Publications by authors named "Peter Vollenweider"

379 Publications

The trans-ancestral genomic architecture of glycemic traits.

Nat Genet 2021 Jun 31;53(6):840-860. Epub 2021 May 31.

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
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http://dx.doi.org/10.1038/s41588-021-00852-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610958PMC
June 2021

Diurnal Salivary Cortisol in Sarcopenic Postmenopausal Women: The OsteoLaus Cohort.

Calcif Tissue Int 2021 May 18. Epub 2021 May 18.

Interdisciplinary Center for Bone Diseases, Service of Rhumatology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Sarcopenia, similar to hypercortisolism, is characterized by loss of muscle mass and strength. Cortisol circadian rhythm changes with aging (blunted late-day nadir values) were suggested to contribute to this decline. We aimed to explore the relationship between diurnal salivary cortisol values and sarcopenia diagnosis and its components in postmenopausal women. This is a cross-sectional study within the OsteoLaus population-based cohort in Lausanne (Switzerland). Participants had a body composition assessment by dual X-ray absorptiometry (DXA), a grip strength (GS) measure, and salivary cortisol measures (at awakening, 30 min thereafter, 11 AM (sc-11AM) and 8 PM (sc-8PM)). Associations between salivary cortisol and sarcopenia diagnosed by six different criteria (based on appendicular lean mass (ALM) assessed by DXA, and muscle strength by GS), and its components, were analyzed. 471 women aged > 50 years (63.0 ± 7.5) were included. Various definitions identified different participants as sarcopenic, who consistently presented higher salivary cortisol at 11 AM and/or 8 PM. There were no associations between salivary cortisol levels and ALM measures, either absolute or after correction to height squared (ALM index) or body mass index. GS was inversely correlated to sc-11AM (r = - 0.153, p < 0.001) and sc-8PM (r = - 0.118, p = 0.002). Each 10 nmol/l increase of sc-11AM, respectively sc-8PM, was associated with a GS decrease of 1.758 (SE 0.472) kg, respectively 2.929 (SE 1.115) kg. In postmenopausal women, sarcopenia is associated with higher salivary cortisol levels at 11 AM and 8 PM. An increase of daily free cortisol levels in the physiological range could participate to sarcopenia development by decreasing muscle function in postmenopausal women.
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http://dx.doi.org/10.1007/s00223-021-00863-yDOI Listing
May 2021

Case Report: Stepwise Anti-Inflammatory and Anti-SARS-CoV-2 Effects Following Convalescent Plasma Therapy With Full Clinical Recovery.

Front Immunol 2021 21;12:613502. Epub 2021 Apr 21.

Interregional Blood Transfusion SRC, Epalinges, Switzerland.

In these times of COVID-19 pandemic, concern has been raised about the potential effects of SARS-CoV-2 infection on immunocompromised patients, particularly on those receiving B-cell depleting agents and having therefore a severely depressed humoral response. Convalescent plasma can be a therapeutic option for these patients. Understanding the underlying mechanisms of convalescent plasma is crucial to optimize such therapeutic approach. Here, we describe a COVID-19 patient who was deeply immunosuppressed following rituximab (anti-CD20 monoclonal antibody) and concomitant chemotherapy for chronic lymphoid leukemia. His long-term severe T and B cell lymphopenia allowed to evaluate the treatment effects of convalescent plasma. Therapeutic outcome was monitored at the clinical, biological and radiological level. Moreover, anti-SARS-CoV-2 antibody titers (IgM, IgG and IgA) and neutralizing activity were assessed over time before and after plasma transfusions, alongside to SARS-CoV-2 RNA quantification and virus isolation from the upper respiratory tract. Already after the first cycle of plasma transfusion, the patient experienced rapid improvement of pneumonia, inflammation and blood cell counts, which may be related to the immunomodulatory properties of plasma. Subsequently, the cumulative increase in anti-SARS-CoV-2 neutralizing antibodies due to the three additional plasma transfusions was associated with progressive and finally complete viral clearance, resulting in full clinical recovery. In this case-report, administration of convalescent plasma revealed a stepwise effect with an initial and rapid anti-inflammatory activity followed by the progressive SARS-CoV-2 clearance. These data have potential implications for a more extended use of convalescent plasma and future monoclonal antibodies in the treatment of immunosuppressed COVID-19 patients.
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http://dx.doi.org/10.3389/fimmu.2021.613502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097002PMC
May 2021

Polypill eligibility and equivalent intake in a Swiss population-based study.

Sci Rep 2021 Mar 25;11(1):6880. Epub 2021 Mar 25.

