Systematic review and meta-analysis of iron therapy in anaemic adults without chronic kidney disease: updated and abridged Cochrane review

AIMS: Anaemia is increasingly recognized as having an independent impact upon patient outcomes in cardiac disease. The role of novel iron therapies to treat anaemia is increasing. This systematic review and meta-analysis assesses the efficacy and safety of iron therapies for the treatment of adults with anaemia. METHODS AND RESULTS: Electronic databases and search engines were searched as per Cochrane methodology. Randomized controlled trials (RCTs) of iron vs. inactive control or placebo, as well as alternative formulations, doses, and routes in anaemic adults without chronic kidney disease or in the peri-partum period were eligible. The primary outcome of interest was mortality at 1 year. Secondary outcomes were blood transfusion, haemoglobin levels, quality of life, serious adverse events, and length of hospital stay. A total of 64 RCTs (including five studies of heart failure patients) comprising 9004 participants were included. None of the studies was at a low risk of bias. There were no statistically significant differences in mortality between iron and inactive control. Both oral and parenteral iron significantly reduced the proportion of patients requiring blood transfusion compared with inactive control [risk ratio (RR) 0.66, 95% confidence interval (CI) 0.48-0.90; and RR 0.84, 95% CI 0.73-0.97, respectively]. Haemoglobin was increased more by both oral and parenteral iron compared with inactive control [mean difference (MD) 0.91 g/dL, 95% CI 0.48 to 1.35; and MD 1.04, 95% CI 0.52 to 1.57, respectively], and parenteral iron demonstrated a greater increase when compared with oral iron (MD 0.53 g/dL, 95% CI 0.31-0.75). In all comparisons, there were no differences in the results comparing patients with and without heart failure. CONCLUSION: Both oral and parenteral iron are shown to decrease the proportion of people who require blood transfusion and increase haemoglobin levels, without any benefit on mortality. Further trials at a low risk of bias, powered to measure clinically significant endpoints, are still required

Incidence, impact, and predictors of cranial nerve palsy and haematoma following carotid endarterectomy in the international carotid stenting study.

OBJECTIVE: Cranial nerve palsy (CNP) and neck haematoma are complications of carotid endarterectomy (CEA). The effects of patient factors and surgical technique were analysed on the risk, and impact on disability, of CNP or haematoma in the surgical arm of the International Carotid Stenting Study (ICSS), a randomized controlled clinical trial of stenting versus CEA in patients with symptomatic carotid stenosis. MATERIALS AND METHODS: A per-protocol analysis of early outcome in patients receiving CEA in ICSS is reported. Haematoma was defined by the surgeon. CNP was confirmed by an independent neurologist. Factors associated with the risk of CNP and haematoma were investigated in a binomial regression analysis. RESULTS: Of the patients undergoing CEA, 45/821 (5.5%) developed CNP, one of which was disabling (modified Rankin score = 3 at 1 month). Twenty-eight (3.4%) developed severe haematoma. Twelve patients with haematoma also had CNP, a significant association (p 14 days (RR 3.33, 95% CI 1.05 to 10.57). The risk of haematoma was increased in women, by the prescription of anticoagulant drugs pre-procedure and in patients with atrial fibrillation, and was decreased in patients in whom a shunt was used and in those with a higher baseline cholesterol level. CONCLUSIONS: CNP remains relatively common after CEA, but is rarely disabling. Women should be warned about an increased risk. Attention to haemostasis might reduce the incidence of CNP. ICSS is a registered clinical trial: ISRCTN 25337470

Genetic improvement of wheat for dry environments - a trait based approach

Item does not contain fulltext23 januari 201

Long Term Restenosis Rate After Carotid Endarterectomy: Comparison of Three Surgical Techniques and Intra-Operative Shunt Use

OBJECTIVE: Closure of the artery during carotid endarterectomy (CEA) can be done with or without a patch, or performed with the eversion technique, while the use of intra-operative shunts is optional. The influence of these techniques on subsequent restenosis is uncertain. Long term carotid restenosis rates and risk of future ipsilateral stroke with these techniques were compared. METHODS: Patients who underwent CEA in the International Carotid Stenting Study were divided into patch angioplasty, primary closure, or eversion endarterectomy. Intra-operative shunt use was reported. Carotid duplex ultrasound was performed at each follow up. Primary outcomes were restenosis of ≥ 50% and ≥ 70%, and ipsilateral stroke after the procedure to the end of follow up. RESULTS: In total, 790 CEA patients had restenosis data at one and five years. Altogether, 511 (64.7%) had patch angioplasty, 232 (29.4%) primary closure, and 47 (5.9%) eversion endarterectomy. The cumulative incidence of ≥ 50% restenosis at one year was 18.9%, 26.1%, and 17.7%, respectively, and at five years it was 25.9%, 37.2%, and 30.0%, respectively. There was no difference in risk between the eversion and patch angioplasty group (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.45 - 1.81; p = .77). Primary closure had a higher risk of restenosis than patch angioplasty (HR 1.45, 95% CI 1.06 - 1.98; p = .019). The cumulative incidence of ≥ 70% restenosis did not differ between primary closure and patch angioplasty (12.1% vs. 7.1%, HR 1.59, 95% CI 0.88 - 2.89; p = .12) or between patch angioplasty and eversion endarterectomy (4.7%, HR 0.45, 95% CI 0.06 - 3.35; p = .44). There was no effect of shunt use on the cumulative incidence of restenosis. Post-procedural ipsilateral stroke was not more common in either of the surgical techniques or shunt use. CONCLUSION: Restenosis was more common after primary closure than conventionally with a patch closure. Shunt use had no effect on restenosis. Patch closure is the treatment of choice to avoid restenosis

