Intelligent techniques using molecular data analysis in leukaemia: an opportunity for personalized medicine support system

The use of intelligent techniques in medicine has brought a ray of hope in terms of treating leukaemia patients. Personalized treatment uses patient’s genetic profile to select a mode of treatment. This process makes use of molecular technology and machine learning, to determine the most suitable approach to treating a leukaemia patient. Until now, no reviews have been published from a computational perspective concerning the development of personalized medicine intelligent techniques for leukaemia patients using molecular data analysis. This review studies the published empirical research on personalized medicine in leukaemia and synthesizes findings across studies related to intelligence techniques in leukaemia, with specific attention to particular categories of these studies to help identify opportunities for further research into personalized medicine support systems in chronic myeloid leukaemia. A systematic search was carried out to identify studies using intelligence techniques in leukaemia and to categorize these studies based on leukaemia type and also the task, data source, and purpose of the studies. Most studies used molecular data analysis for personalized medicine, but future advancement for leukaemia patients requires molecular models that use advanced machine-learning methods to automate decision-making in treatment management to deliver supportive medical information to the patient in clinical practice.Haneen Banjar, David Adelson, Fred Brown, and Naeem Chaudhr

Do ACE inhibitors or ARBs help prevent kidney disease in patients with diabetes and normal BP?

Q: Do ACE inhibitors or ARBs help prevent kidney disease in patients with diabetes and normal BP? Evidence-based answer: Yes for angiotensin-converting enzyme (ACE) inhibitors, no for angiotensin receptor blockers (ARBs). In normotensive patients with type 1 and type 2 diabetes, ACE inhibitor therapy reduces the risk of developing diabetic kidney disease, defined as new-onset microalbuminuria or macroalbuminuria, by 18% (strength of recommendation [SOR]: C, meta-analysis of randomized controlled trials [RCTs], disease-oriented evidence). ACE inhibitor treatment improves all-cause mortality by 16% in patients with diabetes, including patients with and without hypertension. Patients on ACE inhibitor therapy are at increased risk of cough (SOR: A, meta-analysis of RCTs). ARB therapy doesn't lower the risk of developing kidney disease in normotensive patients with type 2 diabetes (SOR: C, meta-analysis of RCTs, disease-oriented evidence); nor does it reduce all-cause mortality in patients with or without hypertension (SOR: A, meta-analysis of RCTs). ARBs aren't associated with significant adverse events (SOR: A, meta-analysis of RCTs)

Cost-effectiveness analysis of tranexamic acid for the treatment of traumatic brain injury, based on the results of the CRASH-3 randomised trial: a decision modelling approach

Introduction An estimated 69 million traumatic brain injuries (TBI) occur each year worldwide, with most in low-income and middle-income countries. The CRASH-3 randomised trial found that intravenous administration of tranexamic acid within 3 hours of injury reduces head injury deaths in patients sustaining a mild or moderate TBI. We examined the cost-effectiveness of tranexamic acid treatment for TBI. Methods A Markov decision model was developed to assess the cost-effectiveness of treatment with and without tranexamic acid, in addition to current practice. We modelled the decision in the UK and Pakistan from a health service perspective, over a lifetime time horizon. We used data from the CRASH-3 trial for the risk of death during the trial period (28 days) and patient quality of life, and data from the literature to estimate costs and long-term outcomes post-TBI. We present outcomes as quality-adjusted life years (QALYs) and 2018 costs in pounds for the UK, and US dollars for Pakistan. Incremental cost-effectiveness ratios (ICER) per QALY gained were estimated, and compared with country specific cost-effective thresholds. Deterministic and probabilistic sensitivity analyses were also performed. Results Tranexamic acid was highly cost-effective for patients with mild TBI and intracranial bleeding or patients with moderate TBI, at £4288 per QALY in the UK, and US$24 per QALY in Pakistan. Tranexamic acid was 99% and 98% cost-effective at the cost-effectiveness thresholds for the UK and Pakistan, respectively, and remained cost-effective across all deterministic sensitivity analyses. Tranexamic acid was even more cost-effective with earlier treatment administration. The cost-effectiveness for those with severe TBI was uncertain. Conclusion Early administration of tranexamic acid is highly cost-effective for patients with mild or moderate TBI in the UK and Pakistan, relative to the cost-effectiveness thresholds used. The estimated ICERs suggest treatment is likely to be cost-effective across all income settings globally

Risk factors for blood transfusion in traumatic and postpartum hemorrhage patients: Analysis of the CRASH-2 and WOMAN trials.

