referral center. J Hosp Infect 56:277\u2013282","journal-title":"J Hosp Infect"},{"key":"1243_CR18","doi-asserted-by":"crossref","unstructured":"Augustin P, Kermarrec N, Muller-Serieys C et al (2010) Risk factors for multidrug resistant bacteria and optimization of empirical antibiotic therapy in postoperative peritonitis. Crit Care 14 (article no. R20)","DOI":"10.1186\/cc8877"},{"key":"1243_CR19","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1093\/jac\/dkp439","volume":"65","author":"P Seguin","year":"2010","unstructured":"Seguin P, Fedun Y, Laviolle B et al (2010) Risk factors for multidrug-resistant bacteria in patients with post-operative peritonitis requiring intensive care. J Antimicrob Chemother 65:342\u2013346","journal-title":"J Antimicrob Chemother"},{"issue":"1","key":"1243_CR20","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/1471-2253-13-13","volume":"13","author":"P Di Carlo","year":"2013","unstructured":"Di Carlo P, Gulotta G, Caruccio A et al (2013) KPC-3 Klebsiella pneumonia ST258 clone infection in postoperative abdominal surgery patients in an intensive care setting: analysis of a case series of 30 patients. BMC Anesthesiol 13(1):13","journal-title":"BMC Anesthesiol"},{"key":"1243_CR21","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1186\/s13054-015-0789-9","volume":"19","author":"P Montravers","year":"2015","unstructured":"Montravers P, Dufour G, Guglielminetti J et al (2015) Dynamic changes of microbioal flora and therapeutic consequences in persistent peritonitis. Crit Care 19:70 (1\u201313)","journal-title":"Crit Care"},{"key":"1243_CR22","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1016\/j.cmi.2015.12.002","volume":"22","author":"ND Friedman","year":"2016","unstructured":"Friedman ND, Temkin E, Carmeli Y (2016) The negative impact of antibiotic resistance. Clin Microbiol Infect 22:416\u2013422","journal-title":"Clin Microbiol Infect"},{"key":"1243_CR23","unstructured":"PNCAR. National Action Plan on Antimicrobial Resistance 2017\u201320 (2017). http:\/\/www.salte.gov.it\/images\/PNCAR. Accessed 1 Nov 2021"},{"key":"1243_CR24","doi-asserted-by":"publisher","first-page":"152S","DOI":"10.1016\/0002-9343(91)90361-Z","volume":"91","author":"DH Culver","year":"1991","unstructured":"Culver DH, Horan TC, Gaynes RP et al (1991) Surgical wound infection rates by wound class, operative procedure, and patient risk index National Nosocomial Infections Surveillance System. Am J Med 91:152S-157S","journal-title":"Am J Med"},{"key":"1243_CR25","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.1016\/S0140-6736(07)61602-X","volume":"370","author":"E von Elm","year":"2007","unstructured":"von Elm E, Altman DG, Egger M et al (2007) The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet 370:1453\u20131457","journal-title":"Lancet"},{"key":"1243_CR26","doi-asserted-by":"publisher","first-page":"2191","DOI":"10.1001\/jama.2013.281053","volume":"310","author":"World Medical A","year":"2013","unstructured":"World Medical A (2013) World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA 310:2191\u20132194","journal-title":"JAMA"},{"key":"1243_CR27","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1097\/01.sla.0000133083.54934.ae","volume":"240","author":"D Dindo","year":"2004","unstructured":"Dindo D, Demartines N, Clavien PA (2004) Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 240:205\u2013213","journal-title":"Ann Surg"},{"key":"1243_CR28","unstructured":"EUCAST Recommendations (2017). http:\/\/www.eucast.org\/clinical-breakpoints\/. Accessed 1 Nov 2021"},{"key":"1243_CR29","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1001\/jama.2016.0287","volume":"315","author":"M Singer","year":"2016","unstructured":"Singer M, Deutschman CS, Seymour CW et al (2016) The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA 315:801\u2013810","journal-title":"JAMA"},{"key":"1243_CR30","unstructured":"DRG TIP TAR_SD OMDCD (2015). https:\/\/www.regione.lombardia.it. Accessed 1 Nov 2021"},{"key":"1243_CR31","unstructured":"AIFA. Agenzia Italiana del Farmaco. Prezzi e rimborso farmaci di classe A e H (2020). http:\/\/aifa.gov.it\/liste-farmaci-a-h. Accessed 1 Nov 2021"},{"key":"1243_CR32","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1093\/ecco-JCC\/JJY017","volume":"697","author":"PA Reuken","year":"2018","unstructured":"Reuken PA, Krnis K, Maaser C et al (2018) Microbial spectrum of intra-abdominal abscesses in perforating Crohn\u2019s disease: results from a prospective German registry. JCC 697:701. https:\/\/doi.org\/10.1093\/ecco-JCC\/JJY017","journal-title":"JCC"},{"key":"1243_CR33","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1097\/SLA.0000000000001558","volume":"264","author":"JA Hyder","year":"2016","unstructured":"Hyder JA, Reznor G, Nakeam N et al (2016) Risk prediction accuracy differs for emergency versus elective cases in the ACS-NSQIP. Ann Surg 264:959\u2013965","journal-title":"Ann Surg"},{"key":"1243_CR34","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/S0196-6553(99)70088-X","volume":"27","author":"AJ Mangram","year":"1999","unstructured":"Mangram AJ, Horan TC, Pearson ML et al (1999) Guideline for prevention of surgical site infection 1999. Am J Infect Control 27:97\u2013134","journal-title":"Am