1,228 research outputs found

    Impact of inhaled corticosteroids on growth in children with asthma: systematic review and meta-analysis

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    Background: Long-term inhaled corticosteroids (ICS) may reduce growth velocity and final height of children with asthma. We aimed to evaluate the association between ICS use of >12 months and growth. Methods: We initially searched MEDLINE and EMBASE in July 2013, followed by a PubMed search updated to December 2014. We selected RCTs and controlled observational studies of ICS use in patients with asthma. We conducted random effects meta-analysis of mean differences in growth velocity (cm/year) or final height (cm) between groups. Heterogeneity was assessed using the I2 statistic. Results: We found 23 relevant studies (twenty RCTs and three observational studies) after screening 1882 hits. Meta-analysis of 16 RCTs showed that ICS use significantly reduced growth velocity at one year follow-up (mean difference -0.48 cm/year (95% CI -0.66 to -0.29)). There was evidence of a dose-response effect in three RCTs. Final adult height showed a mean reduction of -1.20 cm (95% CI -1.90 cm to -0.50 cm) with budesonide versus placebo in a high quality RCT. Meta-analysis of two lower quality observational studies revealed uncertainty in the association between ICS use and final adult height, pooled mean difference -0.85 cm (95% CI -3.35 to 1.65). Conclusion: Use of ICS for >12 months in children with asthma has a limited impact on annual growth velocity. In ICS users, there is a slight reduction of about a centimeter in final adult height, which when interpreted in the context of average adult height in England (175 cm for men and 161 cm for women), represents a 0.7% reduction compared to non-ICS users

    Iterative Evolution of Sympatric Seacow (Dugongidae, Sirenia) Assemblages during the Past ∼26 Million Years

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    Extant sirenians show allopatric distributions throughout most of their range. However, their fossil record shows evidence of multispecies communities throughout most of the past ∼26 million years, in different oceanic basins. Morphological differences among co-occurring sirenian taxa suggest that resource partitioning played a role in structuring these communities. We examined body size and ecomorphological differences (e.g., rostral deflection and tusk morphology) among sirenian assemblages from the late Oligocene of Florida, early Miocene of India and early Pliocene of Mexico; each with three species of the family Dugongidae. Although overlapping in several ecomorphological traits, each assemblage showed at least one dominant trait in which coexisting species differed. Fossil sirenian occurrences occasionally are monotypic, but the assemblages analyzed herein show iterative evolution of multispecies communities, a phenomenon unparalleled in extant sirenian ecology. As primary consumers of seagrasses, these communities likely had a strong impact on past seagrass ecology and diversity, although the sparse fossil record of seagrasses limits direct comparisons. Nonetheless, our results provide robust support for previous suggestions that some sirenians in these extinct assemblages served as keystone species, controlling the dominance of climax seagrass species, permitting more taxonomically diverse seagrass beds (and sirenian communities) than many of those observed today

    Inclusion of KI67 significantly improves performance of the PREDICT prognostication and prediction model for early breast cancer.

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    BACKGROUND: PREDICT (http://www.predict.nhs.uk) is a prognostication and treatment benefit tool for early breast cancer (EBC). The aim of this study was to incorporate the prognostic effect of KI67 status in a new version (v3), and compare performance with the Predict model that includes HER2 status (v2). METHODS: The validation study was based on 1,726 patients with EBC treated in Nottingham between 1989 and 1998. KI67 positivity for PREDICT is defined as >10% of tumour cells staining positive. ROC curves were constructed for Predict models with (v3) and without (v2) KI67 input. Comparison was made using the method of DeLong. RESULTS: In 1274 ER+ patients the predicted number of events at 10 years increased from 196 for v2 to 204 for v3 compared to 221 observed. The area under the ROC curve (AUC) improved from 0.7611 to 0.7676 (p=0.005) in ER+ patients and from 0.7546 to 0.7595 (p=0.0008) in all 1726 patients (ER+ and ER-). CONCLUSION: Addition of KI67 to PREDICT has led to a statistically significant improvement in the model performance for ER+ patients and will aid clinical decision making in these patients. Further studies should determine whether other markers including gene expression profiling provide additional prognostic information to that provided by PREDICT.SEARCH was funded through a programme grant from Cancer Research UK (C490/A10124) and this work is supported by the UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge.This is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/1471-2407-14-90

    The TURis System for Transurethral Resection of the Prostate: A NICE Medical Technology Guidance

