Publications by authors named "Claudia Barth"

33 Publications

A history of previous childbirths is linked to women's white matter brain age in midlife and older age.

Hum Brain Mapp 2021 Jun 12. Epub 2021 Jun 12.

NORMENT, Institute of Clinical Medicine, University of Oslo & Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.

Maternal brain adaptations occur in response to pregnancy, but little is known about how parity impacts white matter and white matter ageing trajectories later in life. Utilising global and regional brain age prediction based on multi-shell diffusion-weighted imaging data, we investigated the association between previous childbirths and white matter brain age in 8,895 women in the UK Biobank cohort (age range = 54-81 years). The results showed that number of previous childbirths was negatively associated with white matter brain age, potentially indicating a protective effect of parity on white matter later in life. Both global white matter and grey matter brain age estimates showed unique contributions to the association with previous childbirths, suggesting partly independent processes. Corpus callosum contributed uniquely to the global white matter association with previous childbirths, and showed a stronger relationship relative to several other tracts. While our findings demonstrate a link between reproductive history and brain white matter characteristics later in life, longitudinal studies are required to establish causality and determine how parity may influence women's white matter trajectories across the lifespan.
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http://dx.doi.org/10.1002/hbm.25553DOI Listing
June 2021

Cognitive impairment profile in adolescent early-onset psychosis using the MATRICS Battery: Age and sex effects.

Neuropsychology 2021 Mar;35(3):300-309

NORMENT Center of Excellence, Institute of Clinical Medicine, University of Oslo.

To examine cognitive performance, stratified by age and sex, in adolescents with early-onset psychosis (EOP), relative to the healthy adolescent standardized scores for the MATRICS Consensus Cognitive Battery (MCCB). Seventy-one EOP patients (12-18 years) were included in the study. Raw scores of nine MCCB tests were converted into age- and sex-corrected scores comprising six domains and global cognition (cognitive composite score). Patient performance, relative to the healthy reference group, was examined using one sample -tests (reference score mean of 50). Age effects were examined using one-way analyses of variance between three age groups (12-14 years, 15-16 years, 17-18 years). Sex differences were examined using independent samples t tests. The patients performed significantly worse than the healthy reference group in all MCCB domains, with a global deficit of -1.6 SD below the reference. Across the domains, the impairments varied from -1.4 SD in speed of processing to -0.6 SD in visual learning and reasoning and problem-solving. Significant age effects were found in speed of processing, attention/vigilance, reasoning and problem-solving, and global cognition. The oldest age group showed largest impairments relative to the age- and sex-corrected reference. Female patients had a significantly higher mean score in verbal learning compared to males. This study provides a MCCB performance profile in EOP, stratified by age and sex, relative to adolescent standardized scores. The results can be used to improve cognitive remediation strategies and subsequent functional outcome, in adolescent EOP and related clinical populations. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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http://dx.doi.org/10.1037/neu0000723DOI Listing
March 2021

Significant association between intracranial volume and verbal intellectual abilities in patients with schizophrenia and a history of birth asphyxia.

Psychol Med 2021 Mar 10:1-10. Epub 2021 Mar 10.

Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.

Background: The etiology of schizophrenia (SZ) is proposed to include an interplay between a genetic risk for disease development and the biological environment of pregnancy and birth, where early adversities may contribute to the poorer developmental outcome. We investigated whether a history of birth asphyxia (ASP) moderates the relationship between intracranial volume (ICV) and intelligence in SZ, bipolar disorder (BD) and healthy controls (HC).

Methods: Two hundred seventy-nine adult patients (18-42 years) on the SZ and BD spectrums and 216 HC were evaluated for ASP based on information from the Medical Birth Registry of Norway. Participants underwent structural magnetic resonance imaging (MRI) to estimate ICV and intelligence quotient (IQ) assessment using the Wechsler Abbreviated Scale of Intelligence (WASI). Multiple linear regressions were used for analyses.

Results: We found a significant three-way interaction (ICV × ASP × diagnosis) on the outcome variable, IQ, indicating that the correlation between ICV and IQ was stronger in patients with SZ who experienced ASP compared to SZ patients without ASP. This moderation by ASP was not found in BD or HC groups. In patients with SZ, the interaction between ICV and a history of the ASP was specifically related to the verbal subcomponent of IQ as measured by WASI.

Conclusions: The significant positive association between ICV and IQ in patients with SZ who had experienced ASP might indicate abnormal neurodevelopment. Our findings give support for ICV together with verbal intellectual abilities as clinically relevant markers that can be added to prediction tools to enhance evaluations of SZ risk.
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http://dx.doi.org/10.1017/S0033291721000489DOI Listing
March 2021

In Vivo Amygdala Nuclei Volumes in Schizophrenia and Bipolar Disorders.

Schizophr Bull 2021 Jan 22. Epub 2021 Jan 22.

Norwegian Centre for Mental Disorders Research, Institute of Clinical Medicine, University of Oslo, Section Vinderen, Oslo, Norway.

Abnormalities in amygdala volume are well-established in schizophrenia and commonly reported in bipolar disorders. However, the specificity of volumetric differences in individual amygdala nuclei is largely unknown. Patients with schizophrenia disorders (SCZ, N = 452, mean age 30.7 ± 9.2 [SD] years, females 44.4%), bipolar disorders (BP, N = 316, 33.7 ± 11.4, 58.5%), and healthy controls (N = 753, 34.1 ± 9.1, 40.9%) underwent T1-weighted magnetic resonance imaging. Total amygdala, nuclei, and intracranial volume (ICV) were estimated with Freesurfer (v6.0.0). Analysis of covariance and multiple linear regression models, adjusting for age, age2, ICV, and sex, were fitted to examine diagnostic group and subgroup differences in volume, respectively. Bilateral total amygdala and all nuclei volumes, except the medial and central nuclei, were significantly smaller in patients relative to controls. The largest effect sizes were found for the basal nucleus, accessory basal nucleus, and cortico-amygdaloid transition area (partial η2 > 0.02). The diagnostic subgroup analysis showed that reductions in amygdala nuclei volume were most widespread in schizophrenia, with the lateral, cortical, paralaminar, and central nuclei being solely reduced in this disorder. The right accessory basal nucleus was marginally smaller in SCZ relative to BP (t = 2.32, P = .05). Our study is the first to demonstrate distinct patterns of amygdala nuclei volume reductions in a well-powered sample of patients with schizophrenia and bipolar disorders. Volume differences in the basolateral complex (lateral, basal, and accessory basal nuclei), an integral part of the threat processing circuitry, were most prominent in schizophrenia.
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http://dx.doi.org/10.1093/schbul/sbaa192DOI Listing
January 2021

Intracranial and subcortical volumes in adolescents with early-onset psychosis: A multisite mega-analysis from the ENIGMA consortium.

