Publications by authors named "Valentin Rousson"

155 Publications

Outcome prediction for hypothermic patients in cardiac arrest.

J Intensive Care 2022 Jul 28;10(1):37. Epub 2022 Jul 28.

Severe Accidental Hypothermia Center, Department of Anaesthesiology and Intensive Care, Medical University of Silesia, Katowice, Poland.

The 5A score predicts in-hospital mortality of patients suffering from accidental hypothermia, including those not in cardiac arrest. The HOPE score was specifically developed to predict survival for the subgroup of hypothermic patients in cardiac considered for extracorporeal life support rewarming. The C-statistic in the external validation study of the HOPE score was 0.825 (95% CI: 0.753-0.897), confirming its excellent discrimination. In addition, its good calibration allows for a reliable interpretation of the corresponding survival probability after rewarming. The HOPE score should be used for predicting outcome and selecting hypothermic patients in cardiac arrest for rewarming.
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http://dx.doi.org/10.1186/s40560-022-00630-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9331069PMC
July 2022

Association of growth with neurodevelopment in extremely low gestational age infants: a population-based analysis.

Eur J Pediatr 2022 Jul 22. Epub 2022 Jul 22.

Department of Neonatology, Newborn Research, University of Zurich and University Hospital Zurich, Zurich, Switzerland.

To assess the association between postnatal growth and neurodevelopment at the age of 2 years in extremely low gestational age newborns (ELGAN, < 28 weeks' gestation). Retrospective population-based cohort study including all live born ELGAN in 2006-2012 in Switzerland. Growth parameters (weight, length, head circumference, body mass index) were assessed at birth, at hospital discharge home, and 2-year follow-up (FU2). Unadjusted and adjusted regression models assessed associations between growth (birth to hospital discharge and birth to FU2) and neurodevelopment at FU2. A total of 1244 infants (mean GA 26.5 ± 1.0 weeks, birth weight 853 ± 189 g) survived to hospital discharge and were included in the analyses. FU2 was documented for 1049 (84.3%) infants. The mean (± SD) mental and a psychomotor development index at 2FU were 88.9 (± 18.0) and 86.9 (± 17.7), respectively. Moderate or severe neurodevelopmental impairment was documented in 23.2% of patients. Changes of z-scores between birth and discharge and between birth and FU2 for weight were - 1.06 (± 0.85) and - 0.140 (± 1.15), for length - 1.36 (± 1.34), and - 0.40 (± 1.33), for head circumference - 0.61 (± 1.04) and - 0.76 (± 1.32) as well as for BMI 0.22 (± 3.36) and - 0.006 (± 1.45). Unadjusted and adjusted analyses showed that none of the four growth parameters was significantly associated with any of the three outcome parameters of neurodevelopment. This was consistent for both time intervals.

Conclusion: In the present population-based cohort of ELGAN, neither growth between birth and hospital discharge nor between birth and FU2 were significantly associated with neurodevelopment at age of 2 years.

What Is Known: • Studies assessing the association between growth and neurodevelopment in extremely low gestational age newborns (28 weeks' gestation) show conflicting results.

What Is New: • Neither growth between birth and hospital discharge nor between birth and corrected age of 2 years were significantly associated with neurodevelopment at age of 2 years. • The role of postnatal growth as a predictor of neurodevelopmental outcome during infancy might be smaller than previously assumed.
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http://dx.doi.org/10.1007/s00431-022-04567-9DOI Listing
July 2022

Clinical efficacy of resin-based direct posterior restorations and glass-ionomer restorations - An updated meta-analysis of clinical outcome parameters.

Dent Mater 2022 05 24;38(5):e109-e135. Epub 2022 Feb 24.

Division of Biostatistics, Center for Primary Care and Public Health, University of Lausanne, Switzerland.

Objective: The present review is an update of a systematic review that has been published in 2012. Meanwhile, many new clinical trials on resin composites had been published. New materials such as bulk fill resin composites and new glass-ionomer (GIC) based materials had been introduced. The focus of this review was to evaluate the longevity in relation to the material class and adhesive class, while adjusting for a possible study bias effect.

Material And Methods: The database PUBMED/SCOPUS were searched for clinical trials on posterior resin composites. The inclusion criteria were: (1) studies published between 2000 and 2019, (2) prospective clinical trial with at least 2 years of observation; (2) minimal number of restorations at last recall = 20; (3) report on drop-out rate; (4) report of operative technique and used materials; (5) utilisation of Ryge, modified Ryge or FDI evaluation criteria. The bias of each study was assessed by two independent reviewers using Cochrane Collaboration's tool for assessing risk of bias in randomised trials. For the statistical analysis, linear mixed models fitted on the individual data recorded along time have been used with random effects to account for study, patients and experiment effects. P-values smaller than 0.05 were considered significant.

Results: Of the 423 clinical trials, 62 studies (including 110 experiments) met the inclusion criteria. Material class was divided according to the composite filler in microhybrid (39 experiments/2807 restorations), nanohybrid (24 experiments/1254 restorations), and hybrid (22 experiments/1255 restorations). So-called bulk fill materials were treated as a separate category (9 experiments/506 restorations) as were the GIC (11 experiments/2121 restorations) and the compomer materials (5 experiments/238 restorations). Only one study (1.6%) had low risk of bias, 42 (67.7%) were assessed to have unclear risk of bias and 19 (30.6%) had a high risk of bias. In 52.3% of the studies Class II and Class I restorations had been placed. After 10 years, the survival rate for resin composite restorations dropped to about 85-90% with no significant difference between hybrid, microhybrid and nao-hybrid resin materials. The main reasons for restoration replacement were bulk fractures and wear, which accounted for a about 70% of replacements. Caries at the restorative margins accounted for about 20% of the replacements, and retention loss, inacceptable colour match or marginal integrity, endodontic treatment or cusp fracture for about 10% of the replacements of the resin composite restorations. For compomer and GIC restorations the mean overall survival rate was about 80% after 6 years. For GIC, the main reasons for failure were substantial loss of anatomical contour along with loss of proximal contacts and retention loss. Mainly fractures reduced the longevity of compomers restorations. Also, there was no statistically significant difference between hybrid, micro-hybrid, nano-hybrid and bulk fill resin composites with regard to colour match, surface texture, material fractures, and anatomical form.

