Incidence of and risk factors for major haemorrhage in patients treated with ibrutinib: An integrated analysis

AbstractAlthough Alzheimer’s disease (AD) is highly heritable, genetic variants known to be associated with AD only explain a small proportion of its heritability. Genetic factors may only convey disease risk in individuals with certain environmental exposures, suggesting that a multi-omics approach could reveal underlying mechanisms contributing to complex traits, such as AD. We developed an integrated network to investigate relationships between metabolomics, genomics, and AD risk factors using Wisconsin Registry for Alzheimer’s Prevention participants. Analyses included 1,111 non-Hispanic Caucasian participants with whole blood expression for 11,376 genes (imputed from dense genome-wide genotyping), 1,097 fasting plasma metabolites, and 17 AD risk factors. A subset of 155 individuals also had 364 fasting cerebral spinal fluid (CSF) metabolites. After adjusting each of these 12,854 variables for potential confounders, we developed an undirected graphical network, representing all significant pairwise correlations upon adjusting for multiple testing. There were many instances of genes being indirectly linked to AD risk factors through metabolites, suggesting that genes may influence AD risk through particular metabolites. Follow-up analyses suggested that glycine mediates the relationship between CPS1 and measures of cardiovascular and diabetes risk, including body mass index, waist-hip ratio, inflammation, and insulin resistance. Further, 38 CSF metabolites explained more than 60% of the variance of CSF levels of tau, a detrimental protein that accumulates in the brain of AD patients and is necessary for its diagnosis. These results further our understanding of underlying mechanisms contributing to AD risk while demonstrating the utility of generating and integrating multiple omics data types.

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Miscellaneous problems

Emergencies in Anaesthesia ◽

10.1093/med/9780198758143.003.0014 ◽

2020 ◽

pp. 417-452

Author(s):

John Isaac ◽

Mark Stoneham ◽

Nerida Williams ◽

Bruce McCormick

Keyword(s):

Risk Factors ◽

Aortic Aneurysm ◽

Major Haemorrhage ◽

Emergency Laparotomy ◽

Anaesthetic Agents ◽

Bone Cement Implantation Syndrome ◽

Aneurysm Repair ◽

Aortic Aneurysm Repair ◽

Transfusion Reactions

The penultimate chapter covers miscellaneous topics not described elsewhere. Major haemorrhage is addressed with sections on controlling haemorrhage, using blood products, and diagnosing/treating acute transfusion reactions. Guidance is given for treating patients with burns, extravasation of anaesthetic agents, intra-arterial injection, inoculation injury, and bone cement implantation syndrome. Advice is presented for managing fire in theatre. Clinical guidance/recipes are given for anaesthetising patients who have bled after tonsillectomy, thyroid surgery, or carotid endarterectomy. The final two sections concern patients undergoing emergency laparotomy or emergency aortic aneurysm repair. Each problem is addressed by firstly its definitions, presentation, investigations, risk factors, and exclusions; then how it can be managed in the immediate, medium-, and long-term situations. Finally, any special considerations are outlined, followed by a list of further reading.

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Skin rash following Administration of Apalutamide in Japanese patients with Advanced Prostate Cancer: an integrated analysis of the phase 3 SPARTAN and TITAN studies and a phase 1 open-label study

BMC Urology ◽

10.1186/s12894-020-00689-0 ◽

2020 ◽

Vol 20 (1) ◽

Cited By ~ 1

Author(s):

Hiroji Uemura ◽

Yosuke Koroki ◽

Yuki Iwaki ◽

Keiichiro Imanaka ◽

Takeshi Kambara ◽

...

Keyword(s):