Hum Brain Mapp 2020 Oct 5. Epub 2020 Oct 5.

Hurvitz Brain Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada.

Early-onset psychosis disorders are serious mental disorders arising before the age of 18 years. Here, we investigate the largest neuroimaging dataset, to date, of patients with early-onset psychosis and healthy controls for differences in intracranial and subcortical brain volumes. The sample included 263 patients with early-onset psychosis (mean age: 16.4 ± 1.4 years, mean illness duration: 1.5 ± 1.4 years, 39.2% female) and 359 healthy controls (mean age: 15.9 ± 1.7 years, 45.4% female) with magnetic resonance imaging data, pooled from 11 clinical cohorts. Patients were diagnosed with early-onset schizophrenia (n = 183), affective psychosis (n = 39), or other psychotic disorders (n = 41). We used linear mixed-effects models to investigate differences in intracranial and subcortical volumes across the patient sample, diagnostic subgroup and antipsychotic medication, relative to controls. We observed significantly lower intracranial (Cohen's d = -0.39) and hippocampal (d = -0.25) volumes, and higher caudate (d = 0.25) and pallidum (d = 0.24) volumes in patients relative to controls. Intracranial volume was lower in both early-onset schizophrenia (d = -0.34) and affective psychosis (d = -0.42), and early-onset schizophrenia showed lower hippocampal (d = -0.24) and higher pallidum (d = 0.29) volumes. Patients who were currently treated with antipsychotic medication (n = 193) had significantly lower intracranial volume (d = -0.42). The findings demonstrate a similar pattern of brain alterations in early-onset psychosis as previously reported in adult psychosis, but with notably low intracranial volume. The low intracranial volume suggests disrupted neurodevelopment in adolescent early-onset psychosis.
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http://dx.doi.org/10.1002/hbm.25212DOI Listing
October 2020

Influence of ovarian hormones on value-based decision-making systems: Contribution to sexual dimorphisms in mental disorders.

Front Neuroendocrinol 2021 01 26;60:100873. Epub 2020 Sep 26.

Department of Psychiatry and Psychotherapy, University of Tuebingen, Tübingen, Germany; International Max Planck Research School for Cognitive and Systems Neuroscience, University of Tübingen, Tuebingen, Germany; TübingenNeuroCampus, University of Tübingen, Tübingen, Germany; LEAD Research School and Graduate Network, University of Tübingen, Tübingen, Germany. Electronic address:

Women and men exhibit differences in behavior when making value-based decisions. Various hypotheses have been proposed to explain these findings, stressing differences in functional lateralization of the brain, functional activation, neurotransmitter involvement and more recently, sex hormones. While a significant interaction of neurotransmitter systems and sex hormones has been shown for both sexes, decision-making in women might be particularly affected by variations of ovarian hormones. In this review we have gathered information from animal and human studies on how ovarian hormones affect decision-making processes in females by interacting with neurotransmitter systems at functionally relevant brain locations and thus modify the computation of decision aspects. We also review previous findings on impaired decision-making in animals and clinical populations with substance use disorder and depression, emphasizing how little we know about the role of ovarian hormones in aberrant decision-making.
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http://dx.doi.org/10.1016/j.yfrne.2020.100873DOI Listing
January 2021

Women's brain aging: Effects of sex-hormone exposure, pregnancies, and genetic risk for Alzheimer's disease.

Hum Brain Mapp 2020 12 28;41(18):5141-5150. Epub 2020 Aug 28.

Department of Psychology, University of Oslo, Oslo, Norway.

Sex hormones such as estrogen fluctuate across the female lifespan, with high levels during reproductive years and natural decline during the transition to menopause. Women's exposure to estrogen may influence their heightened risk of Alzheimer's disease (AD) relative to men, but little is known about how it affects normal brain aging. Recent findings from the UK Biobank demonstrate less apparent brain aging in women with a history of multiple childbirths, highlighting a potential link between sex-hormone exposure and brain aging. We investigated endogenous and exogenous sex-hormone exposure, genetic risk for AD, and neuroimaging-derived biomarkers for brain aging in 16,854 middle to older-aged women. The results showed that as opposed to parity, higher cumulative sex-hormone exposure was associated with more evident brain aging, indicating that i) high levels of cumulative exposure to sex-hormones may have adverse effects on the brain, and ii) beneficial effects of pregnancies on the female brain are not solely attributable to modulations in sex-hormone exposure. In addition, for women using hormonal replacement therapy (HRT), starting treatment earlier was associated with less evident brain aging, but only in women with a genetic risk for AD. Genetic factors may thus contribute to how timing of HRT initiation influences women's brain aging trajectories.
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http://dx.doi.org/10.1002/hbm.25180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670641PMC
December 2020

Bradykinin 1 Receptor Antagonist BI1026706 Does Not Reduce Central Retinal Thickness in Center-Involved Diabetic Macular Edema.

Transl Vis Sci Technol 2020 03 30;9(4):25. Epub 2020 Mar 30.

Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany.

Purpose: The bradykinin 1 receptor may be important in inflammatory retinal vascular leakage in diabetic macular edema. BI 1026706 is an antagonist of bradykinin 1 receptor that has demonstrated efficacy in preclinical studies. Boehringer Ingelheim trial 1320.22 (NCT02732951) was a randomized, double-blind, placebo-controlled study. The pharmacodynamics, safety, and tolerability of oral BI 1026706 for 12 weeks were evaluated in patients with type 1 or type 2 diabetes mellitus and mild visual impairment owing to center-involved diabetic macular edema.

