A randomized trial on the efficacy of an autologous blood drainage and transfusion device in patients undergoing elective knee arthroplasty

The purpose of the study reported here was the determination of the efficacy of a postoperative autologous blood drainage and transfusion device in reducing allogeneic red cell requirements in patients undergoing elective knee arthroplasty. The study was a randomized controlled trial with adult patients undergoing unilateral elective arthroplastic knee surgery. Patients underwent suction drainage, attached to an autologous blood drainage and transfusion device, or standard suction drainage. Allogeneic red cells were given according to strict transfusion guidelines based on blood loss and postoperative hemoglobin values. Outcome measures included the mean number of allogeneic red cell concentrates required and the number of patients in each group who required no transfusion. Patients assigned to standard suction drainage had a mean allogeneic red cell utilization of 1.2 units (SD 1.0), as compared to a mean of 0.4 units (SD 0.8) in the group undergoing drainage with the autologous blood drainage and transfusion device (p = 0.0007). The percentage of patients not requiring allogeneic red cells was significantly higher in the latter group (74.3% vs. 32.5%; p = 0.002). The postoperative drainage and transfusion device was efficacious in reducing the amount of allogeneic red cells required by patients undergoing knee arthroplasty, and its use resulted in a 42 percent reduction in the number of patients requiring allogeneic transfusion.     

Within-population genetic diversity of Plasmodium falciparum vaccine candidate antigens reveals geographic distance from a Central sub-Saharan African origin

Populations of Plasmodium falciparum, the most virulent human malaria parasite, are diverse owing to wide levels of transmission and endemicity of infection. Genetic diversity of P. falciparum antigens, within and between parasite populations, remains a confounding factor in malaria pathogenesis as well as clinical trials of vaccine candidates. Variation of target antigens in parasite populations may arise from immune pressure depending on the levels of acquired immunity. Alternatively, similar to our study in housekeeping genes [Tanabe et al. Curr Biol 2010;70:1–7], within-population genetic diversity of vaccine candidate antigens may also be determined by geographical distance from a postulated origin in Central sub-Saharan Africa. To address this question, we obtained full-length sequences of P. falciparum genes, apical membrane antigen 1 (ama1) (n = 459), circumsporozoite protein (csp) (n = 472) and merozoite surface protein 1 (msp1) (n = 389) from seven geographically diverse parasite populations in Africa, Southeast Asia and Oceania; and, together with previously determined sequences (n = 13 and 15 for csp and msp1, respectively) analyzed within-population single nucleotide polymorphism (SNP) diversity. The three antigen genes showed SNP diversity that supports a model of isolation-by-distance. The standardized number of polymorphic sites per site, expressed as θ_S, indicates that 77–83% can be attributed by geographic distance from the African origin, suggesting that geographic distance plays a significant role in variation in target vaccine candidate antigens. Furthermore, we observed that a large proportion of SNPs in the antigen genes were shared between African and non-African parasite populations, demonstrating long term persistence of those SNPs. Our results provide important implications for developing effective malaria vaccines and better understanding of acquired immunity against falciparum malaria.     

Spontaneous mutations in the Plasmodium falciparum sarcoplasmic/ endoplasmic reticulum Ca2+-ATPase (PfATP6) gene among geographically widespread parasite populations unexposed to artemisinin-based combination therapies