Risk Factors ◽

Skin Rash ◽

Phase 1 ◽

Japanese Patients ◽

Clinical Risk Factors ◽

Integrated Analysis ◽

Plasma Exposure ◽

Phase 3 ◽

Clinical Risk ◽

Link Type

Abstract Background A higher incidence of apalutamide-related skin rash has been observed in Japanese patients with prostate cancer (PC). Methods This integrated analysis of data of Japanese patients from 2 global Phase 3 studies, SPARTAN (NCT01946204; patients with non-metastatic castration-resistant PC [nmCRPC]) and TITAN (NCT02489318; patients with metastatic castration-sensitive PC [mCSPC]), and the Phase 1 study 56021927PCR1008 (NCT02162836; patients with metastatic CRPC [mCRPC]), assessed clinical risk factors of apalutamide-related skin rash as well as the potential correlation with plasma exposure to apalutamide. Kaplan-Meier method was used for time-to-event analyses. Clinical risk factors for skin rash were assessed using odds ratio. Results Data from 68 patients (SPARTAN: n = 34, TITAN: n = 28, 56021927PCR1008: n = 6) receiving apalutamide 240 mg orally once-daily were analyzed. Rash (13 [19.1%]) and maculo-papular rash (11 [16.2%]) were the most frequently reported skin rash. All Grade and Grade 3 skin rash occurred in 35 (51.5%) and 10 (14.7%) patients, respectively. Most (85.7%) skin rash occurred within 4 months of apalutamide initiation and resolved in a median time of 1 month following the use of antihistamines, topical or systemic corticosteroids, with/without apalutamide dose interruptions/reductions. Median time-to-remission of first incidence of rash and maximum grade incidence of rash were 1.0 month (IQR: 0.36–1.81) and 1.0 month (IQR: 0.30–2.43), respectively. No significant clinical risk factors for the incidence of skin rash were observed. Areas under the curve (0–24 h) (AUC0–24, ss) at steady-state of plasma apalutamide concentration were numerically slightly higher in patients with skin rash than those without. Conclusions No clinical risk factors for rash could be detected. There is a potential correlation between incidence of skin rash and plasma exposure to apalutamide. In general, apalutamide-related skin rash is easily managed, with appropriate treatment with or without dose adjustment. Trial registration Retrospective pooled analysis of NCT01946204, NCT02489318, and NCT02162836.

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Social Risk Assessment and Management for Major Construction Projects in China Based on Fuzzy Integrated Analysis

Complexity ◽

10.1155/2019/2452895 ◽

2019 ◽

Vol 2019 ◽

pp. 1-17 ◽

Cited By ~ 1

Author(s):

Junxia Miao ◽

Dechun Huang ◽

Zhengqi He

Keyword(s):

Risk Factors ◽

Construction Projects ◽

Risk Level ◽

Integrated Analysis ◽

Social Risk ◽

Social Risk Factors ◽

Social Risks ◽

The Social ◽

Critical Social ◽

Overall Risk

With the vigorous development of major engineering projects in China, the social risks associated with major construction projects not only challenge the success of projects but also threaten social harmony and stability. Therefore, it is of great practical significance to assess and manage social risks. This paper aims to identify and evaluate the social risk factors by conducting a survey and assess the overall risk level of major construction projects (MCPs) with fuzzy integrated approach. First, 35 social risk factors and related stakeholders were identified based on literature analysis and case study. Then, 18 critical social risk factors (CSRFs) were selected and classified into six groups (CSRGs) based on a questionnaire survey. Next, using fuzzy integrated method, the probability of occurrence (PO), magnitude of impact (MI), the integrated risk level (IRL) of each CSRF and CSRG, and the overall risk of MCPs were calculated. As a result, “unfair compensation for housing demolition and land requisition” was the most critical social risk factor, and “policy/legal risk” was the most critical social risk group. The overall risk of MCPs was between moderate and high. At last, a social risk synthetic management framework was established, which can provide reference for policymakers and project decision makers to effectively manage the social risks.

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Structure-preserving integrated analysis for risk stratification with application to cancer staging

Biostatistics ◽

10.1093/biostatistics/kxab005 ◽

2021 ◽

Author(s):

Tianjie Wang ◽

Rui Chen ◽

Wenshuo Liu ◽

Menggang Yu

Keyword(s):

Risk Factors ◽

Survival Data ◽

Regression Tree ◽

Cancer Staging ◽

Classification And Regression Tree ◽

Integrated Analysis ◽

Data Sets ◽

Cancer Data ◽

Node Involvement ◽

Tree Method

Summary To provide appropriate and practical level of health care, it is critical to group patients into relatively few strata that have distinct prognosis. Such grouping or stratification is typically based on well-established risk factors and clinical outcomes. A well-known example is the American Joint Committee on Cancer staging for cancer that uses tumor size, node involvement, and metastasis status. We consider a statistical method for such grouping based on individual patient data from multiple studies. The method encourages a common grouping structure as a basis for borrowing information, but acknowledges data heterogeneity including unbalanced data structures across multiple studies. We build on the “lasso-tree” method that is more versatile than the well-known classification and regression tree method in generating possible grouping patterns. In addition, the parametrization of the lasso-tree method makes it very natural to incorporate the underlying order information in the risk factors. In this article, we also strengthen the lasso-tree method by establishing its theoretical properties for which Lin and others (2013. Lasso tree for cancer staging with survival data. Biostatistics 14, 327–339) did not pursue. We evaluate our method in extensive simulation studies and an analysis of multiple breast cancer data sets.