Methods: Patients ( = 105) were randomized to receive either oral BI 1026706 100 mg twice daily (morning and evening) or placebo for 12 weeks. The primary end point of the study was week 12 change from baseline in central subfield foveal thickness (CSFT) by spectral domain optical coherence tomography. Additional end points included absolute CSFT values, safety, and pharmacokinetics.

Results: After 12 weeks of treatment, there was no meaningful change from baseline in the adjusted mean CSFT in either treatment group (BI 1026706, 10.3 µm; placebo, -6.2 µm; adjusted mean treatment difference, 16.5 µm [95% confidence interval, -16.2 to 49.1]). There were also no differences in best-corrected visual acuity outcomes between treatment groups. Most reported adverse events were of mild or moderate intensity, and were balanced between treatment groups.

Conclusions: BI 1026706 was not superior to placebo in CSFT week-12 change from baseline. Therefore, BI 1026706 does not reduce CSFT, a morphologic sign of diabetic macular edema.

Translational Relevance: Kinin-kallikrein inhibition effects may not be apparent over 12 weeks for bradykinin 1 receptor inhibition alone.
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http://dx.doi.org/10.1167/tvst.9.4.25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396196PMC
March 2020

Asphyxia at birth affects brain structure in patients on the schizophrenia-bipolar disorder spectrum and healthy participants.

Psychol Med 2020 Aug 10:1-10. Epub 2020 Aug 10.

Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.

Background: Uncertainty exists about what causes brain structure alterations associated with schizophrenia (SZ) and bipolar disorder (BD). Whether a history of asphyxia-related obstetric complication (ASP) - a common but harmful condition for neural tissue - contributes to variations in adult brain structure is unclear. We investigated ASP and its relationship to intracranial (ICV), global brain volumes and regional cortical and subcortical structures.

Methods: A total of 311 patients on the SZ - BD spectrum and 218 healthy control (HC) participants underwent structural magnetic resonance imaging. They were evaluated for ASP using prospective information obtained from the Medical Birth Registry of Norway.

Results: In all groups, ASP was related to smaller ICV, total brain, white and gray matter volumes and total surface area, but not to cortical thickness. Smaller cortical surface areas were found across frontal, parietal, occipital, temporal and insular regions. Smaller hippocampal, amygdala, thalamus, caudate and putamen volumes were reported for all ASP subgroups. ASP effects did not survive ICV correction, except in the caudate, which remained significantly smaller in both patient ASP subgroups, but not in the HC.

Conclusions: Since ASP was associated with smaller brain volumes in all groups, the genetic risk of developing a severe mental illness, alone, cannot easily explain the smaller ICV. Only the smaller caudate volumes of ASP patients specifically suggest that injury from ASP can be related to disease development. Our findings give support for the ICV as a marker of aberrant neurodevelopment and ASP in the etiology of brain development in BD and SZ.
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http://dx.doi.org/10.1017/S0033291720002779DOI Listing
August 2020

The maternal brain: Region-specific patterns of brain aging are traceable decades after childbirth.

Hum Brain Mapp 2020 11 7;41(16):4718-4729. Epub 2020 Aug 7.

Department of Psychology, University of Oslo, Oslo, Norway.

Pregnancy involves maternal brain adaptations, but little is known about how parity influences women's brain aging trajectories later in life. In this study, we replicated previous findings showing less apparent brain aging in women with a history of childbirths, and identified regional brain aging patterns linked to parity in 19,787 middle- and older-aged women. Using novel applications of brain-age prediction methods, we found that a higher number of previous childbirths were linked to less apparent brain aging in striatal and limbic regions. The strongest effect was found in the accumbens-a key region in the mesolimbic reward system, which plays an important role in maternal behavior. While only prospective longitudinal studies would be conclusive, our findings indicate that subcortical brain modulations during pregnancy and postpartum may be traceable decades after childbirth.
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http://dx.doi.org/10.1002/hbm.25152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555081PMC
November 2020

Clinical outcomes following polymer-free sirolimus-eluting stent implantations in unselected patients: A descriptive subgroup analysis in patients with renal impairment.

Medicine (Baltimore) 2020 Jul;99(29):e21244

Department of Medical Scientific Affairs, Avitum, B.Braun Melsungen AG, Melsungen, Germany.

Patients with chronic kidney disease (CKD are frequently excluded from coronary artery disease trials. The aim of this assessment was to study the clinical outcomes of polymer-free sirolimus-eluting stent implantations in patients with impaired renal function.Large-scale, international, single-armed, multicenter, 'all comers' observational studies (ClinicalTrials.gov Identifier: NCT02629575 and NCT02905214) were used for this post-hoc subgroup analysis to compare the clinical outcomes in patients with normal renal function (NRF) to those with renal insufficiency (CKD, dialysis dependence). The accumulated target lesion revascularization rate was the primary endpoint at 9 to 12 months whereas the accumulated major adverse cardiac event, stent thrombosis (ST) and procedural success rates were part of the secondary endpoints.There were 6791 patients with NRF, whereas 369 patients had CKD and 83 patients were dialysis dependent. The target lesion revascularization rate at 9 to 12 months was significantly higher in dialysis patients (2.1% vs 3.3% vs 6.7%, P = .011). The accumulated major adverse cardiac events rates in the dialysis and in the CKD group were significantly higher as compared to patients with NRF (13.3% vs 4.0%, P < .001; 6.5% vs 4.0%, P = .024). Finally, ST rates (NRF: 0.7%, CKD: 0.6%, dialysis: 1.3%) were not statistically different between subgroups (P = .768). All-cause cumulative mortality rates were 3.3% (CKD) and 4.0% (dialysis) respectively.Percutaneous coronary interventions with polymer-free, ultra-thin strut sirolimus-eluting stents have comparable revascularization rates in CKD and dialysis dependent patients as compared to percutaneous coronary interventions with other 2nd generation drug-eluting stents. ST and all-cause mortality rates were low as compared to available literature references.
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http://dx.doi.org/10.1097/MD.0000000000021244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373567PMC
July 2020

Trajectories of brain volume change over 13 years in chronic schizophrenia.