Recent reports on the decline of the efficacy of artemisinin-based combination therapies (ACTs) indicate a serious threat to malaria control. The endoplasmic/sarcoplasmic reticulum Ca(2+)-ATPase ortholog of Plasmodium falciparum (PfSERCA) has been suggested to be the target of artemisinin and its derivatives. It is assumed that continuous artemisinin pressure will affect polymorphism of the PfSERCA gene (serca) if the protein is the target. Here, we investigated the polymorphism of serca in parasite populations unexposed to ACTs to obtain baseline information for the study of potential artemisinin-driven selection of resistant parasites. Analysis of 656 full-length sequences from 13 parasite populations in Africa, Asia, Oceania, and South America revealed 64 single nucleotide polymorphisms (SNPs), of which 43 were newly identified and 38 resulted in amino acid substitutions. No isolates showed L263E and S769N substitutions, which were reportedly associated with artemisinin resistance. Among the four continents, the number of SNPs was highest in Africa. In Africa, Asia, and Oceania, common SNPs, or those with a minor allele frequency of ≥0.05, were less prevalent, with most SNPs noted to be continent specific, whereas in South America, common SNPs were highly prevalent and often shared with those in Africa. Of 50 amino acid haplotypes observed, only one haplotype (3D7 sequence) was seen in all four continents (64%). Forty-eight haplotypes had frequencies of less than 5%, and 40 haplotypes were continent specific. The geographical difference in the diversity and distribution of serca SNPs and haplotypes lays the groundwork for assessing whether some artemisinin resistance-associated mutations and haplotypes are selected by ACTs.     

Pessaries in multiple pregnancy as a prevention of preterm birth: the ProTwin Trial

Background

Preterm labour is the main cause of perinatal morbidity and mortality in the Western world. At present, there is evidence that tocolysis for 48 hours is useful in women with threatened preterm labour at least before 32 weeks. This allows transfer of the patient to a perinatal centre, and maximizes the effect of corticosteroids for improved neonatal survival. It is questionable whether treatment with tocolytics should be maintained after 48 hours.

Methods/Design

The APOSTEL II trial is a multicentre placebo-controlled study. Pregnant women admitted for threatened preterm labour who have been treated with 48 hours corticosteroids and tocolysis will be eligible to participate in the trial between 26⁺⁰ and 32⁺² weeks gestational age. They will be randomly allocated to nifedipine (intervention) or placebo (control) for twelve days or until delivery, whatever comes first. Primary outcome is a composite of perinatal death, and severe neonatal morbidity up to evaluation at 6 months after birth. Secondary outcomes are gestational age at delivery, number of days in neonatal intensive care and total days of the first 6 months out of hospital. In addition a cost-effectiveness analysis will be performed. Analysis will be by intention to treat. The power calculation is based on an expected 11% difference in adverse neonatal outcome. This implies that 406 women have to be randomised (two sided test, β 0.2 at alpha 0.05).

Discussion

This trial will provide evidence as to whether maintenance tocolysis reduces severe perinatal morbidity and mortality in women with threatened preterm labour before 32 weeks.

Trial Registration

Clinical trial registration: http://www.trialregister.nl, NTR 1336, date of registration: June 3^rd 2008.     

Kinetics and 28-day test–retest repeatability and reproducibility of [11C]UCB-J PET brain imaging

[¹¹C]UCB-J is a novel radioligand that binds to synaptic vesicle glycoprotein 2A (SV2A). The main objective of this study was to determine the 28-day test–retest repeatability (TRT) of quantitative [¹¹C]UCB-J brain positron emission tomography (PET) imaging in Alzheimer’s disease (AD) patients and healthy controls (HCs). Nine HCs and eight AD patients underwent two 60 min dynamic [¹¹C]UCB-J PET scans with arterial sampling with an interval of 28 days. The optimal tracer kinetic model was assessed using the Akaike criteria (AIC). Micro-/macro-parameters such as tracer delivery (K₁) and volume of distribution (V_T) were estimated using the optimal model. Data were also analysed for simplified reference tissue model (SRTM) with centrum semi-ovale (white matter) as reference region. Based on AIC, both 1T2k_V_B and 2T4k_V_B described the [¹¹C]UCB-J kinetics equally well. Analysis showed that whole-brain grey matter TRT for V_T, DVR and SRTM BP_ND were –2.2% ± 8.5, 0.4% ± 12.0 and –8.0% ± 10.2, averaged over all subjects. [¹¹C]UCB-J kinetics can be well described by a 1T2k_V_B model, and a 60 min scan duration was sufficient to obtain reliable estimates for both plasma input and reference tissue models. TRT for V_T, DVR and BP_ND was <15% (1SD) averaged over all subjects and indicates adequate quantitative repeatability of [¹¹C]UCB-J PET.     

