PMID- 34154622
OWN - NLM
STAT- MEDLINE
DCOM- 20210629
LR  - 20240402
IS  - 1750-1172 (Electronic)
IS  - 1750-1172 (Linking)
VI  - 16
IP  - 1
DP  - 2021 Jun 21
TI  - Direct and indirect costs and cost-driving factors of Tuberous sclerosis complex 
      in children, adolescents, and caregivers: a multicenter cohort study.
PG  - 282
LID - 10.1186/s13023-021-01899-x [doi]
LID - 282
AB  - BACKGROUND: Tuberous sclerosis complex (TSC), a multisystem genetic disorder, 
      affects many organs and systems, characterized by benign growths. This German 
      multicenter study estimated the disease-specific costs and cost-driving factors 
      associated with various organ manifestations in TSC patients. METHODS: A 
      validated, three-month, retrospective questionnaire was administered to assess 
      the sociodemographic and clinical characteristics, organ manifestations, direct, 
      indirect, out-of-pocket, and nursing care-level costs, completed by caregivers of 
      patients with TSC throughout Germany. RESULTS: The caregivers of 184 patients 
      (mean age 9.8 +/- 5.3 years, range 0.7-21.8 years) submitted questionnaires. The 
      reported TSC disease manifestations included epilepsy (92%), skin disorders 
      (86%), structural brain disorders (83%), heart and circulatory system disorders 
      (67%), kidney and urinary tract disorders (53%), and psychiatric disorders (51%). 
      Genetic variations in TSC2 were reported in 46% of patients, whereas 14% were 
      reported in TSC1. Mean total direct health care costs were EUR 4949 [95% 
      confidence interval (95% CI) EUR 4088-5863, median EUR 2062] per patient over 
      three months. Medication costs represented the largest direct cost category (54% 
      of total direct costs, mean EUR 2658), with mechanistic target of rapamycin 
      (mTOR) inhibitors representing the largest share (47%, EUR 2309). The cost of 
      anti-seizure drugs (ASDs) accounted for a mean of only EUR 260 (5%). Inpatient 
      costs (21%, EUR 1027) and ancillary therapy costs (8%, EUR 407) were also 
      important direct cost components. The mean nursing care-level costs were EUR 1163 
      (95% CI EUR 1027-1314, median EUR 1635) over three months. Total indirect costs 
      totaled a mean of EUR 2813 (95% CI EUR 2221-3394, median EUR 215) for mothers and 
      EUR 372 (95% CI EUR 193-586, median EUR 0) for fathers. Multiple regression 
      analyses revealed polytherapy with two or more ASDs and the use of mTOR 
      inhibitors as independent cost-driving factors of total direct costs. Disability 
      and psychiatric disease were independent cost-driving factors for total indirect 
      costs as well as for nursing care-level costs. CONCLUSIONS: This study revealed 
      substantial direct (including medication), nursing care-level, and indirect costs 
      associated with TSC over three months, highlighting the spectrum of organ 
      manifestations and their treatment needs in the German healthcare setting. TRIAL 
      REGISTRATION: DRKS, DRKS00016045. Registered 01 March 2019, 
      http://www.drks.de/DRKS00016045.
FAU - Grau, Janina
AU  - Grau J
AD  - Epilepsy Center Frankfurt Rhine-Main and Department of Neurology, 
      Goethe-University Frankfurt, Schleusenweg 2-16 (Haus 95), 60528, Frankfurt am 
      Main, Germany.
AD  - Center for Personalized Translational Epilepsy Research (CePTER), 
      Goethe-University Frankfurt, Frankfurt am Main, Germany.
FAU - Zollner, Johann Philipp
AU  - Zollner JP
AD  - Epilepsy Center Frankfurt Rhine-Main and Department of Neurology, 
      Goethe-University Frankfurt, Schleusenweg 2-16 (Haus 95), 60528, Frankfurt am 
      Main, Germany.
AD  - Center for Personalized Translational Epilepsy Research (CePTER), 
      Goethe-University Frankfurt, Frankfurt am Main, Germany.
FAU - Schubert-Bast, Susanne
AU  - Schubert-Bast S
AD  - Epilepsy Center Frankfurt Rhine-Main and Department of Neurology, 
      Goethe-University Frankfurt, Schleusenweg 2-16 (Haus 95), 60528, Frankfurt am 
      Main, Germany.
AD  - Center for Personalized Translational Epilepsy Research (CePTER), 
      Goethe-University Frankfurt, Frankfurt am Main, Germany.
