Category: Statistics

Sci Rep. 2021 Aug 5;11(1):15923. doi: 10.1038/s41598-021-94959-y.

ABSTRACT

Complex genetic diseases may be modulated by a large number of epistatic interactions affecting a polygenic phenotype. Identifying these interactions is difficult due to computational complexity, especially in the case of higher-order interactions where more than two genomic variants are involved. In this paper, we present BitEpi, a fast and accurate method to test all possible combinations of up to four bi-allelic variants (i.e. Single Nucleotide Variant or SNV for short). BitEpi introduces a novel bitwise algorithm that is 1.7 and 56 times faster for 3-SNV and 4-SNV search, than established software. The novel entropy statistic used in BitEpi is 44% more accurate to identify interactive SNVs, incorporating a p-value-based significance testing. We demonstrate BitEpi on real world data of 4900 samples and 87,000 SNPs. We also present EpiExplorer to visualize the potentially large number of individual and interacting SNVs in an interactive Cytoscape graph. EpiExplorer uses various visual elements to facilitate the discovery of true biological events in a complex polygenic environment.

PMID:34354094 | DOI:10.1038/s41598-021-94959-y

Qual Manag Health Care. 2021 Aug 3. doi: 10.1097/QMH.0000000000000320. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Hospitals worldwide are faced with the problem of discharging patients on time. Delayed discharge creates domino effects with significant implications for hospitals. The accountable care team (ACT) is a multidisciplinary, unit-based approach to identifying opportunities to improve patient care and address inefficiencies in care delivery and throughput, including assuring timely discharges. In response to concerns about emergency department boarding times and delays in timely discharge, the ACT recommended a set of strategies to improve communication across team members and to reduce wait times for transportation within and outside the hospital. Collectively these strategies were thought to increase the proportion of patients discharged on time. In this article, we describe and assess changes in timely discharge resulting from the implementation of strategies recommended by the ACT.

METHODS: This study uses a retrospective, quasi-experimental design to compare the percentage of discharges by 1 PM of hospital units implementing the ACT intervention to those units not implementing the intervention. Median discharge time was compared pre- and post-implementation using the Wilcoxon rank sum test. Difference-in-differences modeling was employed to assess whether changes in the percentage of discharges by 1 PM differed between units implementing the intervention and units not implementing the intervention.

RESULTS: One month post-implementation, the percentage discharged by 1 PM was statistically significantly higher for units implementing the intervention (53.6%) compared with comparison units (22.5%, t = -4.48, P < .01). Statistically significant differences in the percentage discharged by 1 PM were also seen at 3 and 6 months post-implementation. The median discharge time showed a statistically significant decrease by 77 minutes from the baseline to intervention period (P < .01).

CONCLUSION: The result from the study suggests that ACTs can be used to develop approaches aimed at improving patient care in general, and discharge efficiencies in particular. Health care organizations are encouraged to utilize and then evaluate the specific activities of multidisciplinary teams aimed at developing recommendations for practice improvement.

PMID:34354033 | DOI:10.1097/QMH.0000000000000320

Nat Commun. 2021 Aug 5;12(1):4715. doi: 10.1038/s41467-021-25017-4.

ABSTRACT

Methane (CH₄) emissions from oil and natural gas (O&NG) systems are an important contributor to greenhouse gas emissions. In the United States, recent synthesis studies of field measurements of CH₄ emissions at different spatial scales are ~1.5-2× greater compared to official greenhouse gas inventory (GHGI) estimates, with the production-segment as the dominant contributor to this divergence. Based on an updated synthesis of measurements from component-level field studies, we develop a new inventory-based model for CH₄ emissions, for the production-segment only, that agrees within error with recent syntheses of site-level field studies and allows for isolation of equipment-level contributions. We find that unintentional emissions from liquid storage tanks and other equipment leaks are the largest contributors to divergence with the GHGI. If our proposed method were adopted in the United States and other jurisdictions, inventory estimates could better guide CH₄ mitigation policy priorities.

PMID:34354066 | DOI:10.1038/s41467-021-25017-4

Ann Surg. 2021 Aug 4. doi: 10.1097/SLA.0000000000005133. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of this study was to build a predictive model of operative difficulty in open liver resections (LRs).

SUMMARY BACKGROUND DATA: Recent attempts at classifying open-LR have been focused on postoperative outcomes and were based on predefined anatomical schemes without taking into account other anatomical/technical factors.