Исследование обобщающих характеристик пузырей подводных газовых факелов

Objective: To decrease the procedural risk of carotid revascularisation it is crucial to understand the mechanisms of procedural stroke. This study analysed the features of procedural strokes associated with carotid artery stenting (CAS) and carotid endarterectomy (CEA) within the International Carotid Stenting Study (ICSS) to identify the underlying pathophysiological mechanism. Materials and methods: Patients with recently symptomatic carotid stenosis (1,713) were randomly allocated to CAS or CEA. Procedural strokes were classified by type (ischaemic or haemorrhagic), time of onset (intraprocedural or after the procedure), side (ipsilateral or contralateral), severity (disabling or non-disabling), and patency of the treated artery. Only patients in whom the allocated treatment was initiated were included. The most likely pathophysiological mechanism was determined using the following classification system: (1) carotid-embolic, (2) haemodynamic, (3) thrombosis or occlusion of the revascularised carotid artery, (4) hyperperfusion, (5) cardio-embolic, (6) multiple, and (7) undetermined. Results: Procedural stroke occurred within 30 days of revascularisation in 85 patients (CAS 58 out of 791 and CEA 27 out of 819). Strokes were predominately ischaemic (77; 56 CAS and 21 CEA), after the procedure (57; 37 CAS and 20 CEA), ipsilateral to the treated artery (77; 52 CAS and 25 CEA), and non-disabling (47; 36 CAS and 11 CEA). Mechanisms of stroke were carotid-embolic (14; 10 CAS and 4 CEA), haemodynamic (20; 15 CAS and 5 CEA), thrombosis or occlusion of the carotid artery (15; 11 CAS and 4 CEA), hyperperfusion (9; 3 CAS and 6 CEA), cardio-embolic (5; 2 CAS and 3 CEA) and multiple causes (3; 3 CAS). In 19 patients (14 CAS and 5 CEA) the cause of stroke remained undetermined. Conclusion: Although the mechanism of procedural stroke in both CAS and CEA is diverse, haemodynamic disturbance is an important mechanism. Careful attention to blood pressure control could lower the incidence of procedural stroke. </p

Lymphatic Filariasis Control in Tanzania: Effect of Six Rounds of Mass Drug Administration with Ivermectin and Albendazole on Infection and Transmission.

Control of lymphatic filariasis (LF) in most countries of sub-Saharan Africa is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole, in order to interrupt transmission. We present findings from a detailed study on the effect of six rounds of MDA with this drug combination as implemented by the National Lymphatic Filariasis Elimination Programme (NLFEP) in a highly endemic rural area of north-eastern Tanzania.\ud The effect of treatment on transmission and human infection was monitored in a community- and a school-based study during an 8-year period (one pre-intervention and 7 post-intervention years) from 2003 to 2011. Before intervention, 24.5% of the community population had microfilariae (mf) in the blood, 53.3% had circulating filarial antigens (CFA) and 78.9% had specific antibodies to the recombinant filarial antigen Bm14. One year after the sixth MDA, these values had decreased considerably to 2.7%, 19.6% and 27.5%, respectively. During the same period, the CFA prevalence among new intakes of Standard 1 pupils in 10 primary schools decreased from 25.2% to 5.6%. In line with this, transmission by the three vectors (Anopheles gambiae, An. funestus and Culex quinquefasciatus) as determined by dissection declined sharply (overall vector infectivity rate by 99.3% and mean monthly transmission potential by 99.2% between pre-intervention and fifth post-intervention period). A major shift in vector species composition, from predominantly anopheline to almost exclusively culicine was observed over the years. This may be largely unrelated to the MDAs but may have important implications for the epidemiology of LF in the area. Six MDAs caused considerable decrease in all the measured indices for transmission and human infection. In spite of this, indices were still relatively high in the late period of the study, and it may take a long time to reach the recommended cut-off levels for interruption of transmission unless extra efforts are made. These should include increased engagement of the target population in the control activities, to ensure higher treatment coverage. It is expected that the recent initiative to distribute insecticide impregnated bed nets to every household in the area will also contribute towards reaching the goal of successful LF elimination

Determinants of the voltage dependence of G protein modulation within calcium channel β subunits

CaVβ subunits of voltage-gated calcium channels contain two conserved domains, a src-homology-3 (SH3) domain and a guanylate kinase-like (GK) domain with an intervening HOOK domain. We have shown in a previous study that, although Gβγ-mediated inhibitory modulation of CaV2.2 channels did not require the interaction of a CaVβ subunit with the CaVα1 subunit, when such interaction was prevented by a mutation in the α1 subunit, G protein modulation could not be removed by a large depolarization and showed voltage-independent properties (Leroy et al., J Neurosci 25:6984–6996, 2005). In this study, we have investigated the ability of mutant and truncated CaVβ subunits to support voltage-dependent G protein modulation in order to determine the minimal domain of the CaVβ subunit that is required for this process. We have coexpressed the CaVβ subunit constructs with CaV2.2 and α2δ-2, studied modulation by the activation of the dopamine D2 receptor, and also examined basal tonic modulation. Our main finding is that the CaVβ subunit GK domains, from either β1b or β2, are sufficient to restore voltage dependence to G protein modulation. We also found that the removal of the variable HOOK region from β2a promotes tonic voltage-dependent G protein modulation. We propose that the absence of the HOOK region enhances Gβγ binding affinity, leading to greater tonic modulation by basal levels of Gβγ. This tonic modulation requires the presence of an SH3 domain, as tonic modulation is not supported by any of the CaVβ subunit GK domains alone