Tag: statistics

Stat Med. 2023 Sep 20;42(21):3745-3763. doi: 10.1002/sim.9829. Epub 2023 Jun 13.

ABSTRACT

Hierarchical data arise when observations are clustered into groups. Multilevel models are practically useful in these settings, but these models are elusive in the context of hierarchical data with mixed multivariate outcomes. In this article, we consider binary and survival outcomes and assume the hierarchical structure is induced by clustering of both outcomes within patients and clustering of patients within hospitals which frequently occur in multicenter studies. We introduce a multilevel joint frailty model that analyzes the outcomes simultaneously to jointly estimate their regression parameters and explicitly model within-patient correlation between the outcomes and within-hospital correlation separately for each outcome. Estimation is facilitated by a computationally efficient residual maximum likelihood method that further predicts cluster-specific frailties for both outcomes and circumvents the formidable challenges induced by multidimensional integration that complicates the underlying likelihood. The performance of the model and estimation procedure is investigated via extensive simulation studies. The practical utility of the model is illustrated through simultaneous modeling of disease-free survival and binary endpoint of platelet recovery in a multicenter allogeneic bone marrow transplantation dataset that motivates this study.

PMID:37593802 | DOI:10.1002/sim.9829

Birth. 2023 Aug 18. doi: 10.1111/birt.12752. Online ahead of print.

ABSTRACT

BACKGROUND: Over one-third of nulliparae planning births either at home or in freestanding midwife-led birthing centers (community births) in high-income countries are transferred during labor. Perinatal data are reported each year in Germany for women planning community birth. So far, data sets have not been linked to describe time-related factors associated with nulliparous transfer to hospital.

OBJECTIVES: To describe the prevalence of referral for nulliparae and assess maternal and labor characteristics associated with intrapartum transfer.

METHODS: Perinatal data from 2010 to 2015 were linked (n = 26,115). Women were reviewed with respect to international eligibility criteria for community birth; 1997 women were excluded (7.6%). Descriptive statistics were reported; unadjusted and adjusted odds ratios with 95% confidence intervals (CI) tested the predictive effect of demographic and labor factors on rates of intrapartum transfer.

RESULTS: One in three nulliparous women (30.6%) were transferred to hospital. Compared with community births, transferred women were significantly more likely to experience longer time intervals during labor: from rupture of membranes (ROM) until birth lasting 5 to 18 h (OR 6.05, CI 5.53-6.61) and 19 to 24 h (OR 10.83, CI 9.45-12.41) compared to one to 4 h; and from onset of labor until birth 11 to 24 h (OR 6.72, CI 6.24-7.23) and 25 to 29 h (OR 26.62, CI 22.77-31.11) compared to one to 10 h. When entering all factors into the model, we found the strongest predictors of transfer to be fetal distress, longer time intervals between ROM until birth and onset of labor until birth.

CONCLUSIONS: Nulliparous transfer rates were similar to rates in other high-income countries; 94% of referrals were non-urgent. Time was found to be an independent risk factor for the transfer of nulliparae planning community birth.

PMID:37593788 | DOI:10.1111/birt.12752

Front Immunol. 2023 Aug 1;14:1235370. doi: 10.3389/fimmu.2023.1235370. eCollection 2023.

ABSTRACT

BACKGROUND: Macrophage colony-stimulating factor 2 (MCSF-2) is an important cytokine that controls how cells of the monocyte/macrophage lineage proliferate, differentiate, and survive in vertebrates. Two isoforms of MCSF have been identified in fish, each exhibiting distinct gene organization and expression patterns. In this study, we investigated a goldfish MCSF-2 gene in terms of its immunomodulatory and functional properties.

