Antibiotics for exacerbations of asthma.

BACKGROUND: Asthma is a chronic respiratory condition that affects over 300 million adults and children worldwide. It is characterised by wheeze, cough, chest tightness, and shortness of breath. Symptoms typically are intermittent and may worsen over a short time, leading to an exacerbation. Asthma exacerbations can be serious, leading to hospitalisation or even death in rare cases. Exacerbations may be treated by increasing an individual's usual medication and providing additional medication, such as oral steroids. Although antibiotics are sometimes included in the treatment regimen, bacterial infections are thought to be responsible for only a minority of exacerbations, and current guidance states that antibiotics should be reserved for cases in which clear signs, symptoms, or laboratory test results are suggestive of bacterial infection. OBJECTIVES: To determine the efficacy and safety of antibiotics in the treatment of asthma exacerbations. SEARCH METHODS: We searched the Cochrane Airways Trials Register, which contains records compiled from multiple electronic and handsearched resources. We also searched trial registries and reference lists of primary studies. We conducted the most recent search in October 2017. SELECTION CRITERIA: We included studies comparing antibiotic therapy for asthma exacerbations in adults or children versus placebo or usual care not involving an antibiotic. We allowed studies including any type of antibiotic, any dose, and any duration, providing the aim was to treat the exacerbation. We included parallel studies of any duration conducted in any setting and planned to include cluster trials. We excluded cross-over trials. We included studies reported as full-text articles, those published as abstracts only, and unpublished data. DATA COLLECTION AND ANALYSIS: At least two review authors screened the search results for eligible studies. We extracted outcome data, assessed risk of bias in duplicate, and resolved discrepancies by involving another review author. We analysed dichotomous data as odds ratios (ORs) or risk differences (RDs), and continuous data as mean differences (MDs), all with a fixed-effect model. We described skewed data narratively. We graded the results and presented evidence in 'Summary of findings' tables for each comparison. Primary outcomes were intensive care unit/high dependence unit (ICU/HDU) admission, duration of symptoms/exacerbations, and all adverse events. Seconday outcomes were mortality, length of hospital admission, relapse after index presentation, and peak expiratory flow rate (PEFR). MAIN RESULTS: Six studies met our inclusion criteria and included a total of 681 adults and children with exacerbations of asthma. Mean age in the three studies in adults ranged from 36.2 to 41.2 years. The three studies in children applied varied inclusion criteria, ranging from one to 18 years of age. Five studies explicitly excluded participants with obvious signs and symptoms of bacterial infection (i.e. those clearly meeting current guidance to receive antibiotics). Four studies investigated macrolide antibiotics, and two studies investigated penicillin (amoxicillin and ampicillin) antibiotics; both studies using penicillin were conducted over 35 years ago. Five studies compared antibiotics versus placebo, and one was open-label. Study follow-up ranged from one to twelve weeks. Trials were of varied methodological quality, and we were able to perform only limited meta-analysis.None of the included trials reported ICU/HDU admission, although one participant in the placebo group of a study including children with status asthmaticus experienced a respiratory arrest and was ventilated. Four studies reported asthma symptoms, but we were able to combine results for only two macrolide studies of 416 participants; the MD in diary card symptom score was -0.34 (95% confidence interval (CI) -0.60 to -0.08), with lower scores (on a 7 point scale) denoting improved symptoms. Two macrolide studies reported symptom-free days. One study of 255 adults authors reported the percentage of symptom-free days at 10 days as 16% in the antibiotic group and 8% in the placebo group. In a further study of 40 children study authors reported significantly more symptom-free days at all time points in the antibiotic group compared with the usual care group. The same study reported the duration in days of the index asthma exacerbation, again favouring the antibiotic group. One study of a penicillin including 69 participants reported asthma symptoms at hospital discharge; the between-group difference for both studies was reported as non-significant.We combined data for serious adverse events from three studies involving 502 participants, but events were rare; the three trials reported only 10 events: five in the antibiotic group and five in the placebo group. We combined data for all adverse events (AEs) from three studies, but the effect estimate is imprecise (OR 0.99, 95% CI 0.69 to 1.43). No deaths were reported in any of the included studies.Two studies investigating penicillins reported admission duration; neither study reported a between-group difference. In one study (263 participants) of macrolides, two participants in each arm were reported as experiencing a relapse, defined as a further exacerbation, by the six-week time points. We combined PEFR endpoint results at 10 days for two macrolide studies; the result favoured antibiotics over placebo (MD 23.42 L/min, 95% CI 5.23 to 41.60). One study in children reported the maximum peak flow recorded during the follow-up period, favouring the clarithromycin group, but the confidence interval includes no difference (MD 38.80, 95% CI -11.19 to 88.79).Grading of outcomes ranged from moderate to very low quality, with quality of outcomes downgraded for suspicion of publication bias, indirectness, imprecision, and poor methodological quality of studies. AUTHORS' CONCLUSIONS: We found limited evidence that antibiotics given at the time of an asthma exacerbation may improve symptoms and PEFR at follow-up compared with standard care or placebo. However, findings were inconsistent across the six heterogeneous studies included, two of the studies were conducted over 30 years ago and most of the participants included in this review were recruited from emergency departments, limiting the applicability of findings to this population. Therefore we have limited confidence in the results. We found insufficient evidence about several patient-important outcomes (e.g. hospital admission) to form conclusions. We were unable to rule out a difference between groups in terms of all adverse events, but serious adverse events were rare