Schizophr Res 2020 Aug 2;222:525-527. Epub 2020 Jun 2.

Norwegian Centre for Mental Disorders Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway; Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet and Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.

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http://dx.doi.org/10.1016/j.schres.2020.05.014DOI Listing
August 2020

Towards an understanding of women's brain aging: the immunology of pregnancy and menopause.

Front Neuroendocrinol 2020 07 3;58:100850. Epub 2020 Jun 3.

Department of Psychology, University of Oslo, Oslo, Norway; Norwegian Centre for Mental Disorders Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK. Electronic address:

Women are at significantly greater risk of developing Alzheimer's disease and show higher prevalence of autoimmune conditions relative to men. Women's brain health is historically understudied, and little is therefore known about the mechanisms underlying epidemiological sex differences in neurodegenerative diseases, and how female-specific factors may influence women's brain health across the lifespan. In this review, we summarize recent studies on the immunology of pregnancy and menopause, emphasizing that these major immunoendocrine transition phases may play a critical part in women's brain aging trajectories.
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http://dx.doi.org/10.1016/j.yfrne.2020.100850DOI Listing
July 2020

Exploring white matter microstructure and the impact of antipsychotics in adolescent-onset psychosis.

PLoS One 2020 29;15(5):e0233684. Epub 2020 May 29.

NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

White matter abnormalities are well-established in adult patients with psychosis. Less is known about abnormalities in the rarely occurring adolescent early onset psychosis (EOP). In particular, whether antipsychotic medication might impact white matter microstructure is not known. Using 3T diffusion weighted imaging, we investigated differences in white matter microstructure and the impact of antipsychotic medication status in medicated (n = 11) and unmedicated (n = 11) EOP patients relative to healthy controls (n = 33), aged between 12-18 years. Using Tract-based Spatial Statistics, we calculate case-control differences in scalar diffusion measures, i.e. fractional anisotropy (FA), axial diffusion (AD) and radial diffusion (RD), and investigated their association with antipsychotic medication in patients. We found significantly lower FA in the left genu of the corpus callosum, the left anterior corona radiata (ACR) and the right superior longitudinal fasciculus in EOP patients relative to healthy controls. AD values were also lower in the left ACR, largely overlapping with the FA findings. Mean FA in the left ACR was significantly associated with antipsychotic medication status (Cohen's d = 1.37, 95% CI [0.01, 2.68], p = 0.008), showing higher FA values in medicated compared to unmedicated EOP patients. The present study is the first to link antipsychotic medication status to altered regional FA in the left ACR, a region hypothesized to contribute to the etiology of psychosis. Replications are warranted to draw firm conclusions about putatively enhancing effects of antipsychotic medication on white matter microstructure in adolescent-onset psychosis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0233684PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7259775PMC
August 2020

Benefits and harms of high-dose haemodiafiltration versus high-flux haemodialysis: the comparison of high-dose haemodiafiltration with high-flux haemodialysis (CONVINCE) trial protocol.

BMJ Open 2020 02 5;10(2):e033228. Epub 2020 Feb 5.

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

Introduction: End-stage kidney disease (ESKD) is a major public health problem affecting more than 2 million people worldwide. It is one of the most severe chronic non-communicable diseases. Haemodialysis (HD) is the most common therapeutic option but is also associated with a risk of cardiovascular events, hospitalisation and suboptimal quality of life. Over the past decades, haemodiafiltration (HDF) has become available. Although high-dose HDF has shown some promising survival advantage compared to conventional HD, the evidence remains controversial. A Cochrane systematic review found, in low-quality trials, with various convective forms of dialysis, a reduction in cardiovascular, but not all-cause mortality and the effects on non-fatal cardiovascular events and hospitalisation were uncertain. In contrast, an individual patient data analysis suggested that high-dose HDF reduced both all-cause and cardiovascular mortality compared to HD. In view of these discrepant results, a definitive trial is required to determine whether high-dose HDF is preferable to high-flux HD. The comparison of high-dose HDF with high-flux HD (CONVINCE) study will assess the benefits and harms of high-dose HDF versus a conventional high-flux HD in adults with ESKD.

Methods And Analysis: This international, prospective, open label, randomised controlled trial aims to recruit 1800 ESKD adults treated with HD in nine European countries. Patients will be randomised 1:1 to high-dose HDF versus continuation of conventional high-flux HD. The primary outcome will be all-cause mortality at 3 years' follow-up. Secondary outcomes will include cause-specific mortality, cardiovascular events, all-cause and infection-related hospitalisations, patient-reported outcomes (eg, health-related quality of life) and cost-effectiveness.

Ethics And Dissemination: The CONVINCE study will address the question of benefits and harms of high-dose HDF compared to high-flux HD for kidney replacement therapy in patients with ESKD with a focus on survival, patient perspectives and cost-effectiveness.

Trial Registration Number: Netherlands National Trial Register (NTR 7138).
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http://dx.doi.org/10.1136/bmjopen-2019-033228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044930PMC
February 2020

Obstetric complications and intelligence in patients on the schizophrenia-bipolar spectrum and healthy participants.

Psychol Med 2020 08 28;50(11):1914-1922. Epub 2019 Aug 28.

Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.

Background: Whether severe obstetric complications (OCs), which harm neural function in offspring, contribute to impaired cognition found in psychiatric disorders is currently unknown. Here, we sought to evaluate how a history of severe OCs is associated with cognitive functioning, indicated by Intelligence Quotient (IQ).

Methods: We evaluated the associations of a history of OCs and IQ in 622 healthy controls (HC) and 870 patients on the schizophrenia (SCZ) - bipolar disorder (BIP) spectrum from the ongoing Thematically Organized Psychosis study cohort, Oslo, Norway. Participants underwent assessments using the NART (premorbid IQ) and the WASI (current IQ). Information about OCs was obtained from the Medical Birth Registry of Norway. Multiple linear regression models were used for analysis.