AD  - Department of Neuropediatrics, Goethe-University Frankfurt, Frankfurt am Main, 
      Germany.
FAU - Kurlemann, Gerhard
AU  - Kurlemann G
AD  - St. Bonifatius Hospital, Lingen, Germany.
FAU - Hertzberg, Christoph
AU  - Hertzberg C
AD  - Department of Neuropediatrics, Vivantes Klinikum Neukolln, Berlin, Germany.
FAU - Wiemer-Kruel, Adelheid
AU  - Wiemer-Kruel A
AD  - Epilepsy Center Kork, Clinic for Children and Adolescents, Kehl-Kork, Germany.
FAU - Bast, Thomas
AU  - Bast T
AD  - Epilepsy Center Kork, Clinic for Children and Adolescents, Kehl-Kork, Germany.
FAU - Bertsche, Astrid
AU  - Bertsche A
AD  - Department of Neuropediatrics, University Hospital for Children and Adolescents, 
      Rostock, Germany.
FAU - Bettendorf, Ulrich
AU  - Bettendorf U
AD  - Neuropediatric Practice, Hirschaid, Germany.
FAU - Fiedler, Barbara
AU  - Fiedler B
AD  - Department of General Pediatrics, Division of Neuropediatrics, University 
      Hospital Munster, Munster, Germany.
FAU - Hahn, Andreas
AU  - Hahn A
AD  - Department of Neuropediatrics, Justus-Liebig-University Giessen, Giessen, Germany.
FAU - Hartmann, Hans
AU  - Hartmann H
AD  - Department of Neuropediatrics, Clinic for Pediatric Kidney, Liver and Metabolic 
      Diseases, Hannover Medical School, Hannover, Germany.
FAU - Hornemann, Frauke
AU  - Hornemann F
AD  - Department of Neuropediatrics, Leipzig University Hospital for Children and 
      Adolescents, Leipzig, Germany.
FAU - Immisch, Ilka
AU  - Immisch I
AD  - Epilepsy Center Hessen and Department of Neurology, Philipps-University Marburg, 
      Marburg (Lahn), Germany.
FAU - Jacobs, Julia
AU  - Jacobs J
AD  - Department of Neuropediatrics and Muscle Disorders, Center for Pediatrics, 
      Medical Center, Faculty of Medicine, University of Freiburg, Freiburg i.Br., 
      Germany.
AD  - Department of Pediatrics and Clinical Neurosciences, Cumming School of Medicine, 
      University of Calgary, Calgary, AB, Canada.
FAU - Kieslich, Matthias
AU  - Kieslich M
AD  - Epilepsy Center Frankfurt Rhine-Main and Department of Neurology, 
      Goethe-University Frankfurt, Schleusenweg 2-16 (Haus 95), 60528, Frankfurt am 
      Main, Germany.
AD  - Department of Neuropediatrics, Goethe-University Frankfurt, Frankfurt am Main, 
      Germany.
FAU - Klein, Karl Martin
AU  - Klein KM
AD  - Epilepsy Center Frankfurt Rhine-Main and Department of Neurology, 
      Goethe-University Frankfurt, Schleusenweg 2-16 (Haus 95), 60528, Frankfurt am 
      Main, Germany.
AD  - Center for Personalized Translational Epilepsy Research (CePTER), 
      Goethe-University Frankfurt, Frankfurt am Main, Germany.
AD  - Departments of Clinical Neurosciences, Medical Genetics and Community Health 
      Sciences, Hotchkiss Brain Institute & Alberta Children's Hospital Research 
      Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, 
      Canada.
FAU - Klotz, Kerstin A
AU  - Klotz KA
AD  - Department of Neuropediatrics and Muscle Disorders, Center for Pediatrics, 
      Medical Center, Faculty of Medicine, University of Freiburg, Freiburg i.Br., 
      Germany.
AD  - Berta-Ottenstein-Programme, Faculty of Medicine, University of Freiburg, Freiburg 
      i.Br., Germany.
FAU - Kluger, Gerhard
AU  - Kluger G
AD  - Clinic for Neuropediatrics and Neurorehabilitation, Epilepsy Center for Children 
      and Adolescents, Schon Clinic Vogtareuth, Vogtareuth, Germany.
AD  - Research Institute, Rehabilitation, Transition and Palliation, PMU Salzburg, 
      Salzburg, Austria.
FAU - Knuf, Markus
AU  - Knuf M
AD  - Department of Pediatrics, Klinikum Worms, Worms, Germany.
