Statistical Association Measures Research Articles

A retrospective identification of severely injured patients using ICD 10 diagnoses codes : Part of the project "Quality of life and ability to work after severe trauma" (LeAf Trauma)

Due to continuous improvements in treatment, more and more severely and seriously injured patients are surviving. The complexity of the injury patterns of these patients means that they are difficult to map in routine data. The aim of the data exploration was to identify ICD 10 diagnoses that show an association with an injury severity score (ISS) ≥ 16 and could therefore be used to operationalize severely injured patients in routine data. The coded four-digit ICD 10 S diagnoses and the calculated ISS of trauma patients from the Armed Forces Central Hospital Koblenz (BwZKrhs) and the University Hospital Düsseldorf (UKD) were analyzed using statistical association measures (phi and Cramer'sV), linear regressions and machine learning methods (e.g., random forest). The S diagnoses of facial, head, thoracic and pelvic injuries, associated with an ISS ≥ 16 were identified. Some S diagnoses showed an association with an ISS ≥ 16 in only 1 of the 2 datasets. Likewise, facial, head, thoracic and pelvic injuries were found in the subgroup of 18-55-year-old patients. The current evaluations show that it is possible to identify ICD 10 S diagnoses that have asignificant association with an ISS ≥ 16. According to the annual report of the trauma register of the German Society for Trauma Surgery (TR-DGU®), injuries with an abbreviated injury scale (AIS) ≥ 3 are particularly common in the head and thoracic regions.

Social life cycle assessment of garments production using the psychosocial risk factors impact pathway

This study presents the application of a Social Life Cycle Assessment (SLCA) methodology to two Italian case studies, allowing to estimate the possible impacts of the production of two garments “A” and “B”. The hours of exposure to health risks have been accounted for the workers since they are the stakeholder group most immediately impacted. They have been analysed through the Psychosocial Risk Factors (PRF) impact pathway, a type II Social Life Cycle Assessment that allows the quantification of hours of exposure per each phase of the product or service life cycle. Using questionnaire, technical data have been gathered and all productive phases quantified and qualified in terms of duration (hours) and working conditions (ergonomics, exposures, postures, etc.). A literature review has been conducted to find relationships between these working conditions with health problems through odds ratios, a statistical measure of association between variables commonly used in retrospective studies. The functional unit chosen is one garment, and the system boundary is from cradle to firm gate; however, due to the lack of specific information concerning the upstream processes, impacts about inputs supplied from external providers were only qualified, but not quantified (background data). In both case studies, the highest psychosocial risk is linked to musculoskeletal disorders (Low back pain and neck and shoulder pain) and visual fatigue and discomfort. These results are due principally to the postures needed during work, the concentration required, repetitive movements, static and dynamic loads, as well as the use of video monitors during some tasks (especially planning and CAD modelling). Apparently, the process of product “B” is more socially impacting than “A”. Actually, this is due because of the internalization of some operations such as (part of) the fabric production and the dyeing processes, which can expose workers to hazardous chemicals and dusts, and the use of trichloroethylene for stain removal. These working conditions, indeed, expose workers to a higher risk of cancers, according to scientific literature. To reduce risks, it is suggested to avoid the use of bleach and trichloroethylene for cleaning, to reduce the exposure to textile dusts (for example with the use of vacuums or masks), to avoid skin contact with the azo dyes and azo pigments, by using protective individual dispositive such as gloves, long-sleeved shirts, and aprons. To improve the ergonomics workplace, it is recommended to take more breaks during the timework, ensure the firmness of chairs and add lumbar support, as well as control the height of chairs and worktops. Promoting employees’ physical activity would be useful to prevent musculoskeletal disorders.

