{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:07:37Z","timestamp":1772168857647,"version":"3.50.1"},"update-to":[{"DOI":"10.12688\/f1000research.154742.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T00:00:00Z","timestamp":1750291200000}},{"DOI":"10.12688\/f1000research.154742.2","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T00:00:00Z","timestamp":1750291200000}}],"reference-count":49,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T00:00:00Z","timestamp":1750291200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The German Ministry for Education and Research (Bundesministerium f\u00fcr Bildung und Forschung","award":["01KG2317"],"award-info":[{"award-number":["01KG2317"]}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns3:p>Introduction Sexual dysfunctions are common yet underreported side effects of antipsychotics for schizophrenia, affecting 30-80% of treated individuals. These side effects can severely impact social interactions and treatment adherence for individuals with schizophrenia, but comprehensive comparative evidence assessing the risk profiles of different antipsychotics is lacking. This study aims to address this gap using network meta-analysis that integrates data from both randomized-controlled trials (RCTs) and non-randomized studies (NRS). Protocol This systematic review will include both RCTs and NRS focusing on participants with schizophrenia or schizophrenia-like psychoses, without restrictions on symptoms, gender, ethnicity, age, or setting. For interventions, all second-generation antipsychotics will be included. The primary outcome will be the occurrence of at least one sexual adverse event of any kind. Secondary outcomes will be the occurrence of any sexual adverse event evaluated in men and women separately, and any adverse event related to the three phases of sexual response cycle separately: desire (e.g. libido, sexual thoughts), arousal (e.g. erection, lubrication) and orgasm (e.g. ejaculation, anorgasmia), and any adverse effect related to breast dysfunction and menstruation irregularities. Study selection and data extraction will be performed independently by two reviewers. The Cochrane Risk of Bias tool 1 and ROBINS-I will be employed to evaluate the risk of bias for RCTs and NRS, respectively. Single-arm meta-analysis of proportions will synthesize the average frequency of sexual adverse events in treated participants. Pairwise and network meta-analysis of RCTs and NRS will be used to evaluate comparative tolerability. Subgroup and sensitivity analyses will explore possible heterogeneity in results and validate the findings\u2019 robustness. The quality of the evidence will be evaluated using GRADE. Discussion This study will provide vital insights into the sexual side effects of antipsychotics by combining evidence from clinical trials and real-world practice, facilitating better decision-making in choosing the optimal antipsychotic for individuals.<\/ns3:p>","DOI":"10.12688\/f1000research.154742.3","type":"journal-article","created":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T12:20:10Z","timestamp":1750335610000},"page":"973","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Sexual dysfunction and other prolactin-related side effects of antipsychotic drugs in schizophrenia: Protocol for a systematic review with single-arm, pairwise, and network meta-analyses of randomized controlled trials and non-randomized studies"],"prefix":"10.12688","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3448-9532","authenticated-orcid":false,"given":"Johannes","family":"Schneider-Thoma","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shimeng","family":"Dong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David D.","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Orestis","family":"Efthimiou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8264-2039","authenticated-orcid":false,"given":"Spyridon","family":"Siafis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wulf Peter","family":"Hansen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elfriede","family":"Scheuring","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl Heinz","family":"M\u00f6hrmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4934-4352","authenticated-orcid":false,"given":"Stefan","family":"Leucht","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2025,6,19]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"153-160","DOI":"10.1136\/ebmental-2019-300117","article-title":"How to perform a meta-analysis with R: a practical tutorial.","volume":"22","author":"S Balduzzi","year":"2019","journal-title":"Evid. Based Ment. Health."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"22-28","DOI":"10.1111\/j.1600-0447.2008.01310.x","article-title":"Side-effects of antipsychotic medication and health-related quality of life in schizophrenia.","volume":"119","author":"P Bebbington","year":"2009","journal-title":"Acta Psychiatr. Scand. Suppl."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"383-389","DOI":"10.1080\/00224499.2013.865111","article-title":"A systematic review of instruments to measure sexual functioning in patients using antipsychotics.","volume":"51","author":"M Boer","year":"2014","journal-title":"J. Sex Res."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"161-176","DOI":"10.1002\/jrsm.57","article-title":"Using network meta-analysis to evaluate the existence of small-study effects in a network of interventions.","volume":"3","author":"A Chaimani","year":"2012","journal-title":"Res. Synth. Methods."