Department of Medicine, Internal Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

The polypill has been advocated for cardiovascular disease (CVD) management. The fraction of the population who could benefit from the polypill in Switzerland is unknown. Assess (1) the prevalence of subjects (a) eligible for the polypill and (b) already taking a polypill equivalent; and (2) the determinants of polypill intake in the first (2009-2012) and second follow-ups (2014-2017) of a population-based prospective study conducted in Lausanne, Switzerland. The first and the second follow-ups included 5038 and 4596 participants aged 40-80 years, respectively. Polypill eligibility was defined as having a high CVD risk as assessed by an absolute CVD risk ≥ 5% with the SCORE equation for Switzerland and/or presenting with CVD. Four polypill equivalents were defined: statin + any antihypertensive with (A) or without (B) aspirin; statin + calcium channel blocker (CCB) (C); and statin + CCB + angiotensin-converting enzyme inhibitor (D). The prevalence of polypill eligibility was 20.6% (95% CI 19.5-21.8) and 27.7% (26.5-29.1) in the first and second follow-up, respectively. However, only around one-third of the eligible 29.5% (95% CI 26.7-32.3) and 30.4% (27.9-33.0) respectively, already took the polypill equivalents. All polypill equivalents were more prevalent among men, elderly and in presence of CVD. After multivariable adjustment, in both periods, male gender was associated with taking polypill equivalent A (OR: 1.93; 95% CI 1.45-2.55 and OR: 1.67; 95% CI 1.27-2.19, respectively) and polypill equivalent B (OR: 1.52; 95% CI 1.17-1.96 and OR: 1.41; 95% CI 1.07-1.85, respectively). Similarly, in both periods, age over 70 years, compared to middle-age, was associated with taking polypill equivalent A (OR: 11.71; CI 6.74-20.33 and OR: 9.56; CI 4.13-22.13, respectively) and equivalent B (OR: 13.22; CI 7.27-24.07 and OR: 20.63; CI 6.51-56.36, respectively). Former or current smoking was also associated with a higher likelihood of taking polypill equivalent A in both periods. A large fraction of the population is eligible for the polypill, but only one-third of them actually benefits from an equivalent, and this proportion did not change over time.
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http://dx.doi.org/10.1038/s41598-021-84455-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994372PMC
March 2021

Brain tissue properties link cardio-vascular risk factors, mood and cognitive performance in the CoLaus|PsyCoLaus epidemiological cohort.

Neurobiol Aging 2021 Feb 16;102:50-63. Epub 2021 Feb 16.

Department of Clinical Neurosciences, Laboratory for Research in Neuroimaging LREN, Centre for Research in Neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland; Neurology Department, Max-Planck-Institute for Human Cognitive and Brain Sciences, Leipzig, Germany. Electronic address:

Given the controversy about the impact of modifiable risk factors on mood and cognition in ageing, we sought to investigate the associations between cardio-vascular risk, mental health, cognitive performance and brain anatomy in mid- to old age. We analyzed a set of risk factors together with multi-parameter magnetic resonance imaging (MRI) in the CoLaus|PsyCoLaus cohort (n > 1200). Cardio-vascular risk was associated with differences in brain tissue properties - myelin, free tissue water, iron content - and regional brain volumes that we interpret in the context of micro-vascular hypoxic lesions and neurodegeneration. The interaction between clinical subtypes of major depressive disorder and cardio-vascular risk factors showed differential associations with brain structure depending on individuals' lifetime trajectory. There was a negative correlation between melancholic depression, anxiety and MRI markers of myelin and iron content in the hippocampus and anterior cingulate. Verbal memory and verbal fluency performance were positively correlated with left amygdala volumes. The concomitant analysis of brain morphometry and tissue properties allowed for a neuro-biological interpretation of the link between modifiable risk factors and brain health.
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http://dx.doi.org/10.1016/j.neurobiolaging.2021.02.002DOI Listing
February 2021

Dietary Patterns are Differentially Associated with Atypical and Melancholic Subtypes of Depression.

Nutrients 2021 Feb 26;13(3). Epub 2021 Feb 26.

Department of Psychiatry, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland.

Diet has been associated with the risk of depression, whereas different subtypes of depression have been linked with different cardiovascular risk factors (CVRFs). In this study, our aims were to 1) identify dietary patterns with exploratory factor analysis, 2) assess cross-sectional associations between dietary patterns and depression subtypes, and 3) examine the potentially mediating effect of dietary patterns in the associations between CVRFs and depression subtypes. In the first follow-up of the population-based CoLaus|PsyCoLaus study (2009-2013, 3554 participants, 45.6% men, mean age 57.5 years), a food frequency questionnaire assessed dietary intake and a semi-structured interview allowed to characterize major depressive disorder into current or remitted atypical, melancholic, and unspecified subtypes. Three dietary patterns were identified: Western, Mediterranean, and Sweet-Dairy. Western diet was positively associated with current atypical depression, but negatively associated with current and remitted melancholic depression. Sweet-Dairy was positively associated with current melancholic depression. However, these dietary patterns did not mediate the associations between CVRFs and depression subtypes. Hence, although we could show that people with different subtypes of depression make different choices regarding their diet, it is unlikely that these differential dietary choices account for the well-established associations between depression subtypes and CVRFs.
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http://dx.doi.org/10.3390/nu13030768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996872PMC
February 2021

Obesity and atypical depression symptoms: findings from Mendelian randomization in two European cohorts.

Transl Psychiatry 2021 Feb 4;11(1):96. Epub 2021 Feb 4.

Institute of Primary Care and Public Health (Unisante), University of Lausanne, Lausanne, Switzerland.