J Infect Control"},{"key":"1243_CR35","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1097\/DCR.0000000000000550","volume":"59","author":"A Bhakta","year":"2016","unstructured":"Bhakta A, Tafen M, Glotzer O et al (2016) Increased incidence of surgical site infection in IBD patients. Dis Colon Rectum 59:316\u2013322","journal-title":"Dis Colon Rectum"},{"key":"1243_CR36","doi-asserted-by":"publisher","first-page":"1338","DOI":"10.1002\/ibd.21519","volume":"17","author":"GC Nguyen","year":"2011","unstructured":"Nguyen GC, Leung W, Weizman AV (2011) Increased risk of vancomycin-resistant Enterococcus (VRE) infection among patients hospitalized for Inflammatory Bowel Disease in the United States. Inflam Bowel Dis 17:1338\u20131342","journal-title":"Inflam Bowel Dis"},{"key":"1243_CR37","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1097\/SLA.0b013e3181ad8935","volume":"250","author":"JT Mullen","year":"2009","unstructured":"Mullen JT, Moorman DW, Davenport DL (2009) The obesity paradox body mass index and outcomes in patients undergoing non bariatric general surgery. Ann Surg 250:166\u2013172","journal-title":"Ann Surg"},{"key":"1243_CR38","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1159\/000018742","volume":"16","author":"V Di Carlo","year":"1999","unstructured":"Di Carlo V, Gianotti L, Balzano G et al (1999) Complications of pancreatic surgery and the role of perioperative nutrition. Dig Surg 16:320\u2013326","journal-title":"Dig Surg"},{"key":"1243_CR39","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1089\/sur.2013.9999","volume":"14","author":"DN Bratzler","year":"2013","unstructured":"Bratzler DN, Dellinger EP, Olsen KM et al (2013) Clinical practice guidelines for antimicrobial prophylaxis in surgery. Surg Infect 14:73\u2013156","journal-title":"Surg Infect"},{"key":"1243_CR40","doi-asserted-by":"publisher","first-page":"1162","DOI":"10.1086\/319757","volume":"32","author":"E Lantenbach","year":"2001","unstructured":"Lantenbach E, Patel JB, Bilker WB et al (2001) Extended-spectrum \u03b2-lactamase-producing Escherichia coli and Klebsiella pneumonia: risk factors for infection and impact of resistance on outcomes. Clin Infect Dis 32:1162\u20131171","journal-title":"Clin Infect Dis"},{"key":"1243_CR41","doi-asserted-by":"crossref","unstructured":"JD Siegel, E Rhinehart, M Jackson, L Chiarello, The HICPA Committee (2007) Guidelines for isolation precautions: preventing transmission of infections agents in healthcare settings. https:\/\/www.cdc.gov\/infectioncontrol\/guidelines\/isolation\/index.html","DOI":"10.1016\/j.ajic.2007.10.007"},{"key":"1243_CR42","doi-asserted-by":"publisher","first-page":"1429","DOI":"10.1016\/S1473-3099(15)00270-4","volume":"15","author":"A Teillant","year":"2015","unstructured":"Teillant A, Gandra S, Barter D et al (2015) Potential burden of antibiotic resistance on surgery and cancer chemotherapy antibiotic prophylaxis in the USA: a literature review and modelling study. Lancet Infect Dis 15:1429\u20131437","journal-title":"Lancet Infect Dis"},{"key":"1243_CR43","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/S0195-6701(08)60017-1","volume":"70","author":"CD Owens","year":"2008","unstructured":"Owens CD, Stoessel K (2008) Surgical site infections: epidemiology, microbiology and prevention. J Hosp Infect 70:3\u201310","journal-title":"J Hosp Infect"}],"container-title":["Updates in Surgery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13304-022-01243-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s13304-022-01243-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13304-022-01243-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T22:08:19Z","timestamp":1663366099000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s13304-022-01243-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,19]]},"references-count":43,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2022,10]]}},"alternative-id":["1243"],"URL":"https:\/\/doi.org\/10.1007\/s13304-022-01243-3","relation":{},"ISSN":["2038-131X","2038-3312"],"issn-type":[{"value":"2038-131X","type":"print"},{"value":"2038-3312","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,19]]},"assertion":[{"value":"6 November 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 January 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 March 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 July 2022","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Update","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Missing Open Access funding information has been added in the Funding Note.","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"None of the authors have conflicts to declare.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The study was submitted to and approved by the Ethic Committee of the L. Sacco Hospital (#00-28004), and an informed consent was obtained from all the patients. The study was conducted according to the ethical standards of the Declaration of Helsinki (2013 version) and reported according to the Strengthening the Reporting of Observational Studies in Epidemiology [STROBE] guidelines.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Research involving human participants and\/or animals and Informed consent"}}]}}