Tag: statistics

Biostatistics. 2021 Apr 10;22(2):233-249. doi: 10.1093/biostatistics/kxz027.

ABSTRACT

Motivated by the study of the molecular mechanism underlying type 1 diabetes with gene expression data collected from both patients and healthy controls at multiple time points, we propose a hybrid Bayesian method for jointly estimating multiple dependent Gaussian graphical models with data observed under distinct conditions, which avoids inversion of high-dimensional covariance matrices and thus can be executed very fast. We prove the consistency of the proposed method under mild conditions. The numerical results indicate the superiority of the proposed method over existing ones in both estimation accuracy and computational efficiency. Extension of the proposed method to joint estimation of multiple mixed graphical models is straightforward.

PMID:33838043 | DOI:10.1093/biostatistics/kxz027

Immun Inflamm Dis. 2021 Apr 10. doi: 10.1002/iid3.420. Online ahead of print.

ABSTRACT

BACKGROUND: Immune thrombocytopenia (ITP), autoimmune hemolytic anemia (AIHA), and autoimmune neutropenia (AIN) are disorders characterized by immune-mediated destruction of hematopoietic cell lineages. A link between pediatric immune cytopenias and inborn errors of immunity (IEI) was established in particular in the combined and chronic forms.

OBJECTIVE: Aim of this study is to provide clinical-immunological parameters to hematologists useful for a prompt identification of children with immune cytopenias deserving a deeper immunological and genetic evaluation.

METHODS: We retrospectively collected 47 pediatric patients with at least one hematological disorder among which persistent/chronic ITP, AIHA, and AIN, aged 0-18 years at onset of immune cytopenias and/or immune-dysregulation. The cohort was divided into two groups (IEI+ and IEI-), based on the presence/absence of underlying IEI diagnosis. IEI+ group, formed by 19/47 individuals, included: common variable immune deficiency (CVID; 9/19), autoimmune lymphoproliferative syndrome (ALPS; 4/19), DiGeorge syndrome (1/19), and unclassified IEI (5/19).

RESULTS: IEI prevalence among patients with ITP, AIHA, AIN, and Evans Syndrome was respectively of 42%, 64%, 36%, and 62%. In IEI+ group the extended immunophenotyping identified the presence of statistically significant (p < .05) specific characteristics, namely T/B lymphopenia, decrease in naїve T-cells%, switched memory B-cells%, plasmablasts%, and/or immunoglobulins, increase in effector/central memory T-cells% and CD21low B-cells%. Except for DiGeorge and three ALPS patients, only 2/9 CVID patients had a molecular diagnosis for IEI: one carrying the pathogenic variant CR2:c.826delT, the likely pathogenic variant PRF1:c.272C> and the compound heterozygous TNFRSF13B variants p.Ser144Ter (pathogenic) and p.Cys193Arg (variant of uncertain significance), the other one carrying the likely pathogenic monoallelic variant TNFRSF13B:p.Ile87Asn.

CONCLUSION: The synergy between hematologists and immunologists can improve and fasten diagnosis and management of patients with immune cytopenias through a wide focused clinical/immunophenotypical characterization, which identifies children worthy of IEI-related molecular analysis, favouring a genetic IEI diagnosis and potentially unveiling new targeted-gene variants responsible for IEI phenotype.

PMID:33838017 | DOI:10.1002/iid3.420

Biostatistics. 2021 Apr 10:kxab010. doi: 10.1093/biostatistics/kxab010. Online ahead of print.

ABSTRACT

Malaria is an infectious disease affecting a large population across the world, and interventions need to be efficiently applied to reduce the burden of malaria. We develop a framework to help policy-makers decide how to allocate limited resources in realtime for malaria control. We formalize a policy for the resource allocation as a sequence of decisions, one per intervention decision, that map up-to-date disease related information to a resource allocation. An optimal policy must control the spread of the disease while being interpretable and viewed as equitable to stakeholders. We construct an interpretable class of resource allocation policies that can accommodate allocation of resources residing in a continuous domain and combine a hierarchical Bayesian spatiotemporal model for disease transmission with a policy-search algorithm to estimate an optimal policy for resource allocation within the pre-specified class. The estimated optimal policy under the proposed framework improves the cumulative long-term outcome compared with naive approaches in both simulation experiments and application to malaria interventions in the Democratic Republic of the Congo.

