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Recent:   

Vitamin D metabolism in critically ill patients with acute kidney injury: a prospective observational study

Cameron et al., Critical Care, doi:10.1186/s13054-024-04869-4, NCT02869919
Apr 2024  
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Non-COVID-19 study of 137 critically ill patients showing significantly lower serum calcitriol in patients with moderate-to-severe acute kidney injury (AKI) compared to critically ill patients without AKI, but no significant difference in serum 25(OH)D concentrations. Authors suggest that calcitriol deficiency may be under-recognized in critically ill patients with moderate to severe AKI, and that supplementation with active vitamin D analogues, rather than cholecalciferol, may be beneficial.
For COVID-19 patients, treatment with calcitriol avoids the delay in conversion from cholecalciferol, but may also be beneficial for AKI patients with impaired ability to convert cholecalciferol to the active form.
Cameron et al., 2 Apr 2024, prospective, United Kingdom, peer-reviewed, 11 authors, trial NCT02869919 (history). Contact: marlies.ostermann@gstt.nhs.uk.
This PaperMiscellaneousAll
Vitamin D metabolism in critically ill patients with acute kidney injury: a prospective observational study
Lynda K Cameron, Lesedi Ledwaba-Chapman, Kieran Voong, Geeta Hampson, Lui G Forni, Nina Seylanova, Dominic J Harrington, Rosario Lim, Aneta Bociek, Wang Yanzhong, Marlies Ostermann
Critical Care, doi:10.1186/s13054-024-04869-4
Background Vitamin D deficiency in critically ill patients is associated with poor outcomes, and vitamin D supplementation is recommended for patients with chronic kidney disease. Whether acute kidney injury (AKI) is associated with altered Vitamin D metabolism is unknown. We aimed to compare the longitudinal profiles of serum 25(OH) D and 1,25(OH) 2 D concentrations in critically ill patients with and without moderate to severe AKI and explore the impact of renal recovery and parathyroid hormone (PTH). Methods In this prospective, observational study in two centres in the UK, critically ill patients with and without AKI underwent serial measurement of serum 25(OH)D and 1,25(OH) 2 D and plasma PTH concentrations for 5 days. Linear mixed model analysis and sensitivity analyses were performed. Results Serial data of 137 patients were analysed. Seventy-one patients had AKI stage II/III of whom 23 recovered kidney function during the 5-day study period; 66 patients did not have AKI at enrolment of whom 14 developed new AKI. On day of enrolment, patients' serum 25(OH)D concentrations were low (median 18 nmol/L) but there was no significant difference between patients with and without AKI. Median serum 1,25(OH) 2 D levels were significantly lower in patients with AKI II/III (41 pmol/L [IQR 26, 58]) compared to similarly unwell patients without AKI (54 pmol/L [IQR 33, 69]) during the 5-day period. Recovery of kidney function in patients with AKI was associated with a rise in 1,25(OH) 2 D concentrations. Plasma PTH results were impacted by serum calcium and magnesium levels but not associated with 1,25(OH) 2 D levels. Conclusions Critically ill patients with moderate-to-severe AKI have significantly lower serum 1,25(OH) 2 D concentrations than similarly sick patients without AKI but there was no difference in serum 25(OH)D concentrations. Recovery of AKI was associated with a rise in serum 1,25(OH) 2 D concentrations. More research is needed to investigate the health benefits and safety of supplementation with active vitamin D in critically ill patients with moderate-tosevere AKI. Trial registration Clinicaltrials.
Supplementary Information The online version contains supplementary material available at https:// doi. org/ 10. 1186/ s13054-024-04869-4. Additional file 1. Author contributions All authors contributed to the study conception and design. Sampling and data collection were performed by LC, RL and AB. The laboratory analyses were performed by KV and GH. DJH assisted with the laboratory analyses. The statistical analyses were done by LLC and WY. The first draft of the manuscript was written by MO. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Declarations Ethics approval and consent to participate The study was approved by a National Research Ethics Committee in the UK (London Camberwell St Giles) (IRAS 196968) and carried out in accordance with the Code of Ethics of the World Medical Association (Declaration of Helsinki). Written informed consent was obtained from participants or provided by a personal or professional consultee if the patient did not have capacity to consent for themselves. In a case where a consultee had given permission for the patient to take part, the patient was invited to give informed consent to continue participation or to withdraw from further participation as soon as they regained capacity. Consent for publication Written consent for publication was obtained from participants or provided by a personal or professional consultee if the patient did not have capacity to consent..
