Has anesthesia care become safer and is anesthesia-related mortality decreasing?

In well-resourced areas of the world anesthesia has become safer over the past decades, and anesthesia mortality does seem to be reducing. However, there is a lack of international agreement over definitions of anesthetic mortality and, therefore, difficulty in knowing exactly what the rate of anesthetic mortality is. Avoidable harm from error is still a problem, and sophisticated analysis suggests that more deaths than generally appreciated may be attributable to factors under the control of anesthetists. Mortality rates in low income areas of the world are unacceptably high. There is more to be done if anesthesia is to become truly safe for all patients

The concentration and biomagnification of trace metals and metalloids across four trophic levels in a marine food web

To be able to assess progress towards “Good Environmental Status” adopted across European Member States, and by the United Kingdom through its 3-stage Marine Strategy, contaminant concentrations and their biological effects need to be assessed in environmental samples by comparison to assessment criteria. This study examines the variability of concentrations (inter- and intra- species variation) of three priority heavy metals (Hg, Cd and Pb) and six additional trace metals and metalloids (As, Ni, Se, Zn, Cu and Cr) in twenty-three species across four trophic levels from different locations around Scotland. Trophic magnification factors (TMFs) were calculated using two methods for metals/metalloids possessing a significant trophic relationship (Hg, Cd, Cu, Ni and Zn) to refine and improve the application of TMFs to assess and predict biomagnification risk of metals/metalloids to biota in the environment. It was concluded that a reasonable balance in sample numbers of lower- versus higher-trophic level organisms is highly recommended when calculating TMFs and appropriate species selection is vital to ensure TMFs accurately represent the selected ecosystem

The concentration and biomagnification of PCBs and PBDEs across four trophic levels in a marine food web.

Contracting Parties to the OSPAR Convention for the Protection of the Maine Environment of the North-East Atlantic are required to undertake monitoring and assessment of both inorganic and organic contaminants. There is a requirement to assess contaminants across different trophic levels on an ecosystem-specific basis. However, this is currently constrained by the availability of relevant samples to cover the full range of trophic levels. This study investigates the variability (inter- and intra-species variation) of the concentrations and distributions of thirty-two polychlorinated biphenyl (PCB) congeners and nine polybrominated diphenyl ether (PBDE) congeners in twenty-six species covering four trophic levels from different geographic locations around Scotland. Trophic magnification factors (TMFs) were calculated using a traditional method and a balanced method for both the ICES-7 PCBs and BDE47, to refine and improve the application of TMFs to assess and predict biomagnification risk to biota in the marine environment. There were clear differences in congener percentage distribution between sample categories and species, with differences influenced by physiological processes and eco-biological parameters. Trophic magnification was found to occur for the ICES-7 PCBs and BDE47 using the traditional method, with the highest degree of trophic magnification reported for CB52. An unbalanced dataset was found to influence the calculated TMF and in some cases, the overall conclusion of the trophic transfer of PCB and PBDE congeners. The balanced method is highly recommended for calculating TMFs to ensure that the TMF is a true indication of the biomagnification potential, particularly when conducting regional comparisons for which sampling requirements are difficult to achieve

Cardiac testing for coronary artery disease in potential kidney transplant recipients.