BACKGROUND: Hemorrhage is a leading cause of death after trauma and childbirth. In response to severe hemorrhage, bleeding patients often receive transfusions of red blood cells, plasma, platelets, or other blood components. We examined risk factors for transfusion in acute severe bleeding in two trials of over 20,000 patients to better understand factors associated with transfusion likelihood. STUDY DESIGN AND METHODS: We conducted a cohort analysis of data from the CRASH-2 and WOMAN trials, two multinational trials that recruited patients with traumatic and postpartum hemorrhage, respectively. For each trial, we examined the effect of 10 factors on blood transfusion likelihood. Univariate and multivariate Poisson regressions were used to analyze the relationship between risk factors and blood transfusion. RESULTS: Of the 20,207 traumatic hemorrhage patients, 10,232 (51%) received blood components. Of the 20,060 women with postpartum hemorrhage, 10,958 (55%) received blood components. For patients who suffered from traumatic hemorrhage, those greater than three hours from injury to hospitalization were more likely to be transfused (ARR 1.37; 95% CI, 1.20-1.56). Postpartum hemorrhage patients had an increased likelihood of transfusion if they gave birth outside the hospital (ARR 1.30; 95% CI 1.22-1.39), gave birth more than three hours before hospitalization (ARR 1.09; 95% CI 1.01-1.17), had a Caesarean section (ARR 1.16; 95% CI 1.08-1.25), and if they had any identifiable causes of hemorrhage other than uterine atony. CONCLUSION: Several risk factors are associated with an increased likelihood of transfusion in traumatic and postpartum hemorrhage patients. Altering modifiable factors, by reducing time from injury or childbirth to hospitalization, for example, might be able to reduce transfusions and their complications. TRIAL REGISTRATION: CRASH-2 is registered as ISRCTN86750102, ClinicalTrials.gov NCT00375258 and South African Clinical Trial Register DOH-27-0607-1919. WOMAN is registered as ISRCTN76912190, ClinicalTrials.gov NCT00872469, PACTR201007000192283, and EudraCT number 2008-008441-38

Poxvirus-Encoded Gamma Interferon Binding Protein Dampens the Host Immune Response to Infection

Ectromelia virus (ECTV), a natural mouse pathogen and the causative agent of mousepox, is closely related to variola virus (VARV), which causes smallpox in humans. Mousepox is an excellent surrogate small-animal model for smallpox. Both ECTV and VARV encode a multitude of host response modifiers that target components of the immune system and that are thought to contribute to the high mortality rates associated with infection. Like VARV, ECTV encodes a protein homologous to the ectodomain of the host gamma interferon (IFN-γ) receptor 1. We generated an IFN-γ binding protein (IFN-γbp) deletion mutant of ECTV to study the role of viral IFN-γbp (vIFN-γbp) in host-virus interaction and also to elucidate the contribution of this molecule to the outcome of infection. Our data show that the absence of vIFN-γbp does not affect virus replication per se but does have a profound effect on virus replication and pathogenesis in mice. BALB/c mice, which are normally susceptible to infection with ECTV, were able to control replication of the mutant virus and survive infection. Absence of vIFN-γbp from ECTV allowed the generation of an elective host immune response that was otherwise diminished by this viral protein. Mice infected with a vIFN-γbp deletion mutant virus, designated ECTV-IFN-γbpΔ, produced increased levels of IFN-γ and generated robust cell-mediated and antibody responses. Using several strains of mice that exhibit differential degrees of resistance to mousepox, we show that recovery or death from ECTV infection is determined by a balance between the host's ability to produce IFN-γ and the virus' ability to dampen its effects

Relationship between method of anastomosis and anastomotic failure after right hemicolectomy and ileo-caecal resection: an international snapshot audit