METHODS: Four intraoperative variables were perceived by the authors as to reflect operative difficulty: operation and transection times, blood loss, and number of Pringle maneuvers. A hierarchical ascendant classification (HAC) was used to identify homogeneous groups of operative difficulty, based on these variables. Predefined technical/anatomical factors were then selected to build a multivariable logistic regression model (DIFF-scOR), to predict the probability of pertaining to the highest difficulty group. Its discrimination/calibration was assessed. Missing data were handled using multiple imputation.

RESULTS: HAC identified 2 clusters of operative difficulty. In the “Difficult LR” group (20.8% of the procedures), operation time (401 min vs 243 min), transection time (150 vs.63 minute), blood loss (900 vs 400 mL), and number of Pringle maneuvers (3 vs 1) were higher than in the “Standard LR” group. Determinants of operative difficulty were body weight, number and size of nodules, biliary drainage, anatomical or combined LR, transection planes between segments 2 and 4, 4, and 8 or 7 and 8, nonanatomical resections in segments 2, 7, or 8, caval resection, bilioentric anastomosis and number of specimens. The c-statistic of the DIFF-scOR was 0.822. By contrast, the discrimination of the DIFF-scOR to predict 90-day mortality and severe morbidity was poor (c-statistic: 0.616 and 0.634, respectively).

CONCLUSION: The DIFF-scOR accurately predicts open-LR difficulty and may be used for various purposes in clinical practice and research.

PMID:34353987 | DOI:10.1097/SLA.0000000000005133

Chin Med J (Engl). 2021 Aug 4. doi: 10.1097/CM9.0000000000001606. Online ahead of print.

ABSTRACT

BACKGROUND: Scoliosis secondary to neurofibromatosis type 1 (NF1) in children aged <10 years is an important etiology of early-onset scoliosis (EOS). This study was performed to investigate the curve evolution of patients with EOS secondary to NF1 undergoing bracing treatment and to analyze high-risk indicators of rapid curve progression.

METHODS: Children with EOS due to NF1 who underwent bracing treatment from 2010 to 2017 were retrospectively reviewed. The angle velocity (AV) at each visit was calculated, and patients with rapid curve progression (AV of >10°/year) were identified. The age at modulation and the AV before and after modulation were obtained. Patients with (n = 18) and without rapid curve progression (n = 10) were statistically compared.

RESULTS: Twenty-eight patients with a mean age of 6.5 ± 1.9 years at the initial visit were reviewed. The mean Cobb angle of the main curve was 41.7° ± 2.4° at the initial visit and increased to 67.1° ± 8.6° during a mean follow-up of 44.1 ± 8.5 months. The overall AV was 6.6° ± 2.4°/year for all patients. At the last follow-up, all patients presented curve progression of >5°, and 20 (71%) patients had progressed by >20°. Rapid curve progression was observed in 18 (64%) patients and was associated with younger age at the initial visit and a higher incidence of modulation change during follow-up (t = 2.868, P = 0.008 and <0.001, respectively). The mean AV was 4.4° ± 1.2°/year before modulation and 11.8° ± 2.7°/year after modulation (t = 11.477, P < 0.010).

CONCLUSIONS: Curve progression of >10°/year is associated with younger age at the initial visit, and modulation change indicated the occurrence of the rapid curve progression phase.

PMID:34354003 | DOI:10.1097/CM9.0000000000001606

J Investig Med. 2021 Aug 5:jim-2020-001497. doi: 10.1136/jim-2020-001497. Online ahead of print.

ABSTRACT

Direct oral anticoagulants (DOACs) have become the treatment of choice in thromboembolism prophylaxis for non-valvular atrial fibrillation, surpassing warfarin. While interruption of DOAC therapy for various reasons is a common eventuality, the body of data from real-world clinical practice on the implications of such interruptions in different clinical settings is still limited. We assessed complication rates from DOAC (apixaban, rivaroxaban, dabigatran) interruption compared with warfarin in hospitalized patients. We performed a retrospective cohort analysis of electronic records of patients hospitalized in Rabin Medical Center between 2010 and 2017. Incidents of anticoagulation interruptions for various reasons (including unintended interruptions) were collected. DOAC-treated patients were excluded if they reported non-compliance, and warfarin-treated patients were excluded if their international normalized ratio measurement on admission was subtherapeutic. Outcomes included ischemic stroke, systemic thromboembolism, myocardial infarction, and all-cause mortality within 90 days of anticoagulation interruption. The median CHA2DS2-VASc score was 5.0 (IQR 4.0-6.0) in both treatment groups. The associated risk of stroke, thromboembolic complications, myocardial infarction, and all-cause mortality after interruption of anticoagulation was not significantly different between the 2 treatment groups. Selective comparison of patients who were well balanced on warfarin before treatment interruption to DOAC-treated patients did not significantly influence the outcomes. This study did not find a significant difference in the complication rate after interruption of DOAC therapy compared with interruption of warfarin therapy in hospitalized patients with a high risk of thromboembolism.