Abstract 12488: Oral Anticoagulation for New Onset Post-Operative Atrial Fibrillation After Combined Coronary Artery Bypass Grafting and Valve Surgery is Not Associated With Improved Outcomes

Introduction: Post-operative atrial fibrillation (POAF) after cardiac surgery is common and is associated with increased risk of stroke and death. The incidence of POAF is highest among patients who undergo combined CABG and valve surgery, at 40-60%. The risks and benefits of oral anticoagulation (OAC) in this high-risk population are not well established. Research Question: Among patients with POAF after combined CABG and valve surgery, what is the association between OAC use and clinical outcomes? Methods: From a population-based registry in Ontario, Canada, we identified consecutive patients >65 years of age who developed POAF after combined CABG and left-sided, non-mechanical valve surgery from Oct/08-Mar/18. The exposure of interest was OAC prescription within 90 days after hospital discharge. Outcomes included death, cardiovascular death, stroke, MI, thromboembolism, and bleeding. Follow-up began at 90 days after discharge and continued for 24 months. Outcomes were analyzed using inverse probability of treatment weighting using the propensity score. Statistical measures of association were reported as hazard ratios with 95% confidence intervals. Results: Among 4,836 patients who had combined CABG/valve surgery, 1,939 (40.1%) developed POAF and these patients had a higher rate of death (HR 1.31, 95% CI 1.01-1.68 P=0.04). OAC was prescribed in 1,153 (59.5%) patients (86% warfarin and 14% DOAC). The use of OAC was not associated with a lower rate of death, stroke/MI/thromboembolism, or cardiovascular death but was associated with an increased rate of bleeding (HR 1.62, 95% CI 1.00-2.61, P=0.048). Conclusion: Among patients with POAF after combined CABG/valve surgery, use of warfarin or DOAC did not improve ischemic cardiovascular outcomes or survival and was associated with higher rates of bleeding. Randomized control trials are needed to define the risk and benefit of OAC use in this high-risk population. Until then, routine use of OAC is not recommended.

Explaining classifiers with measures of statistical association

A new class of probabilistic sensitivity measures that quantifies the degree of association between covariates and generic targets used in classification is proposed, and it is shown that such class possesses the zero-independence property. Corresponding estimators are introduced, asymptotic consistency is proven and bootstrap is used to quantify uncertainty in the estimates. The use of the new dependence measures as explanations in a statistical machine learning context is illustrated. The resulting approach, called Xi-method, is demonstrated through applications involving different data formats: tabular, visual and textual.

Testing simple approaches to map sediment mobilisation hotspots after wildfires

Background The models currently used to predict post-fire soil erosion risks are limited by high data demands and long computation times. An alternative is to map the potential hydrological and sediment connectivity using indices to express the general properties of the burnt landscape.Aims In this study, we aimed to answer the question: Do these tools identify post-fire sediment mobilisation hotspots?Methods To achieve this, we assessed the spatial variability distribution of the location of soil erosion hotspots using the Index of Connectivity, Revised Universal Soil Loss Equation and the Sediment Export, and compared it with the simulation results of a more complex Landscape Evolution Model (LAPSUS model). Additionally, we evaluated statistical measures of association between the four tools.Key results The three tools tested in this study are suitable for identifying sediment mobilisation hotspots, where the erosion rates are above the 95th percentile, and differences between their performance are small.Conclusions The results indicate that these tools help locate extreme erosion locations in recently burnt areas.Implications These results can be considered for post-fire and water contamination risk management, especially for fast prioritisation of areas needing emergency post-fire intervention.

