A systematic review of the effectiveness, compliance, and critical factors for implementation of safety checklists in surgery

A systematic literature review was conducted to assess the effectiveness of, compliance with, and critical factors for the implementation of safety checklists in surgery.

An IEEE 802.11 energy efficient mechanism for continuous media applications

The widespread deployment of wireless mobile communications enables an almost permanent usage of portable devices, which imposes high demands on the battery of these devices. Indeed, battery lifetime is becoming one the most critical factors on the end-users satisfaction when using wireless communications. In this work, the optimized power save algorithm for continuous media applications (OPAMA) is proposed, aiming at enhancing the energy efficiency on end-users devices. By combining the application specific requirements with data aggregation techniques, {OPAMA} improves the standard {IEEE} 802.11 legacy Power Save Mode (PSM) performance. The algorithm uses the feedback on the end-user expected quality to establish a proper tradeoff between energy consumption and application performance. {OPAMA} was assessed in the OMNeT++ simulator, using real traces of variable bitrate video streaming applications, and in a real testbed employing a novel methodology intended to perform an accurate evaluation concerning video Quality of Experience (QoE) perceived by the end-users. The results revealed the {OPAMA} capability to enhance energy efficiency without degrading the end-user observed QoE, achieving savings up to 44 when compared with the {IEEE} 802.11 legacy PSM.

Methodology for GPS Synchronization Evaluation with High Accuracy

Clock synchronization in the order of nanoseconds is one of the critical factors for time-based localization. Currently used time synchronization methods are developed for the more relaxed needs of network operation. Their usability for positioning should be carefully evaluated. In this paper, we are particularly interested in GPS-based time synchronization. To judge its usability for localization we need a method that can evaluate the achieved time synchronization with nanosecond accuracy. Our method to evaluate the synchronization accuracy is inspired by signal processing algorithms and relies on fine grain time information. The method is able to calculate the clock offset and skew between devices with nanosecond accuracy in real time. It was implemented using software defined radio technology. We demonstrate that GPS-based synchronization suffers from remaining clock offset in the range of a few hundred of nanoseconds but the clock skew is negligible. Finally, we determine a corresponding lower bound on the expected positioning error.

A frequent hypofunctional IRAK2 variant is associated with reduced spontaneous hepatitis C virus clearance.

UNLABELLED Patients carrying very rare loss-of-function mutations in interleukin-1 receptor-associated kinase 4 (IRAK4), a critical signaling mediator in Toll-like receptor signaling, are severely immunodeficient, highlighting the paramount role of IRAK kinases in innate immunity. We discovered a comparatively frequent coding variant of the enigmatic human IRAK2, L392V (rs3844283), which is found homozygously in ∼15% of Caucasians, to be associated with a reduced ability to induce interferon-alpha in primary human plasmacytoid dendritic cells in response to hepatitis C virus (HCV). Cytokine production in response to purified Toll-like receptor agonists was also impaired. Additionally, rs3844283 was epidemiologically associated with a chronic course of HCV infection in two independent HCV cohorts and emerged as an independent predictor of chronic HCV disease. Mechanistically, IRAK2 L392V showed intact binding to, but impaired ubiquitination of, tumor necrosis factor receptor-associated factor 6, a vital step in signal transduction. CONCLUSION Our study highlights IRAK2 and its genetic variants as critical factors and potentially novel biomarkers for human antiviral innate immunity.

NOTCH ligands JAG1 and JAG2 as critical pro-survival factors in childhood medulloblastoma.

Medulloblastoma (MB), the most common pediatric malignant brain cancer, typically arises as pathological result of deregulated developmental pathways, including the NOTCH signaling cascade. Unlike the evidence supporting a role for NOTCH receptors in MB development, the pathological functions of NOTCH ligands remain largely unexplored. By examining the expression in large cohorts of MB primary tumors, and in established in vitro MB models, this research study demonstrates that MB cells bear abnormal levels of distinct NOTCH ligands. We explored the potential association between NOTCH ligands and the clinical outcome of MB patients, and investigated the rational of inhibiting NOTCH signaling by targeting specific ligands to ultimately provide therapeutic benefits in MB. The research revealed a significant over-expression of ligand JAG1 in the vast majority of MBs, and proved that JAG1 mediates pro-proliferative signals via activation of NOTCH2 receptor and induction of HES1 expression, thus representing an attractive therapeutic target. Furthermore, we could identify a clinically relevant association between ligand JAG2 and the oncogene MYC, specific for MYC-driven Group 3 MB cases. We describe for the first time a mechanistic link between the oncogene MYC and NOTCH pathway in MB, by identifying JAG2 as MYC target, and by showing that MB cells acquire induced expression of JAG2 through MYC-induced transcriptional activation. Finally, the positive correlation of MYC and JAG2 also with aggressive anaplastic tumors and highly metastatic MB stages suggested that high JAG2 expression may be useful as additional marker to identify aggressive MBs.