Conclusions: Posterior resin composite restorations that were placed with the enamel etch technique showed the best overall performance; the longevity was not significantly influenced by the filler type or viscosity of resin composite material. With regard to colour match, surface texture and anatomical form, nanohybrid resins were not significantly superior to hybrid or microhybrid resin composites. Compomer and GIC restorations demonstrated considerable shortcomings and had a significant shorter longevity.
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http://dx.doi.org/10.1016/j.dental.2021.10.018DOI Listing
May 2022

Development and validation of a knowledge-based score to predict Fried's frailty phenotype across multiple settings using one-year hospital discharge data: The electronic frailty score.

EClinicalMedicine 2022 Feb 10;44:101260. Epub 2022 Jan 10.

Department of Epidemiology and Health Systems, Centre for Primary Care and Public Health (Unisanté), University of Lausanne, 10 Route de la Corniche, Lausanne 1010, Switzerland.

Background: Most claims-based frailty instruments have been designed for group stratification of older populations according to the risk of adverse health outcomes and not frailty itself. We aimed to develop and validate a tool based on one-year hospital discharge data for stratification on Fried's frailty phenotype (FP).

Methods: We used a three-stage development/validation approach. First, we created a clinical knowledge-driven electronic frailty score (eFS) calculated as the number of deficient organs/systems among 18 critical ones identified from the (ICD-10) diagnoses coded in the year before FP assessment. Second, for eFS development and internal validation, we linked individual records from the Lc65+ cohort database to inpatient discharge data from Lausanne University Hospital (CHUV) for the period 2004-2015. The development/internal validation sample included community-dwelling, non-institutionalised residents of Lausanne (Switzerland) recruited in the Lc65+ cohort in three waves (2004, 2009, and 2014), aged 65-70 years at enrolment, and hospitalised at the CHUV at least once in the year preceding the FP assessment. Using this sample, we selected the best performing model for predicting the dichotomised FP, with the eFS or ICD-10-based variables as predictors. Third, we conducted an external validation using 2016 Swiss nationwide hospital discharge data and compared the performance of the eFS model in predicting 13 adverse outcomes to three models relying on well-designed and validated claims-based scores (Claims-based Frailty Index, Hospital Frailty Risk Score, Dr Foster Global Frailty Score).

Findings: In the development/internal validation sample ( = 469), 14·3% of participants ( 67) were frail. Among 34 models tested, the best-subsets logistic regression model with four predictors (age and sex at FP assessment, time since last hospital discharge, eFS) performed best in predicting the dichotomised FP (area under the curve=0·71; F1 score=0·39) and one-year adverse health outcomes. On the external validation sample ( 54,815; 153 acute care hospitals), the eFS model demonstrated a similar performance to the three other claims-based scoring models. According to the eFS model, the external validation sample showed an estimated prevalence of 56·8% ( 31,135) of frail older inpatients at admission.

Interpretation: The eFS model is an inexpensive, transportable and valid tool allowing reliable group stratification and individual prioritisation for comprehensive frailty assessment and may be applied to both hospitalised and community-dwelling older adults.

Funding: The study received no external funding.
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http://dx.doi.org/10.1016/j.eclinm.2021.101260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8760435PMC
February 2022

Hypothermia Outcome Prediction after Extracorporeal Life Support for Hypothermic Cardiac Arrest Patients: Assessing the Performance of the HOPE Score in Case Reports from the Literature.

Int J Environ Res Public Health 2021 11 12;18(22). Epub 2021 Nov 12.

Department of Emergency Medicine, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland.

: The hypothermia outcome prediction after extracorporeal life support (ECLS) score, or HOPE score, provides an estimate of the survival probability in hypothermic cardiac arrest patients undergoing ECLS rewarming. The aim of this study was to assess the performance of the HOPE score in case reports from the literature. : Cases were identified through a systematic review of the literature. We included cases of hypothermic cardiac arrest patients rewarmed with ECLS and not included in the HOPE derivation and validation studies. We calculated the survival probability of each patient according to the HOPE score. : A total of 70 patients were included. Most of them (62/70 = 89%) survived. The discrimination using the HOPE score was good (Area Under the Receiver Operating Characteristic Curve = 0.78). The calibration was poor, with HOPE survival probabilities averaging 54%. Using a HOPE survival probability threshold of at least 10% as a decision criterion for rewarming a patient would have resulted in only five false positives and a single false negative, i.e., 64 (or 91%) correct decisions. : In this highly selected sample, the HOPE score still had a good practical performance. The selection bias most likely explains the poor calibration found in the present study, with survivors being more often described in the literature than non-survivors. Our finding underscores the importance of working with a representative sample of patients when deriving and validating a score, as was the case in the HOPE studies that included only consecutive patients in order to minimize the risk of publication bias and lower the risk of overly optimistic outcomes.
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http://dx.doi.org/10.3390/ijerph182211896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8622062PMC
November 2021

Prevalence of SARS-CoV-2 in Household Members and Other Close Contacts of COVID-19 Cases: A Serologic Study in Canton of Vaud, Switzerland.

Open Forum Infect Dis 2021 Jul 26;8(7):ofab149. Epub 2021 Mar 26.

Center for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne, Switzerland.

Background: Research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission within households and other close settings using serological testing is scarce.

Methods: We invited coronavirus disease 2019 (COVID-19) cases diagnosed between February 27 and April 1, 2020, in Canton of Vaud, Switzerland, to participate, along with household members and other close contacts. Anti-SARS-CoV-2 immunoglobulin G antibodies were measured using a Luminex immunoassay. We estimated factors associated with serological status using generalized estimating equations.