PMID:34353884 | DOI:10.1136/jim-2020-001497

Anat Cell Biol. 2021 Aug 6. doi: 10.5115/acb.21.101. Online ahead of print.

ABSTRACT

The atlas (C1) is known to present congenital anomalies in its anterior and posterior arches. The reported incidence of C1 anomalies is varied among the ethnic groups. We sought to determine the prevalence and various existing variations of C1 arch congenital anomalies in Omani subjects. This study was carried out by reviewing the cervical spine computed tomography scans of all the patients who had been referred to the Radiology Department, Sultan Qaboos University Hospital. Descriptive statistics and chi-square test were employed to analyse the data. A total of 663 subjects aged ≥18 years were included in the present study. Overall prevalence of C1 arch anomalies was 4.37% with 4.07% of isolated posterior arch anomalies, 0.3% of combined anterior and posterior arch anomalies. Among isolated posterior arch anomalies, type A and type B posterior arch defects were found in 3.77% and 0.3% of cases, respectively. Atlanto-occipital assimilation was noted in one case of total study subjects. The prevalence rate of C1 arch anomalies is relatively high in Omani subjects. The baseline data of C1 arch anomalies reported in the present study has a great impact on clinical practice, due to the fact that studying and evaluating the types of congenital anomalies helps in their accurate diagnosis and early intervention.

PMID:34353977 | DOI:10.5115/acb.21.101

J Neurol Neurosurg Psychiatry. 2021 Aug 5:jnnp-2021-326868. doi: 10.1136/jnnp-2021-326868. Online ahead of print.

ABSTRACT

BACKGROUND: Therapeutic trials are now underway in genetic forms of frontotemporal dementia (FTD) but clinical outcome measures are limited. The two most commonly used measures, the Clinical Dementia Rating (CDR)+National Alzheimer’s Disease Coordinating Center (NACC) Frontotemporal Lobar Degeneration (FTLD) and the FTD Rating Scale (FRS), have yet to be compared in detail in the genetic forms of FTD.

METHODS: The CDR+NACC FTLD and FRS were assessed cross-sectionally in 725 consecutively recruited participants from the Genetic FTD Initiative: 457 mutation carriers (77 microtubule-associated protein tau (MAPT), 187 GRN, 193 C9orf72) and 268 family members without mutations (non-carrier control group). 231 mutation carriers (51 MAPT, 92 GRN, 88 C9orf72) and 145 non-carriers had available longitudinal data at a follow-up time point.

RESULTS: Cross-sectionally, the mean FRS score was lower in all genetic groups compared with controls: GRN mutation carriers mean 83.4 (SD 27.0), MAPT mutation carriers 78.2 (28.8), C9orf72 mutation carriers 71.0 (34.0), controls 96.2 (7.7), p<0.001 for all comparisons, while the mean CDR+NACC FTLD Sum of Boxes was significantly higher in all genetic groups: GRN mutation carriers mean 2.6 (5.2), MAPT mutation carriers 3.2 (5.6), C9orf72 mutation carriers 4.2 (6.2), controls 0.2 (0.6), p<0.001 for all comparisons. Mean FRS score decreased and CDR+NACC FTLD Sum of Boxes increased with increasing disease severity within each individual genetic group. FRS and CDR+NACC FTLD Sum of Boxes scores were strongly negatively correlated across all mutation carriers (r_s=-0.77, p<0.001) and within each genetic group (r_s=-0.67 to -0.81, p<0.001 in each group). Nonetheless, discrepancies in disease staging were seen between the scales, and with each scale and clinician-judged symptomatic status. Longitudinally, annualised change in both FRS and CDR+NACC FTLD Sum of Boxes scores initially increased with disease severity level before decreasing in those with the most severe disease: controls -0.1 (6.0) for FRS, -0.1 (0.4) for CDR+NACC FTLD Sum of Boxes, asymptomatic mutation carriers -0.5 (8.2), 0.2 (0.9), prodromal disease -2.3 (9.9), 0.6 (2.7), mild disease -10.2 (18.6), 3.0 (4.1), moderate disease -9.6 (16.6), 4.4 (4.0), severe disease -2.7 (8.3), 1.7 (3.3). Sample sizes were calculated for a trial of prodromal mutation carriers: over 180 participants per arm would be needed to detect a moderate sized effect (30%) for both outcome measures, with sample sizes lower for the FRS.