A differential response to treatment with divalproex sodium in patients with intractable headache

We consecutively recruited 75 patients with intractable headache syndromes, divided them into three groups (frequent migraine = FM, transformed migraine = TM, and tension type headache = TT) based on their headache symptoms and treated all 75 with divalproex sodium. Thirty-six patients (48%) reported a ³ 50% reduction in headache frequency. We noted significantly different treatment response rates in the three patient groups, with FM patients reporting the highest rate of improvement (11/18 = 61%), TM patients an intermediate rate (22/43 = 51%), and TT patients the lowest response rate (3/14 = 21%), These data suggest that prophylactic therapy with divalproex may be effective in selected patients with intractable headache syndromes and that identification of clinically distinct headache subtypes may assist in predicting response to treatment.     

A prospective study to identify the risk factors associated with acute reactions to platelet and red cell transfusions

It is generally assumed that febrile nonhemolytic transfusion reactions are an immunologically mediated reaction involving the recipient's plasma and the white cells in the donor unit. This has led to the use of white cell reduction and pretransfusion medication, to try to minimize these reactions. To better understand febrile transfusion reactions, a prospective study was performed in which all patients receiving platelet and red cell transfusions in a tertiary-care medical center were interviewed before and after transfusion to obtain information about the typical presentation of the syndrome. It was found that transfusion reactions were much more frequently associated with platelet transfusion (30.8%) than with red cell transfusion (6.8%, p < 0.0005). The routine use of antipyretics prevented most episodes of fever but did not prevent the occurrence of other symptoms such as chills, cold, and discomfort. The application of logistic regression analysis revealed that the dominant factor determining the risk of a reaction was not white cell contamination, but the age of the component (p < 0.005). The significant relationship between reaction and the increasing age of the component suggests that cytokines released in the component during storage may be responsible for many reactions to blood components.     

Oral sweet solution reduces pain-related behaviour in preterm infants

To evaluate the effectiveness of oral sucrose in the prevention of pain-induced crying in preterm infants, a sample of 28 healthy neonates (15M, 13F; gestational age at procedure less than 37 weeks) who were having routine blood drawn by arm venipuncture was studied. Infants were randomly allocated to receive by mouth, using a syringe, 2 ml of one of three solutions: spring water (group W) and sucrose 12 and 24% w/v (groups S12 and S24, respectively), all in water vehicle. After 2 min, while awake, arm venipuncture was performed and duration of crying was measured. The time spent crying was reduced in the group treated with the sweetest solution (S24, n = 8, mean =19.1 s). No difference was observed between the S12 group ( n = 8, mean = 63.1 s) and W group ( n = 12, mean = 72.9 s). Physiological measurements were recorded at different time points to evaluate excessive basal and procedural distress.     

Partial flip angle MR imaging

Theoretical analysis predicts that performing magnetic resonance (MR) imaging with partial (less than 90 degrees) flip angles can reduce imaging times two- to fourfold when lesions with elevated T1 values are being examined. This time savings occurs because repetition time (TR) is reduced when imaging is performed with partial flips. Partial flip MR imaging can also improve signal-to-noise ratio (S/N) in fast body imaging. For this study, analytical tools were used to predict image contrast and S/N for short TR, partial flip sequences. Experimental implementation of the short TR, partial flip sequences that analytical work had predicted would be optimal supported the analytical predictions and demonstrated their validity. Partial flip MR imaging is applicable to reducing imaging time only when the ratio of signal differences to noise exceeds threshold values in conventional MR images. Partial flip sequences can be used to advantage in MR imaging of both the head and the body, and the observed effects are predictable through theoretical analysis.