Studies considering the causal role of body mass index (BMI) for the predisposition of major depressive disorder (MDD) based on a Mendelian Randomization (MR) approach have shown contradictory results. These inconsistent findings may be attributable to the heterogeneity of MDD; in fact, several studies have documented associations between BMI and mainly the atypical subtype of MDD. Using a MR approach, we investigated the potential causal role of obesity in both the atypical subtype and its five specific symptoms assessed according to the Statistical Manual of Mental Disorders (DSM), in two large European cohorts, CoLaus|PsyCoLaus (n = 3350, 1461 cases and 1889 controls) and NESDA|NTR (n = 4139, 1182 cases and 2957 controls). We first tested general obesity measured by BMI and then the body fat distribution measured by waist-to-hip ratio (WHR). Results suggested that BMI is potentially causally related to the symptom increase in appetite, for which inverse variance weighted, simple median and weighted median MR regression estimated slopes were 0.68 (SE = 0.23, p = 0.004), 0.77 (SE = 0.37, p = 0.036), and 1.11 (SE = 0.39, p = 0.004). No causal effect of BMI or WHR was found on the risk of the atypical subtype or for any of the other atypical symptoms. Our findings show that higher obesity is likely causal for the specific symptom of increase in appetite in depressed participants and reiterate the need to study depression at the granular level of its symptoms to further elucidate potential causal relationships and gain additional insight into its biological underpinnings.
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http://dx.doi.org/10.1038/s41398-021-01236-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862438PMC
February 2021

Genome-wide association study of circulating interleukin 6 levels identifies novel loci.

Hum Mol Genet 2021 Apr;30(5):393-409

Institute of Cardiovascular Science, University College London, London WC1E 6BT, UK.

Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67 428 (ndiscovery = 52 654 and nreplication = 14 774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (Pcombined = 1.8 × 10-11), HLA-DRB1/DRB5 rs660895 on Chr6p21 (Pcombined = 1.5 × 10-10) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (Pcombined = 1.2 × 10-122). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.
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http://dx.doi.org/10.1093/hmg/ddab023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098112PMC
April 2021

Délibérément généralistes.

Rev Med Suisse 2021 01;17(722):111-112

Unisanté, Lausanne.

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January 2021

Clinical and biological determinants of P-wave duration: cross-sectional data from the population-based CoLaus|PsyCoLaus study.

BMJ Open 2020 11 19;10(11):e038828. Epub 2020 Nov 19.

Internal Medicine, CHUV, Lausanne, Switzerland.

Objectives: P-wave duration (PWD) is associated with the development of atrial arrhythmias, cardiovascular and all-cause mortality. With this study, we aimed to assess the distribution and determinants of PWD in the general population.

Design: Cross-sectional study using data collected between 2014 and 2016.

Setting: In the population-based cohort CoLaus|PsyCoLaus, Lausanne, Switzerland, we used 12-lead ECGs to measure PWD. Potential demographic, clinical and biological determinants of PWD were collected by questionnaire, anthropometry, blood pressure measurement and biological assays.

Participants: Data from 3459 participants (55% women, 62±10 years, 93% Caucasian) were included. Participants were excluded if they presented with (1) no sinus rhythm or paced rhythm on the study ECG or Wolff-Parkinson-White ECG pattern; (2) missing or non-interpretable ECG; and (3) missing phenotypic data.

Primary Outcome Measure: Determine (1) the PWD distribution and (2) the demographic, clinical and biological determinants of PWD in a large population-based cohort.

Results: Median and IQR of PWD was 112 (102-120) ms . In the multivariable analyses, PWD was significantly associated with age (p<0.001) and height (p<0.001), with an adjusted regression coefficient (95% CI) of 0.29 ms/years (0.23 to 0.36) and 0.32 ms/cm (0.28 to 0.37), respectively. PWD, given thereafter in ms with adjusted mean±SE, was significantly (p<0.05) associated with (a) gender (woman 110.0±0.4; man 112.1±0.4), (b) body mass index (normal 110.1±0.4; overweight 110.9±0.4; obese 113.0±0.5), (c) abdominal obesity (no 110.5±0.3; yes 111.7±0.4) and (d) hypertension (no 110.4±0.3; yes 111.7±0.4).

Conclusion: PWD is positively associated with age, height, male gender, obesity markers and hypertension. Clinical interpretation of PWD should take these factors into consideration.
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http://dx.doi.org/10.1136/bmjopen-2020-038828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678386PMC
November 2020

Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability.

Nat Commun 2021 01 5;12(1):24. Epub 2021 Jan 5.

Department of Biostatistics and Data Science, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA.

Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.
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http://dx.doi.org/10.1038/s41467-020-19366-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785747PMC
January 2021

Prognostic and therapeutic considerations of antibodies against c-ter apolipoprotein A-1 in the general population.

Clin Transl Immunology 2020 14;9(12):e1220. Epub 2020 Dec 14.

Department of Internal Medicine Lausanne University Hospital Lausanne Switzerland.

Objectives: Autoantibodies against apolipoprotein A1 (anti-apoA1 IgGs) and its C-terminal region (cter apoA1) have emerged as an independent biomarker for cardiovascular disease. Cter apoA1 mimetic peptides were shown to reverse the deleterious anti-apoA1 IgG effects . We evaluated the association of anti-cter apoA1 IgGs with overall mortality in the general population and tested the ability of a cter apoA1 mimetic peptide to reverse the anti-apoA1 IgG-induced inflammatory response and mortality and , respectively.

Methods: Anti-cter apoA1 IgGs were measured in serum samples of 6386 participants of the CoLaus study of which 5220 were followed for a median duration of 5.6 years. The primary outcome was overall mortality. The peptide inhibitory concentration 50% (IC) was determined on HEK-Blue-4 and RAW cells. ApoE mice were exposed to 16 weeks of anti-apoA1IgG passive immunisation with and without peptide co-incubation.