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Whether acute kidney injury (AKI) is associated with altered Vitamin D metabolism is ' 'unknown. We aimed to compare the longitudinal profiles of serum 25(OH)D and ' '1,25(OH)<jats:sub>2</jats:sub>D concentrations in critically ill patients with and without ' 'moderate to severe AKI and explore the impact of renal recovery and parathyroid hormone ' '(PTH).</jats:p>\n' ' </jats:sec><jats:sec>\n' ' <jats:title>Methods</jats:title>\n' ' <jats:p>In this prospective, observational study in two centres in the UK, ' 'critically ill patients with and without AKI underwent serial measurement of serum 25(OH)D ' 'and 1,25(OH)<jats:sub>2</jats:sub>D and plasma PTH concentrations for 5\xa0days. Linear mixed ' 'model analysis and sensitivity analyses were performed.</jats:p>\n' ' </jats:sec><jats:sec>\n' ' <jats:title>Results</jats:title>\n' ' <jats:p>Serial data of 137 patients were analysed. Seventy-one patients had ' 'AKI stage II/III of whom 23 recovered kidney function during the 5-day study period; 66 ' 'patients did not have AKI at enrolment of whom 14 developed new AKI. On day of enrolment, ' 'patients’ serum 25(OH)D concentrations were low (median 18\xa0nmol/L) but there was no ' 'significant difference between patients with and without AKI. Median serum ' '1,25(OH)<jats:sub>2</jats:sub>D levels were significantly lower in patients with AKI II/III ' '(41\xa0pmol/L [IQR 26, 58]) compared to similarly unwell patients without AKI (54\xa0pmol/L ' '[IQR 33, 69]) during the 5-day period. Recovery of kidney function in patients with AKI was ' 'associated with a rise in 1,25(OH)<jats:sub>2</jats:sub>D concentrations. Plasma PTH results ' 'were impacted by serum calcium and magnesium levels but not associated with ' '1,25(OH)<jats:sub>2</jats:sub>D levels.</jats:p>\n' ' </jats:sec><jats:sec>\n' ' <jats:title>Conclusions</jats:title>\n' ' <jats:p>Critically ill patients with moderate-to-severe AKI have ' 'significantly lower serum 1,25(OH)<jats:sub>2</jats:sub>D concentrations than similarly sick ' 'patients without AKI but there was no difference in serum 25(OH)D concentrations. Recovery of ' 'AKI was associated with a rise in serum 1,25(OH)<jats:sub>2</jats:sub>D concentrations. 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' '2020;74(11):1498–513.', 'journal-title': 'Eur J Clin Nutr'}, { 'issue': '10', 'key': '4869_CR19', 'doi-asserted-by': 'publisher', 'first-page': 'e055435', 'DOI': '10.1136/bmjopen-2021-055435', 'volume': '11', 'author': 'EA Hurst', 'year': '2021', 'unstructured': 'Hurst EA, Mellanby RJ, Handel I, Griffith DM, Rossi AG, Walsh TS, ' 'Shankar-Hari M, Dunning J, Homer NZ, Denham SG, et al. Vitamin D ' 'insufficiency in COVID-19 and influenza A, and critical illness ' 'survivors: a cross-sectional study. BMJ Open. 2021;11(10):e055435.', 'journal-title': 'BMJ Open'}, { 'issue': '12', 'key': '4869_CR20', 'doi-asserted-by': 'publisher', 'first-page': '2028', 'DOI': '10.1007/s00134-009-1642-x', 'volume': '35', 'author': 'P Lee', 'year': '2009', 'unstructured': 'Lee P, Nair P, Eisman JA, Center JR. Vitamin D deficiency in the ' 'intensive care unit: an invisible accomplice to morbidity and mortality? ' 'Intensive Care Med. 2009;35(12):2028–32.', 'journal-title': 'Intensive Care Med'}, { 'issue': '11', 'key': '4869_CR21', 'doi-asserted-by': 'publisher', 'first-page': '1940', 