1410. Methamphetamines and Serious Injection Related Infections: Epidemiology and Outcomes of Alabama’s Drug Crisis

Abstract Background The U.S. is facing a steep increase in infectious consequences of intravenous drug use due to the ongoing opioid crisis, surging methamphetamine use, and health care disruptions caused by COVID-19. We hypothesize that the sociodemographic and clinical outcomes of persons who inject drugs (PWID) differ based on their drug of choice (opioids, methamphetamines). Further, we hypothesize that the OUD (opioid use disorder) continuum, including linkage and retention in OUD treatment, will vary depending on co-occurring methamphetamine use. By elucidating differences in these groups, we aim to identify opportunities for interventions along the care continuum. Methods This is a retrospective study of hospitalized PWID receiving care at the University of Alabama at Birmingham Hospital for a serious injection related infection (SIRI) between 1/11/2016 and 4/24/2021. We queried the EMR for clinical data and health outcomes. We extracted data on substance use disorder(s), treatments, and linkage to care through review of primary and addiction medicine consultation notes. Using statistical measures of association, we compared demographic factors and clinical outcomes among groups; delineating between those with and without methamphetamine use, and without OUD. When appropriate, additional comparisons were made to detect statistical differences between factors and those with and without methamphetamine use. Results Of 370 PWID, 286 had OUD, 94 had OUD and methamphetamine use, and 84 had another substance use disorder. There were significant differences according to drug use disorder with patients with OUD and meth use being mostly White (99%), 42% female, and younger relative to those who use opioids only. Patient directed discharge was most common among those with OUD plus meth use, but death was highest for those with OUD only. The OUD care continuum was similar and alarming for both groups with many gaps in care. Figure 1.OUD Care continuum for PWID with SIRI for those with and without comorbid meth use disorder Conclusion PWID with SIRI are a diverse group with significant differences based on substance of choice, but all experience suboptimal hospital outcomes. There are opportunities to improve linkage and retention across the care continuum, most noticeably outpatient linkage. Disclosures Ellen Eaton, MD, MPH, Gilead HIV Research Scholar: Grant/Research Support|Gilead HIV research scholar: Grant/Research Support.

Distinctive Features of Association Measures Applied to Chinese Character Bigram Extraction Tasks

Studying professional discourse, a researcher has now an opportunity to create collections of texts and apply linguistic analysis software tools to them. However, when it comes to Chinese discourse there is a problem with the reliability of automatic word segmentation of texts. One of the ways to extract lexical units in Chinese texts is to apply statistical association measures for collocations to Chinese character bigrams. The purpose of this work is to conduct a comparative analysis of seven different statistical measures for collocations as a means of extracting two-syllabic lexical units (binomes) in an unsegmented Chinese character text. The subject of the analysis is the lexical, grammatical and frequency characteristics of bigrams with higher values of the statistical measures. Their comparison makes it possible to draw a conclusion about the features of statistical measures, in particular, about the best correspondence of linguistic tasks to statistical measures. The linguistic material of the study was a collection of 560 military-related news texts in Chinese with more than 720 thousand characters. The results show that the statistical measures considered can be divided into three groups according to the characteristics of bigrams receiving the highest values. The first group includes measures MI, MS and logDice, which give priority to rare bigrams with limited compatibility of components, such as the Chinese two-syllable single morpheme words “lianmianzi”. These measures do not extract terms well, but can be used to search for phraseologically related components. The measures of the second group, t-score and log-likelihood, are frequency-oriented, similar to frequency analysis, but they cope with non-lexical bigrams better, while log-likelihood somewhat lowers the rank of numerals and pronouns, picking out best the typical vocabulary of professional discourse. The third group includes measures MI3 and MI.log-f, which average the opposite approaches of the first two groups. The MI3 measure is considered to be the most universal one; it could be used to compare different corpora or collections of texts. It is concluded that applying statistical association measures to Chinese character bi-grams is possible and appropriate, when taking into account the correspondence of their specifics to a research task.

