Albumin versus crystalloid solutions in patients with the acute respiratory distress syndrome: a systematic review and meta-analysis

INTRODUCTION: In patients with acute respiratory distress syndrome (ARDS) fluid therapy might be necessary. The aim of this systematic review and meta-analysis is to determine the effects of colloid therapy compared to crystalloids on mortality and oxygenation in adults with ARDS. METHODS: Randomized controlled trials (RCTs) were identified through a systematic literature search of MEDLINE, EMBASE, CENTRAL and LILACS. Articles published up to 15(th) February 2013 were independently screened, abstracted, and assessed (Cochrane Risk of Bias Tool) to provide evidence-based therapy recommendations. RCTs were eligible if they compared colloid versus crystalloid therapy on lung function, inflammation, damage or mortality in adults with ARDS. Primary outcome parameters were respiratory mechanics, gas exchange lung inflammation and damage as well as hospital mortality. Kidney function, need for renal replacement therapy, hemodynamic stabilization and intensive care unit (ICU) length of stay served as secondary outcomes. RESULTS: A total of 3 RCTs out of 4130 potential trials found in the databases were selected for qualitative and quantitative analysis totaling 206 patients who received either albumin or saline. Overall risk of bias was unclear to high in the identified trials. Calculated pooled risk of death was not statistically significant (albumin 34 of 100 (34.0%) versus 40 of 104 (38.5%), relative risk (RR) = 0.89, 95% confidence interval (CI) 0.62 to 1.28, P = 0.539). Weighted mean difference (WMD) in PaO(2)/FiO(2) (mmHg) improved in the first 48 hours (WMD = 62, 95% CI 47 to 77, P <0.001, I(2) = 0%) after therapy start and remained stable after 7 days (WMD = 20, 95% CI 4 to 36, P = 0.017, I(2) = 0%). CONCLUSIONS: There is a high need for RCTs investigating the effects of colloids in ARDS patients. Based on the findings of this review, colloid therapy with albumin improved oxygenation but did not affect mortality

Understanding unit rooters: a helicopter tour

Econometrics

Mycophenolic acid versus azathioprine as primary immunosuppression for kidney transplant recipients