Patients with chronic kidney disease (CKD) are at increased risk of coronary artery disease (CAD) and adverse cardiac events. Screening for CAD is therefore an important part of preoperative evaluation for kidney transplant candidates. There is significant interest in the role of non-invasive cardiac investigations and their ability to identify patients at high risk of CAD.  We investigated the accuracy of non-invasive cardiac screening tests compared with coronary angiography to detect CAD in patients who are potential kidney transplant recipients. MEDLINE and EMBASE searches (inception to November 2010) were performed to identify studies that assessed the diagnostic accuracy of non-invasive screening tests, using coronary angiography as the reference standard. We also conducted citation tracking via Web of Science and handsearched reference lists of identified primary studies and review articles.   We included in this review all diagnostic cross sectional, cohort and randomised studies of test accuracy that compared the results of any cardiac test with coronary angiography (the reference standard) relating to patients considered as potential candidates for kidney transplantation or kidney-pancreas transplantation at the time diagnostic tests were performed.  We used a hierarchical modelling strategy to produce summary receiver operating characteristic (SROC) curves, and pooled estimates of sensitivity and specificity. Sensitivity analyses to determine test accuracy were performed if only studies that had full verification or applied a threshold of ≥ 70% stenosis on coronary angiography for the diagnosis of significant CAD were included. The following screening investigations included in the meta-analysis were: dobutamine stress echocardiography (DSE) (13 studies), myocardial perfusion scintigraphy (MPS) (nine studies), echocardiography (three studies), exercise stress electrocardiography (two studies), resting electrocardiography (three studies), and one study each of electron beam computed tomography (EBCT), exercise ventriculography, carotid intimal media thickness (CIMT) and digital subtraction fluorography (DSF). Sufficient studies were present to allow hierarchical summary receiver operating characteristic (HSROC) analysis for DSE and MPS. When including all available studies, both DSE and MPS had moderate sensitivity and specificity in detecting coronary artery stenosis in patients who are kidney transplant candidates [DSE (13 studies) - pooled sensitivity 0.79 (95% CI 0.67 to 0.88), pooled specificity 0.89 (95% CI 0.81 to 0.94); MPS (nine studies) - pooled sensitivity 0.74 (95% CI 0.54 to 0.87), pooled specificity 0.70 (95% CI 0.51 to 0.84)]. When limiting to studies which defined coronary artery stenosis using a reference threshold of ≥ 70% stenosis on coronary angiography, there was little change in these pooled estimates of accuracy [DSE (9 studies) - pooled sensitivity 0.76 (95% CI 0.60 to 0.87), specificity 0.88 (95% CI 0.78 to 0.94); MPS (7 studies) - pooled sensitivity 0.67 (95% CI 0.48 to 0.82), pooled specificity 0.77 (95% CI 0.61 to 0.88)]. There was evidence that DSE had improved accuracy over MPS (P = 0.02) when all studies were included in the analysis, but this was not significant when we excluded studies which did not avoid partial verification or use a reference standard threshold of ≥70% stenosis (P = 0.09).   DSE may perform better than MPS but additional studies directly comparing these cardiac screening tests are needed. Absence of significant CAD may not necessarily correlate with cardiac-event free survival following transplantation. Further research should focus on assessing the ability of functional tests to predict postoperative outcome

