Publications by authors named "Marie Collet"

14 Publications

  • Page 1 of 1

Patient and public involvement in contemporary large intensive care trials: Protocol for a meta-epidemiological study.

Acta Anaesthesiol Scand 2021 Oct 12;65(9):1351-1354. Epub 2021 Aug 12.

Department of Intensive Care, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.

Background: Patient and public involvement (PPI) in randomized clinical trials (RCTs) has increased in recent years but remains the exception rather than the rule. We aim to assess the frequency and extent of PPI in large, contemporary RCTs conducted in an intensive care setting.

Methods And Design: We will conduct a meta-epidemiological study of RCTs conducted in intensive care settings published since 2019 and assess their use of PPI. We will extract trial characteristics and verify the use of PPI with trial authors unless specifically stated in the published paper. The primary outcome will be the proportion of trials that use PPI. Secondary outcomes will explore which groups are consulted, at which stage of the trial process this occurs, and by what means these opinions are collected and implemented.

Discussion: This meta-epidemiological study will provide an important insight into the use of PPI in large, contemporary intensive care trials. We wish to reveal ways in which patient involvement could be incorporated more broadly and purposefully here and help to empower clinicians, researchers and patients to collaborate further on future research processes and goals.
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http://dx.doi.org/10.1111/aas.13953DOI Listing
October 2021

Patients' experiences of well-being when being cared for in the intensive care unit-An integrative review.

J Clin Nurs 2021 Jun 22. Epub 2021 Jun 22.

Faculty of Caring Sciences, Work Life and Social Welfare, Borås University, Borås, Sweden.

Objective: The aim of this integrative review was to identify facilitators and barriers to patients' well-being when being cared for in an ICU setting, from the perspective of the patients.

Background: To become critically ill and hospitalised in an ICU is a stressful, chaotic event due to the life-threatening condition itself, as well as therapeutic treatments and the environment. A growing body of evidence has revealed that patients often suffer from physical, psychological and cognitive problems after an ICU stay. Several strategies, such as sedation and pain management, are used to reduce stress and increase well-being during ICU hospitalisation, but the ICU experience nevertheless affects the body and mind. DESIGN; METHODS: Since research exploring patients' sense of well-being in an ICU setting is limited, an integrative review approach was selected. Searches were performed in CINAHL, Medline, Psych Info, Eric and EMBASE. After reviewing 66 studies, 12 studies were included in the integrative review. Thematic analysis was used to analyse the studies. The PRISMA checklist for systematic reviews was used.

Results: The results are presented under one main theme, 'Well-being as a multidimensional experience-interwoven in barriers and facilitators' and six sub-themes representing barriers to and facilitators of well-being in an ICU. Barriers identified were physical stressors, emotional stressors, environmental disturbances and insecurity relating to time and space. Facilitators were meeting physical needs and activities that included dimensions of a caring and relational environment.

Conclusion: Our main findings were that experiences of well-being were multidimensional and included physical, emotional, relational and environmental aspects, and they were more often described through barriers than facilitators of well-being.

Relevance For Clinical Practice: This integrative review has shown that it is necessary to adopt an individual focus on patient well-being in an ICU setting since physical, emotional, relational and environmental stressors might impact each patient differently.
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http://dx.doi.org/10.1111/jocn.15910DOI Listing
June 2021

Does rocking motion calm delirious patients in ICU? A multicentre randomised clinical trial protocol (RockingICU).

Acta Anaesthesiol Scand 2021 08 27;65(7):995-1001. Epub 2021 Mar 27.

Department of Intensive Care, Rigshospitalet University Hospital, Copenhagen, Denmark.

Background: Rocking chair therapy has been explored in patients with dementia to promote the feeling of relaxation, but not in Intensive Care Unit (ICU) patients with delirium.

Aim: The aim is to investigate the effect of a chair with or without rocking motion on the duration of delirium and intensity of agitation in critically ill patients admitted to the ICU.

Design: This is an investigator-initiated pragmatic, multicentre, parallel-grouped, centrally randomised, stratified, data analyst-blinded trial.