PMID:33838029 | DOI:10.1093/biostatistics/kxab010

Int J Nurs Pract. 2021 Apr 10:e12942. doi: 10.1111/ijn.12942. Online ahead of print.

ABSTRACT

BACKGROUND: Incorrect surgical counts are closely related to retained surgical items, which pose a threat to patients. However, the risk factors for incorrect surgical counts have not been identified yet.

AIM: To identify the risk factors associated with incorrect surgical counts during surgery in a tertiary hospital.

DESIGN: An observational case-control study.

METHODS: Seventy cases of incorrect surgical counts were reviewed in this study. Data were collected from January 1, 2014, to April 4, 2019. For each case, we included four randomly selected control cases involving the same surgical procedures by the same surgeon within a 6-month period for comparison. The medical data of these cases were extracted for further statistical analysis.

RESULTS: A higher incidence of incorrect surgical counts was observed among surgical counts performed between 8:00 a.m. to 12:00 a.m., emergency operations, prolonged procedures, and/or after addition of surgical items.

CONCLUSION: Prolonged surgical procedures, emergency operations, time of occurrence, and addition of surgical items were the risk factors related to incorrect surgical counts during surgery.

SUMMARY STATEMENT: What is already known about the topic? Incorrect surgical count is a perplexing problem during operation. Incorrect surgical count is closely associated with retained surgical items which can cause patient injury. The underlaying risk factors of incorrect surgical count were still unknown. What this paper adds? This was the first case-control study for incorrect surgical counts in China. The present research demonstrated that several risk factors were significantly associated with the occurrence of incorrect surgical counts, including the time period, the type of surgery, and the duration of the procedure. Vigilance should be maintained during an emergency operation or a long procedure to reduce the incidence of incorrect surgical counts. The implications of this paper: It is important for nurses to be aware of the factors that can interfere with correct surgical counts, thereby ensuring vigilance during emergency operations or long procedures. By identifying these risk factors, a more comprehensive safety policy in the operation room can be implemented to reduce incorrect surgical counts. Novel technological adjuncts should be promoted in the operating room gradually to improve overall patient safety.

PMID:33837996 | DOI:10.1111/ijn.12942

Neurogastroenterol Motil. 2021 Apr 10:e14158. doi: 10.1111/nmo.14158. Online ahead of print.

ABSTRACT

BACKGROUND: Hiatal hernia is clinically important because it impairs the protective mechanism that prevents gastroesophageal reflux-induced injury. Diagnosing hiatal hernia is more important in neurologically impaired children because hiatal hernia-induced gastroesophageal reflux often causes severe complications such as aspiration pneumonia or malnutrition. We aimed to evaluate the patient characteristics and early predictors of hiatal hernia in neurologically impaired children.

METHODS: We retrospectively investigated 97 neurologically impaired children who underwent esophagogastroduodenoscopy and upper gastrointestinal series between March 2004 and June 2019. Demographic and clinical characteristics, as well as endoscopic and radiological findings, were statistically analyzed.

RESULTS: Of the 97 children recruited, 22 (22.7%) had hiatal hernia. When comparing the non-hiatal hernia group with the hiatal hernia group, neurological disease longer than 6 months (odds ratio 10.9, 95% confidence interval 1.2-96.5), wasting (odds ratio 4.6, 95% confidence interval 1.3-16.3), enteral tube feeding (odds ratio 9.2, 95% confidence interval 1.6-53.0), and history of aspiration pneumonia (odds ratio 6.5, 95% confidence interval 1.2-34.5) were identified as early predictors of hiatal hernia.