'DOI': '10.1007/s00134-018-5107-y', 'volume': '44', 'author': 'K Amrein', 'year': '2018', 'unstructured': 'Amrein K, Oudemans-van Straaten HM, Berger MM. Vitamin therapy in ' 'critically ill patients: focus on thiamine, vitamin C, and vitamin D. ' 'Intensive Care Med. 2018;44(11):1940–4.', 'journal-title': 'Intensive Care Med'}, { 'key': '4869_CR22', 'doi-asserted-by': 'publisher', 'first-page': '139', 'DOI': '10.1146/annurev.nutr.22.120501.150216', 'volume': '22', 'author': 'JL Omdahl', 'year': '2002', 'unstructured': 'Omdahl JL, Morris HA, May BK. Hydroxylase enzymes of the vitamin D ' 'pathway: expression, function, and regulation. Annu Rev Nutr. ' '2002;22:139–66.', 'journal-title': 'Annu Rev Nutr'}, { 'key': '4869_CR23', 'doi-asserted-by': 'publisher', 'first-page': '630951', 'DOI': '10.3389/fnut.2020.630951', 'volume': '7', 'author': 'S Graidis', 'year': '2020', 'unstructured': 'Graidis S, Papavramidis TS, Papaioannou M. Vitamin D and acute kidney ' 'injury: a two-way causality relation and a predictive, prognostic, and ' 'therapeutic role of vitamin D. Front Nutr. 2020;7:630951.', 'journal-title': 'Front Nutr'}, { 'issue': '6', 'key': '4869_CR24', 'doi-asserted-by': 'publisher', 'first-page': '966', 'DOI': '10.1681/ASN.2009080872', 'volume': '21', 'author': 'Y Zhang', 'year': '2010', 'unstructured': 'Zhang Y, Kong J, Deb DK, Chang A, Li YC. Vitamin D receptor attenuates ' 'renal fibrosis by suppressing the renin-angiotensin system. J Am Soc ' 'Nephrol. 2010;21(6):966–73.', 'journal-title': 'J Am Soc Nephrol'}, { 'issue': '4', 'key': '4869_CR25', 'doi-asserted-by': 'publisher', 'first-page': '262', 'DOI': '10.2174/18715281113129990044', 'volume': '12', 'author': 'AB Braun', 'year': '2013', 'unstructured': 'Braun AB, Christopher KB. Vitamin D in acute kidney injury. Inflamm ' 'Allergy Drug Targets. 2013;12(4):262–72.', 'journal-title': 'Inflamm Allergy Drug Targets'}, { 'issue': '13', 'key': '4869_CR26', 'doi-asserted-by': 'publisher', 'first-page': 'e12829', 'DOI': '10.14814/phy2.12829', 'volume': '4', 'author': 'AC de Bragança', 'year': '2016', 'unstructured': 'de Bragança AC, Volpini RA, Mehrotra P, Andrade L, Basile DP. Vitamin D ' 'deficiency contributes to vascular damage in sustained ischemic acute ' 'kidney injury. Physiol Rep. 2016;4(13):e12829.', 'journal-title': 'Physiol Rep'}, { 'issue': '3', 'key': '4869_CR27', 'doi-asserted-by': 'publisher', 'first-page': 'e12331', 'DOI': '10.14814/phy2.12331', 'volume': '3', 'author': 'AC de Bragança', 'year': '2015', 'unstructured': 'de Bragança AC, Volpini RA, Canale D, Gonçalves JG, Shimizu MH, Sanches ' 'TR, Seguro AC, Andrade L. Vitamin D deficiency aggravates ischemic acute ' 'kidney injury in rats. Physiol Rep. 2015;3(3):e12331.', 'journal-title': 'Physiol Rep'}, { 'issue': '9', 'key': '4869_CR28', 'doi-asserted-by': 'publisher', 'first-page': 'e107228', 'DOI': '10.1371/journal.pone.0107228', 'volume': '9', 'author': 'JG Gonçalves', 'year': '2014', 'unstructured': 'Gonçalves JG, de Bragança AC, Canale D, Shimizu MH, Sanches TR, Moysés ' 'RM, Andrade L, Seguro AC, Volpini RA. Vitamin D deficiency aggravates ' 'chronic kidney disease progression after ischemic acute kidney injury. ' 'PLoS ONE. 2014;9(9):e107228.', 'journal-title': 'PLoS ONE'}, { 'issue': '11', 'key': '4869_CR29', 'doi-asserted-by': 'publisher', 'first-page': '231', 'DOI': '10.5414/CN109121', 'volume': '88', 'author': 'S Ersan', 'year': '2017', 'unstructured': 'Ersan S, Celik A, Tanrisev M, Kose I, Cavdar Z, Unlu M, Kocak A, Ural C, ' 'Yilmaz B, Kose T. Pretreatment with paricalcitol attenuates level and ' 'expression of matrix metalloproteinases in a rat model of renal ' 'ischemia-reperfusion injury. Clin Nephrol. 