Intra- and interspecific polymorphisms ofLeishmania donovani andL. tropica minicircle DNA

A pair of degenerate polymerase chain reaction (PCR) primers (LEI-1, TCG GAT CC[C,T] [G,C]TG GGT AGG GGC GT; LEI-2, ACG GAT CC[G,C] [G,C][A,C]C TAT [A,T]TT ACA CC) defining a 0.15-kb segment ofLeishmania minicircle DNA was constructed. These primers amplified not only inter- but also intraspecifically polymorphic sequences. Individual sequences revealed a higher intraspecific than interspecific divergence. It is concluded that individual sequences are of limited relevance for species determination. In contrast, when a data base of 19 different sequences was analyzed in a dendrographic plot, an accurate species differentiation was feasible

Economic evidence for nonpharmacological asthma management interventions: A systematic review

Asthma management, education and environmental interventions have been reported as cost‐effective in a previous review (Pharm Pract (Granada), 2014;12:493), but methods used to estimate costs and outcomes were not discussed in detail. This review updates the previous review by providing economic evidence on the cost‐effectiveness of studies identified after 2012, and a detailed assessment of the methods used in all identified studies. Twelve databases were searched from 1990 to January 2016, and studies included economic evaluations, asthma subjects and nonpharmacological interventions written in English. Sixty‐four studies were included. Of these, 15 were found in addition to the earlier review; 53% were rated fair in quality and 47% high. Education and self‐management interventions were the most cost‐effective, in line with the earlier review. Self‐reporting was the most common method used to gather resource‐use data, accompanied by bottom‐up approaches to estimate costs. Main outcome measures were asthma‐related hospitalizations (69%), quality of life (41%) and utility (38%), with AQLQ and the EQ‐5D being the most common questionnaires measured prospectively at fixed time points. More rigorous costing methods are needed with a more common quality of life tool to aid greater replicability and comparability amongst asthma studies

Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a critical appraisal

Aim Blauvelt et al. (The Lancet 2017; 389: 2287-303) aimed to compare the long-term efficacy and safety of dupilumab with medium-potency topical corticosteroids (TCS) versus placebo with TCS in adults with moderate-to-severe atopic dermatitis (AD). Setting and design This multicentre randomised, double-blinded, placebo-controlled trial was conducted in hospitals, clinics and academic institutions across 161 sites in 14 countries. Study exposure Adults with moderate-to-severe AD were randomly assigned (3:1:3) to receive subcutaneous dupilumab 300mg once weekly (qw) plus TCS, dupilumab 300mg every 2 weeks (q2w) plus TCS, or placebo plus TCS until week-52. Primary outcome measures Co-primary efficacy endpoints were patients (%) achieving Investigator's Global Assessment (IGA) 0/1 and 2-points or higher improvement from baseline, and Eczema Area and Severity Index 75% improvement from baseline (EASI-75) at week-16. Results 740 patients were included in the trial: 319 were randomly assigned to dupilumab qw, 106 to dupilumab q2w and 315 to the placebo arm. At week-16, more patients in the dupilumab groups achieved the co-primary endpoints: IGA 0/1 (39% [125 patients] qw dosing, 39% [41 patients] q2w dosing vs 12% [39 patients] receiving placebo; p<0.0001) and EASI-75 (64% [204] and 69% [73] vs 23% [73]; p<0.0001). Whilst no new safety signals were identified, adverse effects (AEs) were noted in 261 (83%) in those receiving dupilumab qw plus TCS, 97 (88%) dupilumab q2w plus TCS and 266 (84%) for placebo plus TCS. Rates of conjunctivitis, injection site reactions and local herpes simplex infections were higher in the dupilumab groups compared with placebo. Conclusions Blauvelt et al. concluded that dupilumab treatment added to TCS improved AD up to week-52 compared with TCS alone, and also demonstrated acceptable safety

Who should be prioritized for renal transplantation?: Analysis of key stakeholder preferences using discrete choice experiments

Background Policies for allocating deceased donor kidneys have recently shifted from allocation based on Human Leucocyte Antigen (HLA) tissue matching in the UK and USA. Newer allocation algorithms incorporate waiting time as a primary factor, and in the UK, young adults are also favoured. However, there is little contemporary UK research on the views of stakeholders in the transplant process to inform future allocation policy. This research project aimed to address this issue. Methods Discrete Choice Experiment (DCE) questionnaires were used to establish priorities for kidney transplantation among different stakeholder groups in the UK. Questionnaires were targeted at patients, carers, donors / relatives of deceased donors, and healthcare professionals. Attributes considered included: waiting time; donor-recipient HLA match; whether a recipient had dependents; diseases affecting life expectancy; and diseases affecting quality of life. Results Responses were obtained from 908 patients (including 98 ethnic minorities); 41 carers; 48 donors / relatives of deceased donors; and 113 healthcare professionals. The patient group demonstrated statistically different preferences for every attribute (i.e. significantly different from zero) so implying that changes in given attributes affected preferences, except when prioritizing those with no rather than moderate diseases affecting quality of life. The attributes valued highly related to waiting time, tissue match, prioritizing those with dependents, and prioritizing those with moderate rather than severe diseases affecting life expectancy. Some preferences differed between healthcare professionals and patients, and ethnic minority and non-ethnic minority patients. Only non-ethnic minority patients and healthcare professionals clearly prioritized those with better tissue matches. Conclusions Our econometric results are broadly supportive of the 2006 shift in UK transplant policy which emphasized prioritizing the young and long waiters. However, our findings suggest the need for a further review in the light of observed differences in preferences amongst ethnic minorities, and also because those with dependents may be a further priority.</p

Maternal and perinatal outcomes after elective labor induction at 39 weeks in uncomplicated singleton pregnancies: a meta-analysis.

