Publications by authors named "Risch L"

Background And Aims: Dried blood spots (DBS) have been proposed as a cost-effective surveillance method for population-wide screening of SARS-CoV-2 immunity but sensitivity of DBS based on self-collected DBS samples is unknown. To evaluate the success of vaccination strategies, it is necessary to differentiate vaccination from natural infection. Therefore, a test for antibodies against the viral nucleocapsid protein (anti-N) is desirable.

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Purpose: As healthcare workers (HCW) have been disproportionally affected by COVID-19, its post-acute sequelae (PASC) in HCW can impact healthcare systems. We assessed the burden and course of PASC in HCW over a 30-month period.

Methods: In a prospective multicentre HCW cohort in Switzerland, PASC surveys were conducted in 03/2021, 09/2021, 06/2022, 04/2023, and 10/2023.

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Introduction: Muscle fatigue, characterized by diminished force production and contraction sustainability, can impair muscle coordination and increase joint instability. Differing force profiles used in fatiguing tasks, such as prolonged eccentric trunk protocols, might provide insights into individualized strategies and resulting spinal stability. Thus, this study assessed individual differences in fatigue characteristics during an eccentric trunk flexion-extension protocol in a population of asymptomatic individuals.

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Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discover 22 novel gene-sleep duration interaction loci for blood pressure, mapped to 23 genes.

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Background: There is debate about the causes of the recent birth rate decline in high-income countries worldwide. During the pandemic, concern about the effects on reproductive health has caused vaccine hesitancy. We investigated the association of SARS-CoV-2 vaccination and infection with involuntary childlessness.

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Article Synopsis
  • * Results showed that while FC scans generally produced lower muscle thickness measurements (decreasing by 2-3 mm), the intrarater reliability of muscle measurements was variable, with some methods demonstrating good to excellent reproducibility on repositioned scans.
  • * The conclusion highlights that although the foam cast method provides more consistent results for certain measurements, it also shows variability in muscle architecture assessments and organization, which can affect data reliability.
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Aims Of The Study: We aimed to assess the extent of SARS-CoV-2 humoral immunity elicited by previous infections and/or vaccination among healthcare workers, and to identify reasons why healthcare workers decided against vaccination.

Methods: This nested cross-sectional study included volunteer healthcare workers from 14 healthcare institutions in German-speaking Switzerland. In January 2021, SARS-CoV-2 vaccines were available for healthcare workers.

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  • * The research showed that individuals with high polygenic risk scores have significantly higher blood pressure (almost 17 mmHg more) and over seven times the risk of developing hypertension compared to those with low scores.
  • * Incorporating these genetic risk scores into hypertension prediction models improved their accuracy, and excitingly, similar genetic associations were found in a large African-American sample, underscoring the potential of these findings for precision health initiatives.
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Objectives: Primidone is an anticonvulsive drug used in the treatment of epilepsy and essential tremor. It offers beneficial effects in controlling seizures, but its usage is also associated with possible side effects. To ensure optimal therapy, it is crucial to measure its concentration through accurate quantification methods.

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Objectives: A reference measurement procedure (RMP) using isotope dilution liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) was developed and validated with the aim of accurately measuring carbamazepine-10,11-epoxide concentrations in human serum and plasma.

Methods: To establish traceability to SI units, the absolute content of the reference material was determined using quantitative nuclear magnetic resonance (qNMR) spectroscopy. As sample preparation a protein precipitation protocol followed by a high dilution step was established.

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Article Synopsis
  • The study investigates the effects of reducing genomic sequencing on SARS-CoV-2 surveillance outcomes in Switzerland, analyzing over 143,000 sequences.
  • Results show that while some key outcomes like variant detection and cluster analysis could still be achieved with only 35% of the original sequencing effort, this reduction varies significantly by viral lineage.
  • The research highlights the need for genomic surveillance programs to balance cost and public health benefits, emphasizing that reduced sequencing may compromise accuracy in tracking emerging variants of concern.
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Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discover 22 novel gene-sleep duration interaction loci for blood pressure, mapped to genes involved in neurological, thyroidal, bone metabolism, and hematopoietic pathways.

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  • The study examined sex-specific differences in physiological responses to COVID-19 using data from 1,163 participants monitored with a wearable device that measured breathing rate, heart rate, heart rate variability, and skin temperature.
  • Findings revealed that men experienced more significant physiological changes during COVID-19 infection compared to women, including greater increases in skin temperature and breathing rate, as well as greater decreases in heart rate variability.
  • The research highlights the importance of considering sex as a biological variable in health technologies and contributes to the understanding of personalized medicine approaches based on these physiological differences.
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Objectives: Phenobarbital serves as an antiepileptic drug (AED) and finds application in the treatment of epilepsy either as monotherapy or adjunctive therapy. This drug exhibits various pharmacodynamic properties that account for its beneficial effects as well as potential side effects. Accurate measurement of its concentration is critical for optimizing AED therapy through appropriate dose adjustments.