},{"key":"ref5","article-title":"S3 Guideline for Schizophrenia.","year":"2019"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"271-279","DOI":"10.1016\/j.jclinepi.2020.08.019","article-title":"Controversy and Debate: Questionable utility of the relative risk in clinical research: Paper 1: A call for change to practice.","volume":"142","author":"S Doi","year":"2022","journal-title":"J. Clin. Epidemiol."},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.6084\/m9.figshare.26396275.v2","article-title":"Extented data for SexualSE protocol.","author":"S Dong","year":"2024","journal-title":"figshare."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"72-76","DOI":"10.1136\/eb-2018-102911","article-title":"Practical guide to the meta-analysis of rare events.","volume":"21","author":"O Efthimiou","year":"2018","journal-title":"Evid. Based Ment. Health."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1210-1226","DOI":"10.1002\/sim.7223","article-title":"Combining randomized and non-randomized evidence in network meta-analysis.","volume":"36","author":"O Efthimiou","year":"2017","journal-title":"Stat. Med."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"2992-3012","DOI":"10.1002\/sim.8158","article-title":"Network meta-analysis of rare events using the Mantel-Haenszel method.","volume":"38","author":"O Efthimiou","year":"2019","journal-title":"Stat. Med."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"S9","DOI":"10.1016\/j.jval.2021.11.039","article-title":"P41 Crosnma: A New R Package to Synthesize Cross-Design Evidence and Cross-Format Data.","volume":"25","author":"T Hamza","year":"2022","journal-title":"Value Health."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"334-341","DOI":"10.1097\/YIC.0b013e32833db3d8","article-title":"Tolerability of paliperidone: a meta-analysis of randomized, controlled trials.","volume":"25","author":"C Harrington","year":"2010","journal-title":"Int. Clin. Psychopharmacol."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"98-110","DOI":"10.1002\/jrsm.1044","article-title":"Consistency and inconsistency in network meta-analysis: concepts and models for multi-arm studies.","volume":"3","author":"J Higgins","year":"2012","journal-title":"Res. Synth. Methods."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"939-951","DOI":"10.1016\/S0140-6736(19)31135-3","article-title":"Comparative efficacy and tolerability of 32 oral antipsychotics for the acute treatment of adults with multi-episode schizophrenia: a systematic review and network meta-analysis.","volume":"394","author":"M Huhn","year":"2019","journal-title":"Lancet."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"CD000440","DOI":"10.1002\/14651858.CD000440","article-title":"Risperidone versus typical antipsychotic medication for schizophrenia.","volume":"2003","author":"R Hunter","year":"2003","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"777-784","DOI":"10.7326\/M14-2385","article-title":"The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations.","volume":"162","author":"B Hutton","year":"2015","journal-title":"Ann. Intern. Med."},{"key":"ref18","article-title":"MedDRA\u00ae the Medical Dictionary for Regulatory Activities terminology. Version 25.1.","year":"2022"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"sbw172-sbw239","DOI":"10.1093\/schbul\/sbw172","article-title":"Psychosis as a Barrier to the Expression of Sexuality and Intimacy: An Environmental Risk?","volume":"43","author":"J Jager","year":"2017","journal-title":"Schizophr. Bull."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"CD005237","DOI":"10.1002\/14651858.CD005237","article-title":"Risperidone versus olanzapine for schizophrenia.","volume":"2","author":"M Jayaram","year":"2005","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"767-779","DOI":"10.1093\/oxfordjournals.schbul.a007130","article-title":"Sexuality and schizophrenia: a review.","volume":"30","author":"D Kelly","year":"2004","journal-title":"Schizophr. Bull."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"CD006752","DOI":"10.1002\/14651858.CD006752.pub2","article-title":"Sertindole versus other atypical antipsychotics for schizophrenia.","volume":"2","author":"K Komossa","year":"2009","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"CD006626","DOI":"10.1002\/14651858.CD006626.pub2","article-title":"Risperidone versus other atypical antipsychotics for schizophrenia.","volume":"1","author":"K Komossa","year":"2011","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"5414-5429","DOI":"10.1002\/sim.6001","article-title":"Visualizing the flow of evidence in network meta-analysis and characterizing mixed treatment comparisons.","volume":"32","author":"J K\u00f6nig","year":"2013","journal-title":"Stat. Med."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1110-1120","DOI":"10.1001\/jamapsychiatry.2023.2696","article-title":"Sexual Dysfunction in Schizophrenia: A Systematic Review and Meta-Analysis.","volume":"80","author":"T Korchia","year":"2023","journal-title":"JAMA Psychiatry."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"201-208","DOI":"10.1055\/s-0033-1347177","article-title":"Sexual dysfunction related to psychotropic drugs: a critical review part II: antipsychotics.","volume":"46","author":"A La Torre","year":"2013","journal-title":"Pharmacopsychiatry."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"415-422","DOI":"10.1016\/j.eurpsy.2004.06.031","article-title":"Impact of present and past antipsychotic side effects on attitude toward typical antipsychotic treatment and adherence.","volume":"19","author":"M Lambert","year":"2004","journal-title":"Eur. Psychiatry."