Partial event coincidence analysis for distinguishing direct and indirect coupling in functional network construction

Correctly identifying interaction patterns from multivariate time series presents an important step in functional network construction. In this context, the widespread use of bivariate statistical association measures often results in a false identification of links because strong similarity between two time series can also emerge without the presence of a direct interaction due to intermediate mediators or common drivers. In order to properly distinguish such direct and indirect links for the special case of event-like data, we present here a new generalization of event coincidence analysis to a partial version thereof, which is aimed at excluding possible transitive effects of indirect couplings. Using coupled chaotic systems and stochastic processes on two generic coupling topologies (star and chain configuration), we demonstrate that the proposed methodology allows for the correct identification of indirect interactions. Subsequently, we apply our partial event coincidence analysis to multi-channel EEG recordings to investigate possible differences in coordinated alpha band activity among macroscopic brain regions in resting states with eyes open (EO) and closed (EC) conditions. Specifically, we find that direct connections typically correspond to close spatial neighbors while indirect ones often reflect longer-distance connections mediated via other brain regions. In the EC state, connections in the frontal parts of the brain are enhanced as compared to the EO state, while the opposite applies to the posterior regions. In general, our approach leads to a significant reduction in the number of indirect connections and thereby contributes to a better understanding of the alpha band desynchronization phenomenon in the EO state.

Clinical Relevance of Transorbital Ultrasonographic Measurement of Optic Nerve Sheath Diameter (ONSD) for Estimation of Intracranial Pressure Following Cerebrospinal Fluid Diversion Surgery

Background and aimRaised intracranial pressure (ICP) can be estimated by various invasive as well as non-invasive techniques. Optic nerve sheath diameter (ONSD ) is a bedside non-invasive technique for assessment of ICP as a regular follow-up tool and has added advantage over CT scan/MRI, which require patient transfer to the suite. Cerebrospinal fluid (CSF) diversion procedures such as a ventriculoperitoneal shunt or external ventricular drainage are commonly done to relieve symptoms of patients with raised ICP. Change in ICP measured through ONSD after CSF diversion procedures may guide the proper functioning of the shunt and immediate post-operative management. The present study was conducted to compare ONSD before and after CSF diversion procedures and correlate the ONSD with ICP. Our secondary objective was to determine the ONSD cutoff for the prediction of ICP >20mm Hg.Setting, design, and methodsThis prospective, comparative, and observational study was carried out at Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, India. The present study was conducted on 40 adult patients undergoing CSF diversion surgery under general anaesthesia. Ultrasonographic measurement of the ONSD was performed before induction, after induction, after endotracheal intubation, after completion of shunt surgery, and then every two hours for 12 hours. The direct ICP was measured by the neurosurgeon at the time of the initial ventricular puncture.Statistical analysisThe Wilcoxon signed-rank test was used to compare pre and post variables. Qualitative variables were compared using the Chi-Square test/Fisher’s exact test as appropriate. Spearman's rho statistical measure of linear association was applied to measure the strength of linear association between parameters to show how close the points lie to a straight line. A p-value of <0.05 was considered statistically significant.ResultsThe mean value of ONSD before induction and after induction was 6.36 ± 0.61 mm and 6.29 ±0.64 mm, respectively. After endotracheal intubation, ONSD slightly increased to 6.34 ±0.62mm, followed by a consistent decrease in ONSD values. The mean direct ICP recorded was 30.93±6.22 mmHg. Comparison of mean ONSD before induction, after induction, and after intubation with ONSD after surgery was statistically significant (p <0.001). We found a strong positive correlation between direct ICP and ONSD after intubation with a correlation coefficient of 0.969 (P <0.001). Receiver operating characteristic (ROC) curve analysis showed an ONSD cutoff of >5.85, predicted ICP>20 mmHg with a sensitivity of 92.3%, and specificity of 85.7%.ConclusionMeasurement of ONSD by ultrasonography is an important and reliable tool in the assessment of normalization of ICP post CSF diversion procedure.