Results: Overall, 219 cases, 302 household members, and 69 other close contacts participated between May 4 and June 27, 2020. More than half of household members (57.2%; 95% CI, 49.7%-64.3%) had developed a serologic response to SARS-CoV-2, while 19.0% (95% CI, 10.0%-33.2%) of other close contacts were seropositive. After adjusting for individual and household characteristics, infection risk was higher in household members aged ≥65 years than in younger adults (adjusted odds ratio [aOR], 3.63; 95% CI, 1.05-12.60) and in those not strictly adhering to simple hygiene rules like hand washing (aOR, 1.80; 95% CI, 1.02-3.17). The risk was lower when more than 5 people outside home were met during semiconfinement, compared with none (aOR, 0.35; 95% CI, 0.16-0.74). Individual risk of household members to be seropositive was lower in large households (22% less per each additional person).

Conclusions: During semiconfinement, household members of a COVID-19 case were at very high risk of getting infected, 3 times more than close contacts outside home. This highlights the need to provide clear messages on protective measures applicable at home. For elderly couples, who were especially at risk, providing external support for daily basic activities is essential.
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http://dx.doi.org/10.1093/ofid/ofab149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083624PMC
July 2021

Sex- and age-specific reference intervals for diagnostic ratios reflecting relative activity of steroidogenic enzymes and pathways in adults.

PLoS One 2021 8;16(7):e0253975. Epub 2021 Jul 8.

Department of Nephrology and Hypertension and Department of Clinical Research, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

Objective: Diagnostic ratios calculated from urinary steroid hormone metabolites are used as a measure for the relative activity of steroidogenic enzymes or pathways in the clinical investigation of steroid metabolism disorders. However, population-based sex- and age-specific reference intervals and day-night differences in adults are lacking.

Methods: Sixty-five diagnostic ratios were calculated from steroid metabolites measured by GC-MS in day- and night-time and in 24-hour urine from 1128 adults recruited within the Swiss Kidney Project on Genes in Hypertension (SKIPOGH), a population-based, multicenter cohort study. Differences related to sex, age and day- and night-time were evaluated and reference curves in function of age and sex were modelled by multivariable linear mixed regression for diagnostic ratios and were compared to values from the literature.

Results: Most ratios had sex- and age-specific relationships. For each ratio, percentiles were plotted in function of age and sex in order to create reference curves and sex- and age-specific reference intervals derived from 2.5th and 97.5th percentiles were obtained. Most ratios reflected a higher enzyme activity during the day compared to the night.

Conclusions: Sex- and age-specific references for 24 hours, day and night urine steroid metabolite ratios may help distinguishing between health and disease when investigating human disorders affecting steroid synthesis and metabolism. The day-night differences observed for most of the diagnostic ratios suggest a circadian rhythm for enzymes involved in human steroid hormones metabolism.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253975PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266106PMC
November 2021

A first analysis of excess mortality in Switzerland in 2020.

PLoS One 2021 17;16(6):e0253505. Epub 2021 Jun 17.

Center for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne, Switzerland.

Objective: To quantify excess all-cause mortality in Switzerland in 2020, a key indicator for assessing direct and indirect consequences of the COVID-19 pandemic.

Methods: Using official data on deaths in Switzerland, all-cause mortality in 2020 was compared with that of previous years using directly standardized mortality rates, age- and sex-specific mortality rates, and life expectancy.

Results: The standardized mortality rate was 8.8% higher in 2020 than in 2019, returning to the level observed 5-6 years before, around the year 2015. This increase was greater for men (10.6%) than for women (7.2%) and was statistically significant only for men over 70 years of age, and for women over 75 years of age. The decrease in life expectancy in 2020 compared to 2019 was 0.7%, with a loss of 9.7 months for men and 5.3 months for women.

Conclusions: There was an excess mortality in Switzerland in 2020, linked to the COVID-19 pandemic. However, as this excess only concerned the elderly, the resulting loss of life expectancy was restricted to a few months, bringing the mortality level back to 2015.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253505PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211252PMC
July 2021

Survival probability in avalanche victims with long burial (≥60 min): A retrospective study.

Resuscitation 2021 09 6;166:93-100. Epub 2021 Jun 6.

Department of Emergency Medicine, Lausanne University Hospital and University of Lausanne, Rue du Bugnon 21, BH 09, CHUV, 1011 Lausanne, Switzerland. Electronic address:

Background: The survival of completely buried victims in an avalanche mainly depends on burial duration. Knowledge is limited about survival probability after 60 min of complete burial.

Aim: We aimed to study the survival probability and prehospital characteristics of avalanche victims with long burial durations.

Methods: We retrospectively included all completely buried avalanche victims with a burial duration of ≥60 min between 1997 and 2018 in Switzerland. Data were extracted from the registry of the Swiss Institute for Snow and Avalanche Research and the prehospital medical records of the physician-staffed helicopter emergency medical services. Avalanche victims buried for ≥24 h or with an unknown survival status were excluded. Survival probability was estimated by using the non-parametric Ayer-Turnbull method and logistic regression. The primary outcome was survival probability.

Results: We identified 140 avalanche victims with a burial duration of ≥60 min, of whom 27 (19%) survived. Survival probability shows a slight decrease with increasing burial duration (23% after 60 min, to <6% after 1400 min, p = 0.13). Burial depth was deeper for those who died (100 cm vs 70 cm, p = 0.008). None of the survivors sustained CA during the prehospital phase.

Conclusions: The overall survival rate of 19% for completely buried avalanche victims with a long burial duration illustrates the importance of continuing rescue efforts. Avalanche victims in CA after long burial duration without obstructed airway, frozen body or obvious lethal trauma should be considered to be in hypothermic CA, with initiation of cardiopulmonary resuscitation and an evaluation for rewarming with extracorporeal life support.
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http://dx.doi.org/10.1016/j.resuscitation.2021.05.030DOI Listing
September 2021

A comparison of statistical methods for allocating disease costs in the presence of interactions.