Results: Severe OCs were equally common across groups. SCZ patients with OCs had lower performances on both premorbid and current IQ measures, compared to those without OCs. However, having experienced more than one co-occurring severe OC was associated with lower current IQ in all groups.

Conclusions: Severe OCs were associated with lower IQ in the SCZ group and in the BIP and HC groups, but only if they had experienced more than one severe OC. Low IQ might be a neurodevelopmental marker for SCZ; wherein, severe OCs influence cognitive abilities and increase the risk of developing SCZ. Considering OCs as a variable of neurodevelopmental risk for severe mental illness may promote the development of neuroprotective interventions, improve outcome in vulnerable newborns and advance our ability to make clinical prognoses.
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http://dx.doi.org/10.1017/S0033291719002046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477368PMC
August 2020

Glomerular disease patients have higher odds not to reach quality targets in chronic dialysis compared with CAKUT patients: analyses from a nationwide German paediatric dialysis registry.

Pediatr Nephrol 2019 07 6;34(7):1229-1236. Epub 2019 Mar 6.

Pediatric Nephrology, Department of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Straße 62, 50937, Cologne, Germany.

Background: Paediatric dialysis patients still suffer from high morbidity rates. To improve this, quality assurance programs like the German QiNKid (Quality in Nephrology for Children)-Registry have been developed. In our study, the significance of underlying renal disease on a range of clinical and laboratory parameters impacting morbidity and mortality was analysed. Our aim was to evaluate whether or not disease-specific dialysis strategies should be considered in planning dialysis for a patient.

Methods: Inclusion criteria were defined as follows: (1) CAKUT (congenital anomalies of the kidney and urinary tract) or glomerular disease patient, (2) < 18 years of age, (3) haemodialysis or peritoneal dialysis patient. Only measurements obtained from day 90 to 365 after the date of the first dialysis in the registry were analysed. Laboratory (serum albumin, haemoglobin, ferritin, calcium, phosphate, parathyroid hormone) and clinical parameters (height, blood pressure) were analysed using mixed effects models accounting for the correlation of repeated measures in individual patients.

Results: The study cohort comprised n = 167 CAKUT and n = 55 glomerular disease patients. Glomerular disease patients had significantly higher odds of hypoalbuminemia (OR 13.90, 95% CI 1.35-159.99; p = 0.0274), anaemia (OR 3.31, 95% CI 1.22-9.13; p = 0.0197), hyperphosphatemia (OR 9.69, 95% CI 2.65-37.26; p = 0.0006) and diastolic hypertension (OR 3.38, 95% CI 1.20-9.79; p = 0.0212).

Conclusions: Glomerular disease patients might require more intensive dialysis regimens. The evaluation of hydration status should be given more attention, since conditions differing between the cohorts can be linked to overhydration. The QiNKid-Registry allows monitoring of the quality of paediatric dialysis in a nationwide cohort.
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http://dx.doi.org/10.1007/s00467-019-04218-6DOI Listing
July 2019

Effectiveness of a New Single-Needle Single-Pump Dialysis System with Simultaneous Monitoring of Dialysis Dose.

Artif Organs 2018 Aug 16;42(8):814-823. Epub 2018 Apr 16.

Department of Medical Scientific Affairs, B. Braun Avitum AG, Melsungen, Germany.

To date, single-needle (SN) hemodialysis (HD) requires a dialysis machine equipped with two blood pumps-one controlling arterial blood flow (Qb) and one controlling venous Qb. B. Braun has developed an innovative single-pump SN HD system. Therefore, usability is improved by reducing complexity. The aim of this study was to compare dialysis parameters of the new single-pump SN HD system with a double-pump SN HD system available on the market (Fresenius Medical Care [FMC] 5008). In this two-armed crossover study, patients were randomized into two groups (B. Braun - FMC/FMC - B. Braun). Study period was 2 weeks (6 HD sessions) for each SN HD system. Both B. Braun and FMC dialysis machines were operated in the single-needle auto mode. With the FMC dialysis machines, Qb was optimized manually, whereas for B. Braun machines it was optimized automatically using the auto-mode functionality. A phase volume of 25 mL, treatment time, needle type and size, and dialyzer type and size were kept constant per patient throughout the study. Due to technical prerequisites in the SN mode, online dialysis adequacy (Kt/V: K - dialyzer clearance of urea; t - dialysis time; V - volume of distribution of urea) monitoring could only be performed in the B. Braun group. Twelve HD patients (5 male/7 female, mean age 75.5 ± 8.8 years, mean time on dialysis 4.97 ± 3.86 years, 3× weekly HD) were enrolled. Total number of treatments performed: n = 132 (65 B. Braun, 67 FMC) and the mean online Kt/V value in the B. Braun group was 1.26 ± 0.29 (n = 63). Mean dialysis time per session: B. Braun 253.4 ± 19.9 min, FMC 251.6 ± 18.8 min. Mean phase volume: B. Braun 25.1 ± 0.2 mL, FMC 25.4 ± 3.1 mL. Mean cumulated blood volume (CBV): B. Braun 55.0 ± 5.5 L, FMC 40.5 ± 5.9 L (P < 0.0001). Mean Qb: B. Braun 217.8 ± 12.9 mL/min, FMC 178.6 ± 14.9 mL/min (effective Qb) (P < 0.0001), which corresponds to a difference of 39.3 mL/min (22.0%). Higher Qb has an influence on the CBV. To evaluate this effect, CBV was corrected for the difference in Qb by calculating the CBV/Qb rate. The mean CBV/Qb rate was 252.2 ± 19.4 min (B. Braun) and 226.8 ± 27.6 min (FMC) (P < 0.0001) per session. This represents a highly significant difference of 11.4%. To support the in vivo data the dead time for opening/closure of the clamps of the FMC 5008 was measured, resulting in 364 milliseconds. Over a 240 min dialysis session, with a blood flow rate of 250 mL/min and a phase volume of 25 mL, it was estimated at about 14.56 min (6.1% of the session). Similarly, it was estimated that the dead time of the pumps of the FMC 5008 during 240 min dialysis session was 4.7 min (1.9% of the session). In case single needle therapy is the only practical option for a patient, the advantages of the new single-pump single needle system-namely the proven higher cumulative blood volume, the alarm-free auto-regulation of the blood flow and the easier handling for the nursing staff-ensure higher treatment efficiency than conventional double-pump single needle systems.
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http://dx.doi.org/10.1111/aor.13149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6174946PMC
August 2018

Dialysis Access as an Area of Improvement in Elderly Incident Hemodialysis Patients: Results from a Cohort Study from the International Monitoring Dialysis Outcomes Initiative.