METHODS: In this study, goldfish were acclimated for 3 weeks and sedated with TMS prior to handling. Two groups of fish were used for infection experiments, and tissues from healthy goldfish were collected for RNA isolation. cDNA synthesis was performed, and primers were designed based on transcriptome database sequences. Analysis of gfMCSF-2 sequences, including nucleotide and amino acid analysis, molecular mass prediction, and signal peptide prediction, was conducted. Real-time quantitative PCR (qPCR) was used to analyze gene expression levels, while goldfish head kidney leukocytes (HKLs) were isolated using standard protocols. The expression of gfMCSF-2 in activated HKLs was investigated, and recombinant goldfish MCSF-2 was expressed and purified. Western blot analysis, cell proliferation assays, and flow cytometric analysis of HKLs were performed. Gene expression analysis of transcription factors and pro-inflammatory cytokines in goldfish head kidney leukocytes exposed to rgMCSF-2 was conducted. Statistical analysis using one-way ANOVA and Dunnett’s post hoc test was applied.

RESULTS: We performed a comparative analysis of MCSF-1 and MCSF-2 at the protein and nucleotide levels using the Needleman-Wunsch algorithm. The results revealed significant differences between the two sequences, supporting the notion that they represent distinct genes rather than isoforms of the same gene. Sequence alignment demonstrated high sequence identity with MCSF-2 homologs from fish species, particularly C. carpio, which was supported by phylogenetic analysis. Expression analysis in various goldfish tissues demonstrated differential expression levels, with the spleen exhibiting the highest expression. In goldfish head kidney leukocytes, gfMCSF-2 expression was modulated by chemical stimuli and bacterial infection, with upregulation observed in response to lipopolysaccharide (LPS) and live Aeromonas hydrophila. Recombinant gfMCSF-2 (rgMCSF-2) was successfully expressed and purified, showing the ability to stimulate cell proliferation in HKLs. Flow cytometric analysis revealed that rgMCSF-2 induced differentiation of sorted leukocytes at a specific concentration. Moreover, rgMCSF-2 treatment upregulated TNFα and IL-1β mRNA levels and influenced the expression of transcription factors, such as MafB, GATA2, and cMyb, in a time-dependent manner.

CONCLUSION: Collectively, by elucidating the effects of rgMCSF-2 on cell proliferation, differentiation, and the modulation of pro-inflammatory cytokines and transcription factors, our findings provided a comprehensive understanding of the potential mechanisms underlying gfMCSF-2-mediated immune regulation. These results contribute to the fundamental knowledge of MCSF-2 in teleosts and establish a foundation for further investigations on the role of gfMCSF-2 in fish immune responses.

PMID:37593738 | PMC:PMC10431942 | DOI:10.3389/fimmu.2023.1235370

Front Immunol. 2023 Aug 1;14:1208814. doi: 10.3389/fimmu.2023.1208814. eCollection 2023.

ABSTRACT

Alloreactive donor-derived T-cells play a pivotal role in alloimmune responses after allogeneic hematopoietic stem cell transplantation (alloSCT); both in the relapse-preventing Graft-versus-Leukemia (GvL) effect and the potentially lethal complication Graft-versus-Host-Disease (GvHD). The balance between GvL and GvHD can be shifted by removing T-cells via T-cell depletion (TCD) to reduce the risk of GvHD, and by introducing additional donor T-cells (donor lymphocyte infusions [DLI]) to boost the GvL effect. However, the association between T-cell kinetics and the occurrence of allo-immunological events has not been clearly demonstrated yet. Therefore, we investigated the complex associations between the T-cell kinetics and alloimmune responses in a cohort of 166 acute leukemia patients receiving alemtuzumab-based TCD alloSCT. Of these patients, 62 with an anticipated high risk of relapse were scheduled to receive a prophylactic DLI at 3 months after transplant. In this setting, we applied joint modelling which allowed us to better capture the complex interplay between DLI, T-cell kinetics, GvHD and relapse than traditional statistical methods. We demonstrate that DLI can induce detectable T-cell expansion, leading to an increase in total, CD4+ and CD8+ T-cell counts starting at 3 months after alloSCT. CD4+ T-cells showed the strongest association with the development of alloimmune responses: higher CD4 counts increased the risk of GvHD (hazard ratio 2.44, 95% confidence interval 1.45-4.12) and decreased the risk of relapse (hazard ratio 0.65, 95% confidence interval 0.45-0.92). Similar models showed that natural killer cells recovered rapidly after alloSCT and were associated with a lower risk of relapse (HR 0.62, 95%-CI 0.41-0.93). The results of this study advocate the use of joint models to further study immune cell kinetics in different settings.