CONCLUSIONS: Both the FRS and CDR+NACC FTLD measure disease severity in genetic FTD mutation carriers throughout the timeline of their disease, although the FRS may be preferable as an outcome measure. However, neither address a number of key symptoms in the FTD spectrum, for example, motor and neuropsychiatric deficits, which future scales will need to incorporate.

PMID:34353857 | DOI:10.1136/jnnp-2021-326868

BMJ Open Diabetes Res Care. 2021 Aug;9(1):e002177. doi: 10.1136/bmjdrc-2021-002177.

ABSTRACT

INTRODUCTION: Cost-effectiveness analyses are becoming increasingly important in Japan following the introduction of a health technology assessment scheme. The study objective was to develop an economic model to evaluate the cost-effectiveness of two interventions for type 2 diabetes in a Japanese population.

RESEARCH DESIGN AND METHODS: The Japan Diabetes Complications Study/Japanese Elderly Diabetes Intervention Trial risk engine (JJRE) Cost-Effectiveness Model (JJCEM) was developed, incorporating validated risk equations in Japanese patients with type 2 diabetes from the JJRE. Weibull regression models were developed for progression of the model outcomes, and a targeted literature review was performed to inform default values for utilities and costs. To illustrate outcomes, two simulated analyses were performed in younger (aged 40 years) and older (aged 80 years) Japanese populations, comparing a hypothetical treatment with placebo.

RESULTS: The model considers a population based on user-defined values for 11 baseline characteristic parameters and simulates rates of diabetic complications over a defined time horizon. Costs, quality-adjusted life years, and an incremental cost-effectiveness ratio are estimated. The model provides disaggregated results for two competing interventions, allowing visualization of the key drivers of cost and utility. A scatterplot of simulations and cost-effectiveness acceptability curve are generated for each analysis.

CONCLUSIONS: This is the first cost-effectiveness model for East Asian patients with type 2 diabetes, developed using Japan-specific risk equations. This population constitutes the largest share of the global population with diabetes, making this model highly relevant. The model can be used to evaluate the cost-effectiveness of anti-diabetic interventions in patients with type 2 diabetes in Japan and other East Asian populations.

PMID:34353881 | DOI:10.1136/bmjdrc-2021-002177

BMJ Open. 2021 Aug 5;11(8):e051208. doi: 10.1136/bmjopen-2021-051208.

ABSTRACT

INTRODUCTION: Methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia is a frequent condition, with high mortality rates. There is a growing interest in identifying new therapeutic regimens able to reduce therapeutic failure and mortality observed with the standard of care of beta-lactam monotherapy. In vitro and small-scale studies have found synergy between cloxacillin and fosfomycin against S. aureus. Our aim is to test the hypothesis that cloxacillin plus fosfomycin achieves higher treatment success than cloxacillin alone in patients with MSSA bacteraemia.

METHODS: We will perform a superiority, randomised, open-label, phase IV-III, two-armed parallel group (1:1) clinical trial at 20 Spanish tertiary hospitals. Adults (≥18 years) with isolation of MSSA from at least one blood culture ≤72 hours before inclusion with evidence of infection, will be randomly allocated to receive either cloxacillin 2 g/4-hour intravenous plus fosfomycin 3 g/6-hour intravenous or cloxacillin 2 g/4-hour intravenous alone for 7 days. After the first week, sequential treatment and total duration of antibiotic therapy will be determined according to clinical criteria by the attending physician.Primary endpoints: (1) Treatment success at day 7, a composite endpoint comprising all the following criteria: patient alive, stable or with improved quick-Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA at day 7. (2) Treatment success at test of cure (TOC) visit: patient alive and no isolation of MSSA in blood culture or at another sterile site from day 8 until TOC (12 weeks after randomisation).We assume a rate of treatment success of 74% in the cloxacillin group. Accepting alpha risk of 0.05 and beta risk of 0.2 in a two-sided test, 183 subjects will be required in each of the control and experimental groups to obtain statistically significant difference of 12% (considered clinically significant).

ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Ethics Committee of Bellvitge University Hospital (AC069/18) and from the Spanish Medicines and Healthcare Product Regulatory Agency (AEMPS, AC069/18), and is valid for all participating centres under existing Spanish legislation. The results will be presented at international meetings and will be made available to patients and funders.

TRIAL REGISTRATION NUMBER: The protocol has been approved by AEMPS with the Trial Registration Number EudraCT 2018-001207-37. ClinicalTrials.gov Identifier: NCT03959345; Pre-results.

PMID:34353808 | DOI:10.1136/bmjopen-2021-051208