Objective The rate of maternal and perinatal complications increases after 39 weeks' gestation in both unselected and complicated pregnancies. The aim of this study was to synthesize quantitatively the available evidence on the effect of elective induction of labor at 39 weeks on the risk of Cesarean section, and on maternal and perinatal outcomes. Methods PubMed, US Registry of Clinical Trials, SCOPUS and CENTRAL databases were searched from inception to August 2018. Additionally, the references of retrieved articles were searched. Eligible studies were randomized controlled trials of singleton uncomplicated pregnancies in which participants were randomized between 39 + 0 and 39 + 6 gestational weeks to either induction of labor or expectant management. The risk of bias of individual studies was assessed using the Cochrane Risk of Bias Tool. The overall quality of evidence was assessed according to the GRADE guideline. Primary outcomes included Cesarean section, maternal death and admission to the neonatal intensive care unit (NICU). Secondary outcomes included operative delivery, Grade‐3/4 perineal laceration, postpartum hemorrhage, maternal infection, hypertensive disease of pregnancy, maternal thrombotic events, length of maternal hospital stay, neonatal death, need for neonatal respiratory support, cerebral palsy, length of stay in NICU and length of neonatal hospital stay. Pooled risk ratios (RRs) were calculated using random‐effects models. Results The meta‐analysis included five studies (7261 cases). Induction of labor was associated with a decreased risk for Cesarean section (moderate quality of evidence; RR 0.86 (95% CI, 0.78–0.94); I2 = 0.1%), maternal hypertension (moderate quality of evidence; RR 0.65 (95% CI, 0.57–0.75); I2 = 0%) and neonatal respiratory support (moderate quality of evidence; RR 0.73 (95% CI, 0.58–0.95); I2 = 0%). Neonates born after induction weighed, on average, 81 g (95% CI, 63–100 g) less than those born after expectant management. No significant effects were found for the other outcomes with the available data. The main limitation of our analysis was that the majority of data were derived from a single large study. A second limitation arose from the open‐label design of the studies, which may theoretically have affected the readiness of the attending clinician to resort to Cesarean section. Conclusions Elective induction of labor in uncomplicated singleton pregnancy at 39 weeks' gestation is not associated with maternal or perinatal complications and may reduce the need for Cesarean section, risk of hypertensive disease of pregnancy and need for neonatal respiratory support

Relationships between CYP2D6 phenotype, breast cancer and hot flushes in women at high risk of breast cancer receiving prophylactic tamoxifen: results from the IBIS-I trial

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Effect of antiandrogen flutamide on measures of hepatic regeneration in rats

Male rat liver undergoes a process of demasculinization during hepatic regeneration following partial hepatectomy. The possibility that antiandrogens might potentiate this demasculinization process and in so doing augment the hepatic regenerative response was investigated. Adult male Wistar rats were treated with the antiandrogen flutamide (2 mg/rat/day or 5 mg/rat/day subcutaneously) or vehicle for three days prior to and daily after a 70% partial hepatectomy. At various times after hepatectomy, the liver remnants were removed and weighed. Rates of DNA and polyamine synthesis were assessed by measuring thymidine kinase and ornithine decarboxylase activities, respectively. Hepatic estrogen receptor status and the activity of alcohol dehydrogenase, an androgen-sensitive protein, were measured. Prior to surgery, the administration of 5 mg/day flutamide reduced the hepatic cytosolic androgen receptor activity by 98% and hepatic cytosolic estrogen receptor content by 92% compared to that present in vehicle-treated controls. After hepatectomy, however, all differences in sex hormone receptor activity between the treatment groups were abolished. The rate of liver growth after partial hepatectomy in the three groups was identical. Moreover, hepatectomy-induced increases in ornithine decarboxylase activity and thymidine kinase activity were comparable. These data demonstrate that, although flutamide administration initially alters the sex hormone receptor status of the liver, these affects have no effect on the hepatic regenerative response following a partial hepatectomy. © 1989 Plenum Publishing Corporation

Semigroups with operation-compatible Green’s quasiorders

We call a semigroup on which the Green’s quasiorder ≤ J (≤ L, ≤ R) is operation-compatible, a ≤ J-compatible (≤ L-compatible, ≤ R-compatible) semigroup. We study the classes of ≤ J-compatible, ≤ L-compatible and ≤ R-compatible semigroups, using the smallest operation-compatible quasiorders containing Green’s quasiorders as a tool. We prove a number of results, including the following. The class of ≤ L-compatible (≤ R-compatible) semigroups is closed under taking homomorphic images. A regular periodic semigroup is ≤ J-compatible if and only if it is a semilattice of simple semigroups. Every negatively orderable semigroup can be embedded into a negatively orderable ≤ J-compatible semigroup