PMID:37593737 | PMC:PMC10427852 | DOI:10.3389/fimmu.2023.1208814

Front Immunol. 2023 Aug 1;14:1237916. doi: 10.3389/fimmu.2023.1237916. eCollection 2023.

ABSTRACT

BACKGROUND/PURPOSE: Optimizing vaccine efficacy is of particular concern in patients undergoing hematopoietic stem cell transplantation (HSCT), which mainly have an inadequate immune response to primary SARS-CoV-2 vaccination. This investigation aimed to explore the potential prime-boost COVID-19 vaccination strategies following autologous (auto-) HSCT.

METHODS: In a randomized clinical trial, patients who had already received two primary doses of receptor-binding domain (RBD) tetanus toxoid (TT) conjugated SARS-CoV-2 vaccine during three to nine months after auto-HSCT were randomized to receive either a homologous RBD-TT conjugated or heterologous inactivated booster dose four weeks after the primary vaccination course. The primary outcome was comparing the anti-S IgG Immune status ratio (ISR) four weeks after the heterologous versus homologous booster dose. The assessment of safety and reactogenicity adverse events was considered as the secondary outcome.

RESULTS: Sixty-one auto-HSCT recipients were recruited and randomly assigned to receive either homologous or heterologous booster doses four weeks after the primary vaccination course. The mean ISR was 3.40 (95% CI: 2.63- 4.16) before the booster dose with a 90.0% seropositive rate. The ISR raised to 5.12 (95% CI: 4.15- 6.08) with a 100% seropositive rate after heterologous (P= 0.0064) and to 3.42 (95% CI: 2.67- 4.17) with a 93.0% seropositivity after the homologous booster doses (P= 0.96). In addition, the heterologous group suffered more AEs following the booster dosage than the homologous group, but this difference was not statistically significant (p = 0.955). In multivariable analysis, the prime-boost vaccination strategy (heterologous versus homologous), the level of ISR before the booster dose, and the length of time between auto-HSCT and booster dose were the positive predictors of serologic response to a booster dose. No serious adverse event is attributed to booster vaccination.

CONCLUSION: In patients who were primed with two SARS-CoV-2 vaccine doses during the first year after auto-HSCT, heterologous prime-boost COVID-19 vaccination with inactivated platform resulted in considerably enhanced serologic response and non-significantly higher reactogenicity adverse events than homologous RBD-TT conjugated prime-boost COVID-19 vaccination strategy.

PMID:37593732 | PMC:PMC10427916 | DOI:10.3389/fimmu.2023.1237916

Front Public Health. 2023 Aug 1;11:1123888. doi: 10.3389/fpubh.2023.1123888. eCollection 2023.

ABSTRACT

BACKGROUND: Breast cancer is the most important malignancy and the main cause of cancer deaths among women worldwide. Breast cancer screening is an effective way to reduce breast cancer deaths.

OBJECTIVES: The present study aimed to provide breast cancer screening behavior training for female teachers in Isfahan, Iran.

MATERIALS AND METHODS: This randomized controlled trial included 120 teachers who have randomly divided into two groups (60 in the control group and 60 in the intervention group). The data collection tool was a PEN-3 model-based questionnaire. Four 90 min training sessions were held for the intervention group to modify perception and enablers. Breast self-examination (BSE), Clinical breast exam (CBE), and mammography (MMG) were investigated in both groups before and after 6 months after the last training using SPSS20 and appropriate statistical tests.

