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Article ; Online: SMDT1 variants impair EMRE-mediated mitochondrial calcium uptake in patients with muscle involvement.

Bulthuis, Elianne P / Adjobo-Hermans, Merel J W / de Potter, Bastiaan / Hoogstraten, Saskia / Wezendonk, Lisanne H T / Tutakhel, Omar A Z / Wintjes, Liesbeth T / van den Heuvel, Bert / Willems, Peter H G M / Kamsteeg, Erik-Jan / Gozalbo, M Estela Rubio / Sallevelt, Suzanne C E H / Koudijs, Suzanne M / Nicolai, Joost / de Bie, Charlotte I / Hoogendijk, Jessica E / Koopman, Werner J H / Rodenburg, Richard J

Biochimica et biophysica acta. Molecular basis of disease

2023 Volume 1869, Issue 8, Page(s) 166808

Abstract: Ionic calcium ( ... ...

Abstract	Ionic calcium (Ca
MeSH term(s)	Humans ; Calcium/metabolism ; Calcium Channels/genetics ; Calcium Channels/metabolism ; Ion Transport ; Mitochondria/genetics ; Mitochondria/metabolism ; Muscles/metabolism
Chemical Substances	Calcium (SY7Q814VUP) ; Calcium Channels ; SMDT1 protein, human
Language	English
Publishing date	2023-07-16
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	60-7
ISSN	1879-260X ; 1879-2596 ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-260X ; 1879-2596 ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbadis.2023.166808
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Article ; Online: Ontogeny of Small Intestinal Drug Transporters and Metabolizing Enzymes Based on Targeted Quantitative Proteomics.

Kiss, Márton / Mbasu, Richard / Nicolaï, Johan / Barnouin, Karin / Kotian, Apoorva / Mooij, Miriam G / Kist, Nico / Wijnen, Rene M H / Ungell, Anna-Lena / Cutler, Paul / Russel, Frans G M / de Wildt, Saskia N

Drug metabolism and disposition: the biological fate of chemicals

2021 Volume 49, Issue 12, Page(s) 1038–1046

Abstract: Most drugs are administered to children orally. An information gap remains on the protein abundance of small intestinal drug-metabolizing enzymes (DMEs) and drug transporters (DTs) across the pediatric age range, which hinders precision dosing in ... ...

Abstract	Most drugs are administered to children orally. An information gap remains on the protein abundance of small intestinal drug-metabolizing enzymes (DMEs) and drug transporters (DTs) across the pediatric age range, which hinders precision dosing in children. To explore age-related differences in DMEs and DTs, surgical leftover intestinal tissues from pediatric and adult jejunum and ileum were collected and analyzed by targeted quantitative proteomics for apical sodium-bile acid transporter, breast cancer resistance protein (BCRP), monocarboxylate transporter 1 (MCT1), multidrug resistance protein 1 (MDR1), multidrug resistance-associated protein (MRP) 2, MRP3, organic anion-transporting polypeptide 2B1, organic cation transporter 1, peptide transporter 1 (PEPT1), CYP2C19, CYP3A4, CYP3A5, UDP glucuronosyltransferase (UGT) 1A1, UGT1A10, and UGT2B7. Samples from 58 children (48 ileums, 10 jejunums, age range: 8 weeks to 17 years) and 16 adults (8 ileums, 8 jejunums) were analyzed. When comparing age groups, BCRP, MDR1, PEPT1, and UGT1A1 abundance was significantly higher in adult ileum as compared with the pediatric ileum. Jejunal BCRP, MRP2, UGT1A1, and CYP3A4 abundance was higher in the adults compared with children 0-2 years of age. Examining the data on a continuous age scale showed that PEPT1 and UGT1A1 abundance was significantly higher, whereas MCT1 and UGT2B7 abundance was lower in adult ileum as compared with the pediatric ileum. Our data contribute to the deeper understanding of the ontogeny of small intestinal drug-metabolizing enzymes and drug transporters and shows DME-, DT-, and intestinal location-specific, age-related changes. SIGNIFICANCE STATEMENT: This is the first study that describes the ontogeny of small intestinal DTs and DMEs in human using liquid chromatography with tandem mass spectrometry-based targeted quantitative proteomics. The current analysis provides a detailed picture about the maturation of DT and DME abundances in the human jejunum and ileum. The presented results supply age-related DT and DME abundance data for building more accurate PBPK models that serve to support safer and more efficient drug dosing regimens for the pediatric population.
MeSH term(s)	ATP Binding Cassette Transporter, Subfamily G, Member 2/metabolism ; Adult ; Age Factors ; Biological Transport, Active ; Child ; Chromatography, Liquid/methods ; Cytochrome P-450 CYP3A/metabolism ; Enzyme Assays/methods ; Gene Ontology ; Glucuronosyltransferase/metabolism ; Humans ; Inactivation, Metabolic/physiology ; Intestine, Small/drug effects ; Intestine, Small/enzymology ; Intestine, Small/metabolism ; Membrane Transport Proteins/metabolism ; Metabolic Clearance Rate ; Multidrug Resistance-Associated Protein 2/metabolism ; Neoplasm Proteins/metabolism ; Peptide Transporter 1/metabolism ; Tandem Mass Spectrometry/methods
Chemical Substances	ABCC2 protein, human ; ABCG2 protein, human ; ATP Binding Cassette Transporter, Subfamily G, Member 2 ; Membrane Transport Proteins ; Multidrug Resistance-Associated Protein 2 ; Neoplasm Proteins ; Peptide Transporter 1 ; SLC15A1 protein, human ; Cytochrome P-450 CYP3A (EC 1.14.14.1) ; UGT1A1 enzyme (EC 2.4.1.-) ; Glucuronosyltransferase (EC 2.4.1.17)
Language	English
Publishing date	2021-09-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	186795-7
ISSN	1521-009X ; 0090-9556
ISSN (online)	1521-009X
ISSN	0090-9556
DOI	10.1124/dmd.121.000559
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Article: Identifying the Need to Discuss Infertility Concerns Affecting Testicular Cancer Patients: An Evaluation (INDICATE Study).