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"162-163","DOI":"10.1016\/j.schres.2022.01.001","article-title":"About the issue of including or excluding studies from China in systematic reviews.","volume":"240","author":"S Leucht","year":"2022","journal-title":"Schizophr. Res."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"CD001715","DOI":"10.1002\/14651858.CD001715.pub2","article-title":"Sertindole for schizophrenia.","volume":"2005","author":"R Lewis","year":"2005","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"982-991","DOI":"10.1177\/02698811231205688","article-title":"Second International Consensus Study of Antipsychotic Dosing (ICSAD-2).","volume":"37","author":"M McAdam","year":"2023","journal-title":"J. Psychopharmacol."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"67-76","DOI":"10.1093\/epirev\/mxn001","article-title":"Schizophrenia: a concise overview of incidence, prevalence, and mortality.","volume":"30","author":"J McGrath","year":"2008","journal-title":"Epidemiol. Rev."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1186\/s12888-018-1867-8","article-title":"Comparative efficacy and safety between amisulpride and olanzapine in schizophrenia treatment and a cost analysis in China: a systematic review, meta-analysis, and cost-minimization analysis.","volume":"18","author":"P Men","year":"2018","journal-title":"BMC Psychiatry."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"3-11","DOI":"10.1002\/wps.20509","article-title":"The impact of severe mental disorders and psychotropic medications on sexual health and its implications for clinical management.","volume":"17","author":"A Montejo","year":"2018","journal-title":"World Psychiatry."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"331-338","DOI":"10.4088\/jcp.v66n0309","article-title":"Male sexual dysfunction and quality of life in schizophrenia.","volume":"66","author":"M Olfson","year":"2005","journal-title":"J. Clin. Psychiatry."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1186\/s13643-016-0384-4","article-title":"Rayyan-a web and mobile app for systematic reviews.","volume":"5","author":"M Ouzzani","year":"2016","journal-title":"Syst. Rev."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"1121-1128","DOI":"10.4088\/jcp.v63n1206","article-title":"Predictors of noncompliance in patients with schizophrenia.","volume":"63","author":"D Perkins","year":"2002","journal-title":"J. Clin. Psychiatry."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"991-996","DOI":"10.1016\/j.jclinepi.2007.11.010","article-title":"Contour-enhanced meta-analysis funnel plots help distinguish publication bias from other causes of asymmetry.","volume":"61","author":"J Peters","year":"2008","journal-title":"J. Clin. Epidemiol."},{"key":"ref38","doi-asserted-by":"publisher","DOI":"10.32614\/CRAN.package.rjags","article-title":"rjags: Bayesian Graphical Models using MCMC.","author":"M Plummer","year":"2023"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"g5630","DOI":"10.1136\/bmj.g5630","article-title":"A GRADE Working Group approach for rating the quality of treatment effect estimates from network meta-analysis.","volume":"349","author":"M Puhan","year":"2014","journal-title":"BMJ (Clinical Research ed.)."},{"key":"ref41","article-title":"netmeta: Network Meta-Analysis using Frequentist Methods. R package version 1.2-1.","author":"G R\u00fccker","year":"2020"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"824-836","DOI":"10.1016\/S0140-6736(21)01997-8","article-title":"Comparative efficacy and tolerability of 32 oral and long-acting injectable antipsychotics for the maintenance treatment of adults with schizophrenia: a systematic review and network meta-analysis.","volume":"399","author":"J Schneider-Thoma","year":"2022","journal-title":"Lancet."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"726-732","DOI":"10.7326\/0003-4819-152-11-201006010-00232","article-title":"CONSORT 2010 statement: updated guidelines for reporting parallel group randomized trials.","volume":"152","author":"K Schulz","year":"2010","journal-title":"Ann. Intern. Med."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"476-483","DOI":"10.1002\/jrsm.1348","article-title":"Seriously misleading results using inverse of Freeman-Tukey double arcsine transformation in meta-analysis of single proportions.","volume":"10","author":"G Schwarzer","year":"2019","journal-title":"Res. Synth. Methods."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"130-140","DOI":"10.1097\/YIC.0b013e328341e434","article-title":"A meta-analysis of sexual dysfunction in psychiatric patients taking antipsychotics.","volume":"26","author":"A Serretti","year":"2011","journal-title":"Int. Clin. Psychopharmacol."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"Article sgaa061","DOI":"10.1093\/schizbullopen\/sgaa061","article-title":"Cochrane Schizophrenia Group\u2019s Study-Based Register of Randomized Controlled Trials: Development and Content Analysis.","volume":"1","author":"F Shokraneh","year":"2020","journal-title":"Schizophrenia Bulletin Open."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"1354-1363","DOI":"10.1016\/j.jsxm.2021.05.016","article-title":"Erectile and Ejaculatory Dysfunction Associated with Use of Psychotropic Drugs: A Systematic Review.","volume":"18","author":"M Trinchieri","year":"2021","journal-title":"J. Sex. Med."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"818-827","DOI":"10.1093\/ije\/dys041","article-title":"Predicting the extent of heterogeneity in meta-analysis, using empirical data from the Cochrane Database of Systematic Reviews.","volume":"41","author":"R Turner","year":"2012","journal-title":"Int. J. Epidemiol."