Ehealth interventions for people with chronic kidney disease

Background Chronic kidney disease (CKD) is associated with high morbidity and death, which increases as CKD progresses to end-stage kidney disease (ESKD). There has been increasing interest in developing innovative, effective and cost-efficient methods to engage with patient populations and improve health behaviours and outcomes. Worldwide there has been a tremendous increase in the use of technologies, with increasing interest in using eHealth interventions to improve patient access to relevant health information, enhance the quality of healthcare and encourage the adoption of healthy behaviours. Objectives This review aims to evaluate the benefits and harms of using eHealth interventions to change health behaviours in people with CKD. Search methods We searched the Cochrane Kidney and Transplant Register of Studies up to 14 January 2019 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. Selection criteria Randomised controlled trials (RCTs) and quasi-RCTs using an eHealth intervention to promote behaviour change in people with CKD were included. There were no restrictions on outcomes, language or publication type. Data collection and analysis Two authors independently assessed trial eligibility, extracted data and assessed the risk of bias. The certainty of the evidence was assessed using GRADE. Main results We included 43 studies with 6617 participants that evaluated the impact of an eHealth intervention in people with CKD. Included studies were heterogeneous in terms of eHealth modalities employed, type of intervention, CKD population studied and outcomes assessed. The majority of studies (39 studies) were conducted in an adult population, with 16 studies (37%) conducted in those on dialysis, 11 studies (26%) in the pre-dialysis population, 15 studies (35%) in transplant recipients and 1 studies (2%) in transplant candidates We identified six different eHealth modalities including: Telehealth; mobile or tablet application; text or email messages; electronic monitors; internet/websites; and video or DVD. Three studies used a combination of eHealth interventions. Interventions were categorised into six types: educational; reminder systems; self-monitoring; behavioural counselling; clinical decision-aid; and mixed intervention types. We identified 98 outcomes, which were categorised into nine domains: blood pressure (9 studies); biochemical parameters (6 studies); clinical end-points (16 studies); dietary intake (3 studies); quality of life (9 studies); medication adherence (10 studies); behaviour (7 studies); physical activity (1 study); and cost-effectiveness (7 studies). Only three outcomes could be meta-analysed as there was substantial heterogeneity with respect to study population and eHealth modalities utilised. There was found to be a reduction in interdialytic weight gain of 0.13kg (4 studies, 335 participants: MD-0.13, 95% CI-0.28 to 0.01; I = 0%) and a reduction in dietary sodium intake of 197 mg/day (2 studies, 181 participants: MD-197, 95% CI-540.7 to 146.8; I = 0%). Both dietary sodium and fluid management outcomes were graded as being of low evidence due to high or unclear risk of bias and indirectness (interdialytic weight gain) and high or unclear risk of bias and imprecision (dietary sodium intake). Three studies reported death (2799 participants, 146 events), with 45 deaths/1000 cases compared to standard care of 61 deaths/1000 cases (RR 0.74, CI 0.53 to 1.03; P = 0.08). We are uncertain whether using eHealth interventions, in addition to usual care, impact on the number of deaths as the certainty of this evidence was graded as low due to high or unclear risk of bias, indirectness and imprecision. Authors’ conclusions eHealth interventions may improve the management of dietary sodium intake and fluid management. However, overall these data suggest that current evidence for the use of eHealth interventions in the CKD population is of low quality, with uncertain effects due to methodological limitations and heterogeneity of eHealth modalities and intervention types. Our review has highlighted the need for robust, high quality research that reports a core (minimum) data set to enable meaningful evaluation of the literature

Targeting the DNA Double Strand Break Repair Machinery in Prostate Cancer

Regardless of the achievable remissions with first line hormone therapy in patients with prostate cancer (CaP), the disease escapes the hormone dependent stage to a more aggressive status where chemotherapy is the only effective treatment and no treatment is curative. This makes it very important to identify new targets that can improve the outcome of treatment. ATM and DNA-PK are the two kinases responsible for signalling and repairing double strand breaks (DSB). Thus, both kinases are pertinent targets in CaP treatment to enhance the activity of the numerous DNA DSB inducing agents used in CaP treatment such as ionizing radiation (IR). Colony formation assay was used to assess the sensitivity of hormone dependent, p53 wt (LNCaP) and hormone independent p53 mutant (PC3) CaP cell lines to the cytotoxic effect of IR and Doxorubicin in the presence or absence of Ku55933 and NU7441 which are small molecule inhibitors of ATM and DNA-PK, respectively. Flow cytometry based methods were used to assess the effect of the two inhibitors on cell cycle, apoptosis and H2AX foci formation. Neutral comet assay was used to assess the induction of DNA DSBs. Ku55933 or NU7441 alone increased the sensitivity of CaP cell lines to the DNA damaging agents, however combining both inhibitors together resulted in further enhancement of sensitivity. The cell cycle profile of both cell lines was altered with increased cell death, DNA DSBs and H2AX foci formation. This study justifies further evaluation of the ATM and DNA-PK inhibitors for clinical application in CaP patients. Additionally, the augmented effect resulting from combining both inhibitors may have a significant implication for the treatment of CaP patients who have a defect in one of the two DSB repair pathways

Adolescents’ preferences for sexual dimorphism are influenced by relative exposure to male and female faces