Results: Anti-cter apoA1 IgGs were associated with higher interleukin 6 levels and independently predicted overall mortality; an increase of one standard deviation of anti-cter apoA1 IgG level was associated with an 18% increase in mortality risk (hazard ratio: 1.18, 95% confidence interval: 1.04-1.33;  = 0.009). The cterApoA1 analogue reversed the antibody-mediated inflammatory response with an IC of 1 µm but did not rescue the significant anti-apoA1 IgG-induced mortality rate (69% vs. 23%, LogRank  = 0.02).

Conclusion: Anti-cter apoA1 IgG independently predicts overall mortality in the general population. Despite being effective , our cter apoA1 analogue did not reverse the anti-apoA1 IgG-induced mortality in mice. Our data suggest that these autoantibodies are not readily treatable through cognate peptide immunomodulation.
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http://dx.doi.org/10.1002/cti2.1220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734471PMC
December 2020

Clinical factors associated with the intraventricular conduction disturbances in Swiss middle-aged adults: The CoLaus|PsyCoLaus study.

Int J Cardiol 2021 03 10;327:201-208. Epub 2020 Dec 10.

Department of Heart and Vessels, Cardiology, Lausanne University Hospital (CHUV), Rue du Bugnon 46, 1011 Lausanne, Switzerland.

Background: Intraventricular conduction disturbances are associated with an increased risk of adverse cardiovascular outcomes. However, data about factors associated with intraventricular conduction disturbances are sparse. We aimed to identify the clinical factors associated with intraventricular conduction disturbances in the general population.

Methods: Cross-sectional study in a sample of 3704 participants (age range 45-86 years, 55.2% women). Intraventricular conduction disturbances were defined as QRS > 110 ms on electrocardiograms, and classified into right bundle branch block (RBBB), left bundle branch block (LBBB), left anterior fascicular block (LAFB) and non-specific intraventricular conduction disturbances (NIVCD).

Results: The number of participants, the resulting prevalence (square brackets) and 95% CI (round brackets) of intraventricular conduction disturbances and subtypes (RBBB, LBBB, LAFB and NIVCD) were 187 [5.1% (4.4-5.8%)], 103 [2.9%, (2.3-3.4%)], 29 [0.8% (0.6-1.1%)], 31 (0.9% [0.6-1.2%]), and 47 [1.3% (0.9-1.7)], respectively. Multivariable logistic regression identified male sex [odds ratio and (95% CI): 2.55 (1.34-4.86)] and increasing age (p-value for trend <0.001) as being associated with RBBB; hypertension [3.08 (1.20-7.91)] and elevated NT-proBNP [3.26 (1.43-7.41)] as being associated with LBBB; elevated NT-proBNP [3.14 (1.32-7.46)] as being associated with LFAB; and male sex [5.97 (1.91-18.7)] and increased height [1.31 (1.06-1.63)] as being associated with NIVCD.

Conclusion: In a sample of the Swiss middle-aged population, the clinical factors associated with intraventricular conduction disturbances differed according to the intraventricular conduction disturbances subtype: male sex and ageing for RBBB; hypertension and elevated NT-proBNP for LBBB; elevated NT-proBNP for LAFB; and male sex and increased height for NIVCD.
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http://dx.doi.org/10.1016/j.ijcard.2020.12.012DOI Listing
March 2021

[Rhabdomyolysis: early management].

Rev Med Suisse 2020 Nov;16(716):2272-2278

Service de médecine interne, Département de médecine, CHUV, 1011 Lausanne.

Rhabdomyolysis is defined by myalgia, potentially painful myoedema and muscular weakness due to death of muscular fiber in the striated muscle. Frequent etiologies include physical effort, intoxication (alcohol, drugs and medication) and physical trauma. Depletion of myocyte' s adenosine triphosate (ATP) leads to an increase in intracellular calcium and myocyte death. Diagnosis relies on creatine kinase (CK) levels. The clinical spectrum of rhabdomyolysis includes an asymptomatic increased amount of CK as well as severe, life threatening complications such as acute renal failure and electrolyte disorders. Treatment is based on prevention and addressing complications.
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November 2020

[Pharmacogenomics : a toolbox to improve drug prescription].

Rev Med Suisse 2020 Nov;16(716):2259-2263

Service de médecine interne, Département de médecine, CHUV, 1011 Lausanne.

As a result of advances in pharmacogenomics (PGx), the paradigm that a single dose of a drug is extrapolated to an entire population is set to change. Personalising drug prescriptions according to individual genomic determinants would make it possible to increase the effectiveness and tolerance of treatments. In Switzerland, any doctor can prescribe validated PGx tests for five actionable drugs : abacavir, carbamazepine, thiopurines [azathioprine], fluoropyrimidines [5-FU, capecitabine] and irinotecan. Such an approach presupposes that PGx data are shared with trained clinicians and that prescribing aids can guide them.
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November 2020

Médicaments : amis ou faux amis ?

Rev Med Suisse 2020 11;16(716):2239-2240

Chef du Service de médecine interne, Département de médecine, CHUV, Lausanne.

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November 2020

Life-course socioeconomic disadvantage and lung function: a multicohort study of 70 496 individuals.