Critical incident monitoring in paediatric and adult critical care: from reporting to improved patient outcomes?

PURPOSE OF REVIEW: Critical incident reporting alone does not necessarily improve patient safety or even patient outcomes. Substantial improvement has been made by focusing on the further two steps of critical incident monitoring, that is, the analysis of critical incidents and implementation of system changes. The system approach to patient safety had an impact on the view about the patient's role in safety. This review aims to analyse recent advances in the technique of reporting, the analysis of reported incidents, and the implementation of actual system improvements. It also explores how families should be approached about safety issues. RECENT FINDINGS: It is essential to make as many critical incidents as possible known to the intensive care team. Several factors have been shown to increase the reporting rate: anonymity, regular feedback about the errors reported, and the existence of a safety climate. Risk scoring of critical incident reports and root cause analysis may help in the analysis of incidents. Research suggests that patients can be successfully involved in safety. SUMMARY: A persisting high number of reported incidents is anticipated and regarded as continuing good safety culture. However, only the implementation of system changes, based on incident reports, and also involving the expertise of patients and their families, has the potential to improve patient outcome. Hard outcome criteria, such as standardized mortality ratio, have not yet been shown to improve as a result of critical incident monitoring.

Chapter III: Management of cardiovascular risk factors and medical therapy

Critical limb ischaemia (CLI) is a particularly severe manifestation of lower limb atherosclerosis posing a major threat to both limb and life of affected patients. Besides arterial revascularisation, risk-factor modification and administration of antiplatelet therapy is a major goal in the treatment of CLI patients. Key elements of cardiovascular risk management are smoking cessation and treatment of hyperlipidaemia with dietary modification or statins. Moreover, arterial hypertension and diabetes mellitus should be adequately treated. In CLI patients not suitable for arterial revascularisation or subsequent to unsuccessful revascularisation, parenteral prostanoids may be considered. CLI patients undergoing surgical revascularisation should be treated with beta blockers. At present, neither gene nor stem-cell therapy can be recommended outside clinical trials. Of note, walking exercise is contraindicated in CLI patients due to the risk of worsening pre-existing or causing new ischaemic wounds. CLI patients are oftentimes medically frail and exhibit significant comorbidities. Co-existing coronary heart and carotid as well as renal artery disease should be managed according to current guidelines. Considering the above-mentioned treatment goals, interdisciplinary treatment approaches for CLI patients are warranted. Aim of the present manuscript is to discuss currently existing evidence for both the management of cardiovascular risk factors and treatment of co-existing disease and to deduct specific treatment recommendations.

Critical review of the use of erythropoietin in the treatment of anaemia during therapy for chronic hepatitis C

Combined pegylated interferon (PegIFN) and ribavirin represents the standard therapy for patients with chronic hepatitis C (CHC), which allows for sustained viral response (SVR) in up to 90% of patients depending on certain viral and host factors. Clinical studies have demonstrated the importance of adherence to therapy, that is, the ability of patients to tolerate and sustain a fully dosed therapy regimen. Adherence is markedly impaired by treatment-related adverse effects. In particular, haemolytic anaemia often requires dose reduction or termination of ribavirin treatment, which compromises treatment efficacy. Recent evidence points to a beneficial role of recombinant erythropoietin (EPO) in alleviating ribavirin-induced anaemia thereby improving quality of life, enabling higher ribavirin dosage and consequently improving SVR. However, no general consensus exists regarding the use of EPO for specific indications: its optimal dosing, treatment benefits and potential risks or cost efficiency. The Swiss Association for the Study of the Liver (SASL) has therefore organized an expert meeting to critically review and discuss the current evidence and to phrase recommendations for clinical practice. A consensus was reached recommending the use of EPO for patients infected with viral genotype 1 developing significant anaemia below 100 g/L haemoglobin and a haematocrit of <30% during standard therapy to improve quality of life and sustain optimal ribavirin dose. However, the evidence supporting its use in patients with pre-existing anaemia, non-1 viral genotypes, a former relapse or nonresponse, liver transplant recipients and cardiovascular or pulmonary disease is considered insufficient.