Geodiversity assessment with global and local spatial multicriteria analysis

The paper reports on geodiversity assessments of three national parks in Poland, performed independently by experts and volunteers. Each national park selected for the study represents one of three morphogenetically different landscape types: mountains, uplands, and plains. The expert and volunteer assessment data sets were separately processed with two spatial multicriteria methods: Weighted Linear Combination (WLC) - also referred to in the paper as the global version of WLC, and Local Weighted Linear Combination (L-WLC) resulting in two geodiversity maps for each of the parks – one based on WLC and the other on L-WLC output data. The maps were qualitatively evaluated for their efficacy of capturing spatial heterogeneity and differentiating between high and low geodiversity of specific areas within the national parks. The expert-based maps were compared with the volunteer-based maps using statistical measures of association and similarity. The results show that L-WLC is more suitable for geodiversity mapping of mountainous areas characterized by high morphogenetic and morphometric diversity whereas WLC yields better results in less diverse areas such as uplands and lowlands. The use of data originating from volunteer-based assessment requires meeting internal and external data quality standards and should be treated with caution.

Statistical Tests and Association Measures for Business Processes

Through the application of process mining, organisations can improve their business processes by leveraging data recorded as a result of the performance of these processes. Over the past two decades, the field of process mining evolved considerably, offering a rich collection of analysis techniques with different objectives and characteristics. Despite the advances in this field, a solid statistical foundation is still lacking. Such a foundation would allow analysis outcomes to be found or judged using the notion of statistical significance, thus providing a more objective way to assess these outcomes. This paper contributes several statistical tests and association measures that treat process behaviour as a variable. The sensitivity of these tests to their parameters is evaluated and their applicability is illustrated through the use of real-life event logs. The presented tests and measures constitute a key contribution to a statistical foundation for process mining.

Statistics From A (Agreement) to Z (z Score): A Guide to Interpreting Common Measures of Association, Agreement, Diagnostic Accuracy, Effect Size, Heterogeneity, and Reliability in Medical Research.

Researchers reporting results of statistical analyses, as well as readers of manuscripts reporting original research, often seek guidance on how numeric results can be practically and meaningfully interpreted. With this article, we aim to provide benchmarks for cutoff or cut-point values and to suggest plain-language interpretations for a number of commonly used statistical measures of association, agreement, diagnostic accuracy, effect size, heterogeneity, and reliability in medical research. Specifically, we discuss correlation coefficients, Cronbach's alpha, I2, intraclass correlation (ICC), Cohen's and Fleiss' kappa statistics, the area under the receiver operating characteristic curve (AUROC, concordance statistic), standardized mean differences (Cohen's d, Hedge's g, Glass' delta), and z scores. We base these cutoff values on what has been previously proposed by experts in the field in peer-reviewed literature and textbooks, as well as online statistical resources. We integrate, adapt, and/or expand previous suggestions in attempts to (a) achieve a compromise between divergent recommendations, and (b) propose cutoffs that we perceive sensible for the field of anesthesia and related specialties. While our suggestions provide guidance on how the results of statistical tests are typically interpreted, this does not mean that the results can universally be interpreted as suggested here. We discuss the well-known inherent limitations of using cutoff values to categorize continuous measures. We further emphasize that cutoff values may depend on the specific clinical or scientific context. Rule-of-the thumb approaches to the interpretation of statistical measures should therefore be used judiciously.

Comparative Evaluation of Saliva and Serum Proteins in Diabetics and Normo-Glycemics

One of the most probable markers of inflammatory response is serum protein. Recently, serum levels of these some proteins have been proven to be useful in clinical diagnosis. In this study, we comparatively investigated serum and saliva C - reactive protein (CRP), α-amylase and α-glucosidase activities in type II Diabetic and Normo-glycemic humans. Two hundred and thirteen (213) subjects of 173 Diabetics and 40 Non-diabetics (Control) were ethically recruited from the central hospital, warri, Delta State. For each participant, serum and saliva was collected and laboratorily analyzed for α-amylase, α-glucosidase and CRP levels, while comparing mean differences between groups with a student t-test and statistical measure of association (correlation). Result showed a statistically significant increase in CRP and α-amylase activity of diabetics than non-diabetic subjects, with a statistically significant increase in salivary and serum CRP, α-glucosidase and α-amylase levels across groups. This finding is suggestive that saliva and/or serum levels may be useful bioanalytes for non-invasive, alternative diagnosis of blood glucose levels. Similar studies that corroborate the efforts of this study is recommended. Further studies that assay other saliva and serum biomarkers may also be useful and thus recommended.