CONCLUSIONS: Timely identification of predictors of developing hiatal hernia in neurologically impaired children is important for early diagnostic confirmation to initiate optimal medical or surgical treatment of hiatal hernia to avoid serious complications such as aspiration pneumonia and malnutrition.

PMID:33837998 | DOI:10.1111/nmo.14158

Environ Sci Pollut Res Int. 2021 Apr 10. doi: 10.1007/s11356-021-13579-1. Online ahead of print.

ABSTRACT

This study evaluated the quality of groundwater and its suitability for drinking and irrigation in the hilly area of the Taihang Mountains in Henan Province, China. Groundwater samples were collected from 43 unconfined and 20 confined wells and analyzed. The pollution index of groundwater (PIG) was estimated based on the physicochemical parameters, and seven indices, including the sodium adsorption ratio (SAR), sodium percentage (%Na), residual sodium carbonate (RSC), permeability index (PI), magnesium ratio (MR), Kelley’s ratio (KR), and corrosivity ratio (CR), were calculated to qualify the groundwater within the research area for irrigation activities. Multivariate statistical techniques were performed to better understand the hydrochemical processes. Chemical analysis showed that the dominant cation and anion were Ca²⁺ and HCO₃^–, respectively, and the principal hydrochemical facies was Ca-Mg-HCO₃. In terms of pH, total dissolved solids, Na⁺, Cl^–, F^–, and SO₄^2-, most samples were well within the limits prescribed by Chinese standards for drinking water quality, but more than half of the unconfined samples exceeded the specified limits for total hardness and nitrate. The PIG values suggested the pollution level was insignificant for all confined water samples and 72.09% of unconfined water samples, but the PIG distribution map showed that the water in the south central part of the study area had low to moderate pollution. According to the computed values of SAR, %Na, RSC, PI, KR, and MR and the results of a salinity diagram, the results further indicated that most of the studied samples were appropriate for irrigation usage. Only the CR values rendered 41.86% of the unconfined samples and 20% of the confined samples unfit for irrigation. Hence, proper measures are needed to resolve the corrosivity problem. Factor analysis resulted in the extraction of 3 factors that explained 81% of the data variability, and the extracted factors pointed towards geogenic factors governing the groundwater quality.

PMID:33837944 | DOI:10.1007/s11356-021-13579-1

CJEM. 2021 Apr 10. doi: 10.1007/s43678-021-00119-6. Online ahead of print.

ABSTRACT

BACKGROUND: The recommended rocuronium dose for rapid sequence intubation is 1.0 mg/kg; however, the optimal dose for emergency airway management is not clear. We assessed the relationship between rocuronium dose and first-attempt success among emergency department (ED) patients undergoing rapid sequence intubation.

METHODS: This is a secondary analysis of the National Emergency Airway Registry (NEAR), an observational 25-center registry of ED intubations. Ninety percent recording compliance was required from each site for data inclusion. We included all patients > 14 years of age who received rocuronium for rapid sequence intubation from 1 Jan 2016 to 31 Dec 2018. We compared first-attempt success between encounters using alternative rocuronium doses (< 1.0, 1.0-1.1, 1.2-1.3 and ≥1.4 mg/kg). We performed logistic regressions to control for predictors of difficult airways, indication, pre-intubation hemodynamics, operator, body habitus and device. We also performed subgroup analyses stratified by device (direct vs. video laryngoscopy). We calculated univariate descriptive statistics and odds ratios (OR) from multivariable logistic regressions with cluster-adjusted 95% confidence intervals (CI).

