bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/507665

FinDonor 10 000 study: A cohort to identify iron depletion and factors affecting it in Finnish blood donors

Partanen, J.·Niittymaki, P.·Nikiforow, N.·Palokangas, E.·Larjo, A.·Mattila, P.·Castren, J.·Arvas, M.
View original source ↗Export metadata ↓

Abstract

Background and ObjectivesThere is increasing evidence that frequent blood donation depletes the iron stores of some blood donors. The FinDonor 10 000 study was set up to study iron status and factors affecting iron stores in Finnish blood donors. In Finland, iron supplementation for at-risk groups has been in place since the 1980s. Material and Methods2584 blood donors (N= 8003 samples) were recruited into the study alongside the standard donation at three donation sites in the capital region of Finland between 5/2015 and 12/2017. All participants were asked to fill out a questionnaire about their health and lifestyle. Blood samples were collected from the sample pouch of whole blood collection set, kept in cool temperature and processed centrally. Whole blood count, CRP, ferritin and sTFR were measured from the samples and DNA was isolated for GWAS studies. ResultsParticipant demographics, albeit in general similar to the general blood donor population in Finland, indicated some bias toward older and more frequent donors. Participation in the study increased median donation frequency of the donors. Analysis of the effect of time lag from the sampling to the analysis and the time of day when sample was drawn revealed small but significant time-dependent changes. ConclusionThe FinDonor cohort now provides us with tools to identify potential donor groups at increased risk of iron deficiency as factors explaining this risk. The increase in donation frequency during the study suggests that scientific projects can be used to increase the commitment of blood donors.

Source connections

Explore related subjects

epidemiologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Partanen, J., Niittymaki, P., Nikiforow, N., Palokangas, E., Larjo, A., Mattila, P., Castren, J., Arvas, M.. 2018-12-31. FinDonor 10 000 study: A cohort to identify iron depletion and factors affecting it in Finnish blood donors. https://doi.org/10.1101/507665

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2019

Starting antiretroviral therapy within seven days of a positive HIV test increased the risk of loss to follow up in a primary healthcare clinic: a retrospective cohort study in Masaka, Uganda.

BackgroundRetention of patients initiated on antiretroviral therapy (ART) and good adherence remain cornerstones to long-term viral suppression. In this era of test and treat (T&T), ensuring that patients initiated on ART remain connected to HIV clinics will be key to the achievement of the UNAIDS 90-90-90 targets. Currently, limited studies have evaluated the effect instant ART initiation has on loss to follow up in a typical service healthcare setting. We studied the cumulative incidence, incidence rate of loss to follow up (LTFU), and factors associated with loss to follow up (LTFU) in a primary healthcare clinic that has practiced test and treat since 2012.\n\nMethodsWe retrospectively drew routine program data of patients initiated on ART from January 2012 to December 2016. We defined LTFU as failure of a patient to return to the HIV clinic for at least 90 days from the date of their last appointment. We calculated cumulative incidence, incidence rate and fitted a multivariable Cox proportion hazards regression model to determine factors associated with LTFU.\n\nResultsOf the 8,136 patients included in our sample, 3,606 (44.3%) started ART within seven days of HIV diagnosis. Females were 62.3%, median (interquartile range) age at start of ART was 30 (25, 37) years, 50.1% had access to a mobile phone, 54.0% had a baseline CD4 cell count of <350 cells/ml, 14.8% were in either WHO stage 3 or 4 at baseline and 75.9% had a normal body mass index (BMI). There were 1,207 cases of LTFU observed over 15953.0 person years at risk. The overall incidence rate (IR) of LTFU was 7.6 (95% CI=7.2-8.0) per 100 person years of observation (pyo). Cumulative incidence of LTFU increased with duration of follow up from 8.8% (95% CI=8.2-9.4%) and 12.0% (95% CI=11.2-12.7%) at 6 and 12 months, to 17.9% (95% CI=16.9-18.9%) and 20.1% (95% CI=18.9-21.3%) at 36, and 48 months respectively. Predictors of elevated risk of LTFU were; starting ART within 7 days of a positive diagnosis ((aHR) =1.39, 95% CI, 1.13-1.71), lack of access to a telephone set (aHR=1.60, 95% CI, 1.29-1.99) and baseline WHO clinical stage 3 or 4 (aHR =1.53, 95% CI, 1.11-2.11). Factors associated with a reduced risk of LTFU were; baseline age [&ge;]25years, and having a BMI [&ge;] 30 (aHR =0.28, 95% CI, 0.15-0.51).\n\nConclusionInitiation of ART within 7 days of an HIV diagnosis was associated with an elevated risk of loss to follow up. Steep ART initiation needs to be backed by enhanced adherence and retention counseling to reach the 2020 UNAIDS goals and beyond.

epidemiology↗
bioRxiv2019

Evolution and expansion of multidrug resistant malaria in Southeast Asia: a genomic epidemiology study