RESULTS: The frequency of BSE (p = 0.02), CBE (p = 0.04), and MMG (p = 0.01) in the intervention group was significantly higher than in the control group 6 months after training. The mean scores of perception and enablers were significantly higher in the intervention group than in the control group 3 and 6 months after training (p < 0.001). The logistic regression analysis indicated that perception factors were the strongest predictors of breast cancer screening behavior in teachers.

CONCLUSION: Results of the present study indicated that using the PEN-3 model in the educational intervention was effective in improving breast cancer screening behavior.

PMID:37593730 | PMC:PMC10427920 | DOI:10.3389/fpubh.2023.1123888

Front Public Health. 2023 Aug 1;11:1215914. doi: 10.3389/fpubh.2023.1215914. eCollection 2023.

ABSTRACT

OBJECTIVE: Comparative evidence suggests that the impact of COVID-19 on life expectancy has been relatively milder in South Korea. This study aims to examine whether the pandemic has universal or unequal impacts on life expectancy across 250 districts with varying levels of deprivation.

METHODS: Using mortality data from 2012 to 2021 obtained from the Microdata Integrated Service of Statistics Korea, we calculated life expectancy at birth and age 65 for both sexes, by deprivation quintiles, before and during the pandemic. We summarized life expectancy gaps using the slope of the inequality index (SII) and further decomposed the gaps by the contribution of age and cause of death using Arriaga’s method.

RESULTS: Both men and women experienced consistent improvements in life expectancy from 2012 to 2019, but the trend was disrupted during 2020 and 2021, primarily driven by older people. While men in more deprived areas were initially hit harder by the pandemic, the life expectancy gap across deprivation quintiles remained relatively constant and persistent across the study period [SII: -2.48 (CI: -2.70 from -2.27) for 2019 and – 2.84 (CI: -3.06 from -2.63) for 2020]. Middle-aged men from the most deprived areas were the most significant contributors to the life expectancy gap, with liver disease, liver cancer, transport accidents, and intentional injuries being the leading causes, both in the pre and during the pandemic. While these contributors remained largely similar before and during the pandemic, the contribution of transport accidents and liver cancer to the male life expectancy gap slightly decreased during the pandemic, while that of ischemic heart disease and pneumonia slightly increased. A similar increase was also observed for the female life expectancy gap.

CONCLUSION: This study found no clear evidence of an increased life expectancy gap during the pandemic in South Korea, unlike in other countries, although access to emergency healthcare services may have been slightly more disturbed in deprived areas. This achievement can provide lessons for other countries. However, the persistent regional gaps in life expectancy observed over the past decade indicate the need for more targeted public health policies to address this issue.

PMID:37593728 | PMC:PMC10427859 | DOI:10.3389/fpubh.2023.1215914

Front Public Health. 2023 Aug 1;11:1198213. doi: 10.3389/fpubh.2023.1198213. eCollection 2023.

ABSTRACT

INTRODUCTION: The clinical incidence of antimicrobial-resistant fungal infections has dramatically increased in recent years. Certain fungal pathogens colonize various body cavities, leading to life-threatening bloodstream infections. However, the identification and characterization of fungal isolates in laboratories remain a significant diagnostic challenge in medicine and public health. Whole-genome sequencing provides an unbiased and uniform identification pipeline for fungal pathogens but most bioinformatic analysis pipelines focus on prokaryotic species. To this end, TheiaEuk_Illumina_PE_PHB (TheiaEuk) was designed to focus on genomic analysis specialized to fungal pathogens.

METHODS: TheiaEuk was designed using containerized components and written in the workflow description language (WDL) to facilitate deployment on the cloud-based open bioinformatics platform Terra. This species-agnostic workflow enables the analysis of fungal genomes without requiring coding, thereby reducing the entry barrier for laboratory scientists. To demonstrate the usefulness of this pipeline, an ongoing outbreak of C. auris in southern Nevada was investigated. We performed whole-genome sequence analysis of 752 new C. auris isolates from this outbreak. Furthermore, TheiaEuk was utilized to observe the accumulation of mutations in the FKS1 gene over the course of the outbreak, highlighting the utility of TheiaEuk as a monitor of emerging public health threats when combined with whole-genome sequencing surveillance of fungal pathogens.