Pairwise linkage disequilibrium estimation for polyploids.

Many tasks in statistical genetics involve pairwise estimation of linkage disequilibrium (LD). The study of LD in diploids is mature. However, in polyploids, the field lacks a comprehensive characterization of LD. Polyploids also exhibit greater levels of genotype uncertainty than diploids, yet no methods currently exist to estimate LD in polyploids in the presence of such genotype uncertainty. Furthermore, most LD estimation methods do not quantify the level of uncertainty in their LD estimates. Our study contains three major contributions. (i) We characterize haplotypic and composite measures of LD in polyploids. These composite measures of LD turn out to be functions of common statistical measures of association. (ii) We derive procedures to estimate haplotypic and composite LD in polyploids in the presence of genotype uncertainty. We do this by estimating LD directly from genotype likelihoods, which may be obtained from many genotyping platforms. (iii) We derive standard errors of all LD estimators that we discuss. We validate our methods on both real and simulated data. Our methods are implemented in the R package ldsep, available on the Comprehensive R Archive Network https://cran.r-project.org/package=ldsep.

Statistical measures of the association between two ordinal variables

Questionnaire surveys often deal with items by which we would like to identify possible associations. These items/variables can be measured on the basis of nominal, ordinal or interval scale. This paper provides an overview of statistical measures of association between two ordinal variables that are used most commonly. It also offers a display of the outputs from the SPSS program, in addition to the description of correlation coefficient calculations.DOI: https://doi.org/10.24040/sjss.2020.6.2.55-61

Temporal analysis of leprosy in the metropolitan region of Aracaju, Sergipe, Brazil: 2001-2013

The study carried out a temporal analysis and description of the epidemiological profile of leprosy in the metropolitan region of Aracaju, Sergipe, Brazil, from 2001 to 2013. It was a temporal study based on secondary data from the Notifiable Diseases Information System (SINAN). In this study, the variables were analyzed: municipality of residence; number of cases diagnosed per year from 2001 to 2013; age; schooling; race / skin color; operational classification (paucibacillary or multibacillary); clinical form (indeterminate, tuberculoid, dimorphic, virchowian); and degree of disability, assessed at the time of notification and upon medical discharge: Degrees 0, I and II. The data were plotted in a spreadsheet (Microsoft Excel ©) and subsequently analyzed according to the descriptive statistical measure of association and the adhesion test was measured by the Bioestat 5.0 software. For the time trend analysis, it adopted the simple polynomial regression model, the variable time centralization to avoid autocorrelation between the terms of the equations. It was detected a total of 3,519 cases in Aracaju region. The predominant form paucibacillar. Clinical tuberculoid form of leprosy was the most frequent. The temporal analysis showed a declining trend to statistical significance (p &lt;0.05). The multibacillary predominated in the municipalities of Barra dos Coqueiros and Our Lady of Socorro. The results showed that the population did not have access to adequate health program and the Ministry of Health's strategies did not meet the goal of WHO for the elimination of leprosy.

Prevalence of serologic markers of transfusion and sexually transmitted infections and their correlation with clinical features in a large cohort of Brazilian patients with sickle cell disease.