2017;88(11):231–8.', 'journal-title': 'Clin Nephrol'}, { 'key': '4869_CR30', 'doi-asserted-by': 'publisher', 'first-page': '133', 'DOI': '10.1016/j.jsbmb.2015.05.009', 'volume': '152', 'author': 'S Xu', 'year': '2015', 'unstructured': 'Xu S, Chen YH, Tan ZX, Xie DD, Zhang C, Xia MZ, Wang H, Zhao H, Xu DX, ' 'Yu DX. Vitamin D3 pretreatment alleviates renal oxidative stress in ' 'lipopolysaccharide-induced acute kidney injury. J Steroid Biochem Mol ' 'Biol. 2015;152:133–41.', 'journal-title': 'J Steroid Biochem Mol Biol'}, { 'issue': '1–3', 'key': '4869_CR31', 'doi-asserted-by': 'publisher', 'first-page': '301', 'DOI': '10.1016/j.ejphar.2012.03.019', 'volume': '683', 'author': 'JW Park', 'year': '2012', 'unstructured': 'Park JW, Cho JW, Joo SY, Kim CS, Choi JS, Bae EH, Ma SK, Kim SH, Lee J, ' 'Kim SW. Paricalcitol prevents cisplatin-induced renal injury by ' 'suppressing apoptosis and proliferation. Eur J Pharmacol. ' '2012;683(1–3):301–9.', 'journal-title': 'Eur J Pharmacol'}, { 'issue': '1', 'key': '4869_CR32', 'doi-asserted-by': 'publisher', 'first-page': '43', 'DOI': '10.1007/s10157-018-1614-y', 'volume': '23', 'author': 'M Hamzawy', 'year': '2019', 'unstructured': 'Hamzawy M, Gouda SAA, Rashed L, Morcos MA, Shoukry H, Sharawy N. ' '22-oxacalcitriol prevents acute kidney injury via inhibition of ' 'apoptosis and enhancement of autophagy. Clin Exp Nephrol. ' '2019;23(1):43–55.', 'journal-title': 'Clin Exp Nephrol'}, { 'key': '4869_CR33', 'doi-asserted-by': 'publisher', 'first-page': '313528', 'DOI': '10.1155/2013/313528', 'volume': '2013', 'author': 'E Hur', 'year': '2013', 'unstructured': 'Hur E, Garip A, Camyar A, Ilgun S, Ozisik M, Tuna S, Olukman M, Narli ' 'Ozdemir Z, Yildirim Sozmen E, Sen S, et al. The effects of vitamin d on ' 'gentamicin-induced acute kidney injury in experimental rat model. Int J ' 'Endocrinol. 2013;2013:313528.', 'journal-title': 'Int J Endocrinol'}, { 'issue': '4', 'key': '4869_CR34', 'first-page': 'E138', 'volume': '65', 'author': 'N Arfian', 'year': '2020', 'unstructured': 'Arfian N, Budiharjo S, Wibisono DP, Setyaningsih WAW, Romi MM, Saputri ' 'R, Rofiah EK, Rahmanti T, Agustin M, Sari DCR. Vitamin D ameliorates ' 'kidney ischemia reperfusion injury via reduction of inflammation and ' 'myofibroblast expansion. Kobe J Med Sci. 2020;65(4):E138-e143.', 'journal-title': 'Kobe J Med Sci'}, { 'key': '4869_CR35', 'doi-asserted-by': 'publisher', 'first-page': '117331', 'DOI': '10.1016/j.lfs.2020.117331', 'volume': '244', 'author': 'NF Abo El-Magd', 'year': '2020', 'unstructured': 'Abo El-Magd NF, Eraky SM. The molecular mechanism underlining the ' 'preventive effect of vitamin D against hepatic and renal acute toxicity ' 'through the NrF2/ BACH1/ HO-1 pathway. Life Sci. 2020;244:117331.', 'journal-title': 'Life Sci'}, { 'issue': '9', 'key': '4869_CR36', 'doi-asserted-by': 'publisher', 'first-page': '1928', 'DOI': '10.1097/CCM.0000000000001148', 'volume': '43', 'author': 'SA Quraishi', 'year': '2015', 'unstructured': 'Quraishi SA, De Pascale G, Needleman JS, Nakazawa H, Kaneki M, Bajwa EK, ' 'Camargo CA Jr, Bhan I. Effect of cholecalciferol supplementation