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Open Access 18-11-2023 | Status Epilepticus | Original Research Article

Trends and Differences in Status Epilepticus Treatment of Children and Adults Over 10 Years: A Comparative Study of Medical Records (2012–2021) from a University Hospital in Germany

Authors: Leonore Purwien, Susanne Schubert-Bast, Matthias Kieslich, Michael W. Ronellenfitsch, Michael Merker, Marcus Czabanka, Laurent M. Willems, Felix Rosenow, Adam Strzelczyk

Published in: CNS Drugs | Issue 11/2023

Abstract

Background and Objectives

Over the last decade, significant advancements have been made in status epilepticus (SE) management, influenced by landmark trials such as ESETT and RAMPART. The objectives of this study were to explore the evolution of drug treatments for patients with SE, to investigate its association with outcomes and mortality, and to evaluate differences in treatment patterns between adults and children for a potential shift in medication trends due to the above mentioned trials.

Methods

The medical records of patients with SE treated at University Hospital Frankfurt between 2012 and 2021 were evaluated for medication trends and outcomes. Children and adults were analyzed separately and jointly.

Results

This study included 1151 SE episodes in 1021 patients (mean age = 53.3 ± 28.3 years; 52.5 % female [n = 533]). The overall percentage of patients with SE treated prehospital was stable over the last decade. More than half (53.6 %) of children were treated prehospital, compared with less than one-third (26.7 %) of adults. Prehospital midazolam use increased over time, while diazepam use decreased. Lorazepam was the most commonly used benzodiazepine in hospitals in 2012–2013, used in 40.8 % of all episodes. However, its use declined to 27.2 % in 2020–2021, while midazolam use increased to 44.0 %. While the use of older antiseizure medications (ASMs) such as phenobarbital (p = 0.02), phenytoin (p < 0.001), and valproate (p < 0.001) decreased, the use of newer ASMs such as levetiracetam and lacosamide significantly increased (p < 0.001). Propofol and continuous midazolam infusion remained the most used third-line therapy drugs. Overall mortality was 16.5 % at discharge and 18.9 % at 30 days. Mortality rates did not change between 2012 and 2021.

Conclusion

Midazolam has become the preferred benzodiazepine in pre- and in-hospital settings, both in children and adults. The same applies to the increased use of levetiracetam and lacosamide over time in children and adults, while phenobarbital, phenytoin, and valproate use decreased. Continuous midazolam infusion and propofol remain the most frequently used anesthetic drugs. Mortality and outcome remain stable despite changes in medication patterns.

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Shorvon S, Sen A. What is status epilepticus and what do we know about its epidemiology? Seizure. 2020;75:131–6. https://doi.org/10.1016/j.seizure.2019.10.003.CrossRefPubMed

Dham BS, Hunter K, Rincon F. The epidemiology of status epilepticus in the United States. Neurocrit Care. 2014;20(3):476–83. https://doi.org/10.1007/s12028-013-9935-x.CrossRefPubMed

Willems LM, Rosenow F, Strzelczyk A. Therapeutic options for patients with status epilepticus in old age. Z Epileptol. 2022;35:117–22. https://doi.org/10.1007/s10309-022-00544-2.

Leitinger M, Trinka E, Zimmermann G, Granbichler CA, Kobulashvili T, Siebert U. Epidemiology of status epilepticus in adults: apples, pears, and oranges—a critical review. Epilepsy Behav E&B. 2020;2:106720. https://doi.org/10.1016/j.yebeh.2019.106720.CrossRef

Knake S, Rosenow F, Vescovi M, Oertel WH, Mueller HH, Wirbatz A, et al. Incidence of status epilepticus in adults in Germany: a prospective, population-based study. Epilepsia. 2001;42(6):714–8. https://doi.org/10.1046/j.1528-1157.2001.01101.x.CrossRefPubMed

Crawshaw AA, Cock HR. Medical management of status epilepticus: emergency room to intensive care unit. Seizure. 2020;75:145–52. https://doi.org/10.1016/j.seizure.2019.10.006.CrossRefPubMed