Aim The anastomosis technique used following right-sided colonic resection is widely variable and may affect patient outcome. This study aimed to assess the association between leak and anastomosis technique (stapled vs handsewn). Method This was a prospective, multicentre, international audit including patients undergoing elective or emergency right hemicolectomy or ileo-caecal resection operations over a 2-month period in early 2015. The primary outcome measure was the presence of anastomotic leak within 30 days of surgery, determined using a prespecified definition. Mixed effects logistic regression models were used to assess the association between leak and anastomosis method, adjusting for patient, disease and operative cofactors, with centre included as a random-effect variable. Results This study included 3208 patients, of whom 78.4% (n = 2515) underwent surgery for malignancy and 11.7% (n = 375) underwent surgery for Crohn's disease. An anastomosis was performed in 94.8% (n = 3041) of patients, which was handsewn in 38.9% (n = 1183) and stapled in 61.1% (n = 1858). Patients undergoing hand-sewn anastomosis were more likely to be emergency admissions (20.5% handsewn vs 12.9% stapled) and to undergo open surgery (54.7% handsewn vs 36.6% stapled). The overall anastomotic leak rate was 8.1% (245/3041), which was similar following handsewn (7.4%) and stapled (8.5%) techniques (P = 0.3). After adjustment for cofactors, the odds of a leak were higher for stapled anastomosis (adjusted OR = 1.43; 95% CI: 1.04-1.95; P = 0.03). Conclusion Despite being used in lower-risk patients, stapled anastomosis was associated with an increased anastomotic leak rate in this observational study. Further research is needed to define patient groups in whom a stapled anastomosis is safe.This is the peer-reviewed version of the article: Pinkney, T.; Battersby, N.; Bhangu, A.; Chaudhri, S.; El-Hussuna, A.; Frasson, M.; Nepogodiev, D.; Singh, B.; Kovačević, B.; Autora), (i Jos Puno. Relationship between Method of Anastomosis and Anastomotic Failure after Right Hemicolectomy and Ileo-Caecal Resection: An International Snapshot Audit. Colorectal Disease 2017, 19 (8), O296–O311. [https://doi.org/10.1111/codi.13646

'CARE’ in social media: Perceptions of reputation in the healthcare sector

Guided by the growing importance of social-mediated organisational communication, this study examines how communication professionals within healthcare organisations perceive and respond to the impacts of social media on the organisation’s reputation. Although the healthcare sector finds itself in the midst of a (continually) transforming landscape characterized by large amounts of digital health (mis)information and an empowered ‘patient-as-consumer,’ little is known about how professionals in this sector understand the changes and respond to them. Moreover, much extant schol

In vitro modeling of endothelial interaction with macrophages and pericytes demonstrates Notch signaling function in the vascular microenvironment.

Angiogenesis is regulated by complex interactions between endothelial cells and support cells of the vascular microenvironment, such as tissue myeloid cells and vascular mural cells. Multicellular interactions during angiogenesis are difficult to study in animals and challenging in a reductive setting. We incorporated stromal cells into an established bead-based capillary sprouting assay to develop assays that faithfully reproduce major steps of vessel sprouting and maturation. We observed that macrophages enhance angiogenesis, increasing the number and length of endothelial sprouts, a property we have dubbed "angiotrophism." We found that polarizing macrophages toward a pro-inflammatory profile further increased their angiotrophic stimulation of vessel sprouting, and this increase was dependent on macrophage Notch signaling. To study endothelial/pericyte interactions, we added vascular pericytes directly to the bead-bound endothelial monolayer. These pericytes formed close associations with the endothelial sprouts, causing increased sprout number and vessel caliber. We found that Jagged1 expression and Notch signaling are essential for the growth of both endothelial cells and pericytes and may function in their interaction. We observed that combining endothelial cells with both macrophages and pericytes in the same sprouting assay has multiplicative effects on sprouting. These results significantly improve bead-capillary sprouting assays and provide an enhanced method for modeling interactions between the endothelium and the vascular microenvironment. Achieving this in a reductive in vitro setting represents a significant step toward a better understanding of the cellular elements that contribute to the formation of mature vasculature.S