Patients with sickle cell disease (SCD) often require red blood cell (RBC) transfusion for clinical complications, so may be exposed to transfusion-transmitted infections (TTIs). The prevalence of markers for human immunodeficiency virus (HIV), hepatitis C virus (HCV) and B (HBV), human T-cell lymphotropic virus (HTLV-1/2), Chagas disease, and syphilis in an SCD cohort in Brazil were studied. Clinical history, interview data, blood samples, and medical chart review data were collected during cohort enrollment from November 2013 to May 2015. Serologic markers of infection were assessed. Standard measures of statistical association were calculated, and multivariable models were developed for the most prevalent infections to identify associated factors. Infection markers were evident in 5.2% (144/2779) of the enrolled cohort. Anti-HCV was detected in 69 (2.5%), syphilis antibodies in 34 (1.2%), anti-HTLV-1/2 in 17 (0.6%), HBV surface antigen in 13 (0.5%), Chagas disease antibodies in 13 (0.5%), and anti-HIV in 8 (0.3%) of participants. Factors associated with increased odds of being anti-HCV reactive were older age, illegal drug use, increasing number of RBCs, more than three pain crises in the previous year, and geographic location. Syphilis was associated with older age, females, and smoking history. HCV infection was more common in older patients who may have received RBCs before testing was performed on donations, suggesting possible historic transfusion transmission. The cohort showed decreasing rates of infections and a reduction in transfusion transmission markers in younger patients compared to historical literature except for syphilis, indicating contemporary reduced risk of TTI.

Alterations in Serum Magnesium and Electrocardiographic Variables of Adult Hypertensive Humans

As the most important risk factor for cardiovascular diseases worldwide, Hypertension has been found to be a major public health challenge with high prevalence in Africans and Nigerians especially with a rapidly growing population. It has been postulated that hypomagnesemia contributes to the development of hypertension and cardiovascular disease. This study was therefore undertaken to determine the relationship between serum magnesium levels and electrocardiographic changes in adult humans with hypertension. To achieve this, one hundred and sixty two (162) hypertensives were recruited from the University of Benin Teaching Hospital (UBTH), Benin City, Edo State, Nigeria. Participants’ Blood pressure, electrocardiographic changes, antihypertensive medications and serum magnesium (Mg2+) levels were investigated. Using the Pearson Product Moment Correlation Coefficient and ANOVA, Statistical measures of association (correlation) were conducted on obtained variables. A low incidence of hypomagnesaemia was observed on the average, with a high incidence of patients presenting with abnormal ECG changes; including Left Ventricular Hypertrophy. In addition, only weak correlations were observed for ECG parameter and serum Mg2+levels for sampled subjects, with p-value returning a statistically significant decrease upon comparison of means (Using the One-Way Analysis of Variance (ANOVA); Other influences like antihypertensive medications, blood pressure duration and control returned an significant (weak negative) correlation with serum Mg2+ concentration. There is therefore a weak negative correlation between serum magnesium levels and ECG variables, including Q wave duration and QT interval duration in hypertensive adults

Exploration of a diversity of computational and statistical measures of association for genome-wide genetic studies

BackgroundThe principal line of investigation in Genome Wide Association Studies (GWAS) is the identification of main effects, that is individual Single Nucleotide Polymorphisms (SNPs) which are associated with the trait of interest, independent of other factors. A variety of methods have been proposed to this end, mostly statistical in nature and differing in assumptions and type of model employed. Moreover, for a given model, there may be multiple choices for the SNP genotype encoding. As an alternative to statistical methods, machine learning methods are often applicable. Typically, for a given GWAS, a single approach is selected and utilized to identify potential SNPs of interest. Even when multiple GWAS are combined through meta-analyses within a consortium, each GWAS is typically analyzed with a single approach and the resulting summary statistics are then utilized in meta-analyses.ResultsIn this work we use as case studies a Type 2 Diabetes (T2D) and a breast cancer GWAS to explore a diversity of applicable approaches spanning different methods and encoding choices. We assess similarity of these approaches based on the derived ranked lists of SNPs and, for each GWAS, we identify a subset of representative approaches that we use as an ensemble to derive a union list of top SNPs. Among these are SNPs which are identified by multiple approaches as well as several SNPs identified by only one or a few of the less frequently used approaches. The latter include SNPs from established loci and SNPs which have other supporting lines of evidence in terms of their potential relevance to the traits.ConclusionsNot every main effect analysis method is suitable for every GWAS, but for each GWAS there are typically multiple applicable methods and encoding options. We suggest a workflow for a single GWAS, extensible to multiple GWAS from consortia, where representative approaches are selected among a pool of suitable options, to yield a more comprehensive set of SNPs, potentially including SNPs that would typically be missed with the most popular analyses, but that could provide additional valuable insights for follow-up.