Neligan A, Noyce AJ, Gosavi TD, Shorvon SD, Kohler S, Walker MC. Change in mortality of generalized convulsive status epilepticus in high-income countries over time: a systematic review and meta-analysis. JAMA Neurol. 2019;76:897–905. https://doi.org/10.1001/jamaneurol.2019.1268.CrossRefPubMedPubMedCentral

Kellinghaus C, Rossetti AO, Trinka E, Lang N, May TW, Unterberger I, et al. Factors predicting cessation of status epilepticus in clinical practice: data from a prospective observational registry (SENSE). Ann Neurol. 2019;85(3):421–32. https://doi.org/10.1002/ana.25416.CrossRefPubMed

Roberg LE, Monsson O, Kristensen SB, Dahl SM, Ulvin LB, Heuser K, et al. Prediction of long-term survival after status epilepticus using the ACD Score. JAMA Neurol. 2022;79(6):604–13. https://doi.org/10.1001/jamaneurol.2022.0609.CrossRefPubMedPubMedCentral

10.

Rosenow F, Weber J. Status epilepticus im Erwachsenenalter, S2k-Leitlinie. Deutsche Gesellschaft für Neurologie (Hrsg), Leitlinien für Diagnostik und Therapie in der Neurologie. 2020.

11.

Brophy GM, Bell R, Claassen J, Alldredge B, Bleck TP, Glauser T, et al. Guidelines for the evaluation and management of status epilepticus. Neurocrit Care. 2012;17(1):3–23. https://doi.org/10.1007/s12028-012-9695-z.CrossRefPubMed

12.

Glauser T, Shinnar S, Gloss D, Alldredge B, Arya R, Bainbridge J, et al. Evidence-based guideline: treatment of convulsive status epilepticus in children and adults: report of the Guideline Committee of the American Epilepsy Society. Epilepsy Curr. 2016;16(1):48–61. https://doi.org/10.5698/1535-7597-16.1.48.CrossRefPubMedPubMedCentral

13.

Silbergleit R, Durkalski V, Lowenstein D, Conwit R, Pancioli A, Palesch Y, et al. Intramuscular versus intravenous therapy for prehospital status epilepticus. N Engl J Med. 2012;366(7):591–600. https://doi.org/10.1056/NEJMoa1107494.CrossRefPubMedPubMedCentral

14.

Prasad M, Krishnan PR, Sequeira R, Al-Roomi K. Anticonvulsant therapy for status epilepticus. Cochrane Datab Syst Rev. 2014;10(9):CD003723. https://doi.org/10.1002/14651858.CD003723.pub3.CrossRef

15.

Welch RD, Nicholas K, Durkalski-Mauldin VL, Lowenstein DH, Conwit R, Mahajan PV, et al. Intramuscular midazolam versus intravenous lorazepam for the prehospital treatment of status epilepticus in the pediatric population. Epilepsia. 2015;56(2):254–62. https://doi.org/10.1111/epi.12905.CrossRefPubMedPubMedCentral

16.

Trinka E, Hofler J, Leitinger M, Brigo F. Pharmacotherapy for status epilepticus. Drugs. 2015;75(13):1499–521. https://doi.org/10.1007/s40265-015-0454-2.CrossRefPubMedPubMedCentral

17.

Perucca E. Antiepileptic drugs: evolution of our knowledge and changes in drug trials. Epilept Disord. 2019;21(4):319–29. https://doi.org/10.1684/epd.2019.1083.CrossRef

18.

Patsalos PN. Drug interactions with the newer antiepileptic drugs (AEDs)–part 1: pharmacokinetic and pharmacodynamic interactions between AEDs. Clin Pharmacokinet. 2013;52(11):927–66. https://doi.org/10.1007/s40262-013-0087-0.CrossRefPubMed

19.

Kapur J, Elm J, Chamberlain JM, Barsan W, Cloyd J, Lowenstein D, et al. Randomized trial of three anticonvulsant medications for status epilepticus. N Engl J Med. 2019;381(22):2103–13. https://doi.org/10.1056/NEJMoa1905795.CrossRefPubMedPubMedCentral

20.

Chu SS, Wang HJ, Zhu LN, Xu D, Wang XP, Liu L. Therapeutic effect of intravenous levetiracetam in status epilepticus: a meta-analysis and systematic review. Seizure. 2020;74:49–55. https://doi.org/10.1016/j.seizure.2019.11.007.CrossRefPubMed

21.