Eur Respir J 2021 Mar 18;57(3). Epub 2021 Mar 18.

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

Background: Lung function is an important predictor of health and a marker of physical functioning at older ages. This study aimed to quantify the years of lung function lost according to disadvantaged socioeconomic conditions across the life-course.

Methods: This multicohort study used harmonised individual-level data from six European cohorts with information on life-course socioeconomic disadvantage and lung function assessed by forced expiratory volume in 1 s (FEV) and forced vital capacity (FVC). 70 496 participants (51% female) aged 18-93 years were included. Socioeconomic disadvantage was measured in early life (low paternal occupational position), early adulthood (low educational level) and adulthood (low occupational position). Risk factors for poor lung function ( smoking, obesity, sedentary behaviour, cardiovascular and respiratory diseases) were included as potential mediators. The years of lung function lost due to socioeconomic disadvantage were computed at each life stage.

Results: Socioeconomic disadvantage during the life-course was associated with a lower FEV. By the age of 45 years, individuals experiencing disadvantaged socioeconomic conditions had lost 4-5 years of healthy lung function their more advantaged counterparts (low educational level -4.36 (95% CI -7.33--2.37) for males and -5.14 (-10.32--2.71) for females; low occupational position -5.62 (-7.98--4.90) for males and -4.32 (-13.31--2.27) for females), after accounting for the risk factors for lung function. By the ages of 65 years and 85 years, the years of lung function lost due to socioeconomic disadvantage decreased by 2-4 years, depending on the socioeconomic indicator. Sensitivity analysis using FVC yielded similar results to those using FEV.

Conclusion: Life-course socioeconomic disadvantage is associated with lower lung function and predicts a significant number of years of lung function loss in adulthood and at older ages.
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http://dx.doi.org/10.1183/13993003.01600-2020DOI Listing
March 2021

Prevalence and Description of Hyponatremia in a Swiss Tertiary Care Hospital: An Observational Retrospective Study.

Front Med (Lausanne) 2020 11;7:512. Epub 2020 Sep 11.

Department of Internal Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Hyponatremia (serum sodium concentration <135 mEq/L) is the most common electrolyte abnormality among hospitalized patients. Our aim was to study the epidemiology of hyponatremia in hospitalized patients, as well as the short-term mortality rates, the length of stay (LOS), and associated hospital costs. This retrospective cohort study included 6,539 hospitalizations in the internal medicine ward of a Swiss tertiary-care teaching hospital between January 1, 2012, and December 31, 2018 (42.7% women, mean age 69 years). Using serum sodium concentration, we identified hospitalizations with hyponatremia and calculated the prevalence of overall hyponatremia, admission hyponatremia (AH), hospital-acquired hyponatremia (HAH), and persistent hyponatremia (PH) at discharge. We also studied the impact of hyponatremia on 30-day readmissions, in-hospital and 30-day mortality, and hospital LOS and costs, using multivariable logistic regression and Cox proportional hazards models, with normal natremia as reference. Prevalence of overall hyponatremia was 32.5% [95% confidence interval (CI), 31.3-33.6%], while prevalence of PH among hospitalizations with AH and HAH was 33.7% (31.7-35.8%). After multivariable adjustment, hyponatremia was associated with increased hospital costs (CHF 19,025 ± 485 vs. 14,962 ± 341, < 0.001) and LOS (13.4 ± 0.2 vs. 10.7 ± 0.2 days, < 0.001). Increased severity of hyponatremia was associated with higher hospital costs and LOS ( for trend <0.001). There was a trend toward more frequent 30-day readmissions associated with hyponatremia [adjusted odds ratio (OR), 1.15 (1.01-1.31), = 0.032], mainly with PH: adjusted OR = 1.41 (1.17-1.71), < 0.001. No association was found between severity of hyponatremia and readmissions. Hyponatremia was associated with an increase of in-hospital [adjusted OR = 1.94 (1.49-2.53), < 0.001] and 30-day mortality: adjusted OR = 1.80 (1.44-2.24), < 0.001. Increased severity of hyponatremia was associated with higher in-hospital and 30-day mortality ( for trend < 0.001). Hyponatremia is highly prevalent among hospitalized patients and associated with an increase of LOS, early hospital readmission, in-hospital and 30-day mortality, and hospital costs. PH was associated with a substantial increase of the risk of early hospital readmission and 30-day mortality.
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http://dx.doi.org/10.3389/fmed.2020.00512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517335PMC
September 2020

Accelerometry assessed physical activity of older adults hospitalized with acute medical illness - an observational study.

BMC Geriatr 2020 10 2;20(1):382. Epub 2020 Oct 2.

Department of medicine, internal medicine, Lausanne university hospital and University of Lausanne, Rue du Bugnon 46, 1011, Lausanne, Switzerland.

Background: In a hospital setting and among older patients, inactivity and bedrest are associated with a wide range of negative outcomes such as functional decline, increased risk of falls, longer hospitalization and institutionalization. Our aim was to assess the distribution, determinants and predictors of physical activity (PA) levels using wrist-worn accelerometers in older patients hospitalized with acute medical illness.