Am J Nephrol 2017 17;45(6):486-496. Epub 2017 May 17.

Renal Research Institute, New York, NY, USA.

Background: Commencing hemodialysis (HD) using a catheter is associated with a higher risk of adverse outcomes, and early conversion from central-venous catheter (CVC) to arteriovenous fistula/graft (non-CVC) improves outcomes. We investigated CVC prevalence and conversion, and their effects on outcomes during the first year of HD in a multinational cohort of elderly patients.

Methods: Patients ≥70 years from the MONDO Initiative who commenced HD between 2000 and 2010 in Asia-Pacific, Europe, North-, and South-America and survived at least 6 months were included in this investigation. We stratified by age (70-79 years [younger] vs. ≥80 years [older]) and compared access types (at first and last available date) and their changes. We studied the association between access at initiation and conversion, respectively, and all-cause mortality using Kaplan-Meier curve and Cox regression, and predicted the absence of conversion from catheter to non-CVC using adjusted logistic regression.

Results: In 14,966 elderly, incident HD patients, survival was significantly worse when using a CVC at all times. In Europe, the conversion frequency from CVC to non-CVC was higher in the younger fraction. Conversion from non-CVC to CVC was associated with worsened outcomes only in the older fraction.

Conclusion: These results corroborate the need for early HD preparation in the elderly HD population. Treatment of elderly patients who commence HD with a CVC should be planned considering aspects of individual clinical risk assessment. Differences in treatment practices in predialysis care specific to the elderly as a population may influence access care and conversion rate.
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http://dx.doi.org/10.1159/000476003DOI Listing
April 2018

In-vivo Dynamics of the Human Hippocampus across the Menstrual Cycle.

Sci Rep 2016 10 7;6:32833. Epub 2016 Oct 7.

Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.

Sex hormones fluctuate during the menstrual cycle. Evidence from animal studies suggests similar subtle fluctuations in hippocampal structure, predominantly linked to estrogen. Hippocampal abnormalities have been observed in several neuropsychiatric pathologies with prominent sexual dimorphism. Yet, the potential impact of subtle sex-hormonal fluctuations on human hippocampal structure in health is unclear. We tested the feasibility of longitudinal neuroimaging in conjunction with rigorous menstrual cycle monitoring to evaluate potential changes in hippocampal microstructure associated with physiological sex-hormonal changes. Thirty longitudinal diffusion weighted imaging scans of a single healthy female subject were acquired across two full menstrual cycles. We calculated hippocampal fractional anisotropy (FA), a measure sensitive to changes in microstructural integrity, and investigated potential correlations with estrogen. We observed a significant positive correlation between FA values and estrogen in the hippocampus bilaterally, revealing a peak in FA closely paralleling ovulation. This exploratory, single-subject study demonstrates the feasibility of a longitudinal DWI scanning protocol across the menstrual cycle and is the first to link subtle endogenous hormonal fluctuations to changes in FA in vivo. In light of recent attempts to neurally phenotype single humans, our findings highlight menstrual cycle monitoring in parallel with highly sampled individual neuroimaging data to address fundamental questions about the dynamics of plasticity in the adult brain.
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http://dx.doi.org/10.1038/srep32833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5054394PMC
October 2016

Seasonal variations in mortality and clinical indicators in international hemodialysis populations from the MONDO registry.

BMC Nephrol 2015 Aug 14;16:139. Epub 2015 Aug 14.

Maastricht University Medical Center, Maastricht, Netherlands.

Background: Seasonal mortality differences have been reported in US hemodialysis (HD) patients. Here we examine the effect of seasons on mortality, clinical and laboratory parameters on a global scale.

Methods: Databases from the international Monitoring Dialysis Outcomes (MONDO) consortium were queried to identify patients who received in-center HD for at least 1 year. Clinics were stratified by hemisphere and climate zone (tropical or temperate). We recorded mortality and computed averages of pre-dialysis systolic blood pressure (pre-SBP), interdialytic weight gain (IDWG), serum albumin, and log C-reactive protein (CRP). We explored seasonal effects using cosinor analysis and adjusted linear mixed models globally, and after stratification.

Results: Data from 87,399 patients were included (northern temperate: 63,671; northern tropical: 7,159; southern temperate: 13,917; southern tropical: 2,652 patients). Globally, mortality was highest in winter. Following stratification, mortality was significantly lower in spring and summer compared to winter in temperate, but not in tropical zones. Globally, pre-SBP and IDWG were lower in summer and spring as compared to winter, although less pronounced in tropical zones. Except for southern temperate zone, serum albumin levels were higher in winter. CRP levels were highest in winter.

Conclusion: Significant global seasonal variations in mortality, pre-SBP, IDWG, albumin and CRP were observed. Seasonal variations in mortality were most pronounced in temperate climate zones.
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http://dx.doi.org/10.1186/s12882-015-0129-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4542126PMC
August 2015

Relationship of Neutrophil-to-Lymphocyte Ratio and Serum Albumin Levels with C-Reactive Protein in Hemodialysis Patients: Results from 2 International Cohort Studies.

Nephron 2015 15;130(4):263-70. Epub 2015 Jul 15.

Renal Research Institute, Mount Sinai Hospital New York, New York, N.Y., USA.

Background/aim: The neutrophil-to-lymphocyte ratio (NLR), defined as the neutrophil count divided by lymphocyte count, is an inexpensive and readily available parameter, which may serve as a surrogate for inflammation markers, such as C-reactive protein (CRP). The aim of this study was to determine the utility of NLR in the prediction of elevated CRP levels in hemodialysis (HD) patients.