Stat Med 2021 06 11;40(14):3286-3298. Epub 2021 Apr 11.

Center for Primary Care and Public Health, University of Lausanne, Lausanne, Switzerland.

We consider the non-trivial problem of estimating a health cost repartition among diseases from patients' hospital stays' global costs in the presence of multimorbidity, that is, when the patients may suffer from more than one disease. The problem is even harder in the presence of interactions among the disease costs, that is, when the costs of having, for example, two diseases simultaneously do not match the sum of the basic costs of having each disease alone, generating an extra cost which might be either positive or negative. In such a situation, there might be no "true solution" and the choice of the method to be used to solve the problem will depend on how one wishes to allocate the extra costs among the diseases. In this article, we study mathematically how different methods proceed in this regard, namely ordinary least squares (OLS), generalized linear models (GLM), and an iterative proportional repartition (IPR) algorithm, in a simple case with only two diseases. It turned out that only IPR allowed to retrieve the total costs and the unambiguous solution that one would have in a setting without interaction, that is, when no extra cost has to be allocated, while OLS and GLM may produce some negative health costs. Also, contrary to OLS, IPR is taking into account the basic costs of the diseases for the allocation of the extra cost. We conclude that IPR seems to be the most natural method to solve the problem, at least among those considered.
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http://dx.doi.org/10.1002/sim.8950DOI Listing
June 2021

Somatic growth in children with congenital heart disease at 10 years of age: Risk factors and longitudinal growth.

Early Hum Dev 2021 05 10;156:105349. Epub 2021 Mar 10.

Child Development Center, University Children's Hospital Zurich, Switzerland; Children's Research Center, University Children's Hospital Zurich, Switzerland.

Background: Children with congenital heart disease (CHD) are at risk of impaired growth.

Aims: To describe height, weight, head circumference (HC), and body mass index (BMI) at 10 years and identify risk factors for altered longitudinal growth in children with CHD.

Study Design: Growth parameters were evaluated from birth until 10 years using z-scores. The impact of cardiac and noncardiac factors on longitudinal growth was investigated.

Subjects: A total of 135 children with different types of CHD who underwent cardiopulmonary bypass surgery, no genetic disorder.

Outcome Measures: Head circumference, weight, height and BMI.

Results: At 10 years, z-scores for height and BMI did not differ from the Swiss population (P > 0.1). Z-scores for weight and HC were significantly below the norm (-0.38 and - 0.71, P < 0.01). From 1 to 10 years, all growth parameters except BMI increased significantly (P ≤ 0.001, BMI: P = 0.14). Lower gestational age and longer length of hospitalization were associated with either impaired head circumference or length at 10 years, while lower socioeconomic status was associated with higher BMI and weight at 10 years (all P < 0.05).

Conclusion: Despite partial catch-up, somatic growth remains impaired in children with CHD with weight and HC below the norm at 10 years. The only cardiac factor associated with impaired longitudinal growth was duration of hospital stay. Furthermore, lower socioeconomic background may pose a risk of overweight at older age. Close monitoring of growth parameters and parental counselling in all CHD children is advisable beyond early childhood to ensure optimal somatic growth.
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http://dx.doi.org/10.1016/j.earlhumdev.2021.105349DOI Listing
May 2021

[Analysis of Excess Mortality in Switzerland in 2020 before the 2 Wave of COVID-19].

Rev Med Suisse 2021 Mar;17(730):518-520

Unisanté, 1011 Lausanne.

An analysis of excess mortality in Switzerland in 2020 before the 2nd wave of COVID-19 is proposed by comparing the number of deaths observed in 2020 with those of the last five years, while taking into account population growth. Three periods are identified : before, during and after the 1st wave of COVID-19. Over all these periods, a sub-mortality of -3.3 % is obtained at the national level. However, if we restrict the analysis to the period during the first wave and to the cantons most affected by the virus, we obtain an important excess mortality, up to more than 80 % in Ticino, showing that these calculations depend crucially on when, where and for whom the deaths are counted. Such an analysis will have to be repeated once the 2nd wave is over in order to estimate the overall impact of the epidemic on excess mortality in Switzerland.
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March 2021

Estimating the basic reproduction number for COVID-19 in Western Europe.

PLoS One 2021 17;16(3):e0248731. Epub 2021 Mar 17.

Center for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne, Switzerland.

Objective: To estimate the basic reproduction number (R0) for COVID-19 in Western Europe.

Methods: Data (official statistics) on the cumulative incidence of COVID-19 at the start of the outbreak (before any confinement rules were declared) were retrieved in the 15 largest countries in Western Europe, allowing us to estimate the exponential growth rate of the disease. The rate was then combined with estimates of the distribution of the generation interval as reconstructed from the literature.

Results: Despite the possible unreliability of some official statistics about COVID-19, the spread of the disease appears to be remarkably similar in most European countries, allowing us to estimate an average R0 in Western Europe of 2.2 (95% CI: 1.9-2.6).

Conclusions: The value of R0 for COVID-19 in Western Europe appears to be significantly lower than that in China. The proportion of immune persons in the European population required to stop the outbreak could thus be closer to 50% than to 70%.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248731PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968714PMC
March 2021

Vital Signs in Accidental Hypothermia.

High Alt Med Biol 2021 Jun 22;22(2):142-147. Epub 2020 Dec 22.

University of Lausanne, Lausanne, Switzerland.