Study protocol: Transition from localized low back pain to chronic widespread pain in general practice: identification of risk factors, preventive factors and key elements for treatment--a cohort study

Background Chronic localized pain syndromes, especially chronic low back pain (CLBP), are common reasons for consultation in general practice. In some cases chronic localized pain syndromes can appear in combination with chronic widespread pain (CWP). Numerous studies have shown a strong association between CWP and several physical and psychological factors. These studies are population-based cross-sectional and do not allow for assessing chronology. There are very few prospective studies that explore the predictors for the onset of CWP, where the main focus is identifying risk factors for the CWP incidence. Until now there have been no studies focusing on preventive factors keeping patients from developing CWP. Our aim is to perform a cross sectional study on the epidemiology of CLBP and CWP in general practice and to look for distinctive features regarding resources like resilience, self-efficacy and coping strategies. A subsequent cohort study is designed to identify the risk and protective factors of pain generalization (development of CWP) in primary care for CLBP patients. Methods/Design Fifty-nine general practitioners recruit consecutively, during a 5 month period, all patients who are consulting their family doctor because of chronic low back pain (where the pain is lasted for 3 months). Patients are asked to fill out a questionnaire on pain anamnesis, pain-perception, co-morbidities, therapy course, medication, socio demographic data and psychosomatic symptoms. We assess resilience, coping resources, stress management and self-efficacy as potential protective factors for pain generalization. Furthermore, we raise risk factors for pain generalization like anxiety, depression, trauma and critical life events. During a twelve months follow up period a cohort of CLBP patients without CWP will be screened on a regular basis (3 monthly) for pain generalization (outcome: incident CWP). Discussion This cohort study will be the largest study which prospectively analyzes predictors for transition from CLBP to CWP in primary care setting. In contrast to the typically researched risk factors, which increase the probability of pain generalization, this study also focus intensively on protective factors, which decrease the probability of pain generalization.

Hypertriglyceridemia: a potential side effect of propofol sedation in critical illness

Hypertriglyceridemia (hyperTG) is common among intensive care unit (ICU) patients, but knowledge about hyperTG risk factors is scarce. The present study aims to identify risk factors favoring its development in patients requiring prolonged ICU treatment.

Role of retroviral restriction factors in the interferon-α-mediated suppression of HIV-1 in vivo

The antiviral potency of the cytokine IFN-α has been long appreciated but remains poorly understood. A number of studies have suggested that induction of the apolipoprotein B mRNA editing enzyme, catalytic polypeptide 3 (APOBEC3) and bone marrow stromal cell antigen 2 (BST-2/tetherin/CD317) retroviral restriction factors underlies the IFN-α-mediated suppression of HIV-1 replication in vitro. We sought to characterize the as-yet-undefined relationship between IFN-α treatment, retroviral restriction factors, and HIV-1 in vivo. APOBEC3G, APOBEC3F, and BST-2 expression levels were measured in HIV/hepatitis C virus (HCV)-coinfected, antiretroviral therapy-naïve individuals before, during, and after pegylated IFN-α/ribavirin (IFN-α/riba) combination therapy. IFN-α/riba therapy decreased HIV-1 viral load by -0.921 (±0.858) log(10) copies/mL in HIV/HCV-coinfected patients. APOBEC3G/3F and BST-2 mRNA expression was significantly elevated during IFN-α/riba treatment in patient-derived CD4+ T cells (P < 0.04 and P < 0.008, paired Wilcoxon), and extent of BST-2 induction was correlated with reduction in HIV-1 viral load during treatment (P < 0.05, Pearson's r). APOBEC3 induction during treatment was correlated with degree of viral hypermutation (P < 0.03, Spearman's ρ), and evolution of the HIV-1 accessory protein viral protein U (Vpu) during IFN-α/riba treatment was suggestive of increased BST-2-mediated selection pressure. These data suggest that host restriction factors play a critical role in the antiretroviral capacity of IFN-α in vivo, and warrant investigation into therapeutic strategies that specifically enhance the expression of these intrinsic immune factors in HIV-1-infected individuals.