Krouwel, Esmée M / Jansen, Thijs G / Nicolai, Melianthe P J / Dieben, Sandra W M / Luelmo, Saskia A C / Putter, Hein / Pelger, Rob C M / Elzevier, Henk W

Cancers

2021 Volume 13, Issue 3

Abstract: Men with testicular cancer (TC) risk impaired fertility. Fertility is a major concern for TC patients due to diagnosis in almost always reproductive ages and high overall survival. This study assessed counselling in regards to the risk of impaired ... ...

Abstract	Men with testicular cancer (TC) risk impaired fertility. Fertility is a major concern for TC patients due to diagnosis in almost always reproductive ages and high overall survival. This study assessed counselling in regards to the risk of impaired fertility and sperm cryopreservation. A cross-sectional survey was performed on 566 TC patients diagnosed between 1995-2015. Of the 566 survivors, 201 questionnaires were completed (35.5%). Eighty-eight percent was informed about possible impaired fertility, 9.5% was not informed. The majority (47.3%) preferred the urologist to provide information. Collecting sperm was troublesome but successful for 25.6%, 4.8% did not succeed in collecting sperm. The reasons were high pressure due to disease, pain after surgery and uncomfortable setting. Due to impaired fertility, 19% of the respondents reported grief and 9.3% stated as being less satisfied in life. Sperm cryopreservation was performed by 41.3% (
Language	English
Publishing date	2021-02-01
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13030553
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Article ; Online: Pediatric Pharmacokinetics and Dose Predictions: A Report of a Satellite Meeting to the 10th Juvenile Toxicity Symposium.

van Groen, Bianca D / Pilla Reddy, Venkatesh / Badée, Justine / Olivares-Morales, Andrés / Johnson, Trevor N / Nicolaï, Johan / Annaert, Pieter / Smits, Anne / de Wildt, Saskia N / Knibbe, Catherijne A J / de Zwart, Loeckie

Clinical and translational science

2020 Volume 14, Issue 1, Page(s) 29–35

Abstract: On April 24, 2019, a symposium on Pediatric Pharmacokinetics and Dose Predictions was held as a satellite meeting to the 10th Juvenile Toxicity Symposium. This symposium brought together scientists from academia, industry, and clinical research ... ...