BackgroundA multidrug resistant co-lineage of Plasmodium falciparum malaria, named KEL1/PLA1, spread across Cambodia c.2008-2013, causing high treatment failure rates to the frontline combination therapy dihydroartemisinin-piperaquine. Here, we report on the evolution and spread of KEL1/PLA1 in subsequent years.\n\nMethodsWe analysed whole genome sequencing data from 1,673 P. falciparum clinical samples collected in 2008-2018 from northeast Thailand, Laos, Cambodia and Vietnam. By investigating genome-wide relatedness between parasites, we inferred patterns of shared ancestry in the KEL1/PLA1 population.\n\nFindingsKEL1/PLA1 spread rapidly from 2015 into all of the surveyed countries and now exceeds 80% of the P. falciparum population in several regions. These parasites maintained a high level of genetic relatedness reflecting their common origin. However, several genetic subgroups have recently emerged within this co-lineage with diverse geographical distributions. Some of these emerging KEL1/PLA1 subgroups carry recent mutations in the chloroquine resistance transporter (crt) gene, which arise on a specific genetic background comprising multiple genomic regions.\n\nInterpretationAfter emerging and circulating for several years within Cambodia, the P. falciparum KEL1/PLA1 co-lineage diversified into multiple subgroups and acquired new genetic features including novel crt mutations. These subgroups have rapidly spread into neighbouring countries, suggesting enhanced fitness. These findings highlight the urgent need for elimination of this increasingly drug-resistant parasite co-lineage, and the importance of genetic surveillance in accelerating elimination efforts.\n\nFundingWellcome Trust, Bill & Melinda Gates Foundation, UK Medical Research Council, UK Department for International Development.\n\nResearch in context O_TEXTBOXEvidence before this studyThis study updates our previous work describing the emergence and spread of a multidrug resistant P. falciparum co-lineage (KEL1/PLA1) within Cambodia up to 2013. Since then, a regional genetic surveillance project, GenRe-Mekong, has reported that markers of dihydroartemisinin-piperaquine (DHA-PPQ) resistance have increased in frequency in neighbouring countries. A PubMed search (terms: \"artemisinin\", \"piperaquine\", \"resistance\", \"southeast asia\") for articles listed since our previous study (from 30/10/2017 to 05/01/2019) yielded 28 results, including reports of a recent sharp decline in DHA-PPQ clinical efficacy in Vietnam; the spread of genetic markers of DHA-PPQ resistance into neighbouring countries by Imwong and colleagues; and multiple reports associating mutations in the crt gene with piperaquine resistance, including newly emerging crt variants in Southeast Asia.\n\nAdded value of this studyWe analysed P. falciparum whole genomes collected up to early 2018 from Eastern Southeast Asia (Cambodia and surrounding regions), describing the fine-scale epidemiology of multiple KEL1/PLA1 genetic subgroups that have spread out from Cambodia since 2015 and taken over indigenous parasite populations in northeastern Thailand, southern and central Vietnam and parts of southern Laos. Several newly emerging crt mutations accompanied the spread and expansion of KEL1/PLA1 subgroups, suggesting an active proliferation of biologically fit, multidrug resistant parasites.\n\nImplications of all the available evidenceThe problem of P. falciparum multidrug resistance has dramatically worsened in Eastern Southeast Asia since previous reports. KEL1/PLA1 has diversified and spread widely across Eastern Southeast Asia since 2015, becoming the predominant parasite group in several regions. This may have been fuelled by continued parasite exposure to DHA-PPQ, resulting in sustained selection after KEL1/PLA1 became established. Continued drug pressure enabled the acquisition of further mutations, resulting in higher levels of resistance. These data demonstrate the value of pathogen genetic surveillance and the urgent need to eliminate these dangerous parasites.\n\nC_TEXTBOX

epidemiology↗
bioRxiv2019

Adding noise to Markov cohort models

Following its introduction over thirty years ago, the Markov state-transition cohort model has been used extensively to model population trajectories over time in decision modeling and cost-effectiveness studies. We recently showed that a cohort model represents the average of a continuous-time stochastic process on a multidimensional integer lattice governed by a master equation (ME), which represents the time-evolution of the probability function of a integer-valued random vector. From this theoretical connection, this study introduces an alternative modeling method, stochastic differential equation (SDE), which captures not only the mean behavior but also the variance. We first derive the continuous approximation to the master equation by relaxing integrality constraint of the state space in the form of Fokker Planck equation (FPE), which represents the time-evolution of the probability function of a real-valued random vector. Instead of working with the FPE, the SDE method constitutes time-evolution of the random vector of population counts. We derive the SDE from first principles and describe an algorithm to construct an SDE and solve the SDE via simulation for use in practice. We show the applications of SDE in two case studies. The first example demonstrates that the population trajectories, the mean and the variance, from the SDE and other commonly-used methods match. The second examples shows that users can readily apply the SDE method in their existing works without the need for additional inputs. In addition, in both examples, the SDE is superior to microsimulation in terms of computational speed. In summary, the SDE provides an alternative modeling framework and is less computationally expensive that microsimulation for a typical modeling problem in decision analyses.

epidemiology↗