Pasquier, Mathieu, Evelien Cools, Ken Zafren, Pierre-Nicolas Carron, Vincent Frochaux, and Valentin Rousson. Vital signs in accidental hypothermia. . 22: 142-147, 2021. Clinical indicators are used to stage hypothermia and to guide management of hypothermic patients. We sought to better characterize the influence of hypothermia on vital signs, including level of consciousness, by studying cases of patients suffering from accidental hypothermia. We retrospectively included patients aged ≥18 years admitted to the hospital with a core temperature below 35°C. We identified the cases from a literature review and from a retrospective case series of hypothermic patients admitted to the hospital between 1994 and 2016. Patients who experienced cardiac arrest, as well as those with potential confounders such as concomitant diseases or intoxications, were excluded. Relationships between core temperature and heart rate, systolic blood pressure, respiratory rate, and level of consciousness were explored via correlations and regression. Of the 305 cases reviewed, 216 met the criteria for inclusion. The mean temperature was 29.7°C ± 4.2°C (range 19.3°C-34.9°C). The relationships between temperature and each of the four vital signs were generally linear and significantly positive, with Spearman correlations for respiratory rate, heart rate, systolic blood pressure, and Glasgow Coma Score (GCS) of 0.29 ( = 0.024), 0.44 ( < 0.001), 0.47 ( < 0.001), and 0.78 ( < 0.001), respectively. Based on linear regression, the mean decrease of a vital sign associated with a 1°C decrease of temperature was estimated to be 0.50 minute for respiratory rate, 2.54 minutes for heart rate, 4.36 mmHg for systolic blood pressure, and 0.88 for GCS. There is a significant positive correlation between core temperature and heart rate, systolic blood pressure, respiratory rate, and GCS. The relationship between vital signs and temperature is generally linear. This knowledge might help clinicians make appropriate decisions when determining whether the clinical condition of a patient should be attributed to hypothermia. This could enhance clinical care and help to guide future research.
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http://dx.doi.org/10.1089/ham.2020.0179DOI Listing
June 2021

Impact of body mass index and socio-economic status on motor development in children and adolescents.

Eur J Pediatr 2021 Jun 28;180(6):1777-1787. Epub 2021 Jan 28.

Child Development Center, University Children's Hospital Zurich, Steinwiesstrasse 75, CH-8032, Zurich, Switzerland.

This study assessed the impact of body mass index (BMI) and socioeconomic status (SES) on the Zurich Neuromotor Assessment, second version (ZNA-2), a battery of tests of motor development in typically developing children between 3 and 18 years of age. BMI measurements and international socio-economic index data were taken from the normative sample of the ZNA-2 for 321 children (158 boys, 163 girls) with a median age of 9.3 years. The age- and gender-adjusted motor performance of these children was quantified and grouped into five components: fine, pure, and gross motor tasks, static balance, and contralateral associated movements. A total score was also calculated. The associations of BMI and SES with the motor scores contribute to less than 5.1% of the total variance.Conclusion: The ZNA-2 for motor development is suitable for measuring motor abilities' development as it is largely independent of the BMI of the child and the SES of the family. What is Known: • Typical motor development, as measured with the Zurich Neuromotor Assessment, second edition (ZNA-2), is strongly dependent on age and gender. • The ZNA-2 focusses on motor performance, motor quality and simple motor skills. What is New: • Higher socio-economic status (SES) is associated with slightly better motor performance as measured by the ZNA-2 total score. • In the ZNA-2 less than 5.1% of the variability in motor performance is attributable to the combined effect of body mass index and SES.
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http://dx.doi.org/10.1007/s00431-021-03945-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105210PMC
June 2021

Qualification for Extracorporeal Life Support in Accidental Hypothermia: The HOPE Score.

Ann Thorac Surg 2021 04 25;111(4):1408. Epub 2020 Sep 25.

Center of Primary Care and Public Health, University of Lausanne, Lausanne, Switzerland.

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http://dx.doi.org/10.1016/j.athoracsur.2020.06.146DOI Listing
April 2021

Pregnancy outcome following first-trimester exposure to fingolimod: A collaborative ENTIS study.

Mult Scler 2021 03 15;27(3):475-478. Epub 2020 Jun 15.

Swiss Teratogen Information Service, Service de Pharmacologie Clinique, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

This prospective multicentre cohort study investigated pregnancy outcomes after fingolimod use for multiple sclerosis during pregnancy. Pregnancy outcomes of 63 fingolimod and 62 interferon-β-exposed pregnancies were compared. Rates of major congenital anomalies (MCA) were 4.8% (2/42) in the fingolimod group versus 2.3% (1/44) in the interferon-β group (odds ratio, 2.2; 95% confidence interval, 0.2-24.6). The adjusted hazard ratio for spontaneous abortion in fingolimod versus interferon-β-exposed pregnancies was 0.6 (95% confidence interval, 0.2-1.8). Further studies are needed to definitely rule out a moderately increased MCA risk after fingolimod exposure during pregnancy.
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http://dx.doi.org/10.1177/1352458520929628DOI Listing
March 2021

Estimating Health Cost Repartition Among Diseases in the Presence of Multimorbidity.

Health Serv Res Manag Epidemiol 2019 Jan-Dec;6:2333392819891005. Epub 2019 Dec 3.

Center for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne, Switzerland.

We consider the nontrivial problem of estimating the health cost repartition among different diseases in the common case where the patients may have multiple diseases. To tackle this problem, we propose to use an iterative proportional repartition (IPR) algorithm, a nonparametric method which is simple to understand and to implement, allowing (among other) to avoid negative cost estimates and to retrieve the total health cost by summing up the estimated costs of the different diseases. This method is illustrated with health costs data from Switzerland and is compared in a simulation study with other methods such as linear regression and general linear models. In the case of an additive model without interactions between disease costs, a situation where the truth is clearly defined such that the methods can be compared on an objective basis, the IPR algorithm clearly outperformed the other methods with respect to efficiency of estimation in all the settings considered. In the presence of interactions, the situation is more complex and will deserve further investigation.
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http://dx.doi.org/10.1177/2333392819891005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6891012PMC
December 2019

Identifying an accurate self-reported screening tool for alcohol use disorder: evidence from a Swiss, male population-based assessment.