Methods: Observational study conducted from February to November 2018 at an acute internal medicine unit in the University hospital of Lausanne, Switzerland. We enrolled 177 patients aged ≥65 years, able to walk prior to admission. PA during acute hospital stay was continuously recorded via a 3D wrist accelerometer. Clinical data was collected from medical records or by interview. Autonomy level prior to inclusion was assessed using Barthel Index score. PA levels were defined as < 30 mg for inactivity, 30-99 mg for light and ≥ 100 for moderate PA. Physically active patients were defined as 1) being in the highest quartile of time spent in light and moderate PA or 2) spending ≥20 min/day in moderate PA.

Results: Median [interquartile range - IQR] age was 83 [74-87] years and 60% of participants were male. The median [IQR] time spent inactive and in light PA was 613 [518-663] and 63 [30-97] minutes/day, respectively. PA peaked between 8 and 10 am, at 12 am and at 6 pm. Less than 10% of patients were considered physically active according to definition 2. For both definitions, active patients had a lower prevalence of walking aids and a lower dependency level according to Barthel Index score. For definition 1, use of medical equipment was associated with a 70% reduction in the likelihood of being active: odds ratio (OR) 0.30 [0.10-0.92] p = 0.034; for definition 2, use of walking aids was associated with a 75% reduction in the likelihood of being active: OR = 0.24 [0.06-0.89], p = 0.032.

Conclusion: Older hospitalized patients are physically active only 10% of daily time and concentrate their PA around eating periods. Whether a Barthel Index below 95 prior to admission may be used to identify patients at risk of inactivity during hospital stay remains to be proven.
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http://dx.doi.org/10.1186/s12877-020-01763-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532621PMC
October 2020

Genome-wide association study identifies 48 common genetic variants associated with handedness.

Nat Hum Behav 2021 01 28;5(1):59-70. Epub 2020 Sep 28.

Institute of Biological Psychiatry, Mental Health Services of Copenhagen, Copenhagen, Denmark.

Handedness has been extensively studied because of its relationship with language and the over-representation of left-handers in some neurodevelopmental disorders. Using data from the UK Biobank, 23andMe and the International Handedness Consortium, we conducted a genome-wide association meta-analysis of handedness (N = 1,766,671). We found 41 loci associated (P < 5 × 10) with left-handedness and 7 associated with ambidexterity. Tissue-enrichment analysis implicated the CNS in the aetiology of handedness. Pathways including regulation of microtubules and brain morphology were also highlighted. We found suggestive positive genetic correlations between left-handedness and neuropsychiatric traits, including schizophrenia and bipolar disorder. Furthermore, the genetic correlation between left-handedness and ambidexterity is low (r = 0.26), which implies that these traits are largely influenced by different genetic mechanisms. Our findings suggest that handedness is highly polygenic and that the genetic variants that predispose to left-handedness may underlie part of the association with some psychiatric disorders.
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http://dx.doi.org/10.1038/s41562-020-00956-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116623PMC
January 2021

Life worth living: cross-sectional study on the prevalence and determinants of the wish to die in elderly patients hospitalized in an internal medicine ward.

BMC Geriatr 2020 09 14;20(1):348. Epub 2020 Sep 14.

Service of Internal Medicine, Lausanne University Hospital, Rue du Bugnon 46, 1011, Lausanne, Switzerland.

Background: Elderly people frequently express the wish to die: this ranges from a simple wish for a natural death to a more explicit request for death. The frequency of the wish to die and its associated factors have not been assessed in acute hospitalization settings. This study aimed to investigate the prevalence and determinants of the wish to die in elderly (≥65 years) patients hospitalized in an internal medicine ward.

Methods: This cross-sectional study was conducted between 1 May, 2018, and 30 April, 2019, in an acute care internal medicine ward in a Swiss university hospital. Participants were a consecutive sample of 232 patients (44.8% women, 79.3 ± 8.1 years) with no cognitive impairment. Wish to die was assessed using the Schedule of Attitudes toward Hastened Death-senior and the Categories of Attitudes toward Death Occurrence scales.

Results: Prevalence of the wish to die was 8.6% (95% confidence interval [CI]: 5.3-13.0). Bivariate analysis showed that patients expressing the wish to die were older (P = .014), had a lower quality of life (P < .001), and showed more depressive symptoms (P = .044). Multivariable analysis showed that increased age was positively (odds ratio [OR] for a 5-year increase: 1.43, 95% CI 0.99-2.04, P = .048) and quality of life negatively (OR: 0.54, 95% CI 0.39-0.75, P < 0.001) associated with the likelihood of wishing to die. Participants did not experience stress during the interview.

Conclusions: Prevalence of the wish to die among elderly patients admitted to an acute hospital setting is low, but highly relevant for clinical practice. Older age increases and better quality of life decreases the likelihood of wishing to die. Discussion of death appears to be well tolerated by patients.
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http://dx.doi.org/10.1186/s12877-020-01762-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7491164PMC
September 2020

Whipple disease: a 15-year retrospective study on 36 patients with positive polymerase chain reaction for Tropheryma whipplei.

Clin Microbiol Infect 2021 Jun 4;27(6):910.e9-910.e13. Epub 2020 Sep 4.