Increased Litterfall in Tropical Forests Boosts the Transfer of Soil CO2 to the Atmosphere

Aboveground litter production in forests is likely to increase as a consequence of elevated atmospheric carbon dioxide (CO2) concentrations, rising temperatures, and shifting rainfall patterns. As litterfall represents a major flux of carbon from vegetation to soil, changes in litter inputs are likely to have wide-reaching consequences for soil carbon dynamics. Such disturbances to the carbon balance may be particularly important in the tropics because tropical forests store almost 30% of the global soil carbon, making them a critical component of the global carbon cycle; nevertheless, the effects of increasing aboveground litter production on belowground carbon dynamics are poorly understood. We used long-term, large-scale monthly litter removal and addition treatments in a lowland tropical forest to assess the consequences of increased litterfall on belowground CO2 production. Over the second to the fifth year of treatments, litter addition increased soil respiration more than litter removal decreased it; soil respiration was on average 20% lower in the litter removal and 43% higher in the litter addition treatment compared to the controls but litter addition did not change microbial biomass. We predicted a 9% increase in soil respiration in the litter addition plots, based on the 20% decrease in the litter removal plots and an 11% reduction due to lower fine root biomass in the litter addition plots. The 43% measured increase in soil respiration was therefore 34% higher than predicted and it is possible that this ‘extra’ CO2 was a result of priming effects, i.e. stimulation of the decomposition of older soil organic matter by the addition of fresh organic matter. Our results show that increases in aboveground litter production as a result of global change have the potential to cause considerable losses of soil carbon to the atmosphere in tropical forests

Arbuscular mycorrhizal fungal community composition is altered by long-term litter removal but not litter addition in a lowland tropical forest

Tropical forest productivity is sustained by the cycling of nutrients through decomposing organic matter. Arbuscular mycorrhizal (AM) fungi play a key role in the nutrition of tropical trees, yet there has been little experimental investigation into the role of AM fungi in nutrient cycling via decomposing organic material in tropical forests. We evaluated the responses of AM fungi in a long-term leaf litter addition and removal experiment in a tropical forest in Panama. We described AM fungal communities using 454-pyrosequencing, quantified the proportion of root length colonised by AM fungi using microscopy, and estimated AM fungal biomass using a lipid biomarker. AM fungal community composition was altered by litter removal but not litter addition. Root colonisation was substantially greater in the superficial organic layer compared with the mineral soil. Overall colonisation was lower in the litter removal treatment, which lacked an organic layer. There was no effect of litter manipulation on the concentration of the AM fungal lipid biomarker in the mineral soil. We hypothesise that reductions in organic matter brought about by litter removal may lead to AM fungi obtaining nutrients from recalcitrant organic or mineral sources in the soil, besides increasing fungal competition for progressively limited resources.Smithsonian Tropical Research Institute; Cambridge Home and European Scholarship; Department of Plant Sciences, Cambridge; Cambridge Philosophical Society; European Research Council; European Union's Seventh Framework Programme. Grant Number: FP/2007-201

Arbuscular mycorrhizal fungal community composition is altered by long-term litter removal but not litter addition in a lowland tropical forest