Abstract	On April 24, 2019, a symposium on Pediatric Pharmacokinetics and Dose Predictions was held as a satellite meeting to the 10th Juvenile Toxicity Symposium. This symposium brought together scientists from academia, industry, and clinical research organizations with the aim to update each other on the current knowledge on pediatric drug development. Through more knowledge on specific ontogeny profiles of drug metabolism and transporter proteins, integrated into physiologically-based pharmacokinetic (PBPK) models, we have gained a more integrated understanding of age-related differences in pharmacokinetics (PKs), Relevant examples were presented during the meeting. PBPK may be considered the gold standard for pediatric PK prediction, but still it is important to know that simpler methods, such as allometry, allometry combined with maturation function, functions based on the elimination pathway, or linear models, also perform well, depending on the age range or the mechanisms involved. Knowledge from different methods and information sources should be combined (e.g., microdosing can reveal early read-out of age-related differences in exposure), and such results can be a value to verify models. To further establish best practices for dose setting in pediatrics, more in vitro and in vivo research is needed on aspects such as age-related changes in the exposure-response relationship and the impact of disease on PK. New information coupled with the refining of model-based drug development approaches will allow faster targeting of intended age groups and allow more efficient design of pediatric clinical trials.
MeSH term(s)	Age Factors ; Child ; Child Development/physiology ; Clinical Trials as Topic ; Congresses as Topic ; Cytochrome P-450 Enzyme System/genetics ; Cytochrome P-450 Enzyme System/metabolism ; Dose-Response Relationship, Drug ; Gene Expression Regulation, Developmental ; Glucuronosyltransferase/genetics ; Glucuronosyltransferase/metabolism ; Humans ; Metabolic Clearance Rate/physiology ; Models, Biological ; Research Design ; Tissue Distribution
Chemical Substances	Cytochrome P-450 Enzyme System (9035-51-2) ; Glucuronosyltransferase (EC 2.4.1.17)
Language	English
Publishing date	2020-08-03
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2433157-0
ISSN	1752-8062 ; 1752-8054
ISSN (online)	1752-8062
ISSN	1752-8054
DOI	10.1111/cts.12843
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Article ; Online: SMDT1 variants impair EMRE-mediated mitochondrial calcium uptake in patients with muscle involvement

Bulthuis, Elianne P. / Adjobo-Hermans, Merel J.W. / de Potter, Bastiaan / Hoogstraten, Saskia / Wezendonk, Lisanne H.T. / Tutakhel, Omar A.Z. / Wintjes, Liesbeth T. / van den Heuvel, Bert / Willems, Peter H.G.M. / Kamsteeg, Erik Jan / Rubio Gozalbo, M.E. / Sallevelt, Suzanne C.E.H. / Koudijs, Suzanne M. / Nicolai, Joost / de Bie, Charlotte I. / Hoogendijk, Jessica E. / Koopman, Werner J.H. / Rodenburg, Richard J.

Biochimica et Biophysica Acta - Molecular Basis of Disease

2023 Volume 1869, Issue 8

Abstract: Ionic calcium (Ca2+) is a key messenger in signal transduction and its mitochondrial uptake plays an important role in cell physiology. This uptake is mediated by the mitochondrial Ca2+ uniporter (MCU), which is regulated by EMRE (essential MCU regulator) ...

Abstract	Ionic calcium (Ca2+) is a key messenger in signal transduction and its mitochondrial uptake plays an important role in cell physiology. This uptake is mediated by the mitochondrial Ca2+ uniporter (MCU), which is regulated by EMRE (essential MCU regulator) encoded by the SMDT1 (single-pass membrane protein with aspartate rich tail 1) gene. This work presents the genetic, clinical and cellular characterization of two patients harbouring SMDT1 variants and presenting with muscle problems. Analysis of patient fibroblasts and complementation experiments demonstrated that these variants lead to absence of EMRE protein, induce MCU subcomplex formation and impair mitochondrial Ca2+ uptake. However, the activity of oxidative phosphorylation enzymes, mitochondrial morphology and membrane potential, as well as routine/ATP-linked respiration were not affected. We hypothesize that the muscle-related symptoms in the SMDT1 patients result from aberrant mitochondrial Ca2+ uptake.
Keywords	Calcium ; EMRE ; MCU ; Mitochondria ; Muscle involvement ; SMDT1
Language	English
Publishing country	nl
Document type	Article ; Online
ZDB-ID	60-7
ISSN	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Multicenter randomized clinical trial of supervised exercise therapy with or without feedback versus walking advice for intermittent claudication.