on ' 'vitamin D status and cathelicidin levels in sepsis: a randomized ' 'placebo-controlled trial. Crit Care Med. 2015;43(9):1928–37.', 'journal-title': 'Crit Care Med'}, { 'issue': '15', 'key': '4869_CR37', 'doi-asserted-by': 'publisher', 'first-page': '1520', 'DOI': '10.1001/jama.2014.13204', 'volume': '312', 'author': 'K Amrein', 'year': '2014', 'unstructured': 'Amrein K, Schnedl C, Holl A, Riedl R, Christopher KB, Pachler C, Urbanic ' 'Purkart T, Waltensdorfer A, Münch A, Warnkross H, et al. Effect of ' 'high-dose vitamin D3 on hospital length of stay in critically ill ' 'patients with vitamin D deficiency: the VITdAL-ICU randomized clinical ' 'trial. JAMA. 2014;312(15):1520–30.', 'journal-title': 'JAMA'}, { 'issue': '11', 'key': '4869_CR38', 'doi-asserted-by': 'publisher', 'first-page': '2313', 'DOI': '10.1097/CCM.0000000000001201', 'volume': '43', 'author': 'P Nair', 'year': '2015', 'unstructured': 'Nair P, Venkatesh B, Lee P, Kerr S, Hoechter DJ, Dimeski G, Grice J, ' 'Myburgh J, Center JR. A randomized study of a single dose of ' 'intramuscular cholecalciferol in critically Ill adults. Crit Care Med. ' '2015;43(11):2313–20.', 'journal-title': 'Crit Care Med'}, { 'issue': '2', 'key': '4869_CR39', 'doi-asserted-by': 'publisher', 'first-page': '178', 'DOI': '10.1038/ki.1978.25', 'volume': '13', 'author': 'J Pietrek', 'year': '1978', 'unstructured': 'Pietrek J, Kokot F, Kuska J. Serum 25-hydroxyvitamin D and parathyroid ' 'hormone in patients with acute renal failure. Kidney Int. ' '1978;13(2):178–85.', 'journal-title': 'Kidney Int'}, { 'issue': '12', 'key': '4869_CR40', 'doi-asserted-by': 'publisher', 'first-page': '747', 'DOI': '10.1159/000534228', 'volume': '147', 'author': 'JA Neyra', 'year': '2023', 'unstructured': 'Neyra JA, Moe OW. Bone dysregulation in acute kidney injury. Nephron. ' '2023;147(12):747–53.', 'journal-title': 'Nephron'}, { 'issue': '2', 'key': '4869_CR41', 'doi-asserted-by': 'publisher', 'first-page': '216', 'DOI': '10.1681/ASN.2010020186', 'volume': '22', 'author': 'R Kumar', 'year': '2011', 'unstructured': 'Kumar R, Thompson JR. The regulation of parathyroid hormone secretion ' 'and synthesis. J Am Soc Nephrol. 2011;22(2):216–24.', 'journal-title': 'J Am Soc Nephrol'}, { 'issue': '1–2', 'key': '4869_CR42', 'doi-asserted-by': 'publisher', 'first-page': '124', 'DOI': '10.1159/000355860', 'volume': '124', 'author': 'M Raimundo', 'year': '2013', 'unstructured': 'Raimundo M, Crichton S, Lei K, Sanderson B, Smith J, Brooks J, Ng J, ' 'Lemmich Smith J, McKenzie C, Beale R, et al. Maintaining normal levels ' 'of ionized calcium during citrate-based renal replacement therapy is ' 'associated with stable parathyroid hormone levels. Nephron Clin Pract. ' '2013;124(1–2):124–31.', 'journal-title': 'Nephron Clin Pract'}, { 'issue': '2', 'key': '4869_CR43', 'doi-asserted-by': 'publisher', 'first-page': '309', 'DOI': '10.3390/biology12020309', 'volume': '12', 'author': 'OS Thein', 'year': '2023', 'unstructured': 'Thein OS, Ali NA, Mahida RY, Dancer RCA, Ostermann M, Amrein K, Martucci ' 'G, Scott A, Thickett DR, Parekh D. Raised FGF23 correlates to increased ' 'mortality in critical illness, independent of vitamin D. Biology. ' '2023;12(2):309.', 'journal-title': 'Biology'}, { 'issue': '1', 'key': '4869_CR44', 'doi-asserted-by': 'publisher', 'first-page': '1505', 'DOI': '10.1038/s41598-020-58115-2', 'volume': '10', 'author': 'M Ostermann', 'year': '2020', 'unstructured': 'Ostermann M, Summers J, Lei K, Card D, Harrington DJ, Sherwood R, Turner ' 'C, Dalton N, Peacock J, Bear DE. Micronutrients in critically ill ' 'patients with severe acute kidney injury—a prospective study. Sci Rep. ' '2020;10(1):1505.', 'journal-title': 'Sci Rep'}], 'container-title': 'Critical Care', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://link.springer.com/content/pdf/10.1186/s13054-024-04869-4.