Methods: We analyzed 43,272 HD patients from 2 distinct cohorts within the Monitoring Dialysis Outcomes research collaboration in whom contemporaneous measurements of neutrophil and lymphocyte counts, serum albumin and CRP levels were available. Logistic regression was used to determine the relationship of trichotomized NLR (<2.5, 2.5-5 and >5.0) and albumin levels (<3.1, 3.1-4.0 and >4.0 g/dl) with elevated CRP levels (>10.0, >20.0 and >30.0 mg/l). Congruence of the prediction models was examined by comparing the regression parameters and by cross-validating each regression equation within the other cohort.

Results: We found that NLR >5.0 vs. <2.5 (cohort 1: OR 2.3; p < 0.0001 and cohort 2: OR 2.0; p < 0.0001) was associated with CRP levels >10.0 mg/l. Stepwise increase in odds ratio for CRP >10.0 mg/l was observed with the combination of high NLR and low albumin levels (NLR >5.0 and albumin <3.1) (cohort 1: OR 7.6; p < 0.0001 and cohort 2: OR 11.9; p < 0.0001). Cross-validation of the 2 regression models revealed a predictive accuracy of 0.68 and 0.69 in the respective cohorts.

Conclusion: This study suggests that NLR could serve as a potential surrogate marker for CRP. Our results may add to diagnostic abilities in settings where CRP is not measured routinely in HD patients. NLR is easy to integrate into daily practice and may be used as a marker of systemic inflammation.
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http://dx.doi.org/10.1159/000437005DOI Listing
May 2016

Preferences of patients undergoing hemodialysis - results from a questionnaire-based study with 4,518 patients.

Patient Prefer Adherence 2015 26;9:847-55. Epub 2015 Jun 26.

Department of Non-Drug Interventions, Institute for Quality and Efficiency in Health Care, Cologne, Germany.

Background: Chronic kidney disease is an increasing health problem worldwide and in its final stage (stage V) can only be treated by renal replacement therapy, mostly hemodialysis. Hemodialysis has a major influence on the everyday life of patients and many patients report dissatisfaction with treatment. Little is known about which aspects of treatment are considered important by hemodialysis patients. The objective of this study was to rate the relative importance of different outcomes for hemodialysis patients and to analyze whether the relative importance differed among subgroups of patients.

Patients And Methods: Within the framework of a yearly questionnaire which is distributed among patients receiving hemodialysis by the largest hemodialysis provider in Germany, we assessed the relative importance of 23 outcomes as rated on a discrete visual analog scale. Descriptive statistics were used to rank the outcomes. Subgroup analyses were performed using Mann-Whitney U or Kruskal-Wallis tests.

Results: Questionnaires of 4,518 hemodialysis patients were included in the analysis. The three most important outcomes were safety of treatment, health-related quality of life, and satisfaction with care. Further important outcomes were hospital stays, accompanying symptoms, hemodialysis duration, and the improvement or preservation of a good emotional state. Age, profession, and education had the strongest influence on relevant differences of preferences for outcomes; no relevant influence of sex or comorbidity was observed.

Conclusion: Outcomes concerning the delivery or provision of care and aspects influencing quality of life are rated by patients to be at least as important as clinical outcomes. Many of the outcomes judged to be important by the patients are not regularly considered in research, evaluation studies, or quality programs.
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http://dx.doi.org/10.2147/PPA.S79559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4492657PMC
July 2015

Progesterone mediates brain functional connectivity changes during the menstrual cycle-a pilot resting state MRI study.

Front Neurosci 2015 23;9:44. Epub 2015 Feb 23.

Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences Leipzig, Germany ; Clinic of Cognitive Neurology, University of Leipzig Leipzig, Germany.

The growing interest in intrinsic brain organization has sparked various innovative approaches to generating comprehensive connectivity-based maps of the human brain. Prior reports point to a sexual dimorphism of the structural and functional human connectome. However, it is uncertain whether subtle changes in sex hormones, as occur during the monthly menstrual cycle, substantially impact the functional architecture of the female brain. Here, we performed eigenvector centrality (EC) mapping in 32 longitudinal resting state fMRI scans of a single healthy subject without oral contraceptive use, across four menstrual cycles, and assessed estrogen and progesterone levels. To investigate associations between cycle-dependent hormones and brain connectivity, we performed correlation analyses between the EC maps and the respective hormone levels. On the whole brain level, we found a significant positive correlation between progesterone and EC in the bilateral dorsolateral prefrontal cortex (DLPFC) and bilateral sensorimotor cortex. In a secondary region-of-interest analysis, we detected a progesterone-modulated increase in functional connectivity of both bilateral DLPFC and bilateral sensorimotor cortex with the hippocampus. Our results suggest that the menstrual cycle substantially impacts intrinsic functional connectivity, particularly in brain areas associated with contextual memory-regulation, such as the hippocampus. These findings are the first to link the subtle hormonal fluctuations that occur during the menstrual cycle, to significant changes in regional functional connectivity in the hippocampus in a longitudinal design, given the limitation of data acquisition in a single subject. Our study demonstrates the feasibility of such a longitudinal Resting-state functional Magnetic Resonance Imaging (rs-fMRI) design and illustrates a means of creating a personalized map of the human brain by integrating potential mediators of brain states, such as menstrual cycle phase.
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http://dx.doi.org/10.3389/fnins.2015.00044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4337344PMC
March 2015

Sex hormones affect neurotransmitters and shape the adult female brain during hormonal transition periods.

Front Neurosci 2015 20;9:37. Epub 2015 Feb 20.

Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences Leipzig, Germany ; Clinic of Cognitive Neurology, University of Leipzig Leipzig, Germany.