Background Modern immunosuppressive regimens after kidney transplantation usually use a combination of two or three agents of different classes to prevent rejection and maintain graft function. Most frequently, calcineurin‐inhibitors (CNI) are combined with corticosteroids and a proliferation‐inhibitor, either azathioprine (AZA) or mycophenolic acid (MPA). MPA has largely replaced AZA as a first line agent in primary immunosuppression, as MPA is believed to be of stronger immunosuppressive potency than AZA. However, treatment with MPA is more costly, which calls for a comprehensive assessment of the comparative effects of the two drugs. Objectives This review of randomised controlled trials (RCTs) aimed to look at the benefits and harms of MPA versus AZA in primary immunosuppressive regimens after kidney transplantation. Both agents were compared regarding their efficacy for maintaining graft and patient survival, prevention of acute rejection, maintaining graft function, and their safety, including infections, malignancies and other adverse events. Furthermore, we investigated potential effect modifiers, such as transplantation era and the concomitant immunosuppressive regimen in detail. Search methods We searched Cochrane Kidney and Transplant's Specialised Register (to 21 September 2015) through contact with the Trials' Search Co‐ordinator using search terms relevant to this review. Selection criteria All RCTs about MPA versus AZA in primary immunosuppression after kidney transplantation were included, without restriction on language or publication type. Data collection and analysis Two authors independently determined study eligibility, assessed risk of bias and extracted data from each study. Statistical analyses were performed using the random‐effects model and the results were expressed as risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes with 95% confidence intervals (CI). Main results We included 23 studies (94 reports) that involved 3301 participants. All studies tested mycophenolate mofetil (MMF), an MPA, and 22 studies reported at least one outcome relevant for this review. Assessment of methodological quality indicated that important information on factors used to judge susceptibility for bias was infrequently and inconsistently reported. MMF treatment reduced the risk for graft loss including death (RR 0.82, 95% CI 0.67 to 1.0) and for death‐censored graft loss (RR 0.78, 95% CI 0.62 to 0.99, P < 0.05). No statistically significant difference for MMF versus AZA treatment was found for all‐cause mortality (16 studies, 2987 participants: RR 0.95, 95% CI 0.70 to 1.29). The risk for any acute rejection (22 studies, 3301 participants: RR 0.65, 95% CI 0.57 to 0.73, P < 0.01), biopsy‐proven acute rejection (12 studies, 2696 participants: RR 0.59, 95% CI 0.52 to 0.68) and antibody‐treated acute rejection (15 studies, 2914 participants: RR 0.48, 95% CI 0.36 to 0.65, P < 0.01) were reduced in MMF treated patients. Meta‐regression analyses suggested that the magnitude of risk reduction of acute rejection may be dependent on the control rate (relative risk reduction (RRR) 0.34, 95% CI 0.10 to 1.09, P = 0.08), AZA dose (RRR 1.01, 95% CI 1.00 to 1.01, P = 0.10) and the use of cyclosporin A micro‐emulsion (RRR 1.27, 95% CI 0.98 to 1.65, P = 0.07). Pooled analyses failed to show a significant and meaningful difference between MMF and AZA in kidney function measures. Data on malignancies and infections were sparse, except for cytomegalovirus (CMV) infections. The risk for CMV viraemia/syndrome (13 studies, 2880 participants: RR 1.06, 95% CI 0.85 to 1.32) was not statistically significantly different between MMF and AZA treated patients, whereas the likelihood of tissue‐invasive CMV disease was greater with MMF therapy (7 studies, 1510 participants: RR 1.70, 95% CI 1.10 to 2.61). Adverse event profiles varied: gastrointestinal symptoms were more likely in MMF treated patients and thrombocytopenia and elevated liver enzymes were more common in AZA treatment. Authors' conclusions MMF was superior to AZA for improvement of graft survival and prevention of acute rejection after kidney transplantation. These benefits must be weighed against potential harms such as tissue‐invasive CMV disease. However, assessment of the evidence on safety outcomes was limited due to rare events in the observation periods of the studies (e.g. malignancies) and inconsistent reporting and definitions (e.g. infections, adverse events). Thus, balancing benefits and harms of the two drugs remains a major task of the transplant physician to decide which agent the individual patient should be started on

Identification of Caribbean ciguatoxins from benthic dinoflagellates advances knowledge on toxin chemistry and analysis

publishedVersio

New Evidence on the Puzzles. Results from Agnostic Identification on Monetary Policy and Exchange Rates

Past empirical research on monetary policy in open economies has found evidence of the 'delayed overshooting', the 'forward discount' and the 'exchange rate' puzzles. We revisit the effects of monetary policy on exchange rates by applying Uhlig's (2005) identification procedure that involves sign restrictions on the impulse responses of selected variables. We impose no restrictions on the exchange rate to leave the key question as open as possible. The sign restriction methodology avoids the price puzzles of the identification strategies used by Eichenbaum-Evans (1995) and by Grilli-Roubini (1995, 1996), which are particularly pronounced, when using an updated data set. We find that the puzzles regarding the exchange rates are still there, but that the quantitative features are different. In response to US monetary policy shocks, the peak appreciation happens during the first year after the shock for the US-German and the US-UK pair, and during the first two years for the US-Japan pair. This is consirably quicker than the three-year horizon found by Eichenbaum-Evans. There is a robust forward discount puzzle implying a large risk premium. We study this issue, introducing and calculating conditional Sharpe ratios for a Bayesian investor investing in a hedged position following a US monetary policy shock. For foreign monetary policy shocks, we find more robust results than with the Grilli-Roubini recursive identification strategy: the posterior distribution regarding the exchange reaction looks rather similar across countries and VAR specifications. In particular, we find that there seems to be considerable uncertainty regarding the initial reaction of the exchange rate. Quantitatively, monetary policy shocks seem to have a minor impact on exchange rate fluctuations

Approximate Solutions to Dynamic Models - Linear Methods

Linear Methods are often used to compute approximate solutions to dynamic models, as these models often cannot be solved analytically. Linear methods are very popular, as they can easily be implemented. Also, they provide a useful starting point for understanding more elaborate numerical methods. It shall be described here first for the example of a simple real business cycle model, including how to easily generate the log-linearized equations needed before solving the linear system. For a general framework, formulas are provided for calculating the recursive law of motion. The algorithm described here is implemented with the toolkit programs available per http://www.wiwi.hu-berlin.de/wpol/html/toolkit.htm

Immunodeficiency, autoimmune thrombocytopenia and enterocolitis caused by autosomal recessive deficiency of PIK3CD-encoded phosphoinositide 3-kinase δ.