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://link.springer.com/article/10.1186/s13054-024-04869-4/fulltext.html', 'content-type': 'text/html', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://link.springer.com/content/pdf/10.1186/s13054-024-04869-4.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2024, 4, 2]], 'date-time': '2024-04-02T15:07:56Z', 'timestamp': 1712070476000}, 'score': 1, 'resource': {'primary': {'URL': 'https://ccforum.biomedcentral.com/articles/10.1186/s13054-024-04869-4'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2024, 4, 2]]}, 'references-count': 44, 'journal-issue': {'issue': '1', 'published-online': {'date-parts': [[2024, 12]]}}, 'alternative-id': ['4869'], 'URL': 'http://dx.doi.org/10.1186/s13054-024-04869-4', 'relation': {}, 'ISSN': ['1364-8535'], 'subject': ['Critical Care and Intensive Care Medicine'], 'container-title-short': 'Crit Care', 'published': {'date-parts': [[2024, 4, 2]]}, 'assertion': [ { 'value': '2 January 2024', 'order': 1, 'name': 'received', 'label': 'Received', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '11 March 2024', 'order': 2, 'name': 'accepted', 'label': 'Accepted', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '2 April 2024', 'order': 3, 'name': 'first_online', 'label': 'First Online', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, {'order': 1, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Declarations'}}, { 'value': 'The study was approved by a National Research Ethics Committee in the UK ' '(London Camberwell St Giles) (IRAS 196968) and carried out in accordance with ' 'the Code of Ethics of the World Medical Association (Declaration of Helsinki). ' 'Written informed consent was obtained from participants or provided by a ' 'personal or professional consultee if the patient did not have capacity to ' 'consent for themselves. In a case where a consultee had given permission for ' 'the patient to take part, the patient was invited to give informed consent to ' 'continue participation or to withdraw from further participation as soon as ' 'they regained capacity.', 'order': 2, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Ethics approval and consent to participate'}}, { 'value': 'Written consent for publication was obtained from participants or provided by a ' 'personal or professional consultee if the patient did not have capacity to ' 'consent for themselves. In a case where a consultee gave permission for the ' 'patient to take part, the patient was informed and invited to give informed ' 'consent for publication as soon as they regained capacity.', 'order': 3, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Consent for publication'}}, { 'value': 'The authors declare no conflict of interest related to this manuscript.', 'order': 4, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Competing interests'}}], 'article-number': '108'}
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