AD  - Department of Pediatrics, University Medicine Mainz, Mainz, Germany.
FAU - Mayer, Thomas
AU  - Mayer T
AD  - Epilepsy Center Kleinwachau, Dresden-Radeberg, Germany.
FAU - Marquard, Klaus
AU  - Marquard K
AD  - Department of Pediatric Neurology, Psychosomatics and Pain Management, Klinikum 
      Stuttgart, Stuttgart, Germany.
FAU - Meyer, Sascha
AU  - Meyer S
AD  - Department of Neuropediatrics, Children's Hospital at University Medical Center 
      Homburg, Homburg, Germany.
FAU - Muhle, Hiltrud
AU  - Muhle H
AD  - Department of Neuropediatrics, Christian-Albrechts-University Kiel & University 
      Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
FAU - Muller-Schluter, Karen
AU  - Muller-Schluter K
AD  - Epilepsy Center for Children, Brandenburg Medical School, University Hospital 
      Neuruppin, Neuruppin, Germany.
FAU - Noda, Anna H
AU  - Noda AH
AD  - Epilepsy Center Frankfurt Rhine-Main and Department of Neurology, 
      Goethe-University Frankfurt, Schleusenweg 2-16 (Haus 95), 60528, Frankfurt am 
      Main, Germany.
AD  - Center for Personalized Translational Epilepsy Research (CePTER), 
      Goethe-University Frankfurt, Frankfurt am Main, Germany.
FAU - Ruf, Susanne
AU  - Ruf S
AD  - Department of Neuropediatrics, University Hospital Tubingen, Tubingen, Germany.
FAU - Sauter, Matthias
AU  - Sauter M
AD  - Klinikum Kempten, Klinikverbund Allgau, Kempten (Allgau), Germany.
FAU - Schlump, Jan-Ulrich
AU  - Schlump JU
AD  - Department of Neuropediatrics, University of Witten/Herdecke, Herdecke, Germany.
FAU - Syrbe, Steffen
AU  - Syrbe S
AD  - Division of Pediatric Epileptology, Centre for Paediatrics and Adolescent 
      Medicine, University Hospital Heidelberg, Heidelberg, Germany.
FAU - Thiels, Charlotte
AU  - Thiels C
AD  - Department of Neuropediatrics and Socialpediatrics, University Hospital of Ruhr 
      University Bochum, Bochum, Germany.
FAU - Trollmann, Regina
AU  - Trollmann R
AD  - Department of Neuropediatrics, Friedrich-Alexander University of 
      Erlangen-Nurnberg, Erlangen, Germany.
FAU - Wilken, Bernd
AU  - Wilken B
AD  - Department of Neuropediatrics, Klinikum Kassel, Kassel, Germany.
FAU - Willems, Laurent M
AU  - Willems LM
AD  - Epilepsy Center Frankfurt Rhine-Main and Department of Neurology, 
      Goethe-University Frankfurt, Schleusenweg 2-16 (Haus 95), 60528, Frankfurt am 
      Main, Germany.
AD  - Center for Personalized Translational Epilepsy Research (CePTER), 
      Goethe-University Frankfurt, Frankfurt am Main, Germany.
FAU - Rosenow, Felix
AU  - Rosenow F
AD  - Epilepsy Center Frankfurt Rhine-Main and Department of Neurology, 
      Goethe-University Frankfurt, Schleusenweg 2-16 (Haus 95), 60528, Frankfurt am 
      Main, Germany.
AD  - Center for Personalized Translational Epilepsy Research (CePTER), 
      Goethe-University Frankfurt, Frankfurt am Main, Germany.
FAU - Strzelczyk, Adam
AU  - Strzelczyk A
AUID- ORCID: 0000-0001-6288-9915
AD  - Epilepsy Center Frankfurt Rhine-Main and Department of Neurology, 
      Goethe-University Frankfurt, Schleusenweg 2-16 (Haus 95), 60528, Frankfurt am 
      Main, Germany. strzelczyk@med.uni-frankfurt.de.
AD  - Center for Personalized Translational Epilepsy Research (CePTER), 
      Goethe-University Frankfurt, Frankfurt am Main, Germany. 
      strzelczyk@med.uni-frankfurt.de.
AD  - Epilepsy Center Hessen and Department of Neurology, Philipps-University Marburg, 
      Marburg (Lahn), Germany. strzelczyk@med.uni-frankfurt.de.