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Real-world effectiveness of teriparatide on fracture reduction in patients with osteoporosis and comorbidities or risk factors for fractures: Integrated analysis of 4 prospective observational studies

Bone ◽

10.1016/j.bone.2018.07.013 ◽

2018 ◽

Vol 116 ◽

pp. 58-66 ◽

Cited By ~ 16

Author(s):

Bente L. Langdahl ◽

Stuart Silverman ◽

Saeko Fujiwara ◽

Ken Saag ◽

Nicola Napoli ◽

...

Keyword(s):

Risk Factors ◽

Real World ◽

Observational Studies ◽

Fracture Reduction ◽

Integrated Analysis

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The Nexus+ approach applied to studies of Impacts, vulnerability and adaptation to climate change in Brazil

Sustentabilidade em Debate ◽

10.18472/sustdeb.v11n3.2020.33514 ◽

2020 ◽

Vol 11 (3) ◽

pp. 24-56

Author(s):

Sonia Maria Viggiani Coutinho ◽

Diogo Victor Santos ◽

Marcel Bursztyn ◽

José Antônio Marengo ◽

Saulo Rodrigues-Filho ◽

...

Keyword(s):

Climate Change ◽

Risk Factors ◽

Integrated Assessment ◽

Integrated Approach ◽

Coastal Areas ◽

Integrated Analysis ◽

Adaptation To Climate Change ◽

Methodological Choice ◽

Trade Offs ◽

Adaptation Options

This paper aims to present the methodology developed within the Impacts, Vulnerability and Adaptation (IVA) to climate change component of the Fourth National Communication (4CN) of Brazil. The methodological choice of this 4CN involves the application of the nexus+ integrated approach, based on studies of impacts and vulnerabilities for water, energy, food and socio-environmental securities, in the different in the territories of Brazilian biomes, coastal areas and cities. For each of these securities it were identified the observed impacts; analysis of risk conditions; definition and assessments of integrated analysis of key impacts at territorial level; inventory, selection and analysis of adaption options in the context of Nexus+, identifying synergies and trade-offs. This process made possible an integrated assessment among the conditioning risk factors, impacts and interactions among proposed adaptation options.

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Skin Rash Following Administration of Apalutamide in Japanese Patients with Advanced Prostate Cancer: An Integrated Analysis of the Phase 3 SPARTAN and TITAN Studies and a Phase 1 Open-Label Study

10.21203/rs.3.rs-26754/v2 ◽

2020 ◽

Author(s):

Hiroji Uemura ◽

Yosuke Koroki ◽

Yuki Iwaki ◽

Keiichiro Imanaka ◽

Takeshi Kambara ◽

...

Keyword(s):

Prostate Cancer ◽

Risk Factors ◽

Skin Rash ◽

Phase 1 ◽

Japanese Patients ◽

Clinical Risk Factors ◽

Integrated Analysis ◽

Plasma Exposure ◽

Phase 3 ◽

Clinical Risk

Abstract Background: A higher incidence of apalutamide-related skin rash has been observed in Japanese patients with prostate cancer (PC). Methods: This integrated analysis of data of Japanese patients from 2 global Phase 3 studies, SPARTAN (NCT01946204; patients with non‑metastatic castration-resistant PC [nmCRPC]) and TITAN (NCT02489318; patients with metastatic castration-sensitive PC [mCSPC]), and the Phase 1 study 56021927PCR1008 (NCT02162836; patients with metastatic CRPC [mCRPC]), assessed clinical risk factors of apalutamide-related skin rash as well as the potential correlation with plasma exposure to apalutamide. Kaplan-Meier method was used for time-to-event analyses. Clinical risk factors for skin rash were assessed using odds ratio. Results: Data from 68 patients ( SPARTAN: n=34, TITAN: n=28, 56021927PCR1008: n=6) receiving apalutamide 240 mg orally once-daily were analyzed. Rash (13 [19.1%]) and maculo-papular rash (11 [16.2%]) were the most frequently reported skin rash. All Grade and Grade 3 skin rash occurred in 35 (51.5%) and 10 (14.7%) patients, respectively. Most (85.7%) skin rash occurred within 4 months of apalutamide initiation and resolved in a median time of 1 month following the use of antihistamines, topical or systemic corticosteroids, with/without apalutamide dose interruptions/reductions. Median time-to-remission of first incidence of rash and maximum grade incidence of rash were 1.0 month (IQR: 0.36-1.81) and 1.0 month (IQR: 0.30-2.43), respectively. No significant clinical risk factors for the incidence of skin rash were observed. Areas under the curve (0-24 hours) (AUC 0-24, ss ) at steady‑state of plasma apalutamide concentration were numerically slightly higher in patients with skin rash than those without. Conclusions: No clinical risk factors for rash could be detected. There is a potential correlation between incidence of skin rash and plasma exposure to apalutamide. In general, apalutamide‑related skin rash is easily managed, with appropriate treatment with or without dose adjustment.

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