Phosphoinositide 3-kinase δ (PI3Kδ), a lipid kinase consisting of a catalytic (p110δ, encoded by PIK3CD) and a regulatory subunit (p85, encoded by PIK3R1), generates the second messenger phosphatidylinositol (3,4,5)-trisphosphate (PIP3) in the plasma membrane of leukocytes downstream of antigen and cytokine receptors.1 Signaling via PDK1, AKT, mTOR and downstream targets such as FOXO1, contributes to the metabolic and transcriptional changes required for the expansion, differentiation and effector function of lymphocytes. Activating germline mutations in PIK3CD cause the immune dysregulatory disease activated PI3Kδ syndrome (APDS), usually presenting with recurrent sinopulmonary infections in childhood, herpesvirus infections and CD4+ lymphopenia, underscoring the important role of balanced p110δ activity in human adaptive immunity. Ablation of p110δ in mice leads to aberrant T cell responses and intestinal inflammation. In humans, immune dysregulation including severe colitis is present in many cancer patients who are treated with the p110δ-specific inhibitor Idelalisib. Recently, one patient with autosomal recessive deficiency of p85α and two patients with loss-of function mutations in p110δ have been described who developed humoral immunodeficiency and colitis

Intraoperative mechanical ventilation practice in thoracic surgery patients and its association with postoperative pulmonary complications: Results of a multicenter prospective observational study

Abstract: Background: Intraoperative mechanical ventilation may influence postoperative pulmonary complications (PPCs). Current practice during thoracic surgery is not well described. Methods: This is a post-hoc analysis of the prospective multicenter cross-sectional LAS VEGAS study focusing on patients who underwent thoracic surgery. Consecutive adult patients receiving invasive ventilation during general anesthesia were included in a one-week period in 2013. Baseline characteristics, intraoperative and postoperative data were registered. PPCs were collected as composite endpoint until the 5th postoperative day. Patients were stratified into groups based on the use of one lung ventilation (OLV) or two lung ventilation (TLV), endoscopic vs. non-endoscopic approach and ARISCAT score risk for PPCs. Differences between subgroups were compared using χ2 or Fisher exact tests or Student’s t-test. Kaplan–Meier estimates of the cumulative probability of development of PPC and hospital discharge were performed. Cox-proportional hazard models without adjustment for covariates were used to assess the effect of the subgroups on outcome. Results: From 10,520 patients enrolled in the LAS VEGAS study, 302 patients underwent thoracic procedures and were analyzed. There were no differences in patient characteristics between OLV vs. TLV, or endoscopic vs. open surgery. Patients received VT of 7.4 ± 1.6 mL/kg, a PEEP of 3.5 ± 2.4 cmH2O, and driving pressure of 14.4 ± 4.6 cmH2O. Compared with TLV, patients receiving OLV had lower VT and higher peak, plateau and driving pressures, higher PEEP and respiratory rate, and received more recruitment maneuvers. There was no difference in the incidence of PPCs in OLV vs. TLV or in endoscopic vs. open procedures. Patients at high risk had a higher incidence of PPCs compared with patients at low risk (48.1% vs. 28.9%; hazard ratio, 1.95; 95% CI 1.05–3.61; p = 0.033). There was no difference in the incidence of severe PPCs. The in-hospital length of stay (LOS) was longer in patients who developed PPCs. Patients undergoing OLV, endoscopic procedures and at low risk for PPC had shorter LOS. Conclusion: PPCs occurred frequently and prolonged hospital LOS following thoracic surgery. Proportionally large tidal volumes and high driving pressure were commonly used in this sub-population. However, large RCTs are needed to confirm these findings. Trial registration: This trial was prospectively registered at the Clinical Trial Register (www.clinicaltrials.gov; NCT01601223; registered May 17, 2012.