RESULTS: 19,071 encounters were recorded during the 3-year period. Of these, 8,034 utilized rocuronium for rapid sequence intubation. Overall, first attempt success was 88.4% for < 1.0 mg/kg, 88.1% for 1.0-1.1 mg/kg, 89.7% for 1.2-1.3 mg/kg, and 92.2% for ≥1.4 mg/kg. Logistic regression demonstrated that when direct laryngoscopy was used and when compared to the standard dosing range of 1.0-1.1 mg/kg, the adjusted odds of a first attempt success was significantly higher in ≥1.4 mg/kg group at 1.9 (95% CI 1.3-2.7) relative to the other dosing ranges, OR 0.9 (95% CI 0.7-1.2) for < 1.0 mg/kg and OR 1.2 (95% CI 0.9-1.7) for the 1.2-1.3 mg/kg group. First-attempt success was similar across all rocuronium doses among patients utilizing video laryngoscopy. Patients who were hypotensive (SBP < 100 mmHg) prior to intubation had higher first-attempt success 94.9% versus 88.6% when higher doses of rocuronium were used. The rates of all peri-intubation adverse events and desaturation were similar between dosing groups, laryngoscope type utilized and varying pre-intubation hemodynamics.

CONCLUSIONS: Rocuronium dosed ≥1.4 mg/kg was associated with higher first attempt success when using direct laryngoscopy and among patients with pre-intubation hypotension with no increase in adverse events. We recommend further prospective evaluation of the dosing of rocuronium prior to offering definitive clinical guidance.

PMID:33837951 | DOI:10.1007/s43678-021-00119-6

J Am Geriatr Soc. 2021 Apr 10. doi: 10.1111/jgs.17156. Online ahead of print.

ABSTRACT

BACKGROUND: Older patients with acute decompensated heart failure (ADHF) have severely impaired physical function (PF) and quality of life (QOL). However, relationships between impairments in PF and QOL are unknown but are relevant to clinical practice and trial design.

METHODS: We assessed 202 consecutive patients hospitalized with ADHF in the multicenter Rehabilitation Therapy in Older Acute HF Patients (REHAB-HF) Trial. PF measures included Short Physical Performance Battery (SPPB) and 6-min walk distance (6MWD). Disease-specific QOL was assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ). General QOL was assessed by the Short Form-12 (SF-12) and EuroQol-5D-5L. PF was evaluated as a predictor of QOL using stepwise regression adjusted for age, sex, race, and New York Heart Association class.

RESULTS: Participants were 72 ± 8 years, 54% women, 55% minority race, 52% with reduced ejection fraction, and body mass index 33 ± 9 kg/m² . Participants had severe impairments in PF (6MWD 185 ± 99 m, SPPB 6.0 ± 2.5 units) and disease-specific QOL (KCCQ Overall Score 41 ± 21 and Physical Score 47 ± 24) and general QOL (SF-12 Physical Score 28 ± 9 and EuroQol Visual Analog Scale 57 ± 23). There were modest, statistically significant correlations between 6MWD and KCCQ Overall, KCCQ Physical Limitation, and SF-12 Physical Scores (r = 0.23, p < 0.001; r = 0.30, p < 0.001; and r = 0.24, p = 0.001, respectively); and between SPPB and KCCQ Physical and SF-12 Physical Scores (r = 0.20, p = 0.004, and r = 0.19, p = 0.007, respectively). Both 6MWD and SPPB were correlated with multiple components of the EuroQol-5D-5L. 6MWD was a significant, weak predictor of KCCQ Overall Score and SF-12 Physical Score (estimate = 0.05 ± 0.01, p < 0.001 and estimate = 0.05 ± 0.02, p = 0.012, respectively). SPPB was a significant, weak predictor of KCCQ Physical Score and SF-12 Physical Score (estimate = 1.37 ± 0.66, p = 0.040 and estimate = 0.54 ± 0.25, p = 0.030, respectively).

CONCLUSION: In older, hospitalized ADHF patients, PF and QOL are both severely impaired but are only modestly related, suggesting that PF and QOL provide complementary information and assessment of both should be considered to fully assess clinically meaningful patient-oriented outcomes.

PMID:33837953 | DOI:10.1111/jgs.17156

J Med Virol. 2021 Apr 10. doi: 10.1002/jmv.27011. Online ahead of print.

ABSTRACT

INTRODUCTION: We have read with great interest the meta-analysis that examined the impact of increased red cell distribution width (RDW) and COVID-19 outcomes, conducted by Lee and colleagues, and recently published in the Journal of Medical Virology. The authors concluded that elevations in RDW were associated with adverse COVID-19 outcomes. However, the impact of elevation of RDW independent of anemia in COVID-19 remains to be clarified.