Addiction 2020 03 12;115(3):426-436. Epub 2019 Dec 12.

School of Health Sciences, HES-SO University of Applied Sciences and Arts of Western Switzerland, Fribourg, Switzerland.

Background And Aims: Short screenings for alcohol use disorder (AUD) are crucial for public health purposes, but current self-reported measures have several pitfalls and may be unreliable. The main aim of our study was to provide empirical evidence on the psychometric performance of self-reports currently used. Our research questions were: compared with a gold standard clinical interview, how accurate are (1) self-reported AUD, (2) self-reported alcohol use over time and (3) biomarkers of alcohol use among Swiss men? Finally, we aimed to identify an alternative screening tool.

Design: A single-center study with a cross-sectional design and a stratified sample selection.

Setting: Lausanne University Hospital (Switzerland) from October 2017 to June 2018.

Participants: We selected participants from the French-speaking participants of the ongoing Cohort Study on Substance Use and Risk Factors (n = 233). The sample included young men aged on average 27.0 years.

Measurements: We used the Diagnostic Interview for Genetic Studies as the gold standard for DSM-5 AUD. The self-reported measures included 11 criteria for AUD, nine alcohol-related consequences, and previous 12 months' alcohol use. We also assessed biomarkers of chronic excessive drinking (ethyl glucuronide and phosphatidylethanol).

Findings: None of the self-reported measures/biomarkers taken alone displayed both sensitivity and specificity close to 100% with respect to the gold standard (e.g. self-reported AUD: sensitivity = 92.3%, specificity = 45.8%). The best model combined eight self-reported criteria of AUD and four alcohol-related consequences. Using a cut-off of three, this screening tool yielded acceptable sensitivity (83.3%) and specificity (78.7%).

Conclusions: Neither self-reported alcohol use disorder nor heavy alcohol use appear to be adequate to screen for alcohol use disorder among young men from the Swiss population. The best screening alternative for alcohol use disorder among young Swiss men appears to be a combination of eight symptoms of alcohol use disorder and four alcohol-related consequences.
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http://dx.doi.org/10.1111/add.14864DOI Listing
March 2020

Cohort and Individual Neurodevelopmental Stability between 1 and 6 Years of Age in Children with Congenital Heart Disease.

J Pediatr 2019 12 25;215:83-89.e2. Epub 2019 Sep 25.

Child Development Center, University Children's Hospital Zurich, Zurich, Switzerland; Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland.

Objective: To assess cohort and individual neurodevelopmental stability in children with congenital heart disease across childhood.

Study Design: The Reachout Study is a cohort study at the University Children's Hospital Zurich. Data from 148 children with congenital heart disease who underwent cardiopulmonary bypass surgery and 1-, 4-, and 6-year neurodevelopmental assessment were analyzed using mixed models.

Results: Cognitive and motor functions of the total cohort improved over time (cognitive: P = .01; motor: P <.001). The prevalence of children with cognitive impairment at age 6 years was 22.3%. Socioeconomic status showed a significant interaction with age on cognitive and motor development (cognitive: P <.001; motor: P = .001): higher socioeconomic status was associated with better neurodevelopmental outcome over time. Weight and head circumference at birth showed a significant interaction with age on motor development (weight: P = .048; head: P = .006). The correlation between test scores at different ages was weak to moderate (cognition: age 1-6 years: rho = 0.20, age 4-6 years: rho = 0.56, motor: age 1-6 years: rho = 0.23, age 4-6 years: rho = 0.50).

Conclusions: Children with congenital heart disease show a mild improvement in cognitive and motor functions within the first 6 years of life, particularly those with higher socioeconomic status and larger head circumference and weight at birth. However, individual stability is moderate at best. Therefore, follow-up assessments are crucial to target therapeutic intervention effectively.
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http://dx.doi.org/10.1016/j.jpeds.2019.08.036DOI Listing
December 2019

Cognitive outcome of early school-aged children born very preterm is not predicted by early short-term amplitude-integrated electroencephalography.

Acta Paediatr 2020 01 17;109(1):78-84. Epub 2019 Jul 17.

Child Development Centre, University Children's Hospital Zurich, Zurich, Switzerland.

Aim: We investigated the association between early amplitude-integrated electroencephalography (aEEG) and cognitive outcome in very preterm infants at early school-age.

Methods: This prospective cohort study, conducted in the Department of Neonatology, University Hospital Zurich, Switzerland, from 2009 to 2012, comprised of infants born at <32 weeks of gestation, who underwent continuous aEEG recording during the first 4 days of life. Cognitive outcome was assessed with the Kaufman-Assessment Battery for Children at 5 years. Univariate and multivariate logistic regressions were calculated between aEEG parameters and normal cognitive outcome, defined as an intelligence quotient (IQ) of at least 85.

Results: The 118 (52.5% male) infants were born at a mean gestational age of 29.9 weeks and a mean birth weight of 1235 ± 363 g. We followed up 89 children at the age of five, and they had a mean IQ of 97.8 ± 12.7 with 21.3% under 85-and 2.2% had cerebral palsy. Univariate analyses found associations between aEEG measures and normal cognitive outcome, but these were no longer significant after adjustment for confounders. Socioeconomic status and neonatal morbidity were independent predictors of cognitive outcome.

Conclusion: Early short-term aEEG did not predict later cognitive outcome in our cohort of very preterm infants.
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http://dx.doi.org/10.1111/apa.14919DOI Listing
January 2020

Reply to: The integration of prehospital standard operating procedures and in-hospital HOPE score for management of hypothermic patients in cardiac arrest.

Resuscitation 2019 08 22;141:214-215. Epub 2019 Jun 22.