Method: We will include patients for 1:1 web-based randomisation, stratified by site in patients 18 y or older with a positive delirium score identified by a validated tool. We will exclude patients mainly due to mobilisation restrictions, body weight exceeding 130 kg, inability to provide consent, and presence of multiresistant bacteria or viral droplet infections. The intervention group will receive a minimum of 20 min of rocking therapy daily. The control group will be transferred to the same type of chair but without rocking therapy daily. A power calculation with a risk reduction of 20%, a power of 80% with an alpha cut-off on 5% and further 20% inclusion gives 76 patients in intervention and control group reaching a total of n = 152 inclusion in the trial.

Conclusion: The RockingICU trial will provide important new knowledge and raise research questions regarding nonpharmacological interventions to alleviate delirium in ICU patients.
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http://dx.doi.org/10.1111/aas.13821DOI Listing
August 2021

Risk factors for long-term cognitive impairment in ICU survivors: A multicenter, prospective cohort study.

Acta Anaesthesiol Scand 2021 01 12;65(1):92-99. Epub 2020 Sep 12.

Department of Intensive Care, Copenhagen University Hospital, Rigshospitalet, Denmark.

Purpose: To describe the incidence of and risk factors for impaired cognitive function in intensive care unit (ICU) survivors. We hypothesized that age, severity of illness, and days in coma, delirium, mechanical ventilation in the ICU would be associated with impaired cognitive function.

Methods: We included all adults, alive 6 months after acute admission to one of the 24 Danish ICUs participating in the AID-ICU cohort study. Trained professionals assessed cognitive function in patients' homes or in outpatient clinics using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) 6 months after ICU admission. Potential risk factors for cognitive impairment were analyzed with linear regression models.

Results: In total, 237 ICU patients were alive 6 months after ICU admission and did not meet the exclusion criteria. A total of 106 patients completed the cognitive assessment. The median RBANS global cognitive score was 76 (interquartile range, 62-91), and 52% had a global cognitive score 1.5 SD below the normative mean and 36% displayed a global cognitive score 2 SD below the normative mean, similar to that of Alzheimer's disease. Higher age was associated with poorer RBANS global cognitive score (estimate -0.35 [95% confidence interval -0.63 to -0.07] per year).

Conclusions: In this multicenter study of adult ICU survivors, cognitive impairment was frequent and severe in those assessed at 6 months. Higher age was a risk factor for cognitive impairment, but events related to the ICU stay were not associated with poorer cognitive performance at 6 months.
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http://dx.doi.org/10.1111/aas.13692DOI Listing
January 2021

Insects and incest: Sib-mating tolerance in natural populations of a parasitoid wasp.

Mol Ecol 2020 02 2;29(3):596-609. Epub 2020 Jan 2.

Laboratoire de Biométrie et Biologie Evolutive UMR5558, CNRS, Université Lyon 1, Univ Lyon, Villeurbanne, France.

Sib-mating avoidance is a pervasive behaviour that is expected to evolve in species subject to inbreeding depression. Although laboratory studies provide elegant demonstrations, small-scaled bioassays minimize the costs of mate finding and choice, and thus may produce spurious findings. We therefore combined laboratory experiments with field observations to examine the existence of inbreeding avoidance using the parasitoid wasp Venturia canescens. In the laboratory, our approach consisted of mate-choice experiments to assess kin discrimination in population cages with competitive interactions. A higher mating probability after sib rejections suggested that females could discriminate their sibs; however, in contrast to previous findings, sib-mating avoidance was not observed. To compare our laboratory results to field data, we captured 241 individuals from two populations. Females laid eggs in the lab, and 226 daughters were obtained. All individuals were genotyped at 18 microsatellite loci, which allowed inference of the genotype of each female's mate and subsequently the relatedness within each mating pair. We found that the observed rate of sib-mating did not differ from the probability that sibs encountered one another at random in the field, which is consistent with an absence of sib-mating avoidance. In addition, we detected a weak but significant male-biased dispersal, which could reduce encounters between sibs. We also found weak fitness costs associated with sib-mating. As such, the sex-biased dispersal that we found is probably sufficient to mitigate these costs. These results imply that kin discrimination has probably evolved for purposes other than mate choice, such as superparasitism avoidance.
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http://dx.doi.org/10.1111/mec.15340DOI Listing
February 2020

Trends and recommendations for critical care nursing research in the Nordic countries: Triangulation of review and survey data.