Nicolaï, Saskia P A / Teijink, Joep A W / Prins, Martin H

Journal of vascular surgery

2010 Volume 52, Issue 2, Page(s) 348–355

Abstract: ... in the WA group, 310 (145-995) in the SET group, and 360 (173-697) in the SET with feedback group (P < .001 ...

Abstract	Objective: The initial treatment for intermittent claudication is supervised exercise therapy (SET). Owing to limited capacity and patient transports costs of clinic-based SET, a concept of SET provided by local physiotherapists was developed. We hypothesized that provision of daily feedback with an accelerometer in addition to SET would further increase walking distance. Methods: This multicenter randomized trial was set in vascular surgery outpatient clinics and included 304 patients with intermittent claudication. Patients were randomized to exercise therapy in the form of "go home and walk" advice (WA), SET, or SET with feedback. Local physiotherapists provided SET. The primary outcome measure was the change in absolute claudication distance. Secondary outcomes were the change in functional claudication distance and results on the Walking Impairment Questionnaire (WIQ) and Short-Form 36 (SF-36) Health Survey after 12 months. Results: In 11 centers, 102, 109, and 93 patients were included, respectively, in the WA, SET, and SET with feedback groups, and data for 83, 93, and 76, respectively, could be analyzed. The median (interquartile range) change in walking distance between 12 months and baseline in meters was 110 (0-300) in the WA group, 310 (145-995) in the SET group, and 360 (173-697) in the SET with feedback group (P < .001 WA vs SET). WIQ scores and relevant domains of the SF-36 improved statistically significantly in the SET groups. Conclusions: SET is more effective than WA in improving walking distance, WIQ scores, and quality of life for patients with intermittent claudication. Additional feedback with an accelerometer did not result in further improvement. SET programs should be made available for all patients with intermittent claudication.
MeSH term(s)	Actigraphy/instrumentation ; Aged ; Ambulatory Care Facilities ; Biofeedback, Psychology ; Exercise Therapy ; Female ; Humans ; Intermittent Claudication/physiopathology ; Intermittent Claudication/psychology ; Intermittent Claudication/therapy ; Male ; Middle Aged ; Netherlands ; Patient Compliance ; Quality of Life ; Recovery of Function ; Surveys and Questionnaires ; Time Factors ; Treatment Outcome ; Walking
Language	English
Publishing date	2010-08
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	605700-7
ISSN	1097-6809 ; 0741-5214
ISSN (online)	1097-6809
ISSN	0741-5214
DOI	10.1016/j.jvs.2010.02.022
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Article ; Online: The ubiquitin ligase RFWD3 is required for translesion DNA synthesis.

Gallina, Irene / Hendriks, Ivo A / Hoffmann, Saskia / Larsen, Nicolai B / Johansen, Joachim / Colding-Christensen, Camilla S / Schubert, Lisa / Sellés-Baiget, Selene / Fábián, Zita / Kühbacher, Ulrike / Gao, Alan O / Räschle, Markus / Rasmussen, Simon / Nielsen, Michael L / Mailand, Niels / Duxin, Julien P

Molecular cell

2020 Volume 81, Issue 3, Page(s) 442–458.e9

Abstract: Lesions on DNA uncouple DNA synthesis from the replisome, generating stretches of unreplicated single-stranded DNA (ssDNA) behind the replication fork. These ssDNA gaps need to be filled in to complete DNA duplication. Gap-filling synthesis involves ... ...