Emergency Department, Lausanne University Hospital, Lausanne, Switzerland. Electronic address:

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http://dx.doi.org/10.1016/j.resuscitation.2019.06.275DOI Listing
August 2019

Hypothermia outcome prediction after extracorporeal life support for hypothermic cardiac arrest patients: An external validation of the HOPE score.

Resuscitation 2019 06 30;139:321-328. Epub 2019 Mar 30.

Emergency Department, Lausanne University Hospital, Lausanne, Switzerland. Electronic address:

Aims: The HOPE score, based on covariates available at hospital admission, predicts the probability of in-hospital survival after extracorporeal life support (ECLS) rewarming of a given hypothermic cardiac arrest patient with accidental hypothermia. Our goal was to externally validate the HOPE score.

Methods: We included consecutive hypothermic arrested patients who underwent rewarming with ECLS. The sample comprised 122 patients. The six independent predictors of survival included in the HOPE score were collected for each patient: age, sex, mechanism of hypothermia, core temperature at admission, serum potassium level at admission and duration of CPR. The primary outcome parameter was survival to hospital discharge.

Results: Overall, 51 of the 122 included patients survived, resulting in an empirical (global) probability of survival of 42% (95% CI = [33-51%]). This was close to the average HOPE survival probability of 38% calculated for patients from the validation cohort, while the Hosmer-Lemeshow test comparing empirical and HOPE (i.e. estimated) probabilities of survival was not significant (p = 0.08), suggesting good calibration. The corresponding area under the receiver operating characteristic curve was 0.825 (95% CI = [0.753-0.897]), confirming the excellent discrimination of the model. The negative predictive value of a HOPE score cut-off of <0.10 was excellent (97%).

Conclusions: This study provides the first external validation of the HOPE score reaching good calibration and excellent discrimination. Clinically, the prediction of the HOPE score remains accurate in the validation sample. The HOPE score may replace serum potassium in the future as the triage tool when considering ECLS rewarming of a hypothermic cardiac arrest victim.
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http://dx.doi.org/10.1016/j.resuscitation.2019.03.017DOI Listing
June 2019

Reference intervals for the urinary steroid metabolome: The impact of sex, age, day and night time on human adult steroidogenesis.

PLoS One 2019 29;14(3):e0214549. Epub 2019 Mar 29.

Department of Nephrology and Hypertension and Department of Clinical Research, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

Objective: Urinary steroid metabolomics by GC-MS is an established method in both clinical and research settings to describe steroidogenic disorders. However, population-based reference intervals for adults do not exist.

Methods: We measured daytime and night time urinary excretion of 40 steroid metabolites by GC-MS in 1128 adult participants of European ancestry, aged 18 to 90 years, within a large population-based, multicentric, cross-sectional study. Age and sex-related patterns in adjacent daytime and night time urine collections over 24 hours were modelled for each steroid metabolite by multivariable linear mixed regression. We compared our results with those obtained through a systematic literature review on reference intervals of urinary steroid excretion.

Results: Flexible models were created for all urinary steroid metabolites thereby estimating sex- and age-related changes of the urinary steroid metabolome. Most urinary steroid metabolites showed an age-dependence with the exception of 6β-OH-cortisol, 18-OH-cortisol, and β-cortol. Reference intervals for all metabolites excreted during 24 hours were derived from the 2.5th and 97.5th percentile of modelled reference curves. The excretion rate per period of metabolites predominantly derived from the adrenals was mainly higher during the day than at night and the correlation between day and night time metabolite excretion was highly positive for most androgens and moderately positive for glucocorticoids.

Conclusions: This study gives unprecedented new insights into sex- and age-specificity of the human adult steroid metabolome and provides further information on the day/night variation of urinary steroid hormone excretion. The population-based reference ranges for 40 GC-MS-measured metabolites will facilitate the interpretation of steroid profiles in clinical practice.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214549PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440635PMC
December 2019

Hybrid fiber alterations in exercising seniors suggest contribution to fast-to-slow muscle fiber shift.

J Cachexia Sarcopenia Muscle 2019 06 25;10(3):687-695. Epub 2019 Mar 25.

Aging and Muscle Metabolism Lab, Department of Physiology & Institute of Sport Sciences, University of Lausanne, Lausanne, Switzerland.

Background: Human skeletal muscle is composed of a functional and metabolic continuum of slow (Type I) and fast fibers (IIa and IIx). Hybrid fibers co-expressing different myosin heavy chains are also present and seem to be more prominent in aging muscle. Their role is debated; hybrid fibers were reported either in a transitional state, between slow and fast fibers, or as fixed individual entities. This study examined the fate of hybrid fibers with an endurance exercise intervention in an elderly sedentary population.

Methods: Twenty-two sedentary healthy elderly men and women underwent a 16-week supervised endurance exercise intervention. Eighteen endurance-trained age- and gender-matched volunteers served as controls. Fiber type distribution was determined by immunohistochemistry on vastus lateralis muscle biopsies pre-intervention and post-intervention.

Results: A total of 13840 fibers were analyzed. At baseline, a Type II dominant fiber profile was observed compared with the control group, with more Type IIa (P = 0.0301) and Type IIx fibers (P = 0.0328). Hybrid fibers represented almost 5% of total muscle fibers in both groups. There was no significant difference between groups (I-IIa, P = 0.6719 and IIa-IIx, P = 0.0998). Intervention triggered qualitative dynamics towards an increase in Type I, and decrease in Type II fibers, paralleled by an increase in I-IIa hybrids (P = 0.0301).

Conclusions: The present study is, to our knowledge, the first to examine hybrid muscle fiber type adaptations to an endurance exercise intervention in the elderly. Hybrid fiber proportions did not differ between chronic sedentary state and chronic endurance-trained state. Exercise intervention increased Type I-IIa hybrid fibers along with shift dynamics in other fiber types suggesting the contribution of hybrid fiber to a fast-to-slow fiber type transition, eventually serving as intermediate reservoir from one monomorphic myosin heavy chain expressing fiber type to another. This finding favours the transitional theory regarding hybrid muscle fibers and exercise, crucial to understanding reversible mechanisms of sarcopenia and development of prevention measures.
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http://dx.doi.org/10.1002/jcsm.12410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6596392PMC
June 2019

A quick and qualitative assessment of gross motor development in preschool children.