Intensive Crit Care Nurs 2020 Feb 1;56:102765. Epub 2019 Nov 1.

Department of Anaesthesiology and Intensive Care, Vejle and Middelfart Hospitals, Beriderbakken 4, 7100 Vejle, Denmark; Institute of Regional Health Research, University of Southern Denmark, J.B. Winsløwsvej 19, 5000 Odense, Denmark. Electronic address:

Background: Priorities for critical care nursing research have evolved with societal trends and values. In the 1980s priorities were the nursing workforce, in 1990s technical nursing, in 2000s evidence-based nursing and in 2010s symptom management and family-centred care.

Objectives: To identify current trends and future recommendations for critical care nursing research in the Nordic countries.

Methods: We triangulated the results of a literature review and a survey. A review of two selected critical care nursing journals (2016-2017) was conducted using content analysis to identify contemporary published research. A self-administered computerised cross-sectional survey of Nordic critical care nursing researchers (2017) reported current and future areas of research.

Results: A review of 156 papers identified research related to the patient (13%), family (12%), nurse (31%), and therapies (44%). Current trends in the survey (n = 76, response rate 65%) included patient and family involvement, nurse performance and education, and evidence-based protocols. The datasets showed similar trends, but aftercare was only present in the survey. Future trends included symptom management, transitions, rehabilitation, and new nursing roles.

Conclusion: Critical care nursing research is trending toward increased collaboration with patient and family, delineating a shift toward user values. Recommendations include long-term outcomes and impact of nursing.
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http://dx.doi.org/10.1016/j.iccn.2019.102765DOI Listing
February 2020

Haloperidol for the treatment of delirium in critically ill patients: A systematic review with meta-analysis and Trial Sequential Analysis.

Acta Anaesthesiol Scand 2020 02 23;64(2):254-266. Epub 2019 Nov 23.

Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen, Denmark.

Background: Haloperidol is the most frequently used drug to treat delirium in the critically ill patients. Yet, no systematic review has focussed on the effects of haloperidol in critically ill patients with delirium.

Methods: We conducted a systematic review with meta-analysis and Trial Sequential Analysis of randomized clinical trials (RCTs) assessing the effects of haloperidol vs any intervention on all-cause mortality, serious adverse reactions/events, days alive without delirium, health-related quality of life (HRQoL), cognitive function and delirium severity in critically ill patients with delirium. We also report on QTc prolongation, delirium resolution and extrapyramidal symptoms.

Results: We included 8 RCTs with 11 comparisons (n = 951). We adjudicated one trial as having overall low risk of bias. Three trials used rescue haloperidol; excluding these, we did not find an effect of haloperidol vs control on all-cause mortality (RR 1.01; 95% CI 0.33-3.06; I  = 0%; 112 participants; 3 trials; 4 comparisons; very low certainty) or delirium severity (SMD -0.15; 95% CI -0.61-0.30; I  = 27%; 134 participants; 3 trials; 4 comparisons; very low certainty). No trials reported adequately on serious adverse reactions/events. Only one trial reported on days alive without delirium, cognitive function and QTc prolongation, and no trials reported on HRQoL. Sensitivity analyses, including trials using rescue haloperidol, did not change the results.

Conclusions: The evidence for the use of haloperidol to treat critically ill patients with delirium is sparse, of low quality and inconclusive. We therefore have no certainty regarding any beneficial, harmful or neutral effects of haloperidol in these patients.
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http://dx.doi.org/10.1111/aas.13501DOI Listing
February 2020

External validation of the Simplified Mortality Score for the Intensive Care Unit (SMS-ICU).

Acta Anaesthesiol Scand 2019 10 4;63(9):1216-1224. Epub 2019 Jul 4.

Department of Intensive Care 4131, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.

Background: The Simplified Mortality Score for the Intensive Care Unit (SMS-ICU) is a clinical prediction model, which estimates the risk of 90-day mortality in acutely ill adult ICU patients using 7 readily available variables. We aimed to externally validate the SMS-ICU and compare its discrimination with existing prediction models used with 90-day mortality as the outcome.