Brigo F, Del Giovane C, Nardone R, Trinka E, Lattanzi S. Intravenous antiepileptic drugs in adults with benzodiazepine-resistant convulsive status epilepticus: a systematic review and network meta-analysis. Epilepsy Behav. 2019;101(Pt B): 106466. https://doi.org/10.1016/j.yebeh.2019.106466.CrossRefPubMed

22.

Brigo F, Lattanzi S, Nardone R, Trinka E. Intravenous brivaracetam in the treatment of status epilepticus: a systematic review. CNS Drugs. 2019;33(8):771–81. https://doi.org/10.1007/s40263-019-00652-0.CrossRefPubMed

23.

Hanaya R, Arita K. The new antiepileptic drugs: their neuropharmacology and clinical indications. Neurol Med Chir (Tokyo). 2016;56(5):205–20. https://doi.org/10.2176/nmc.ra.2015-0344.CrossRefPubMed

24.

von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;370(9596):1453–7. https://doi.org/10.1016/S0140-6736(07)61602-X.CrossRef

25.

Trinka E, Cock H, Hesdorffer D, Rossetti AO, Scheffer IE, Shinnar S, et al. A definition and classification of status epilepticus—report of the ILAE Task Force on Classification of Status Epilepticus. Epilepsia. 2015;56(10):1515–23. https://doi.org/10.1111/epi.13121.CrossRefPubMed

26.

Betjemann JP, Lowenstein DH. Status epilepticus in adults. Lancet Neurol. 2015;14(6):615–24. https://doi.org/10.1016/S1474-4422(15)00042-3.CrossRefPubMed

27.

Holtkamp M. Pharmacotherapy for refractory and super-refractory status epilepticus in adults. Drugs. 2018;78(3):307–26. https://doi.org/10.1007/s40265-017-0859-1.CrossRefPubMed

28.

Leitinger M, Beniczky S, Rohracher A, Gardella E, Kalss G, Qerama E, et al. Salzburg consensus criteria for non-convulsive status epilepticus–approach to clinical application. Epilepsy Behav. 2015;49:158–63. https://doi.org/10.1016/j.yebeh.2015.05.007.CrossRefPubMed

29.

Leitinger M, Trinka E, Gardella E, Rohracher A, Kalss G, Qerama E, et al. Diagnostic accuracy of the Salzburg EEG criteria for non-convulsive status epilepticus: a retrospective study. Lancet Neurol. 2016;15(10):1054–62. https://doi.org/10.1016/S1474-4422(16)30137-5.CrossRefPubMed

30.

Fisher RS, Cross JH, French JA, Higurashi N, Hirsch E, Jansen FE, et al. Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017;58(4):522–30. https://doi.org/10.1111/epi.13670.CrossRefPubMed

31.

Scheffer IE, Berkovic S, Capovilla G, Connolly MB, French J, Guilhoto L, et al. ILAE classification of the epilepsies: position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017;58(4):512–21. https://doi.org/10.1111/epi.13709.CrossRefPubMedPubMedCentral

32.

Specchio N, Wirrell EC, Scheffer IE, Nabbout R, Riney K, Samia P, et al. International League Against Epilepsy classification and definition of epilepsy syndromes with onset in childhood: Position paper by the ILAE Task Force on Nosology and Definitions. Epilepsia. 2022;63(6):1398–442. https://doi.org/10.1111/epi.17241.CrossRefPubMed

33.

Guterman EL, Betjemann JP, Aimetti A, Li JW, Wang Z, Yin D, et al. Association between treatment progression, disease refractoriness, and burden of illness among hospitalized patients with status epilepticus. JAMA Neurol. 2021;78(5):588–95. https://doi.org/10.1001/jamaneurol.2021.0520.CrossRefPubMed

34.

Gutierrez-Viedma A, Parejo-Carbonell B, Romeral-Jimenez M, Sanz-Graciani I, Serrano-Garcia I, Cuadrado ML, et al. Therapy delay in status epilepticus extends its duration and worsens its prognosis. Acta Neurol Scand. 2021;143(3):281–9. https://doi.org/10.1111/ane.13363.CrossRefPubMed

35.

