The use of ‘PICO for synthesis’ and methods for synthesis without meta-analysis: protocol for a survey of current practice in systematic reviews of health interventions

INTRODUCTION: Systematic reviews involve synthesis of research to inform decision making by clinicians, consumers, policy makers and researchers. While guidance for synthesis often focuses on meta-analysis, synthesis begins with specifying the ’PICO for each synthesis’ (i.e. the criteria for deciding which populations, interventions, comparators and outcomes are eligible for each analysis). Synthesis may also involve the use of statistical methods other than meta-analysis (e.g. vote counting based on the direction of effect, presenting the range of effects, combining P values) augmented by visual display, tables and text-based summaries. This study examines these two aspects of synthesis. OBJECTIVES: To identify and describe current practice in systematic reviews of health interventions in relation to: (i) approaches to grouping and definition of PICO characteristics for synthesis; and (ii) methods of summary and synthesis when meta-analysis is not used. METHODS: We will randomly sample 100 systematic reviews of the quantitative effects of public health and health systems interventions published in 2018 and indexed in the Health Evidence and Health Systems Evidence databases. Two authors will independently screen citations for eligibility. Two authors will confirm eligibility based on full text, then extract data for 20% of reviews on the specification and use of PICO for synthesis, and the presentation and synthesis methods used (e.g. statistical synthesis methods, tabulation, visual displays, structured summary). The remaining reviews will be confirmed as eligible and data extracted by a single author. We will use descriptive statistics to summarise the specification of methods and their use in practice. We will compare how clearly the PICO for synthesis is specified in reviews that primarily use meta-analysis and those that do not. CONCLUSION: This study will provide an understanding of current practice in two important aspects of the synthesis process, enabling future research to test the feasibility and impact of different approaches

Critical elements of synthesis questions are incompletely reported: survey of systematic reviews of intervention effects

Objectives: To examine the characteristics of population, intervention and outcome groups and the extent to which they were completely reported for each synthesis in a sample of systematic reviews (SRs) of interventions. Study design and setting: We coded groups that were intended (or used) for comparisons in 100 randomly sampled SRs of public health and health systems interventions published in 2018 from the Health Evidence and Health Systems Evidence databases. Results: Authors commonly used population, intervention and outcome groups to structure comparisons, but these groups were often incompletely reported. For example, of 41 SRs that identified and/or used intervention groups for comparisons, 29 (71%) identified the groups in their methods description before reporting of the results (e.g., in the Background or Methods), 12 (29%) defined the groups in enough detail to replicate decisions about which included studies were eligible for each synthesis, 6 (15%) provided a rationale, and 24 (59%) stated that the groups would be used for comparisons. Sixteen (39%) SRs used intervention groups in their synthesis without any mention in the methods. Reporting for population, outcome and methodological groups was similarly incomplete. Conclusion: Complete reporting of the groups used for synthesis would improve transparency and replicability of reviews, and help ensure that the synthesis is not driven by what is reported in the included studies. Although concerted effort is needed to improve reporting, this should lead to more focused and useful reviews for decision-makers

The Oral and Skin Microbiomes of Captive Komodo Dragons Are Significantly Shared with Their Habitat.

Examining the way in which animals, including those in captivity, interact with their environment is extremely important for studying ecological processes and developing sophisticated animal husbandry. Here we use the Komodo dragon (Varanus komodoensis) to quantify the degree of sharing of salivary, skin, and fecal microbiota with their environment in captivity. Both species richness and microbial community composition of most surfaces in the Komodo dragon's environment are similar to the Komodo dragon's salivary and skin microbiota but less similar to the stool-associated microbiota. We additionally compared host-environment microbiome sharing between captive Komodo dragons and their enclosures, humans and pets and their homes, and wild amphibians and their environments. We observed similar host-environment microbiome sharing patterns among humans and their pets and Komodo dragons, with high levels of human/pet- and Komodo dragon-associated microbes on home and enclosure surfaces. In contrast, only small amounts of amphibian-associated microbes were detected in the animals' environments. We suggest that the degree of sharing between the Komodo dragon microbiota and its enclosure surfaces has important implications for animal health. These animals evolved in the context of constant exposure to a complex environmental microbiota, which likely shaped their physiological development; in captivity, these animals will not receive significant exposure to microbes not already in their enclosure, with unknown consequences for their health. IMPORTANCE Animals, including humans, have evolved in the context of exposure to a variety of microbial organisms present in the environment. Only recently have humans, and some animals, begun to spend a significant amount of time in enclosed artificial environments, rather than in the more natural spaces in which most of evolution took place. The consequences of this radical change in lifestyle likely extend to the microbes residing in and on our bodies and may have important implications for health and disease. A full characterization of host-microbe sharing in both closed and open environments will provide crucial information that may enable the improvement of health in humans and in captive animals, both of which experience a greater incidence of disease (including chronic illness) than counterparts living under more ecologically natural conditions