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20210621
PL  - England
TA  - Orphanet J Rare Dis
JT  - Orphanet journal of rare diseases
JID - 101266602
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Caregivers
MH  - Child
MH  - Child, Preschool
MH  - Cohort Studies
MH  - Germany
MH  - Humans
MH  - Infant
MH  - Retrospective Studies
MH  - *Tuberous Sclerosis
MH  - Young Adult
PMC - PMC8218507
OTO - NOTNLM
OT  - Anti-seizure medication
OT  - Epilepsy
OT  - Everolimus
OT  - Rhabdomyoma
OT  - Seizure
OT  - mTOR inhibitor
COIS- JPZ reports speakers' honoraria and travel grants from Eisai and Desitin 
      Arzneimittel. SS-B reports personal fees from Eisai, Desitin Pharma, GW 
      Pharmaceuticals companies, LivaNova, UCB, and Zogenix. GK reports personal fees 
      from Desitin Arzneimittel, Eisai, GW Pharmaceuticals companies, UCB, Novartis, 
      Takeda, and Zogenix. AW-K reports personal fees from Desitin Arzneimittel, GW 
      Pharmaceuticals companies, Nutricia GmbH, Vitaflo, and UCB. TB reports personal 
      fees from Eisai, Desitin Arzneimittel, GW Pharma, Novartis, Nutricia, Shire, 
      Takeda, UCB Pharma and Zogenix. AB reports personal fees from Desitin 
      Arzneimittel GmbH, Eisai GmbH, Shire GmbH, UCB Pharma GmbH, and ViroPharma GmbH. 
      BF reports personal fees from Desitin Arzneimittel, Novartis and UCB. JJ reports 
      personal fees from Eisai, GW Pharmaceuticals companies, Zogenix and has been 
      supported by the German Research Foundation (DFG; JA 1725/4-1). KMK reports 
      personal fees from UCB Pharma, Novartis Pharma AG, Eisai, and GW Pharmaceuticals, 
      grants from the federal state Hessen through the LOEWE program and from the 
      Canadian Institutes of Health Research. KAK reports personal fees from GW 
      Pharmaceuticals companies and Zogenix and was supported by the 
      Berta-Ottenstein-Program for Clinician Scientists from the Faculty of Medicine, 
      University of Freiburg. TM reports personal fees and grants from Arvelle 
      Therapeutics, Eisai, GW Pharmaceuticals companies, UCB, and Zogenix. HM reports 
      personal fees from Desitin Arzneimittel, UCB, Novartis and Zogenix. SM reports 
      grants from Novartis, UCB, Shire, Deutsche Forschungsgemeinschaft and 
      Epilepsiestiftung Dr. Wolf. KMS reports personal fees from Nutricia, Desitin 
      Arzneimittel, Shire, Medice, Novartis and UCB. MS reports personal fees from 
      Novartis. RT reports personal fees from Eisai, Desitin, PTC Therap., Roche, 
      Sanofi Genzyme. BW reports fees and compensation for travel expenses from Eisai, 
      Takeda/Shire, Ipsen and PharmAllergan. FR reports personal fees from Arvelle 
      Therapeutics, Desitin Arzneimittel, Eisai, GW Pharmaceuticals companies, 
      Novartis, Medtronic, and UCB, and grants from the Detlev-Wrobel-Fonds for 
      Epilepsy Research, the Deutsche Forschungsgemeinschaft, the LOEWE Programme of 
      the State of Hesse, and the European Union. AS reports personal fees and grants 
      from Arvelle Therapeutics, Desitin Arzneimittel, Eisai, GW Pharmaceuticals 
      companies, Marinus Pharma, UCB, and Zogenix. The other authors declare that they 
      have no competing interests.
EDAT- 2021/06/23 06:00
MHDA- 2021/06/30 06:00
PMCR- 2021/06/21
CRDT- 2021/06/22 05:38
PHST- 2020/11/21 00:00 [received]
PHST- 2021/05/29 00:00 [accepted]
PHST- 2021/06/22 05:38 [entrez]
PHST- 2021/06/23 06:00 [pubmed]
PHST- 2021/06/30 06:00 [medline]
PHST- 2021/06/21 00:00 [pmc-release]
AID - 10.1186/s13023-021-01899-x [pii]
AID - 1899 [pii]
AID - 10.1186/s13023-021-01899-x [doi]
PST - epublish
SO  - Orphanet J Rare Dis. 2021 Jun 21;16(1):282. doi: 10.1186/s13023-021-01899-x.