Royal London Group (United Kingdom)

The author has no conflicts of interest. None.

Rapid infusion of warmed blood products is the cornerstone of trauma resuscitation and treatment of surgical and obstetric massive hemorrhage. Integral to optimizing this delivery is selection of an intravenous (IV) catheter and use of a rapid infusion device (RID). We investigated which IV catheter and RID system enabled the greatest infusion rate of blood products and the governing catheter characteristics. The maximum flow rates of nine IV catheters were measured while infusing a mixture of packed red blood cells and fresh frozen plasma at a 1:1 ratio using a RID with and without a patient line extension. To account for IV catheters that achieved the RID's maximum 1000 ml/min, the conductance of each infusion circuit configuration was calculated. IV catheters of 7-Fr caliber or higher reached the maximum pressurized flow rate. The 9-Fr multi-lumen access catheter (MAC) achieved the greatest conductance, over sevenfold greater than the 18 g peripheral catheter (4.6 vs. 0.6ml/min/mmHg, p <.001). Conductance was positively correlated with internal radius (β= 1.098, 95% CI 4.286-5.025, p <.001) and negatively correlated with length (β= -0.495, 95% CI -0.007 to 0.005, p <.001). Use of an extension line (β= -0.094, 95% CI -0.505 to -0.095, p= .005) was independently associated with reduced conductance in large caliber catheters. Short, large-diameter catheters provided the greatest infusion rates of massive transfusion blood products for the least pressure. For patients requiring the highest transfusion flow rates, extension tubing should be avoided when possible.

Dopamine and cyclic‐AMP activated phosphoprotein Mr32kDa (DARPP‐32) is a central signalling protein in neurotransmission. Following DARPP‐32 phosphorylation by protein kinase A (PKA), DARPP‐32 becomes a potent protein phosphatase 1 (PP1) inhibitor. DARPP‐32 can itself inhibit PKA following DARPP‐32 phosphorylation by cyclin‐dependent kinase 5 (Cdk5). Increasing evidence indicates a role for DARPP‐32 and its associated signalling pathways in cancer; however, its role in ovarian cancer remains unclear. Using immunohistochemistry, expression of DARPP‐32, PP1 and Cdk5 was determined in a large cohort of primary tumours from ovarian cancer patients (n = 428, 445 and 434 respectively) to evaluate associations between clinical outcome and clinicopathological criteria. Low cytoplasmic and nuclear DARPP‐32 expression was associated with shorter patient overall survival and progression‐free survival (P = .001, .001, .004 and .037 respectively). Low nuclear and cytoplasmic DARPP‐32 expression remained significantly associated with overall survival in multivariate Cox regression (P = .045, hazard ratio (HR) = 0.734, 95% confidence interval (CI) = 0.542‐0.993 and P = .001, HR = 0.494, 95% CI = 0.325‐0.749, respectively). High cytoplasmic and nuclear PP1 expression was associated with shorter patient overall survival and high cytoplasmic PP1 expression with shorter progression‐free survival (P = .005, .033, and .037, respectively). High Cdk5 expression was associated with shorter progression‐free survival (P = .006). These data suggest a role for DARPP‐32 and associated signalling kinases as prognostic markers with clinical utility in ovarian cancer.