Sex hormones have been implicated in neurite outgrowth, synaptogenesis, dendritic branching, myelination and other important mechanisms of neural plasticity. Here we review the evidence from animal experiments and human studies reporting interactions between sex hormones and the dominant neurotransmitters, such as serotonin, dopamine, GABA and glutamate. We provide an overview of accumulating data during physiological and pathological conditions and discuss currently conceptualized theories on how sex hormones potentially trigger neuroplasticity changes through these four neurochemical systems. Many brain regions have been demonstrated to express high densities for estrogen- and progesterone receptors, such as the amygdala, the hypothalamus, and the hippocampus. As the hippocampus is of particular relevance in the context of mediating structural plasticity in the adult brain, we put particular emphasis on what evidence could be gathered thus far that links differences in behavior, neurochemical patterns and hippocampal structure to a changing hormonal environment. Finally, we discuss how physiologically occurring hormonal transition periods in humans can be used to model how changes in sex hormones influence functional connectivity, neurotransmission and brain structure in vivo.
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http://dx.doi.org/10.3389/fnins.2015.00037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4335177PMC
March 2015

Serotonergic modulation of intrinsic functional connectivity.

Curr Biol 2014 Oct 18;24(19):2314-8. Epub 2014 Sep 18.

Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany; Clinic of Cognitive Neurology, University Hospital Leipzig, 04103 Leipzig, Germany; Berlin School of Mind and Brain, Mind and Brain Institute, Charité and Humboldt University, 10099 Berlin, Germany. Electronic address:

Serotonin functions as an essential neuromodulator that serves a multitude of roles, most prominently balancing mood. Serotonergic challenge has been observed to reduce intrinsic functional connectivity in brain regions implicated in mood regulation. However, the full scope of serotonergic action on functional connectivity in the human brain has not been explored. Here, we show evidence that a single dose of a serotonin reuptake inhibitor dramatically alters functional connectivity throughout the whole brain in healthy subjects (n = 22). Our network-centrality analysis reveals a widespread decrease in connectivity in most cortical and subcortical areas. In the cerebellum and thalamus, however, we find localized increases. These rapid and brain-encompassing connectivity changes linked to acute serotonin transporter blockade suggest a key role for the serotonin transporter in the modulation of the functional macroscale connectome.
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http://dx.doi.org/10.1016/j.cub.2014.08.024DOI Listing
October 2014

Knowing what we do and doing what we should: quality assurance in hemodialysis.

Nephron Clin Pract 2014 15;126(3):135-43. Epub 2014 Apr 15.

Medical and Safety Office, Gambro AB, Lund, Sweden.

An international group of around 50 nephrologists and scientists, including representatives from large dialysis provider organisations, formulated recommendations on how to develop and implement quality assurance measures to improve individual hemodialysis patient care, population health and cost effectiveness. Discussed were methods thought to be of highest priority, those clinical indicators which might be most related to meaningful patient outcomes, tools to control treatment delivery and the role of facilitating computerized expert systems. Emphasis was given to the use of new technologies such as measurement of online dialysance and ways of assessing fluid status. The current evidence linking achievement of quality criteria with patient outcomes was reviewed. This paper summarizes useful processes and quality measures supporting quality assurance that have been agreed across the expert panel. It also notes areas where more understanding is required.
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http://dx.doi.org/10.1159/000361050DOI Listing
February 2015

Monitoring dialysis outcomes across the world--the MONDO Global Database Consortium.

Blood Purif 2013 20;36(3-4):165-72. Epub 2013 Dec 20.

Cologne University Medical Center, Cologne, Germany.

Background/aims: Dialysis providers frequently collect detailed longitudinal and standardized patient data, providing valuable registries of routine care. However, even large organizations are restricted to certain regions, limiting their ability to separate effects of local practice from the pathophysiology shared by most dialysis patients. To overcome this limitation, the MONDO (MONitoring Dialysis Outcomes) research consortium has created a platform for the joint analysis of data from almost 200,000 dialysis patients worldwide.

Methods: We examined design and operation of MONDO as well as its methodology with respect to patient inclusion, descriptive data and other study parameters.

Results: MONDO partners contribute primary databases of anonymized patient data and collaboratively analyze populations across national and regional boundaries. To that end, datasets from different electronic health record systems are converted into a uniform structure. Patients are enrolled without systematic exclusions into open cohorts representing the diversity of patients. A large number of patient level treatment and outcome data is recorded frequently and can be analyzed with little delay. Detailed variable definitions are used to determine if a parameter can be studied in a subset or all databases.

Conclusion: MONDO has created a large repository of validated dialysis data, expanding the opportunities for outcome studies in dialysis patients. The density of longitudinal information facilitates in particular trend analysis. Limitations include the paucity of uniform definitions and standards regarding descriptive information (e.g. comorbidities), which limits the identification of patient subsets. Through its global outreach, depth, breadth and size, MONDO advances the observational study of dialysis patients and care.
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http://dx.doi.org/10.1159/000356088DOI Listing
October 2014

Interdialytic weight gain, systolic blood pressure, serum albumin, and C-reactive protein levels change in chronic dialysis patients prior to death.

Kidney Int 2013 Jul 20;84(1):149-57. Epub 2013 Mar 20.

Renal Research Institute, New York, New York 10128, USA.

Reports from a United States cohort of chronic hemodialysis patients suggested that weight loss, a decline in pre-dialysis systolic blood pressure, and decreased serum albumin may precede death. However, no comparative studies have been reported in such patients from other countries. Here we analyzed dynamic changes in these parameters in hemodialysis patients and included 3593 individuals from 5 Asian countries; 35,146 from 18 European countries; 8649 from Argentina; and 4742 from the United States. In surviving prevalent patients, these variables appeared to have notably different dynamics than in patients who died. While in all populations the interdialytic weight gain, systolic blood pressure, and serum albumin levels were stable in surviving patients, these indicators declined starting more than a year ahead in those who died with the dynamics similar irrespective of gender and geographic region. In European patients, C-reactive protein levels were available on a routine basis and indicated that levels of this acute-phase protein were low and stable in surviving patients but rose sharply before death. Thus, relevant fundamental biological processes start many months before death in the majority of chronic hemodialysis patients. Longitudinal monitoring of these dynamics may help to identify patients at risk and aid the development of an alert system to initiate timely interventions to improve outcomes.
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http://dx.doi.org/10.1038/ki.2013.73DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3697046PMC
July 2013
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