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Article Synopsis
  • During the COVID-19 pandemic, the Dr. Risch medical group utilized a specific RT-PCR testing kit for diagnosing infections in Switzerland and Liechtenstein, which targeted three genes essential for identifying the virus.
  • The emergence of the Alpha variant (B.1.1.7) led to a notable diagnostic issue, where the S-gene target was absent due to genetic deletions, marking it as an early indicator of new variants; this phenomenon was also seen in Omicron but not with the Delta variant.
  • Over two years, the group studied the significance of S-gene target failure (SGTF) as a signal for identifying variants, confirming that differences in cycle threshold values could help distinguish true SGTF cases from discrepancies
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Introduction: The purpose of this study was to investigate inter- and intra-rater reliability as well as the inter-rater interpretation error of ultrasound measurements assessing skeletal muscle architecture and tissue organization of the gastrocnemius medialis (GM) and vastus lateralis (VL) muscle.

Methods: The GM and VL of 13 healthy adults (22 ± 3 years) were examined thrice with sagittal B-mode ultrasound: intraday test-retest examination by one investigator (intra-rater) and separate examinations by two investigators (inter-rater). Additionally, images from one investigator were analysed by two interpretators (interpretation error).

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Introduction: Switzerland was amongst the first countries to offer cell-free fetal DNA (cffDNA) testing covered by the health insurance to pregnant women with a risk ≥ 1:1000 for trisomies at first trimester combined screening (FTCS). The aim of this study is to evaluate the implementation of this contingent model in a single tertiary referral centre and its effect on gestational age at diagnosing trisomy 21.

Materials And Methods: Between July 2015 and December 2020 all singleton pregnancies at 11-14 weeks of gestation without major fetal malformation were included and stratified according to their risk at FTCS.

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Article Synopsis
  • In late 2021, there was a notable increase in N-gene target failures (NGTF) when using the TaqPath COVID-19 test kit, prompting researchers to conduct whole-genome sequencing to investigate the issue.
  • Out of over 168,000 positive samples tested, only 194 (0.12%) failed to amplify the N-gene, predominantly linked to the Delta variant and featuring specific mutations.
  • The study found that specific nucleotide substitutions and deletions were associated with these NGTFs, highlighting the need for combining sequencing with RT-PCR to better tackle diagnostic inaccuracies and monitor emerging variants.
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Objectives: To describe and validate an isotope dilution-liquid chromatograph-tandem mass spectrometry (ID-LC-MS/MS) based reference measurement procedure (RMP) for zonisamide to accurately measure serum and plasma concentrations.

Methods: Quantitative nuclear magnetic resonance (qNMR) spectroscopy was employed to determine the absolute content of the reference material used in order to establish traceability to SI units. Separation of zonisamide from known or unknown interferences was performed on a C8 column.

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Objectives: An isotope dilution liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS)-based candidate reference measurement procedure (RMP) was developed and validated to accurately measure serum and plasma concentrations of carbamazepine.

Methods: Quantitative nuclear magnetic resonance (qNMR) spectroscopy was used to determine the absolute content of the reference material, ensuring its traceability to SI units. The separation of carbamazepine from potential interferences, whether known or unknown, was achieved using a C18 column.

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There is a need for blood biomarkers to detect individuals at different Alzheimer's disease (AD) stages because obtaining cerebrospinal fluid-based biomarkers is invasive and costly. Plasma phosphorylated tau proteins (p-tau) have shown potential as such biomarkers. This systematic review was conducted according to the PRISMA guidelines and aimed to determine whether quantification of plasma tau phosphorylated at threonine 181 (p-tau181), threonine 217 (p-tau217) and threonine 231 (p-tau231) is informative in the diagnosis of AD.

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The soluble urokinase plasminogen activator receptor (suPAR), as a correlate of chronic low-grade inflammation, may be used to predict individual cardiovascular risk. Since chronic low-grade inflammation is thought to be associated with the development of cardiovascular disease, this study aimed to evaluate if suPAR plasma levels are correlated with cardiovascular risk factors in young and healthy adults (aged 25-41 years). Consequently, data from the GAPP (genetic and phenotypic determinants of blood pressure and other cardiovascular risk factors) study were used to investigate suPAR plasma levels in relation to the following cardiovascular risk factors and laboratory parameters: BMI, physical activity, alcohol consumption, smoking status, blood pressure parameters, glucose status, and lipid levels.

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Objectives: Topiramate is an antiepileptic drug (AED) used for the monotherapy or adjunctive treatment of epilepsy and for the prophylaxis of migraine. It has several pharmacodynamic properties that contribute to both its clinically useful properties and observed adverse effects. Accurate measurement of its concentration is therefore essential for dose adjustment/optimisation of AED therapy.

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It is unknown whether neurological symptoms are associated with brain injury after SARS-CoV-2 infections and whether brain injury and related symptoms also emerge in Long-COVID patients. Biomarkers such as serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) can be used to elucidate neuro-axonal and astroglial injuries. We investigated whether these biomarkers are associated with COVID-19 infection status, associated symptoms and Long-COVID.

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Aim: We aimed to develop a risk score to calculate a person's individual risk for a severe COVID-19 course (POINTED score) to support prioritization of especially vulnerable patients for a (booster) vaccination.

Subject And Methods: This cohort study was based on German claims data and included 623,363 individuals with a COVID-19 diagnosis in 2020. The outcome was COVID-19 related treatment in an intensive care unit, mechanical ventilation, or death after a COVID-19 infection.

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