Reindl C, Sprugel MI, Sembill JA, Mueller TM, Hagen M, Gerner ST, et al. Influence of new versus traditional antiepileptic drugs on course and outcome of status epilepticus. Seizure. 2020;74:20–5. https://doi.org/10.1016/j.seizure.2019.11.003.CrossRefPubMed

36.

Sutter R, Marsch S, Fuhr P, Kaplan PW, Ruegg S. Anesthetic drugs in status epilepticus: risk or rescue? A 6-year cohort study. Neurology. 2014;82(8):656–64. https://doi.org/10.1212/WNL.0000000000000009.CrossRefPubMedPubMedCentral

37.

Kortland LM, Alfter A, Bähr O, Carl B, Dodel R, Freiman TM, et al. Costs and cost-driving factors for acute treatment of adults with status epilepticus: a multicenter cohort study from Germany. Epilepsia. 2016;57(12):2056–66. https://doi.org/10.1111/epi.13584.CrossRefPubMed

38.

Mitchell C, Chatterton Dickson L, Ramsay A, Mesalles-Naranjo O, Leonard P, Brand C, et al. Epidemiology and outcome of status epilepticus in children: a Scottish population cohort study. Dev Med Child Neurol. 2021;63(9):1075–84. https://doi.org/10.1111/dmcn.14900.CrossRefPubMed

39.

Ulvin LB, Heuser K, Olsen KB, Tauboll E. Factors associated with refractoriness and outcome in an adult status epilepticus cohort. Seizure. 2018;61:111–8. https://doi.org/10.1016/j.seizure.2018.07.020.CrossRefPubMed

40.

Rantsch K, Walter U, Wittstock M, Benecke R, Rosche J. Treatment and course of different subtypes of status epilepticus. Epilepsy Res. 2013;107(1–2):156–62. https://doi.org/10.1016/j.eplepsyres.2013.08.001.CrossRefPubMed

41.

Bauer K, Rosenow F, Knake S, Willems LM, Kämppi L, Strzelczyk A. Clinical characteristics and outcomes of patients with recurrent status epilepticus episodes. Neurol Res Pract. 2023;5(1):34. https://doi.org/10.1186/s42466-023-00261-9.

42.

Meyer S, Langer J, Poryo M, Bay JG, Wagenpfeil S, Heinrich B, et al. Epileptic Status in a PEDiatric cohort (ESPED) requiring intensive care treatment: A multicenter national two‐year prospective surveillance study. Epilepsia Open. 2023;8(2):411–424. https://doi.org/10.1002/epi4.12707.

43.

Beuchat I, Novy J, Rossetti AO. Newer antiepileptic drugs for status epilepticus in adults: what’s the evidence? CNS Drugs. 2018;32(3):259–67. https://doi.org/10.1007/s40263-018-0509-5.CrossRefPubMed

44.

Jaques L, Rossetti AO. Newer antiepileptic drugs in the treatment of status epilepticus: impact on prognosis. Epilepsy Behav. 2012;24(1):70–3. https://doi.org/10.1016/j.yebeh.2012.02.026.CrossRefPubMed

45.

Beuchat I, Novy J, Rossetti AO. Newer antiepileptic drugs in status epilepticus: prescription trends and outcomes in comparison with traditional agents. CNS Drugs. 2017;31(4):327–34. https://doi.org/10.1007/s40263-017-0424-1.CrossRefPubMed

46.

Kämppi L, Mustonen H, Soinila S. Analysis of the delay components in the treatment of status epilepticus. Neurocrit Care. 2013;19(1):10–8. https://doi.org/10.1007/s12028-013-9862-x.CrossRefPubMed

47.

Kämppi L, Mustonen H, Soinila S. Factors related to delays in pre-hospital management of status epilepticus. Neurocrit Care. 2015;22(1):93–104. https://doi.org/10.1007/s12028-014-0016-6.CrossRefPubMed

48.

Kadel J, Bauer S, Hermsen AM, Immisch I, Kay L, Klein KM, et al. Use of emergency medication in adult patients with epilepsy: a multicentre cohort study from Germany. CNS Drugs. 2018;32(8):771–81. https://doi.org/10.1007/s40263-018-0544-2.CrossRefPubMed

49.