RESULTS: A primary result of this work is a curated fungal database containing 5,667 unique genomes representing 245 species. TheiaEuk also incorporates taxon-specific submodules for specific species, including clade-typing for Candida auris (C. auris). In addition, for several fungal species, it performs dynamic reference genome selection and variant calling, reporting mutations found in genes currently associated with antifungal resistance (FKS1, ERG11, FUR1). Using genome assemblies from the ATCC Mycology collection, the taxonomic identification module used by TheiaEuk correctly assigned genomes to the species level in 126/135 (93.3%) instances and to the genus level in 131/135 (97%) of instances, and provided zero false calls. Application of TheiaEuk to actual specimens obtained in the course of work at a local public health laboratory resulted in 13/15 (86.7%) correct calls at the species level, with 2/15 called at the genus level. It made zero incorrect calls. TheiaEuk accurately assessed clade type of Candida auris in 297/302 (98.3%) of instances.

DISCUSSION: TheiaEuk demonstrated effectiveness in identifying fungal species from whole genome sequence. It further showed accuracy in both clade-typing of C. auris and in the identification of mutations known to associate with drug resistance in that organism.

PMID:37593727 | PMC:PMC10428623 | DOI:10.3389/fpubh.2023.1198213

R Soc Open Sci. 2023 Aug 16;10(8):202326. doi: 10.1098/rsos.202326. eCollection 2023 Aug.

ABSTRACT

The COVID-19 outbreak has led to an exponential increase of publications and preprints about the virus, its causes, consequences, and possible cures. COVID-19 research has been conducted under high time pressure and has been subject to financial and societal interests. Doing research under such pressure may influence the scrutiny with which researchers perform and write up their studies. Either researchers become more diligent, because of the high-stakes nature of the research, or the time pressure may lead to cutting corners and lower quality output. In this study, we conducted a natural experiment to compare the prevalence of incorrectly reported statistics in a stratified random sample of COVID-19 preprints and a matched sample of non-COVID-19 preprints. Our results show that the overall prevalence of incorrectly reported statistics is 9-10%, but frequentist as well as Bayesian hypothesis tests show no difference in the number of statistical inconsistencies between COVID-19 and non-COVID-19 preprints. In conclusion, the literature suggests that COVID-19 research may on average have more methodological problems than non-COVID-19 research, but our results show that there is no difference in the statistical reporting quality.

PMID:37593717 | PMC:PMC10427813 | DOI:10.1098/rsos.202326

R Soc Open Sci. 2023 Aug 16;10(8):230873. doi: 10.1098/rsos.230873. eCollection 2023 Aug.

ABSTRACT

This research develops a novel system science approach to examine the potential risk of outbreaks caused by geographical clustering of underimmunized individuals for an infectious disease like measles. We use an activity-based population network model and school immunization records to identify underimmunized clusters of zip codes in the Commonwealth of Virginia. Although Virginia has high vaccine coverage for measles at the state level, finer-scale investigation at the zip code level finds three statistically significant underimmunized clusters. This research examines why some underimmunized geographical clusters are more critical in causing outbreaks and how their criticality changes with a possible drop in overall vaccination coverage. Results show that different clusters can cause vastly different outbreaks in a region, depending on their size, location, immunization rate and network characteristics. Among the three underimmunized clusters, we find one to be critical and the other two to be benign in terms of an outbreak risk. However, when the vaccine coverage among children drops by just 5% (or 0.8% overall in the population), one of the benign clusters becomes highly critical. This work also examines the demographic and network properties of these clusters to identify factors that are responsible for affecting the criticality of the clusters. Although this work focuses on measles, the methodology is generic and can be applied to study other infectious diseases.

PMID:37593709 | PMC:PMC10427811 | DOI:10.1098/rsos.230873