METHODS: Patients ≥18 years who were diagnosed with COVID-19 at the Mount Sinai Health System between March 1 and April 1, 2020 and had a complete blood count (CBC) at presentation (n=2562) were selected to assess the association between RDW and mortality. Multivariable Cox proportional hazards regression models, stratified by presence of anemia, were performed to assess the independent association of RDW with mechanical ventilation and mortality.

RESULTS: At univariate analysis, elevated RDW was statistically significantly associated with mechanical ventilation (p = 0.0109) and mortality (p < 0.0001). We found that elevated RDW was statistically associated with higher risk of both being placed on a ventilator (HRadj: 1.66, 95% CI: 1.19-2.32) and mortality (HRadj: 1.60, 95% CI: 1.18-2.15) in non-anemic patients, but there was no association in anemic patients. These associations were independent of the effects of age, sex, race, and CCI.

DISCUSSION: In this study, we show that the elevated RDW association with mortality and mechanical ventilation is present exclusively in non-anemic patients. Therefore, we propose that RDW be considered by clinicians, especially in non-anemic patients, when risk-stratifying COVID-19 patients. This article is protected by copyright. All rights reserved.

PMID:33837966 | DOI:10.1002/jmv.27011

Drug Saf. 2021 Apr 10. doi: 10.1007/s40264-021-01063-1. Online ahead of print.

ABSTRACT

INTRODUCTION: Genetic variations of enzymes that affect the pharmacokinetics and hence effects of medications differ between ethnicities, resulting in variation in the risk of adverse drug reactions (ADR) between different populations. Previous work has demonstrated that risk-group considerations can be incorporated into approaches of statistical signal detection. It is unknown whether databases of individual case safety reports (ICSRs) are sensitive to pharmacogenomic differences between populations.

OBJECTIVE: The aim of this study was to explore the sensitivity of a global database of ICSRs to known pharmacogenomic risk variants common in Japan.

METHODS: The data source was VigiBase, the global database of ICSRs, including all reports entered in the version frozen on 5 January 2020. Subgroup disproportionality analysis was used to compare ICSRs of two subgroups, Japan and rest of world (RoW). Reports for UGT1A1-metabolized irinotecan and the CYP2C19-metabolized drugs voriconazole, escitalopram and clopidogrel were selected for comparison between the subgroups based upon known genetic polymorphisms with high prevalence in Japan. Contrast between the subgroups was quantified by IC delta [Formula: see text]), a robust shrinkage observed-to-expected (OE) ratio on a log scale. Harmonic mean p values (HMP) were calculated for each drug to evaluate whether a list of pre-specified ADRs were collectively significantly over- (or under-)reported as hypothesized. Daily drug dosages were calculated for ICSRs with sufficient information, and dose distributions were compared between Japan and RoW and related to differences in regionally approved doses.

RESULTS: The predictions of over-reporting patterns for specific ADRs were observed and confirmed in bootstrap HMP analyses (p = 0.004 for irinotecan and p < 0.001 for each of voriconazole, escitalopram and clopidogrel) and compared with similar drugs with different metabolic pathways. The impact of proactive regulatory action, such as recommended dosing and therapeutic drug monitoring (TDM), was also observable within the global database. For irinotecan and escitalopram, there was evidence of use of lower dosages as recommended in the Japanese labels; for voriconazole, there was evidence of use of TDM with an over-reporting of terms related to drug level measurements and an under-reporting of liver toxicity.

CONCLUSIONS: Pharmaco-ethnic vulnerabilities caused by pharmacogenomic differences between populations may contribute to differences in ADR reporting between countries in a global database of ICSRs. Regional analyses within a global database can inform on the effectiveness of local risk minimization measures and should be leveraged to catalyse the conversion of real-world usage into safer use of drugs in ethnically tailored ways.

PMID:33837924 | DOI:10.1007/s40264-021-01063-1