McMullan J, Sasson C, Pancioli A, Silbergleit R. Midazolam versus diazepam for the treatment of status epilepticus in children and young adults: a meta-analysis. Acad Emerg Med. 2010;17(6):575–82. https://doi.org/10.1111/j.1553-2712.2010.00751.x.CrossRefPubMedPubMedCentral

50.

Scott RC, Besag FM, Neville BG. Buccal midazolam and rectal diazepam for treatment of prolonged seizures in childhood and adolescence: a randomised trial. Lancet. 1999;353(9153):623–6. https://doi.org/10.1016/S0140-6736(98)06425-3.CrossRefPubMed

51.

European Medicines Agency. EPAR summary for the public Buccolam EMA/522148/2011. 2011 [accessed 02/28/2023]; https://www.ema.europa.eu/en/documents/overview/buccolam-epar-summary-public_en.pdf.

52.

Hessisches Ministerium für Soziales und Integration. Algorithmen zur Notfallversorgung, Lehrmeinung für die Notfallsanitäter-Ausbildung an den hessischen Rettungsdienstschulen. 2021 [accessed 02/25/2023]; https://rettungsdienstschule-gelnhausen.de/algorithmus/Algorithmen-Notfallversorgung-NotSan.pdf.

53.

Kay L, Merkel N, von Blomberg A, Willems LM, Bauer S, Reif PS, et al. Intranasal midazolam as first-line inhospital treatment for status epilepticus: a pharmaco-EEG cohort study. Ann Clin Transl Neurol. 2019;6(12):2413–25. https://doi.org/10.1002/acn3.50932.CrossRefPubMedPubMedCentral

54.

Mevius A, Joeres L, Gille P, Molzan M, Foskett N, Wilke T, et al. Epidemiology, real-world treatment and mortality of patients with status epilepticus in Germany: insights from a large healthcare database. Brain Commun. 2023;5(3):fcad145. https://doi.org/10.1093/braincomms/fcad145.CrossRefPubMedPubMedCentral

55.

Dell’Aquila J, Soti V. Treating status epilepticus: phenytoin versus levetiracetam. Cureus. 2021;13(10): e18515. https://doi.org/10.7759/cureus.18515.CrossRefPubMedPubMedCentral

56.

Noureen N, Khan S, Khursheed A, Iqbal I, Maryam M, Sharib SM, et al. Clinical efficacy and safety of injectable levetiracetam versus phenytoin as second-line therapy in the management of generalized convulsive status epilepticus in children: an open-label randomized controlled trial. J Clin Neurol. 2019;15(4):468–72. https://doi.org/10.3988/jcn.2019.15.4.468.CrossRefPubMedPubMedCentral

57.

Kuffer I, Novy J, Rossetti AO. Status epilepticus prognosis following levetiracetam administration: analysis of loading doses. Eur J Neurol. 2023;30(7):1957–62. https://doi.org/10.1111/ene.15791.CrossRefPubMed

58.

Lyttle MD, Rainford NEA, Gamble C, Messahel S, Humphreys A, Hickey H, et al. Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial. Lancet. 2019;393(10186):2125–34. https://doi.org/10.1016/S0140-6736(19)30724-X.CrossRefPubMedPubMedCentral

59.

Dalziel SR, Borland ML, Furyk J, Bonisch M, Neutze J, Donath S, et al. Levetiracetam versus phenytoin for second-line treatment of convulsive status epilepticus in children (ConSEPT): an open-label, multicentre, randomised controlled trial. Lancet. 2019;393(10186):2135–45. https://doi.org/10.1016/S0140-6736(19)30722-6.CrossRefPubMed

60.

European Medicines Agency. Keppra Scientific Discussion Procedure No. EMEA/H/C/277/X/46. 2006 [accessed 02/16/2023]; https://www.ema.europa.eu/en/documents/scientific-discussion-variation/keppra-h-c-277-x-0046-epar-scientific-discussion-extension_en.pdf.

61.

Tomson T, Battino D, Perucca E. Teratogenicity of antiepileptic drugs. Curr Opin Neurol. 2019;32(2):246–52. https://doi.org/10.1097/WCO.0000000000000659.CrossRefPubMed

62.