Methods: We externally validated the SMS-ICU using data from 3282 patients included in the Stress Ulcer Prophylaxis in the Intensive Care Unit trial, which randomised acutely ill adult ICU patients with risk factors for gastrointestinal bleeding to prophylactic pantoprazole or placebo in 33 ICUs in Europe. We assessed discrimination, calibration and overall performance of the SMS-ICU and compared discrimination with the commonly used and more complex SAPS II and SOFA scores.

Results: Mortality at day 90 was 30.7%. The discrimination (area under the receiver operating characteristic curve) for the SMS-ICU was 0.67 (95% CI: 0.65-0.69), as compared with 0.68 (95% CI: 0.66-0.70, P = 0.35) for SAPS II and 0.63 (95% CI: 0.61-0.65, P < 0.001) for the SOFA score. Calibration (intercept and slope) was 0.001 and 0.786, respectively, and Nagelkerke's R (overall performance) was 0.06. The proportions of missing data for the SMS-ICU, SAPS II and SOFA scores were 0.2%, 8.5% and 6.8%, respectively.

Conclusions: Discrimination for 90-day mortality of the SMS-ICU in this cohort was poor, but similar to SAPS II and better than that of the SOFA score with markedly less missing data.
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http://dx.doi.org/10.1111/aas.13422DOI Listing
October 2019

Pharmacological interventions for prevention and management of delirium in intensive care patients: a systematic overview of reviews and meta-analyses.

BMJ Open 2019 02 19;9(2):e024562. Epub 2019 Feb 19.

Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Objectives: We assessed the evidence from reviews and meta-analyses of randomised clinical trials on the effects of pharmacological prevention and management of delirium in intensive care unit (ICU) patients.

Methods: We searched for reviews in July 2017 in: Cochrane Library, MEDLINE, Embase, Science Citation Index, BIOSIS Previews, CINAHL and LILACS. We assessed whether reviews were systematic according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and assessed the methodological quality using ROBIS.

Outcome Measures: Primary outcomes: all-cause mortality, serious adverse events, prevention of delirium and management of delirium.

Secondary Outcomes: quality of life; non-serious adverse events and cognitive function.

Results: We included 378 reviews: 369 narrative reviews, eight semisystematic reviews which failed on a maximum of two arbitrary PRISMA criteria and one systematic review fulfilling all 27 PRISMA criteria. For the prevention of delirium, we identified the one systematic review and eight semisystematic reviews all assessing the effects of alpha-2-agonists. None found evidence of a reduction of mortality (systematic review RR 0.99, 95% CI 0.79 to 1.24). The systematic review and three semisystematic reviews found no evidence of an effect for the prevention of delirium (systematic review RR 0.85, 0.63 to 1.14). Conversely, four semisystematic reviews found a beneficial effect. Serious adverse events, quality of life, non-serious adverse events and cognitive function were not assessed. We did not identify any systematic or semisystematic reviews addressing other pharmacological interventions for the prevention of delirium. For the management of manifest delirium, we did not identify any systematic or semisystematic review assessing any pharmacological agents.

Conclusion: Based on systematic reviews, the evidence for the use of pharmacological interventions for prevention or management of delirium is poor or sparse. A systematic review with low risk of bias assessing the effects of pharmacological prevention of delirium and management of manifest delirium in ICU patients is urgently needed.

Prospero Registration Number: CRD42016046628.
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http://dx.doi.org/10.1136/bmjopen-2018-024562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6377549PMC
February 2019

Prevalence and risk factors related to haloperidol use for delirium in adult intensive care patients: the multinational AID-ICU inception cohort study.

Intensive Care Med 2018 07 16;44(7):1081-1089. Epub 2018 May 16.

Department of Intensive Care, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

Purpose: We assessed the prevalence and variables associated with haloperidol use for delirium in ICU patients and explored any associations of haloperidol use with 90-day mortality.