Exposure to a particular population of faces can increase ratings of the normality and attractiveness of similar-looking faces. Such exposure can also refine the perceived boundaries of that face population, such that other faces are more readily perceived as dissimilar. We predicted that relatively less exposure to opposite-sex faces, as experienced by children at single-sex compared with mixed-sex schools, would decrease ratings of the attractiveness of sexual dimorphism in opposite-sex faces (that is, boys at single-sex schools would show a decreased preference for feminised faces, and girls at single-sex schools would show a decreased preference for masculinised faces). Consistent with this prediction, girls at single-sex compared with mixed-sex schools demonstrated significantly stronger preferences for facial femininity in both male and female faces. Boys at single-sex compared with mixed-sex schools demonstrated marginally stronger preferences for facial masculinity in male faces, but did not differ in their ratings of female faces. These effects were attenuated among some single-sex school pupils by the presence of adolescent opposite-sex siblings. These data add to the evidence that long-term exposure to a particular face population can influence judgements of other faces, and contribute to our understanding of the factors leading to individual differences in face preferences

Treatment for lupus nephritis

BackgroundCyclophosphamide, in combination with corticosteroids has been used to induce remission in proliferative lupus nephritis, the most common kidney manifestation of the multisystem disease, systemic lupus erythematosus. Cyclophosphamide therapy has reduced mortality from over 70% in the 1950s and 1960s to less than 10% in recent years. Cyclophosphamide combined with corticosteroids preserves kidney function but is only partially effective and may cause ovarian failure, infection and bladder toxicity. Several new agents, including mycophenolate mofetil (MMF), suggest reduced toxicity with equivalent rates of remission. This is an update of a Cochrane review first published in 2004.ObjectivesTo assess the benefits and harms of different immunosuppressive treatments in biopsy-proven proliferative lupus nephritis.Search methodsFor this update, we searched the Cochrane Renal Group's Specialised Register (up to 15 April 2012) through contact with the Trials' Search Coordinator using search terms relevant to this review.Selection criteriaRandomised controlled trials (RCTs) and quasi-RCTs comparing any treatments for biopsy-proven lupus nephritis in both adult and paediatric patients with class III, IV, V + III and V + IV lupus nephritis were included. All immunosuppressive treatments were considered.Data collection and analysisData were abstracted and quality assessed independently by two authors, with differences resolved by discussion. Dichotomous outcomes were reported as risk ratio (RR) and measurements on continuous scales reported as mean differences (MD) with 95% confidence intervals (CI).Main resultsWe identified 50 RCTs involving 2846 participants. Of these, 45 studies (2559 participants) investigated induction therapy, and six studies (514 participants), considered maintenance therapy.Compared with intravenous (IV) cyclophosphamide, MMF was as effective in achieving stable kidney function (5 studies, 523 participants: RR 1.05, 95% CI 0.94 to 1.18) and complete remission of proteinuria (6 studies, 686 participants: RR 1.16, 95% CI 0.85 to 1.58). No differences in mortality (7 studies, 710 participants: RR 1.02, 95% CI 0.52 to 1.98) or major infection (6 studies, 683 participants: RR 1.11, 95% CI 0.74 to 1.68) were observed. A significant reduction in ovarian failure (2 studies, 498 participants: RR 0.15, 95% CI 0.03 to 0.80) and alopecia (2 studies, 522 participants: RR 0.22, 95% CI 0.06 to 0.86) was observed with MMF. In maintenance therapy, the risk of renal relapse (3 studies, 371 participants: RR 1.83, 95% CI 1.24 to 2.71) was significantly higher with azathioprine compared with MMF. Multiple other interventions were compared but outcome data were relatively sparse. Overall study quality was variable. The internal validity of the design, conduct and analysis of the included RCTs was difficult to assess in some studies because of the omission of important methodological details. No study adequately reported all domains of the risk of bias assessment so that elements of internal bias may be present.Authors' conclusionsMMF is as effective as cyclophosphamide in inducing remission in lupus nephritis, but is safer with a lower risk of ovarian failure. MMF is more effective than azathioprine in maintenance therapy for preventing relapse with no increase in clinically important side effects. Adequately powered trials with long term follow-up are required to more accurately define the risks and eventual harms of specific treatment regimens