Immunosuppressive drugs in organ transplant recipients--rationale for critical selection

Transplantation is the treatment of choice for many different organ failures. Despite growing experience in surgery and immunosuppression protocols, the long-term mortality of the procedure remains much higher than in the general population. Second only to cardiovascular diseases as the cause of death in organ transplant recipients, cancer is now known to be at least partly related to the immunosuppression regimen. Nevertheless, if calcineurin inhibitors have a demonstrated pro-oncogenic effect, other classes, such as mTOR inhibitors, are antiproliferative, and even demonstrated as an efficient therapy in some advanced oncological situations. Therefore, the adaptation of the therapy protocol evolves now towards an individualized medicine based on the risk factors of each transplant recipient in terms of cardiovascular, infectious and oncological diseases. As the first organ involved by tumor is the skin, many different guidelines have been published to try and adapt the therapy to the occurrence of a new lesion. If, for example, limited actinic keratosis or the first episode of a non-melanoma skin cancer usually requires no change of the immunosuppressive therapy, but a local specialized care and frequent clinical controls, more advanced lesions imply the adaptation of the drug regimen. In any case, the collaboration between general practitioners, dermatologists and the transplantation team is mandatory.

Extrinsic causes of erosion. Diet. Chemical factors

pH value, calcium, and phosphate and to a lesser extent fluoride content of a drink or foodstuff are important factors explaining erosive attack. They determine the degree of saturation with respect to tooth minerals, which is the driving force for dissolution. Solutions oversaturated with respect to dental hard tissue will not dissolve it. Addition of calcium (and phosphate) salts to erosive drinks showed protection of surface softening. Today, several Ca-enriched soft drinks are on the market or products with naturally high content in Ca and P are available (such as yoghurt), which do not soften the dental hard tissue. The greater the buffering capacity of the drink or food, the longer it will take for the saliva to neutralize the acid. The buffer capacity of a solution has a distinct effect on the erosive attack when the solution remains adjacent to the tooth surface and is not replaced by saliva. A higher buffer capacity of a drink or foodstuff will enhance the processes of dissolution because more ions from the tooth mineral are needed to render the acid inactive for further demineralization. Further, the amount of drink in the mouth in relation to the amount of saliva present will modify the process of dissolution. There is no clear-cut critical pH for erosion as there is for caries. Even at a low pH, it is possible that other factors are strong enough to prevent erosion.

An old dream revitalised: preconditioning strategies to protect surgical flaps from critical ischaemia and ischaemia-reperfusion injury

The prevention of ischaemia and the adequate restitution of blood flow to ischaemic tissue are pivotal to halt the progression of cellular injury associated with decreased oxygen and nutrient supply. Accordingly, the search for novel strategies which aim at preventing ischaemia-reperfusion-induced tissue damage is still of major interest in flap surgery. Preconditioning represents an elegant approach to render the tissue more resistant against deleterious ischaemic insults. For many decades, 'surgical delay' has been the standard method of tissue preconditioning. During the last 10 years, ischaemic preconditioning was added to the repertoire of plastic surgeons to protect flaps from ischaemic necrosis. The invasiveness and expenditure of time of these procedures, however, have always been major drawbacks, hindering a wide distribution in clinical practice. Consequently, the motivation has all along been to further refine and simplify protective strategies. Recent experimental studies have now shown that efficient protection from ischaemic necrosis can also be achieved by remote preconditioning or pretreatment with chemical agents and growth factors, which mimic the action of surgical delay and ischaemic preconditioning. In addition, the local application of unspecific stressors, including both heating and cooling, have been shown to effectively improve flap microcirculation and, thus, tissue survival. In view of successful translational research, it is now time that the efficacy of these novel preconditioning procedures is proven in prospective randomised clinical trials.