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    The transurethral resection in saline (TURis) system was notified by the company Olympus Medical to the National Institute of Health and Care Excellence’s (NICE’s) Medical Technologies Evaluation Programme. Following selection for medical technologies guidance, the company developed a submission of clinical and economic evidence for evaluation. TURis is a bipolar surgical system for treating men with lower urinary tract symptoms due to benign prostatic enlargement. The comparator is any monopolar transurethral resection of the prostate (mTURP) system. Cedar, a collaboration between Cardiff and Vale University Health Board, Cardiff University and Swansea University in the UK, acted as an External Assessment Centre (EAC) for NICE to independently critique the company’s submission of evidence. Eight randomised trials provided evidence for TURis, demonstrating efficacy equivalent to that of mTURP for improvement of symptoms. The company presented meta-analyses of key outcome measures, and the EAC made methodological modifications in response to the heterogeneity of the trial data. The EAC analysis found that TURis substantially reduced the relative risks of transurethral resection syndrome (relative risk 0.18 [95 % confidence interval 0.05–0.62]) and blood transfusion (relative risk 0.35 [95 % confidence interval 0.19–0.65]). The company provided a de novo economic model comparing TURis with mTURP. The EAC critiqued the model methodology and made modifications. This found TURis to be cost saving at £70.55 per case for existing Olympus customers and cost incurring at £19.80 per case for non-Olympus customers. When an additional scenario based on the only available data on readmission (due to any cause) from a single trial was modelled, the estimated cost saving per case was £375.02 for existing users of Olympus electrosurgery equipment and £284.66 per case when new Olympus equipment would need to be purchased. Meta-analysis of eight randomised trials showed that TURis is associated with a statistically significantly reduced risk of transurethral resection syndrome and a reduced need for blood transfusion—two factors that may drive cost saving for the National Health Service. The clinical data are equivocal as to whether TURis shortens the hospital stay. Limited data from a single study suggest that TURis may reduce the rate of readmission after surgery. The NICE guidance supports adoption of the TURis technology for performing transurethral resection of the prostate in men with lower urinary tract symptoms due to benign prostatic enlargemen

    PIMMS43 is required for malaria parasite immune evasion and sporogonic development in the mosquito vector.

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    After being ingested by a female Anopheles mosquito during a bloodmeal on an infected host, and before they can reach the mosquito salivary glands to be transmitted to a new host, Plasmodium parasites must establish an infection of the mosquito midgut in the form of oocysts. To achieve this, they must first survive a series of robust innate immune responses that take place prior to, during, and immediately after ookinete traversal of the midgut epithelium. Understanding how parasites may evade these responses could highlight new ways to block malaria transmission. We show that an ookinete and sporozoite surface protein designated as PIMMS43 (Plasmodium Infection of the Mosquito Midgut Screen 43) is required for parasite evasion of the Anopheles coluzzii complement-like response. Disruption of PIMMS43 in the rodent malaria parasite Plasmodium berghei triggers robust complement activation and ookinete elimination upon mosquito midgut traversal. Silencing components of the complement-like system through RNAi largely restores ookinete-to-oocyst transition but oocysts remain small in size and produce a very small number of sporozoites that additionally are not infectious, indicating that PIMMS43 is also essential for sporogonic development in the oocyst. Antibodies that bind PIMMS43 interfere with parasite immune evasion when ingested with the infectious blood meal and significantly reduce the prevalence and intensity of infection. PIMMS43 genetic structure across African Plasmodium falciparum populations indicates allelic adaptation to sympatric vector populations. These data add to our understanding of mosquito-parasite interactions and identify PIMMS43 as a target of malaria transmission blocking

    Fitness benefits of prolonged post-reproductive lifespan in women

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    Most animals reproduce until they die, but in humans, females can survive long after ceasing reproduction. In theory, a prolonged post-reproductive lifespan will evolve when females can gain greater fitness by increasing the success of their offspring than by continuing to breed themselves. Although reproductive success is known to decline in old age, it is unknown whether women gain fitness by prolonging lifespan post-reproduction. Using complete multi-generational demographic records, we show that women with a prolonged post-reproductive lifespan have more grandchildren, and hence greater fitness, in pre-modern populations of both Finns and Canadians. This fitness benefit arises because post-reproductive mothers enhance the lifetime reproductive success of their offspring by allowing them to breed earlier, more frequently and more successfully. Finally, the fitness benefits of prolonged lifespan diminish as the reproductive output of offspring declines. This suggests that in female humans, selection for deferred ageing should wane when one's own offspring become post-reproductive and, correspondingly, we show that rates of female mortality accelerate as their offspring terminate reproduction

    Mycobacterium ulcerans disease: experience with primary oral medical therapy in an Australian cohort

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    Mycobacterium ulcerans (MU) is responsible for disfiguring skin infections which are challenging to treat. The recommended treatment for MU has continued to evolve from surgery to remove all involved tissue, to the use of effective combination oral antibiotics with surgery as required. Our study describes the oral medical treatment utilised for consecutive cases of MU infection over a 15 month period at our institution, in Victoria, Australia. Managing patients primarily with oral antibiotics results in high cure rates and excellent cosmetic outcomes. The success with medical treatment reported in this study will aid those treating cases of MU infection, and will add to the growing body of knowledge about the relative roles of antibiotics and surgery for treating this infection
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