Background:In chronic ITP, subcutaneous administration of romiplostim by a healthcare professional (HCP) is approved in many countries. Self‐administration (SA) by patients/caregivers can offer time and cost savings to providers and is convenient for patients because the need for weekly clinic visits is eliminated. SA is available in Europe for trained patients with stable platelet count (≥50 x 109/L for ≥4 weeks [wks] without dose adjustment).Aims:This analysis examined the safety and efficacy of romiplostim SA.Methods:Data were pooled from 5 romiplostim clinical trials in adults (≥18 years) with ITP. In all trials, and at investigators’ discretion, patients who achieved a stable dose for ≥3 consecutive wks (≥4 wks in 3 trials; ≥3 wks in 2 trials) could self‐inject romiplostim (or have it administered by a caregiver). The SA analysis group included patients who ever self‐administered romiplostim in any of these 5 trials. To provide a meaningful comparator, an HCP‐dosed subgroup of patients from the 5 trials were included in the analysis. Patients in this comparator subgroup were required to have received the same stable romiplostim dose for ≥5 consecutive wks (duration selected to provide a conservative comparison) with platelet response and with all doses administered by an HCP. Thus, patients in the HCP comparator group may have been eligible for SA provided they had received physician approval and adequate training. In the SA group, the analysis index date was the 1st day a patient self‐injected romiplostim. In the HCP group, the index date was the date of the 5th consecutive stable dose. Safety parameters were adjusted for differences in romiplostim treatment duration in the SA and HCP groups (duration‐adjusted values reported herein). Platelet response was defined as weekly platelet counts ≥50 x 109/L without any use of rescue medication within 4 wks prior to date of the platelet measurement. Statistical analyses were descriptive.Results:At baseline, in the SA (N = 621) vs HCP (N = 133) groups, respectively, median age was 53 vs 58 years, median time since primary ITP diagnosis was 3.7 vs 2.5 years, median baseline platelet count was 19 vs 20 × 109/L, and 34% vs 28% had undergone splenectomy. Median romiplostim treatment duration was 89 and 52 wks for SA and HCP groups, respectively. Respective median total number of doses were 81 and 50. The median weekly romiplostim dose was 3.6 μg/kg in the SA group and 3.1 μg/kg in the HCP group. As shown in the table, duration‐adjusted event rates were numerically lower in the SA vs HCP group for all treatment‐emergent adverse events (TEAEs), Grade ≥3 TEAEs, serious TEAEs, TEAEs leading to discontinuation and fatal TEAEs. Duration‐adjusted rates of bleeding TEAEs, Grade ≥3 bleeding TEAEs and serious bleeding TEAEs were also numerically lower for the SA vs the HCP group (see Table). Following the index date, 95% of patients in the SA group and all patients (100%) in the HCP group achieved a platelet response at least once during the analysis period. The median % of wks in response in the SA vs HCP groups were 95% vs 96%, respectively. Overall, rescue medication was used in 37% vs 40% of patients in the SA vs HCP groups, respectively. Adjusting for the duration of treatment, the romiplostim dose adjustment rates/100 subject‐wks were 1.24 vs 1.60 in the SA vs HCP groups, respectively.Summary/Conclusion:Romiplostim self‐administration appears well tolerated and effective in eligible patients with ITP who have stable platelet counts ≥50 × 109/L for ≥4 consecutive wks and have undergone training.image

The Kyoto Protocol was intended to cut the greenhouse gas emissions of developed countries to 5 per cent less than they were in 1990, and this was to be achieved by the end of 2012. As that deadline approaches it is time to take stock of what has actually happened. There is some good news and some bad news: The bad news is that political solutions to mitigate global warming lack the ambition to deliver what the scientists demand—a limit on the increase in temperature of 28C. The good news is that, 20 years after the Rio Earth Summit, the ‘Environment’ is firmly on the corporate agenda and as economies emerge from recession the green shoots of growth can be truly green. But we need more commitment from our politicians. This is difficult to achieve as international recession drags on because policies to boost growth at any price are better vote-winners than policies that increase environmental costs.

Background: Although it is a known predictor of mortality, there is a relative lack of recent information about anaemia in kidney transplant recipients. Thus, we now report data about the prevalence and management of post-transplant anaemia (PTA) in Europe 5 years after the TRansplant European Survey on Anemia Management (TRESAM) study. Methods: In a cross-sectional study enrolling the largest number of patients to date, data were obtained from 5,834 patients followed at 10 outpatient transplant clinics in four European countries using the American Society of Transplantation anaemia guideline. Results: More than one third (42%) of the patients were anaemic. The haemoglobin (Hb) concentration was significantly correlated with the estimated glomerular filtration rate (eGFR) (r = 0.4, p < 0.001). In multivariate analysis, eGFR, serum ferritin, age, gender, time since transplantation and centres were independently and significantly associated with Hb. Only 24% of the patients who had a Hb concentration <110 g/l were treated with an erythropoiesis-stimulating agent. The prevalence of anaemia and also the use of erythropoiesis-stimulating agents were significantly different across the different centres, suggesting substantial practice variations. Conclusions: PTA is still common and under-treated. The prevalence and management of PTA have not changed substantially since the TRESAM survey.

Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) are characterized by acute hypoxemic respiratory failure and bilateral pulmonary infiltrates that are not attributable to left atrial hypertension [1]. ALI/ARDS is a heterogeneous disease with a complex pathophysiology that may occur in response to a direct pulmonary or indirect systemic injury [1]. ALI and ARDS are different spectrums of the same condition. ALI is characterized by a PaO2/FiO2 ratio of less than 300 mmHg (40 kPa). ARDS, the more severe end of the spectrum on the basis of oxygenation criteria, is defined by a PaO2/FiO2 ratio of less than 200 mmHg (26 kPa). A recent prospective cohort study estimated the incidence of ALI to be 79/100,000 person years [2]. Mortality remains high although more recent trials have reported a lower mortality [3, 4].KeywordsLung InjuryAcute Lung InjuryAcute Respiratory Distress SyndromeRespir CritEndothelial BarrierThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.