Institute of Microbiology, University of Lausanne, Lausanne, Switzerland. Electronic address:

Our institution has performed microbiological diagnosis of Tropheryma whipplei since 2001, initially with a PCR targeting 16S rRNA before the development of a quantitative PCR in 2012. Here we report the clinical characteristics of a cohort of patients suffering from Whipple disease (WD) and evaluate the impact of these molecular techniques. Patients with a positive PCR for T. whipplei between 2001 and 2016 were retrospectively collected from microbiological databases. Two infectious diseases specialists reviewed their medical records and classified them as definite WD, probable WD or carriage of T. whipplei without disease. A total of 1153 samples were tested for T. whipplei; 76 samples taken from 36 patients were positive. Fifteen were considered as presenting a definite WD, seven as a probable WD and 14 as carriers. Median age was 56.4 years (extremes, 6.6-76.1). Median time from symptoms to diagnosis was 3 years (2.5 months to 13.3 years). About 60% were immunosuppressed. The most frequent clinical presentations were joint pain (16/22), weight loss (15/22) and/or digestive tract disorder (15/22); 41% had neurological manifestations, 32% pulmonary involvement and 32% lymphadenopathies. Bacterial load in faeces or saliva were 88 425 copies/mL (IQR 6175-292 725) in definite and probable WD and 311 copies/mL (IQR 253-2090) in carriers, respectively. We observed a 90% PPV above 32 200 copies/mL in faeces. WD is a chronic multisystemic disease with frequent pulmonary involvement. Underlying immunodeficiency is commonly observed leading to more complex clinical presentation. Positive T. whipplei PCR in both stool and saliva has a high positive predictive value. Moreover, patients with WD present higher bacterial load in faeces with a threshold of >32 200 copies/mL predicting ongoing infection.
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http://dx.doi.org/10.1016/j.cmi.2020.08.036DOI Listing
June 2021

Use of lipoprotein(a) for refining cardiovascular risk prediction in a low-risk population: The CoLaus/PsyCoLaus study.

Eur J Prev Cardiol 2020 Jul 5:2047487320938271. Epub 2020 Jul 5.

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

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http://dx.doi.org/10.1177/2047487320938271DOI Listing
July 2020

SPHN - The Swiss Aging Citizen Reference (SACR).

Stud Health Technol Inform 2020 Jun;270:1168-1169

Swiss Tropical and Public Health Institute.

In Switzerland by 2045, we expect 2.7 Mio citizens aged 65+ of whom 1.0 Mio. aged 80+. A priority and focus of personalized health research is therefore aging biology to extend healthy life expectancy. Novel molecular and imaging features will emerge as candidate targets for risk prediction and screening of chronic diseases. It is of utmost importance to test the clinical and public health utility of candidate biomarkers evolving from this research in citizen reference cohorts. We will build a Swiss Aging Citizen Reference (SACR), a testable and scalable reference cohort offering interoperable, searchable, and accessible data. 1000 participants from existing Swiss citizen cohorts will be combined and analyzed for DNA methylation and MRI brain imaging. SACR will serve as a testbed for clinical and public health utility of candidate biomarkers. As for a proof-of-concept study, we will conduct an agnostic search for structural and functional brain features associated with epigenetic aging acceleration to examine the potential of epigenetic age acceleration as the intermediate aging biomarker and to better understand the aging mechanism in brain.
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http://dx.doi.org/10.3233/SHTI200347DOI Listing
June 2020

The well-being of Swiss general internal medicine residents.

Swiss Med Wkly 2020 Jun 18;150:w20255. Epub 2020 Jun 18.

Department of General Internal Medicine, Bern University Hospital, Inselspital, Bern, Switzerland.

Background: Physician well-being has an impact on productivity and quality of care. Residency training is a particularly stressful period.

Objective: To assess the well-being of general internal medicine (GIM) residents and its association with personal and work-related factors.

Methods: We conducted an anonymous electronic survey among GIM residents from 13 Swiss teaching hospitals. We explored the association between a reduced well-being (≥5 points based on the Physician Well-Being Index [PWBI]) and personal and work-related factors using multivariable mixed-effects logistic regression.

Results: The response rate was 54% (472/880). Overall, 19% of residents had a reduced well-being, 60% felt burned out (emotional exhaustion), 47% were worried that their work was hardening them emotionally (depersonalisation), and 21% had career choice regret. Age (odds ratio [OR] 1.19, 95% confidence interval [CI] 1.05–1.34), working hours per week (OR 1.04 per hour, 95% CI 1.01–1.07) and <2.5 rewarding work hours per day (OR 3.73, 95% CI 2.01–6.92) were associated with reduced well-being. Administrative workload and satisfaction with the electronic medical record were not. We found significant correlations between PWBI score and job satisfaction (rs = -0.54, p<0.001), medical errors (rs = 0.18, p<0.001), suicidal ideation (rs = 0.12, p = 0.009) and the intention to leave clinical practice (rs = 0.38, p <0.001) CONCLUSIONS: Approximately 20% of Swiss GIM residents appear to have a reduced well-being and many show signs of distress or have career choice regret. Having few hours of rewarding work and a high number of working hours were the most important modifiable predictors of reduced well-being. Healthcare organisations have an ethical responsibility to implement interventions to improve physician well-being.
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http://dx.doi.org/10.4414/smw.2020.20255DOI Listing
June 2020

Risk factors of excessive daytime sleepiness in a prospective population-based cohort.

J Sleep Res 2021 04 15;30(2):e13069. Epub 2020 May 15.

Center for Investigation and Research in Sleep (CIRS), Lausanne University Hospital (CHUV), University of Lausanne, Lausanne, Switzerland.