Eur J Pediatr 2019 Apr 7;178(4):565-573. Epub 2019 Feb 7.

Child Development Center, University Children's Hospital Zürich, Steinwiesstrasse 75, CH-8032, Zürich, Switzerland.

There is a need for a quick, qualitative, reliable, and easy tool to assess gross motor development for practitioners. The aim of this cross-sectional study is to present the Zurich Neuromotor Assessment-Q (ZNA-Q), which assesses static and dynamic balance in children between 3 and 6 years of age in less than 5 min. A total of 216 children (103 boys; 113 girls; median age 4 years, 4 months; interquartile range 1 year, 3 months) were enrolled from day-care centers, kindergartens, and schools, and were tested with 5 different gross motor tasks: standing on one leg, tandem stance, hopping on one leg, walking on a straight line, and jumping sideways. All ordinal measures (consisting of qualitative measures and scales) featured a marked developmental trend and substantial inter-individual variability. Test-retest reliability was assessed on 37 children. It varied from .17 for tandem stance to .43 for jumping sideways for the individual tasks, and it was .41 and .67 for the static and dynamic balance components, respectively. For the whole ZNA-Q, test-retest reliability was .7.Conclusion: Ordinal scales enable practitioners to gather data on children's gross motor development in a fast and uncomplicated way. It offers the practitioner with an instrument for the exploration of the current developmental motor status of the child. What is Known: • Measurement of gross motor skills in the transitional period between motor mile stones and quantitative assessments is difficult. • Assessment of gross motor skills is relatively easy. What is New: • Supplementary and quick gross motor test battery for children for practitioners. • Normative values of five gross motor skills measured with ordinal scales.
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http://dx.doi.org/10.1007/s00431-019-03327-6DOI Listing
April 2019

Growth and Intellectual Abilities of Six-Year-Old Children with Congenital Heart Disease.

J Pediatr 2019 01 16;204:24-30.e10. Epub 2018 Oct 16.

Child Development Center, University Children's Hospital, Zurich, Switzerland; Children's Research Center, University Children's Hospital, Zurich, Switzerland.

Objective: To determine growth and its relationship to IQ in children with congenital heart disease (CHD) undergoing cardiopulmonary bypass surgery within the first year of life.

Study Design: Prospective single-center cohort study on 143 children (91 males) with different types of CHD (29 univentricular). Children with recognized genetic disorders were excluded. Growth (weight, height, and head circumference [HC]) was assessed at birth, before surgery, and at 1, 4, and 6 years and compared with Swiss growth charts. IQ was assessed at 6 years using standardized tests. Univariate and multivariable linear regressions were performed to determine predictors of HC and IQ at 6 years.

Results: HC at birth was in the low average range (33rd percentile, P = .03), and weight (49th percentile, P = .23) and length (47th percentile, P = .06) were normal. All growth measures declined until the first surgery, with a catch-up growth until 6 years for height (44th percentile, P = .07) but not for weight (39th percentile, P = .003) or for HC (23rd percentile, P < .001). Children undergoing univentricular palliation showed poorer height growth than other types of CHD (P = .01). Median IQ at 6 years was 95 (range 50-135). Lower IQ at 6 years was independently predicted by lower HC at birth, lower socioeconomic status, older age at first bypass surgery, and longer length of intensive care unit stay.

Conclusions: Smaller HC at birth and postnatal factors are predictive of impaired intellectual abilities at school age. Early identification should alert clinicians to provide early childhood interventions to optimize developmental potential.
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http://dx.doi.org/10.1016/j.jpeds.2018.08.060DOI Listing
January 2019

Decision curve analysis: a technical note.

Ann Transl Med 2018 Aug;6(15):308

Department of Surgery, University of Virginia, Charlottesville, VA, USA.

Multivariable regression models are widely used in medical literature for the purpose of diagnosis or prediction. Conventionally, the adequacy of these models is assessed using metrics of diagnostic performances such as sensitivity and specificity, which fail to account for clinical utility of a specific model. Decision curve analysis (DCA) is a widely used method to measure this utility. In this framework, a clinical judgment of the relative value of benefits (treating a true positive case) and harms (treating a false positive case) associated with prediction models is made. As such, the preferences of patients or policy-makers are accounted for by using a metric called threshold probability. A decision analytic measure called net benefit is then calculated for each possible threshold probability, which puts benefits and harms on the same scale. The article is a technical note on how to perform DCA in R environment. The decision curve is depicted with the system. Correction for overfitting is done via either bootstrap or cross-validation. Confidence interval and P values for the comparison of two models are calculated using bootstrap method. Furthermore, we describe a method for computing area under net benefit for the comparison of two models. The average deviation about the probability threshold (ADAPT), which is a more recently developed index to measure the utility of a prediction model, is also introduced in this article.
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http://dx.doi.org/10.21037/atm.2018.07.02DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6123195PMC
August 2018

Corrigendum to "Estimation of reference curves for the urinary steroid metabolome in the first year of life in healthy children: Tracing the complexity of human postnatal steroidogenesis" [J. Steroid Biochem. Mol. Biol. 154 (2015) 226-236].

J Steroid Biochem Mol Biol 2018 Oct 16;183:238. Epub 2018 Aug 16.

Department of Pediatrics (Pediatric Endocrinology and Diabetology, University Children's Hospital) and Department of Clinical Research, University of Bern, Freiburgstrasse 15, 3010, Switzerland. Electronic address:

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http://dx.doi.org/10.1016/j.jsbmb.2018.08.005DOI Listing
October 2018
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