Methods: All acutely admitted, adult ICU patients were screened during a 2-week inception period. We followed the patient throughout their ICU stay and assessed 90-day mortality. We assessed patients and their variables in the first 24 and 72 h in ICU and studied their association together with that of ICU characteristics with haloperidol use.

Results: We included 1260 patients from 99 ICUs in 13 countries. Delirium occurred in 314/1260 patients [25% (95% confidence interval 23-27)] of whom 145 received haloperidol [46% (41-52)]. Other interventions for delirium were benzodiazepines in 36% (31-42), dexmedetomidine in 21% (17-26), quetiapine in 19% (14-23) and olanzapine in 9% (6-12) of the patients with delirium. In the first 24 h in the ICU, all subtypes of delirium [hyperactive, adjusted odds ratio (aOR) 29.7 (12.9-74.5); mixed 10.0 (5.0-20.2); hypoactive 3.0 (1.2-6.7)] and circulatory support 2.7 (1.7-4.3) were associated with haloperidol use. At 72 h after ICU admission, circulatory support remained associated with subsequent use of haloperidol, aOR 2.6 (1.1-6.9). Haloperidol use within 0-24 h and within 0-72 h of ICU admission was not associated with 90-day mortality [aOR 1.2 (0.5-2.5); p = 0.66] and [aOR 1.9 (1.0-3.9); p = 0.07], respectively.

Conclusions: In our study, haloperidol was the main pharmacological agent used for delirium in adult patients regardless of delirium subtype. Benzodiazepines, other anti-psychotics and dexmedetomidine were other frequently used agents. Haloperidol use was not statistically significantly associated with increased 90-day mortality.
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http://dx.doi.org/10.1007/s00134-018-5204-yDOI Listing
July 2018

Simplified Mortality Score for the Intensive Care Unit (SMS-ICU): protocol for the development and validation of a bedside clinical prediction rule.

BMJ Open 2017 03 9;7(3):e015339. Epub 2017 Mar 9.

Department of Intensive Care 4131, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.

Introduction: Mortality prediction scores are widely used in intensive care units (ICUs) and in research, but their predictive value deteriorates as scores age. Existing mortality prediction scores are imprecise and complex, which increases the risk of missing data and decreases the applicability bedside in daily clinical practice. We propose the development and validation of a new, simple and updated clinical prediction rule: the Simplified Mortality Score for use in the Intensive Care Unit (SMS-ICU).

Methods And Analysis: During the first phase of the study, we will develop and internally validate a clinical prediction rule that predicts 90-day mortality on ICU admission. The development sample will comprise 4247 adult critically ill patients acutely admitted to the ICU, enrolled in 5 contemporary high-quality ICU studies/trials. The score will be developed using binary logistic regression analysis with backward stepwise elimination of candidate variables, and subsequently be converted into a point-based clinical prediction rule. The general performance, discrimination and calibration of the score will be evaluated, and the score will be internally validated using bootstrapping. During the second phase of the study, the score will be externally validated in a fully independent sample consisting of 3350 patients included in the ongoing Stress Ulcer Prophylaxis in the Intensive Care Unit trial. We will compare the performance of the SMS-ICU to that of existing scores.

Ethics And Dissemination: We will use data from patients enrolled in studies/trials already approved by the relevant ethical committees and this study requires no further permissions. The results will be reported in accordance with the Transparent Reporting of multivariate prediction models for Individual Prognosis Or Diagnosis (TRIPOD) statement, and submitted to a peer-reviewed journal.
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http://dx.doi.org/10.1136/bmjopen-2016-015339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5353313PMC
March 2017

Diploid male production correlates with genetic diversity in the parasitoid wasp : a genetic approach with new microsatellite markers.

Ecol Evol 2016 Sep 31;6(18):6721-6734. Epub 2016 Aug 31.

UMR 1355-7254 Institut Sophia Agrobiotech CNRS Université Nice Sophia Antipolis INRA 06900 Sophia Antipolis France.