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"W-94","DOI":"10.7326\/0003-4819-147-8-200710160-00010-w1","article-title":"Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): explanation and elaboration.","volume":"147","author":"J Vandenbroucke","year":"2007","journal-title":"Ann. Intern. Med."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"1476-1488","DOI":"10.1016\/j.jsxm.2020.03.005","article-title":"Is There an Association Between Schizophrenia and Sexual Dysfunction in Both Sexes? A Systematic Review and Meta-Analysis.","volume":"17","author":"S Zhao","year":"2020","journal-title":"J. Sex. Med."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"i157","DOI":"10.1136\/bmj.i157","article-title":"PRISMA harms checklist: improving harms reporting in systematic reviews.","volume":"352","author":"L Zorzela","year":"2016","journal-title":"BMJ (Clinical Research ed.)."}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/13-973\/v3\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/13-973\/v3\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/13-973\/v3\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T12:20:11Z","timestamp":1750335611000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/13-973\/v3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,19]]},"references-count":49,"URL":"https:\/\/doi.org\/10.12688\/f1000research.154742.3","relation":{"has-version":[{"id-type":"doi","id":"10.12688\/f1000research.154742.2","asserted-by":"subject"},{"id-type":"doi","id":"10.12688\/f1000research.154742.1","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.183803.r393283","asserted-by":"object"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,19]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/13-973\/v3#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.169806.r319278, Sofia Brissos, Centro Hospitalar Psiqui\u00e1trico de Lisboa, Lisboa, 20 Sep 2024, version 1, 2 approved with reservations","URL":"https:\/\/f1000research.com\/articles\/13-973\/v1#referee-response-319278","order":0,"name":"referee-response-319278","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Shimeng Dong<\/b>; \n<i>Posted: 12 Dec 2024<\/i>; 1) The authors focus on an important aspect of schizophrenia patients' treatment, but again, they will focus on data that has been previously collected, which may not be sufficient. For instance, the majority of these clinical trials have a small number of female patients, and many real-life patients have been excluded due to the &quot;rigorous&quot; inclusion criteria. Nevertheless, I am happy to see that the authors will conduct independent analysis in men and women separately. In that sense, although the authors plan to include real-world observational studies, we will have access to the reported side-effects of those studies only.  \n<b>Our response:<\/b> We thank the reviewer for the important point. We acknowledge that RCTs are highly selective in terms of recruiting participants and even non-randomized studies may not truly reflect the real-world setting. However, there are also advantages to be recognized because RCTs allow the estimation of the effect directly coming from a single antipsychotic, for instance, by restricting the use of concomitant drugs. Non-randomized studies usually do not make such restrictions, and whether the effect is truly caused by the antipsychotic becomes less clear, but at the same time allowing what the effect might be in real-life patients. Therefore, it is of high importance to examine both randomized and non-randomized studies, make comparisons, and provide more comprehensive evidence. We agree with the reviewer that although we plan to include observational studies, we will have access to the reported side-effects of those studies only. We will address this limitation by contacting the authors of the studies that do not necessarily report sexual side effects but potentially have them recorded (e.g., studies that only report common side effects, such as &gt; 5% incidence).  2) Finally, I myself do not find of great interest a manuscript on what will be done; I think what is of interest to the reader is the result of what the authors are planning to analyze, and not just their intentions.  \n<b>Our response:<\/b> We understand that protocols may not be as interesting to read as published results, but it is important for systematic reviews to have protocols before their implementation and make them public so that bias can be reduced and readers can see whether what was originally planned was actually done. We will of course publish the results later.","URL":"https:\/\/f1000research.com\/articles\/13-973\/v3#referee-comment-12946","order":1,"name":"referee-comment-12946","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.175947.r365735, Angel L Montejo, Hospital Universitario de Salamanca, University of Salamanca, Salamanca, 12 Feb 2025, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/13-973\/v2#referee-response-365735","order":2,"name":"referee-response-365735","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.175947.r383765, James MacCabe, King's College London, London, England, 04 Jun 2025, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/13-973\/v2#referee-response-383765","order":3,"name":"referee-response-383765","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This project is funded by the German Ministry for Education and Research (Bundesministerium f\u00fcr Bildung und Forschung (BMBF)), grant number 01KG2317. The funding agency has no role in the study design, data collection, data analysis, interpretation of results, or writing of the report. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":4,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}