PB2132 DARATUMUMAB MONOTHERAPY FOR RELAPSED AND REFRACTORY MULTIPLE MYELOMA REAL CLINICAL PRACTICE. A MULTICENTRIC RETROSPECTIVE STUDY

Background:Daratumumab (DARA) was first approved as monotherapy for patients (P) with relapsed and refractory (RR) multiple myeloma (MM) after treatment with immunomodulatory drugs and proteasome inhibitors, and who have progressed on the last therapy, based on data from the phase 2 SIRIUS trial. Its results show 29% of P with at least partial response, progression‐free survival (Sv) (PFS) of 3.7 months(m) and overall survival (OS) of 17.5 m, and acceptable toxicity.Aims:So far, there are scarce data on treatment with DARA monotherapy in routine clinical practice.MethodsObservational, retrospective and multicenter study of P with RRMM treated with DARA in monotherapy outside clinical trial (CT) in various Spanish regions: Galicia, Asturias, Cantabria y Castilla y León. Statistical descriptive analysis with SPSS®: Sv curves by Kaplan‐Meier and measures of statistical association using Chi2.Results:There were 80 P (61% males) evaluable. Characteristics at diagnosis: age 64.8 years (y) (IQR 57.1‐73.3); previous COPD/asthma: 11.25%; myeloma stage ISS 3: 37.5%, and 2: 31.25%; adverse cytogenetics (del17p, t(4;14), t(14;16)): 21.25%. Characteristics at starting of DARA: age 70.5 y (IQR 60.9‐76.1); adverse cytogenetics: 17/33 P (52.5%); previous lines of treatment: median 3 (1‐10), in 52.5% of P including carfilzomib and/or pomalidomide; previous ASCT: 51.25%.The median of DARA doses administered per patient were 10 (1‐26); it should be pointed out tha t5 P only received 1 dose. The majority (78.7%) received the 1st dose hospitalized, and in 38.7% montelukast was associated to the conventional premedication. The rate of infusion‐ related reactions (IRR) is 23.7% for the 1st dose (grade 1: 78.9%, grade 3: 15.8%), with no difference according to premedication. Only 3 P suffered IRR grade 1 after 2nd dose.Response. Overall R (OR) 66.6% (CR 13.3%, PR + VGPR 33.3%, MR/SD 20%), progression 33.3%. With a median follow‐up of 243 days (IQR 113‐392), 48.7% have died (cause of death 79.4% MM) with no toxic mortality, and 25% continue treatment. PFS and OS are 111 days (87‐252) and 280 days (173‐700), respectively.Adverse events. Any grade adverse events occurred in 38.7%, being the most frequent neutropenia and/or infection (52%), thrombocytopenia (26%), nausea/vomiting (10%) and peripheral neuropathy (4%). All grade 3 (34%), and 4 (18%) adverse events were due to myelotoxicity and infection. In 25% of P a dose of DARA was delayed, for an average of 11 days (2‐30), 55% of them due to infection. None had to discontinue DARA because of toxicity.Summary/Conclusion:Our experience outside clinical trials confirms that DARA monotherapy is a safe and well‐tolerated drug, even in this population of elderly P with advanced disease and multiple previous lines of therapy. There are no serious IRR and the main toxicity, as otherwise should be expected, has been myelosuppression and infections. The OR rate is high, highlighting 46.6% with at least PR, but in spite of this PFS and OS are short, 3.7 m and 9.3 m respectively; in special OS is much lower than previously referred in SIRIUS trial. It should be noted out that 17 P did not complete the 1st cycle of DARA (4 doses) and 5P received only 1 dose, so a better selection of candidates for this Trt will probably improve these results.