Abstract	Lesions on DNA uncouple DNA synthesis from the replisome, generating stretches of unreplicated single-stranded DNA (ssDNA) behind the replication fork. These ssDNA gaps need to be filled in to complete DNA duplication. Gap-filling synthesis involves either translesion DNA synthesis (TLS) or template switching (TS). Controlling these processes, ubiquitylated PCNA recruits many proteins that dictate pathway choice, but the enzymes regulating PCNA ubiquitylation in vertebrates remain poorly defined. Here we report that the E3 ubiquitin ligase RFWD3 promotes ubiquitylation of proteins on ssDNA. The absence of RFWD3 leads to a profound defect in recruitment of key repair and signaling factors to damaged chromatin. As a result, PCNA ubiquitylation is inhibited without RFWD3, and TLS across different DNA lesions is drastically impaired. We propose that RFWD3 is an essential coordinator of the response to ssDNA gaps, where it promotes ubiquitylation to drive recruitment of effectors of PCNA ubiquitylation and DNA damage bypass.
MeSH term(s)	Animals ; Cell Line, Tumor ; Chromatin/genetics ; Chromatin/metabolism ; DNA Breaks, Single-Stranded ; DNA Repair ; DNA Replication ; DNA-Directed DNA Polymerase/metabolism ; Female ; Humans ; Proliferating Cell Nuclear Antigen/genetics ; Proliferating Cell Nuclear Antigen/metabolism ; Substrate Specificity ; Ubiquitin-Protein Ligases/genetics ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitination ; Xenopus laevis
Chemical Substances	Chromatin ; PCNA protein, human ; Proliferating Cell Nuclear Antigen ; RFWD3 protein, human (EC 2.3.2.27) ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; DNA-Directed DNA Polymerase (EC 2.7.7.7)
Language	English
Publishing date	2020-12-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1415236-8
ISSN	1097-4164 ; 1097-2765
ISSN (online)	1097-4164
ISSN	1097-2765
DOI	10.1016/j.molcel.2020.11.029
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Article: The ubiquitin ligase RFWD3 is required for translesion DNA synthesis

Molecular cell. 2021 Feb. 04, v. 81, no. 3

2021

Abstract	Lesions on DNA uncouple DNA synthesis from the replisome, generating stretches of unreplicated single-stranded DNA (ssDNA) behind the replication fork. These ssDNA gaps need to be filled in to complete DNA duplication. Gap-filling synthesis involves either translesion DNA synthesis (TLS) or template switching (TS). Controlling these processes, ubiquitylated PCNA recruits many proteins that dictate pathway choice, but the enzymes regulating PCNA ubiquitylation in vertebrates remain poorly defined. Here we report that the E3 ubiquitin ligase RFWD3 promotes ubiquitylation of proteins on ssDNA. The absence of RFWD3 leads to a profound defect in recruitment of key repair and signaling factors to damaged chromatin. As a result, PCNA ubiquitylation is inhibited without RFWD3, and TLS across different DNA lesions is drastically impaired. We propose that RFWD3 is an essential coordinator of the response to ssDNA gaps, where it promotes ubiquitylation to drive recruitment of effectors of PCNA ubiquitylation and DNA damage bypass.
Keywords	DNA damage ; DNA replication ; chromatin ; single-stranded DNA ; ubiquitin-protein ligase
Language	English
Dates of publication	2021-0204
Size	p. 442-458.e9.
Publishing place	Elsevier Inc.
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	1415236-8
ISSN	1097-4164 ; 1097-2765
ISSN (online)	1097-4164
ISSN	1097-2765
DOI	10.1016/j.molcel.2020.11.029
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Article ; Online: Ginkgo biloba for intermittent claudication.

Nicolaï, Saskia P A / Kruidenier, Lotte M / Bendermacher, Bianca L W / Prins, Martin H / Stokmans, Rutger A / Broos, Pieter P H L / Teijink, Joep A W

The Cochrane database of systematic reviews

2013 , Issue 6, Page(s) CD006888

Abstract: ... with an overall effect size of 3.57 kilocalories (confidence interval (CI) -0.10 to 7.23, P = 0.06), compared ...