Although excessive daytime sleepiness is commonly evaluated in clinical and research settings using the Epworth Sleepiness Scale, few studies have assessed the factors associated with its incidence in the general population. We prospectively investigated the predictors of incident and persistent excessive daytime sleepiness in 2,751 subjects (46.1% men, mean age 56.0 ± 9.8 years) from the CoLaus-PsyCoLaus population-based cohort (Lausanne, Switzerland) over 5 years. Participants completed the Epworth Sleepiness Scale and the Pittsburgh Sleep Quality Index, and underwent a full clinical evaluation at baseline and 5 years afterwards. Ambulatory polysomnography was performed at baseline in a sub-sample of 1,404 subjects. Among the 2,438 subjects without excessive daytime sleepiness (Epworth Sleepiness Scale ≤ 10) at baseline, the 5-year incidence of excessive daytime sleepiness was 5.1% (n = 124). Multivariate logistic regression revealed that male sex, depressive symptoms, reported poor sleep quality and moderate to severe obstructive sleep apnea were independent predictors of incident excessive daytime sleepiness, while older age, moderate coffee consumption, periodic leg movement during sleep and hypertension were independent protective factors. Stratified analysis according to sex and age showed some distinctive associations. Among the 313 patients with excessive daytime sleepiness at baseline, 137 (43.8%) had persistent excessive daytime sleepiness 5 years later. Our findings provide new insights into the predictors of incident excessive daytime sleepiness, but interventional studies are needed to understand the impact of treating these risk factors on the incidence of excessive daytime sleepiness.
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http://dx.doi.org/10.1111/jsr.13069DOI Listing
April 2021

[Medical students at the bedside of COVID-19 patients : motivations and challenges].

Rev Med Suisse 2020 May;16(692):958-961

Service de médecine interne, CHUV, 1011 Lausanne.

The SARS-CoV-2 pandemic is putting our healthcare system under exceptional pressure, given the number of affected patients. In a context of limited human healthcare resources, senior medical students represent a valuable workforce that can quickly be mobilized for patient care. This is the approach followed in Switzerland and other countries, in several outpatient structures or inpatient services, including the Department of Internal Medicine, of the Lausanne University Hospital (CHUV). In this article, we first give the floor to students who responded to our call. We conclude with important considerations in terms of students' clinical supervision. It is reminded that the involvement of students in the care of COVID-19 patients should only occur on a vo luntary basis.
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May 2020

[Organizational Impacts and Clinical Challenges of the COVID-19 Pandemic on a Swiss Tertiary Internal Medicine Department].

Rev Med Suisse 2020 Apr;16(N° 691-2):869-874

Service de médecine interne, CHUV, 1011 Lausanne.

The rapid progression of COVID-19 is an organizational challenge for all hospitals. To secure the patient overflow, the Department internal medicine of the University Hospital of Lausanne increased nurse and medical workforces as well as bed capacity by 65 %, with extraordinary help from other departments. The implemented crisis management stood upon three pillars : a crisis management team, steering documents and internal communication. In this new form, the Department had already taken care of 442 COVID-19 admissions by April 16, 2020. Alongside organizational challenges, clinical issues such as rapid respiratory distress, clinical suspicions with negative PCR and treatment uncertainties in the absence of sufficient evidence were overcome. Despite the peak of the pandemic appearing to have passed, the next phase could be just as complicated.
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April 2020

Generalized Anxiety Disorder is Prospectively Associated With Decreased Levels of Interleukin-6 and Adiponectin Among Individuals from the Community.

J Affect Disord 2020 06 3;270:114-117. Epub 2020 Apr 3.

Department of Consultation-Liaison Psychiatry and Psychosomatic Medicine, University Hospital Zurich, and University of Zurich, Zurich, Switzerland.

Background: Anxiety disorders have been related to cardiovascular diseases via low-grade inflammation, but longitudinal studies on the association between generalized anxiety disorder (GAD) and inflammatory biomarkers are sparse. Furthermore, no studies have examined the association between GAD and the "cardio-protective" adipocytokine adiponectin in this context so far.

Methods: In a Swiss population-based sample of 2,415 adults participating in baseline and follow-up exams (mean follow-up duration=5.5 years), we diagnosed a total of 55 persons (2.3%) with GAD using a validated semi-structured psychiatric interview. We prospectively examined the relation between GAD and circulating levels of inflammatory biomarkers (i.e., C-reactive protein, interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and adiponectin), in linear regression models, statistically controlled for the baseline inflammatory marker, socioeconomic status, cardiovascular risk factors, health behaviors, and psychiatric disorders.

Results: Compared to those without GAD, individuals with GAD had lower IL-6 (β=-0.249, 95%-CI -0.493-(-0.004), p=0.046), and adiponectin (β=-0.264, 95%-CI -0.482-(-0.045), p=0.018) levels at follow-up after adjustment for all covariates. Moreover, GAD was unrelated to several other inflammatory measures.

Conclusion: Individuals with GAD do not seem to exhibit chronic low-grade inflammation, suggesting different underlying biobehavioral mechanisms to those from other anxiety disorders. Low adiponectin levels may be linked to symptoms of GAD through brain areas directly involved in the processing of fear and anxiety.
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http://dx.doi.org/10.1016/j.jad.2020.03.123DOI Listing
June 2020