Sex determination is ruled by haplodiploidy in Hymenoptera, with haploid males arising from unfertilized eggs and diploid females from fertilized eggs. However, diploid males with null fitness are produced under complementary sex determination (CSD), when individuals are homozygous for this locus. Diploid males are expected to be more frequent in genetically eroded populations (such as islands and captive populations), as genetic diversity at the locus should be low. However, only a few studies have focused on the relation between population size, genetic diversity, and the proportion of diploid males in the field. Here, we developed new microsatellite markers in order to assess and compare genetic diversity and diploid male proportion (DMP) in populations from three distinct habitat types - mainland, island, or captive -, in the parasitoid wasp . Eroded genetic diversity and higher DMP were found in island and captive populations, and habitat type had large effect on genetic diversity. Therefore, DMP reflects the decreasing genetic diversity in small and isolated populations. Thus, Hymenopteran populations can be at high extinction risk due to habitat destruction or fragmentation.
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http://dx.doi.org/10.1002/ece3.2370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5058541PMC
September 2016

Phenotype and genotype in 52 patients with Rubinstein-Taybi syndrome caused by EP300 mutations.

Am J Med Genet A 2016 12 20;170(12):3069-3082. Epub 2016 Sep 20.

Department of Molecular Medicine and Surgery, and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.

Rubinstein-Taybi syndrome (RSTS) is a developmental disorder characterized by a typical face and distal limbs abnormalities, intellectual disability, and a vast number of other features. Two genes are known to cause RSTS, CREBBP in 60% and EP300 in 8-10% of clinically diagnosed cases. Both paralogs act in chromatin remodeling and encode for transcriptional co-activators interacting with >400 proteins. Up to now 26 individuals with an EP300 mutation have been published. Here, we describe the phenotype and genotype of 42 unpublished RSTS patients carrying EP300 mutations and intragenic deletions and offer an update on another 10 patients. We compare the data to 308 individuals with CREBBP mutations. We demonstrate that EP300 mutations cause a phenotype that typically resembles the classical RSTS phenotype due to CREBBP mutations to a great extent, although most facial signs are less marked with the exception of a low-hanging columella. The limb anomalies are more similar to those in CREBBP mutated individuals except for angulation of thumbs and halluces which is very uncommon in EP300 mutated individuals. The intellectual disability is variable but typically less marked whereas the microcephaly is more common. All types of mutations occur but truncating mutations and small rearrangements are most common (86%). Missense mutations in the HAT domain are associated with a classical RSTS phenotype but otherwise no genotype-phenotype correlation is detected. Pre-eclampsia occurs in 12/52 mothers of EP300 mutated individuals versus in 2/59 mothers of CREBBP mutated individuals, making pregnancy with an EP300 mutated fetus the strongest known predictor for pre-eclampsia. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/ajmg.a.37940DOI Listing
December 2016

High incidence and variable clinical outcome of cardiac hypertrophy due to ACAD9 mutations in childhood.

Eur J Hum Genet 2016 08 16;24(8):1112-6. Epub 2015 Dec 16.

Departments of Pediatric, Cardiology and Genetics and INSERM U1163, Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Hôpital Necker-Enfants-Malades, Paris, France.

Acyl-CoA dehydrogenase family, member 9 (ACAD9) mutation is a frequent, usually fatal cause of early-onset cardiac hypertrophy and mitochondrial respiratory chain complex I deficiency in early childhood. We retrospectively studied a series of 20 unrelated children with cardiac hypertrophy and isolated complex I deficiency and identified compound heterozygosity for missense, splice site or frame shift ACAD9 variants in 8/20 patients (40%). Age at onset ranged from neonatal period to 9 years and 5/8 died in infancy. Heart transplantation was possible in 3/8. Two of them survived and one additional patient improved spontaneously. Importantly, the surviving patients later developed delayed-onset neurologic or muscular symptoms, namely cognitive impairment, seizures, muscle weakness and exercise intolerance. Other organ involvement included proximal tubulopathy, renal failure, secondary ovarian failure and optic atrophy. We conclude that ACAD9 mutation is the most frequent cause of cardiac hypertrophy and isolated complex I deficiency. Heart transplantation in children surviving neonatal period should be considered with caution, as delayed-onset muscle and brain involvement of various severity may occur, even if absent prior to transplantation.
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http://dx.doi.org/10.1038/ejhg.2015.264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4970679PMC
August 2016
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