Abstract	Background: People with intermittent claudication (IC) suffer from pain in the muscles of the leg occurring during exercise which is relieved by a short period of rest. Symptomatic relief can be achieved by (supervised) exercise therapy and pharmacological treatments. Ginkgo biloba is a vasoactive agent and is used to treat IC. Objectives: To assess the effect of Ginkgo biloba on walking distance in people with intermittent claudication. Search methods: For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (March 2013) and CENTRAL (2013, Issue 2). Selection criteria: Randomised controlled trials of Ginkgo biloba extract, irrespective of dosage, versus placebo in people with IC. Data collection and analysis: Two authors independently assessed trials for selection, assessed study quality and extracted data. We extracted number of patients, mean walking distances or times and standard deviations. To standardise walking distance or time, caloric expenditures were used to express the difference between the different treadmill protocols, which were calculated from the speed and incline of the treadmill. Main results: Fourteen trials with a total of 739 participants were included. Eleven trials involving 477 participants compared Ginkgo biloba with placebo and assessed the absolute claudication distance (ACD). Following treatment with Ginkgo biloba at the end of the study the ACD increased with an overall effect size of 3.57 kilocalories (confidence interval (CI) -0.10 to 7.23, P = 0.06), compared with placebo. This translates to an increase of just 64.5 ( CI -1.8 to 130.7) metres on a flat treadmill with an average speed of 3.2 km/h. Publication bias leading to missing data or "negative" trials is likely to have inflated the effect size. Authors' conclusions: Overall, there is no evidence that Ginkgo biloba has a clinically significant benefit for patients with peripheral arterial disease.
MeSH term(s)	Ginkgo biloba ; Humans ; Intermittent Claudication/drug therapy ; Phytotherapy ; Randomized Controlled Trials as Topic ; Treatment Outcome ; Vasodilator Agents/therapeutic use
Chemical Substances	Vasodilator Agents
Language	English
Publishing date	2013-06-06
Publishing country	England
Document type	Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't ; Review ; Systematic Review
ISSN	1469-493X
ISSN (online)	1469-493X
DOI	10.1002/14651858.CD006888.pub3
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Article ; Online: Optimizing supervised exercise therapy for patients with intermittent claudication.

Nicolaï, Saskia P A / Hendriks, Erik J M / Prins, Martin H / Teijink, Joep A W

Journal of vascular surgery

2010 Volume 52, Issue 5, Page(s) 1226–1233

Abstract: Background: The first-line intervention for intermittent claudication is usually supervised exercise therapy (SET). The literature describes a range of exercise programs varying in setting, duration, and content. The purpose of the present study was to ... ...

Abstract	Background: The first-line intervention for intermittent claudication is usually supervised exercise therapy (SET). The literature describes a range of exercise programs varying in setting, duration, and content. The purpose of the present study was to examine the exercise protocols offered and to identify the impact of the intensity of the SET programs (in terms of frequency, duration, and type of exercise) on improvements in walking distance (response) in the first 3 months. The present study is part of the Exercise Therapy in Peripheral Arterial Disease (EXITPAD) study, a multicenter randomized clinical trial comparing the effects of SET provided by regional physiotherapists, with or without daily feedback, on the level of activities with the effects of walking advice. Methods: The analysis included patients randomized to receive SET with or without feedback. The physical therapists administering the SET were asked to fill out therapy evaluation sheets stating frequency, duration, and type of exercises. The relationship between training volume and the impact on walking distance was explored by dividing training volume data into tertiles and relating them to the median change in maximum walking distance at 3 and 12 months. Results: Data of 169 patients were included in the analysis. A SET program consisting of at least two training sessions per week each lasting over 30 minutes, during the first 3 months of a 1-year program tailored to individual patients' needs led to better results in terms of walking distance after 3 and 12 months than the other variants. The results of our analysis dividing training volume into tertiles suggest that there is a relationship between training volume and improvement in walking distance and that at least 590 minutes of training should be offered in the first 3 months. No differences were found between program involving only walking and a combination of exercises, nor between individual and group training. Conclusion: A SET programs consisting of at least two training sessions a week, each lasting over 30 minutes, should be offered during the first 3 months of the SET program to optimize improvement in terms of maximum walking distance.
MeSH term(s)	Aged ; Exercise Therapy ; Exercise Tolerance ; Feedback, Psychological ; Female ; Humans ; Intermittent Claudication/physiopathology ; Intermittent Claudication/psychology ; Intermittent Claudication/therapy ; Male ; Middle Aged ; Time Factors ; Treatment Outcome ; Walking
Language	English
Publishing date	2010-11
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	605700-7
ISSN	1097-6809 ; 0741-5214
ISSN (online)	1097-6809
ISSN	0741-5214
DOI	10.1016/j.jvs.2010.06.106
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