Tropical forest productivity is sustained by the cycling of nutrients through decomposing organic matter. Arbuscular mycorrhizal (AM) fungi play a key role in the nutrition of tropical trees, yet there has been little experimental investigation into the role of AM fungi in nutrient cycling via decomposing organic material in tropical forests. We evaluated the responses of AM fungi in a long-term leaf litter addition and removal experiment in a tropical forest in Panama. We described AM fungal communities using 454-pyrosequencing, quantified the proportion of root length colonised by AM fungi using microscopy, and estimated AM fungal biomass using a lipid biomarker. AM fungal community composition was altered by litter removal but not litter addition. Root colonisation was substantially greater in the superficial organic layer compared with the mineral soil. Overall colonisation was lower in the litter removal treatment, which lacked an organic layer. There was no effect of litter manipulation on the concentration of the AM fungal lipid biomarker in the mineral soil. We hypothesise that reductions in organic matter brought about by litter removal may lead to AM fungi obtaining nutrients from recalcitrant organic or mineral sources in the soil, besides increasing fungal competition for progressively limited resources.Smithsonian Tropical Research Institute; Cambridge Home and European Scholarship; Department of Plant Sciences, Cambridge; Cambridge Philosophical Society; European Research Council; European Union's Seventh Framework Programme. Grant Number: FP/2007-201

Childhood socioeconomic position and objectively measured physical capability levels in adulthood: a systematic review and meta-analysis

<p><b>Background:</b> Grip strength, walking speed, chair rising and standing balance time are objective measures of physical capability that characterise current health and predict survival in older populations. Socioeconomic position (SEP) in childhood may influence the peak level of physical capability achieved in early adulthood, thereby affecting levels in later adulthood. We have undertaken a systematic review with meta-analyses to test the hypothesis that adverse childhood SEP is associated with lower levels of objectively measured physical capability in adulthood.</p> <p><b>Methods and Findings:</b> Relevant studies published by May 2010 were identified through literature searches using EMBASE and MEDLINE. Unpublished results were obtained from study investigators. Results were provided by all study investigators in a standard format and pooled using random-effects meta-analyses. 19 studies were included in the review. Total sample sizes in meta-analyses ranged from N = 17,215 for chair rise time to N = 1,061,855 for grip strength. Although heterogeneity was detected, there was consistent evidence in age adjusted models that lower childhood SEP was associated with modest reductions in physical capability levels in adulthood: comparing the lowest with the highest childhood SEP there was a reduction in grip strength of 0.13 standard deviations (95% CI: 0.06, 0.21), a reduction in mean walking speed of 0.07 m/s (0.05, 0.10), an increase in mean chair rise time of 6% (4%, 8%) and an odds ratio of an inability to balance for 5s of 1.26 (1.02, 1.55). Adjustment for the potential mediating factors, adult SEP and body size attenuated associations greatly. However, despite this attenuation, for walking speed and chair rise time, there was still evidence of moderate associations.</p> <p><b>Conclusions:</b> Policies targeting socioeconomic inequalities in childhood may have additional benefits in promoting the maintenance of independence in later life.</p&gt

How patient and community involvement in diabetes research influences health outcomes : a realist review

Background Patient and public involvement in diabetes research is an international requirement, but little is known about the relationship between the process of involvement and health outcomes. Objective This realist review identifies who benefits from different types of involvement across different contexts and circumstances. Search strategies Medline, CINAHL and EMBASE were searched to identify interventions using targeted, embedded or collaborative involvement to reduce risk and promote self‐management of diabetes. People at risk/with diabetes, providers and community organizations with an interest in addressing diabetes were included. There were no limitations on date, language or study type. Data extraction and synthesis Data were extracted from 29 projects using elements from involvement frameworks. A conceptual analysis of involvement types was used to complete the synthesis. Main results Projects used targeted (4), embedded (8) and collaborative (17) involvement. Productive interaction facilitated over a sufficient period of time enabled people to set priorities for research. Partnerships that committed to collaboration increased awareness of diabetes risk and mobilized people to co‐design and co‐deliver diabetes interventions. Cultural adaptation increased relevance and acceptance of the intervention because they trusted local delivery approaches. Local implementation produced high levels of recruitment and retention, which project teams associated with achieving diabetes health outcomes. Discussion and Conclusions Achieving understanding of community context, developing trusting relationships across sectors and developing productive partnerships were prerequisites for designing research that was feasible and locally relevant. The proportion of diabetes studies incorporating these elements is surprisingly low. Barriers to resourcing partnerships need to be systematically addressed