Beuchat I, Rosenow F, Kellinghaus C, Trinka E, Unterberger I, Ruegg S, et al. Refractory status epilepticus: risk factors and analysis of intubation in the multicenter SENSE registry. Neurology. 2022;99(16):e1824–34. https://doi.org/10.1212/WNL.0000000000201099.CrossRefPubMed

63.

Kienitz R, Kay L, Beuchat I, Gelhard S, von Brauchitsch S, Mann C, et al. Benzodiazepines in the management of seizures and status epilepticus: a review of routes of delivery, pharmacokinetics, efficacy, and tolerability. CNS Drugs. 2022;36(9):951–75. https://doi.org/10.1007/s40263-022-00940-2.CrossRefPubMedPubMedCentral

64.

Amengual-Gual M, Sanchez Fernandez I, Vasquez A, Abend NS, Anderson A, Arya R, et al. Pediatric status epilepticus management by Emergency Medical Services (the pSERG cohort). Seizure. 2023;111:51–5. https://doi.org/10.1016/j.seizure.2023.07.010.CrossRefPubMed

65.

Diagnosis and management of epilepsy in adults. Scottish Intercollegiate Guidelines Network (SIGN). 2015. https://www.sign.ac.uk/our-guidelines/diagnosis-and-management-of-epilepsy-in-adults/.

66.

Fung EL, Fung BB, Subcommittee on the Consensus Statement of the Hong Kong Epilepsy S. Review and update of the Hong Kong Epilepsy Guideline on status epilepticus. Hong Kong Med J. 2017;23(1):67–73. https://doi.org/10.12809/hkmj166025.

67.

Steinhoff BJ, Bast T. Vademecum Antiepilepticum 2021/2022. Deutsche Gesellschaft für Epileptologie e.V., Berlin.

68.

McKenzie KC, Hahn CD, Friedman JN. Emergency management of the paediatric patient with convulsive status epilepticus. Paediatr Child Health. 2021;26(1):50–66. https://doi.org/10.1093/pch/pxaa127.CrossRefPubMedPubMedCentral

69.

Vasquez A, Gainza-Lein M, Abend NS, Amengual-Gual M, Anderson A, Arya R, et al. First-line medication dosing in pediatric refractory status epilepticus. Neurology. 2020;95(19):e2683–96. https://doi.org/10.1212/WNL.0000000000010828.CrossRefPubMedPubMedCentral

70.

Wilfong A. Management of convulsive status epilepticus in children. UpToDate, Waltham, MA, USA. [accessed 02/15/2023] https://www.uptodate.com/contents/management-of-convulsive-status-epilepticus-in-children

71.

Translating Emergency Knowledge for Kids EIaICTaE. EIIC-TREKK Pediatric Status Epilepticus Algorithm. 2022 [accessed 02/13/2023]; https://emscimprovement.center/education-and-resources/peak/peak-status-epilepticus/trekk-eiic-pediatric-status-epilepticus-practice-guideline/.

Title: Trends and Differences in Status Epilepticus Treatment of Children and Adults Over 10 Years: A Comparative Study of Medical Records (2012–2021) from a University Hospital in Germany
Authors: Leonore Purwien
Susanne Schubert-Bast
Matthias Kieslich
Michael W. Ronellenfitsch
Michael Merker
Marcus Czabanka
Laurent M. Willems
Felix Rosenow
Adam Strzelczyk
Publication date: 18-11-2023
Publisher: Springer International Publishing
Keywords: Status Epilepticus
Midazolam
Levetiracetam
Benzodiazepine
Phenytoin
Lorazepam
Valproate
Diazepam
Lacosamide
Phenobarbital
Phenobarbital
Published in: CNS Drugs / Issue 11/2023
Print ISSN: 1172-7047
Electronic ISSN: 1179-1934
DOI: https://doi.org/10.1007/s40263-023-01049-w

At a glance: The STEP trials

Springer Medicine

Trends and Differences in Status Epilepticus Treatment of Children and Adults Over 10 Years: A Comparative Study of Medical Records (2012–2021) from a University Hospital in Germany

Abstract

Background and Objectives

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Background and Objectives

Methods

Results

Conclusion

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