Interleukin 2 Receptor Antagonists for Kidney Transplant Recipients

Background Interleukin 2 receptor antagonists (IL2Ra) are used as induction therapy for prophylaxis against acute rejection in kidney transplant recipients. Use of IL2Ra has increased steadily since their introduction, but the proportion of new transplant recipients receiving IL2Ra differs around the globe, with 27% of new kidney transplant recipients in the United States, and 70% in Australasia receiving IL2Ra in 2007. Objectives To systematically identify and summarise the effects of using an IL2Ra, as an addition to standard therapy, or as an alternative to another immunosuppressive induction strategy. Search methods We searched the Cochrane Renal Group’s specialised register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE to identify new records, and authors of included reports were contacted for clarification where necessary. Selection criteria Randomised controlled trials (RCTs) in all languages comparing IL2Ra to placebo, no treatment, other IL2Ra or other antibody therapy. Data collection and analysis Data was extracted and assessed independently by two authors, with differences resolved by discussion. Dichotomous outcomes are reported as relative risk (RR) and continuous outcomes as mean difference (MD) with 95% confidence intervals (CI). Main results We included 71 studies (306 reports, 10,520 participants). Where IL2Ra were compared with placebo (32 studies; 5,854 patients) graft loss including death with a functioning graft was reduced by 25% at six months (16 studies: RR 0.75, 95% CI 0.58 to 0.98) and one year (24 studies: RR 0.75, 95% CI 0.62 to 0.90), but not beyond this. At one year biopsy‐proven acute rejection was reduced by 28% (14 studies: RR 0.72, 95% CI 0.64 to 0.81), and there was a 19% reduction in CMV disease (13 studies: RR 0.81, 95% CI 0.68 to 0.97). There was a 64% reduction in early malignancy within six months (8 studies: RR 0.36, 95% CI 0.15 to 0.86), and creatinine was lower (7 studies: MD ‐8.18 µmol/L 95% CI ‐14.28 to ‐2.09) but these differences were not sustained. When IL2Ra were compared to ATG (18 studies, 1,844 participants), there was no difference in graft loss at any time point, or for acute rejection diagnosed clinically, but the was benefit of ATG therapy over IL2Ra for biopsy‐proven acute rejection at one year (8 studies:, RR 1.30 95% CI 1.01 to 1.67), but at the cost of a 75% increase in malignancy (7 studies: RR 0.25 95% CI 0.07 to 0.87) and a 32% increase in CMV disease (13 studies: RR 0.68 95% CI 0.50 to 0.93). Serum creatinine was significantly lower for IL2Ra treated patients at six months (4 studies: MD ‐11.20 µmol/L 95% CI ‐19.94 to ‐2.09). ATG patients experienced significantly more fever, cytokine release syndrome and other adverse reactions to drug administration and more leucopenia but not thrombocytopenia. There were no significant differences in outcomes according to cyclosporine or tacrolimus use, azathioprine or mycophenolate, or to the study populations baseline risk for acute rejection. There was no evidence that effects were different according to whether equine or rabbit ATG was used. Authors' conclusions Given a 38% risk of rejection, per 100 recipients compared with no treatment, nine recipients would need treatment with IL2Ra to prevent one recipient having rejection, 42 to prevent one graft loss, and 38 to prevent one having CMV disease over the first year post‐transplantation. Compared with ATG treatment, ATG may prevent some experiencing acute rejection, but 16 recipients would need IL2Ra to prevent one having CMV, but 58 would need IL2Ra to prevent one having malignancy. There are no apparent differences between basiliximab and daclizumab. IL2Ra are as effective as other antibody therapies and with significantly fewer side effects