The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure

Strong microsite control of seedling recruitment in tundra

The inclusion of environmental variation in studies of recruitment is a prerequisite for realistic predictions of the responses of vegetation to a changing environment. We investigated how seedling recruitment is affected by seed availability and microsite quality along a steep environmental gradient in dry tundra. A survey of natural seed rain and seedling density in vegetation was combined with observations of the establishment of 14 species after sowing into intact or disturbed vegetation. Although seed rain density was closely correlated with natural seedling establishment, the experimental seed addition showed that the microsite environment was even more important. For all species, seedling emergence peaked at the productive end of the gradient, irrespective of the adult niches realized. Disturbance promoted recruitment at all positions along the environmental gradient, not just at high productivity. Early seedling emergence constituted the main temporal bottleneck in recruitment for all species. Surprisingly, winter mortality was highest at what appeared to be the most benign end of the gradient. The results highlight that seedling recruitment patterns are largely determined by the earliest stages in seedling emergence, which again are closely linked to microsite quality. A fuller understanding of microsite effects on recruitment with implications for plant community assembly and vegetation change is provided

Saliva levels of Abeta1-42 as potential biomarker of Alzheimer's disease: a pilot study

<p>Abstract</p> <p>Background</p> <p>Simple, non-invasive tests for early detection of degenerative dementia by use of biomarkers are urgently required. However, up to the present, no validated extracerebral diagnostic markers for the early diagnosis of Alzheimer disease (AD) are available. The clinical diagnosis of probable AD is made with around 90% accuracy using modern clinical, neuropsychological and imaging methods. A biochemical marker that would support the clinical diagnosis and distinguish AD from other causes of dementia would therefore be of great value as a screening test. A total of 126 samples were obtained from subjects with AD, and age-sex-matched controls. Additionally, 51 Parkinson's disease (PD) patients were used as an example of another neurodegenerative disorder. We analyzed saliva and plasma levels of β amyloid (Aβ) using a highly sensitive ELISA kit.</p> <p>Results</p> <p>We found a small but statistically significant increase in saliva Aβ₄₂levels in mild AD patients. In addition, there were not differences in saliva concentration of Aβ₄₂between patients with PD and healthy controls. Saliva Aβ₄₀expression was unchanged within all the studied sample. The association between saliva Aβ₄₂levels and AD was independent of established risk factors, including age or Apo E, but was dependent on sex and functional capacity.</p> <p>Conclusions</p> <p>We suggest that saliva Aβ₄₂levels could be considered a potential peripheral marker of AD and help discrimination from other types of neurodegenerative disorders. We propose a new and promising biomarker for early AD.</p

Leaf litter decomposition in temperate deciduous forest stands with a decreasing fraction of beech (Fagus sylvatica)

We hypothesised that the decomposition rates of leaf litter will increase along a gradient of decreasing fraction of the European beech (Fagus sylvatica) and increasing tree species diversity in the generally beech-dominated Central European temperate deciduous forests due to an increase in litter quality. We studied the decomposition of leaf litter including its lignin fraction in monospecific (pure beech) stands and in stands with up to five tree genera (Acer spp., Carpinus betulus, Fagus sylvatica, Fraxinus excelsior, Tilia spp.) using a litterbag approach. Litter and lignin decomposition was more rapid in stand-representative litter from multispecific stands than in litter from pure beech stands. Except for beech litter, the decomposition rates of species-specific tree litter did not differ significantly among the stand types, but were most rapid in Fraxinus excelsior and slowest in beech in an interspecific comparison. Pairwise comparisons of the decomposition of beech litter with litter of the other tree species (except for Acerplatanoides) revealed a “home field advantage” of up to 20% (more rapid litter decomposition in stands with a high fraction of its own species than in stands with a different tree species composition). Decomposition of stand-representative litter mixtures displayed additive characteristics, not significantly more rapid than predicted by the decomposition of litter from the individual tree species. Leaf litter decomposition rates were positively correlated with the initial N and Ca concentrations of the litter, and negatively with the initial C:N, C:P and lignin:N ratios. The results support our hypothesis that the overall decomposition rates are mainly influenced by the chemical composition of the individual litter species. Thus, the fraction of individual tree species in the species composition seems to be more important for the litter decomposition rates than tree species diversity itself