Observation of An Evolving Magnetic Flux Rope Prior To and During A Solar Eruption

Explosive energy release is a common phenomenon occurring in magnetized plasma systems ranging from laboratories, Earth's magnetosphere, the solar corona and astrophysical environments. Its physical explanation is usually attributed to magnetic reconnection in a thin current sheet. Here we report the important role of magnetic flux rope structure, a volumetric current channel, in producing explosive events. The flux rope is observed as a hot channel prior to and during a solar eruption from the Atmospheric Imaging Assembly (AIA) telescope on board the Solar Dynamic Observatory (SDO). It initially appears as a twisted and writhed sigmoidal structure with a temperature as high as 10 MK and then transforms toward a semi-circular shape during a slow rise phase, which is followed by fast acceleration and onset of a flare. The observations suggest that the instability of the magnetic flux rope trigger the eruption, thus making a major addition to the traditional magnetic-reconnection paradigm.Comment: 13 pages, 3 figure

Evaluating the impact of domestication and captivity on the horse gut microbiome.

The mammal gut microbiome, which includes host microbes and their respective genes, is now recognized as an essential second genome that provides critical functions to the host. In humans, studies have revealed that lifestyle strongly influences the composition and diversity of the gastrointestinal microbiome. We hypothesized that these trends in humans may be paralleled in mammals subjected to anthropogenic forces such as domestication and captivity, in which diets and natural life histories are often greatly modified. We investigated fecal microbiomes of Przewalski's horse (PH; Equus ferus przewalskii), the only horses alive today not successfully domesticated by humans, and herded, domestic horse (E. f. caballus) living in adjacent natural grasslands. We discovered PH fecal microbiomes hosted a distinct and more diverse community of bacteria compared to domestic horses, which is likely partly explained by different plant diets as revealed by trnL maker data. Within the PH population, four individuals were born in captivity in European zoos and hosted a strikingly low diversity of fecal microbiota compared to individuals born in natural reserves in France and Mongolia. These results suggest that anthropogenic forces can dramatically reshape equid gastrointestinal microbiomes, which has broader implications for the conservation management of endangered mammals

Hypernovae and Other Black-Hole-Forming Supernovae

During the last few years, a number of exceptional core-collapse supernovae (SNe) have been discovered. Their kinetic energy of the explosions are larger by more than an order of magnitude than the typical values for this type of SNe, so that these SNe have been called `Hypernovae'. We first describe how the basic properties of hypernovae can be derived from observations and modeling. These hypernovae seem to come from rather massive stars, thus forming black holes. On the other hand, there are some examples of massive SNe with only a small kinetic energy. We suggest that stars with non-rotating black holes are likely to collapse "quietly" ejecting a small amount of heavy elements (Faint supernovae). In contrast, stars with rotating black holes are likely to give rise to very energetic supernovae (Hypernovae). We present distinct nucleosynthesis features of these two types of "black-hole-forming" supernovae. Hypernova nucleosynthesis is characterized by larger abundance ratios (Zn,Co,V,Ti)/Fe and smaller (Mn,Cr)/Fe. Nucleosynthesis in Faint supernovae is characterized by a large amount of fall-back. We show that the abundance pattern of the most Fe deficient star, HE0107-5240, and other extremely metal-poor carbon-rich stars are in good accord with those of black-hole-forming supernovae, but not pair-instability supernovae. This suggests that black-hole-forming supernovae made important contributions to the early Galactic (and cosmic) chemical evolution.Comment: 49 pages, to be published in "Stellar Collapse" (Astrophysics and Space Science; Kluwer) ed. C. L. Fryer (2003

Economic evaluation of the NET intervention versus guideline dissemination for management of mild head injury in hospital emergency departments

BACKGROUND: Evidence-based guidelines for the management of mild traumatic brain injury (mTBI) in the emergency department (ED) are now widely available, and yet, clinical practice remains inconsistent with the guidelines. The Neurotrauma Evidence Translation (NET) intervention was developed to increase the uptake of guideline recommendations and improve the management of minor head injury in Australian emergency departments (EDs). However, the adoption of this type of intervention typically entails an upfront investment that may or may not be fully offset by improvements in clinical practice, health outcomes and/or reductions in health service utilisation. The present study estimates the cost and cost-effectiveness of the NET intervention, as compared to the passive dissemination of the guideline, to evaluate whether any improvements in clinical practice or health outcomes due to the NET intervention can be obtained at an acceptable cost. METHODS AND FINDINGS: Study setting: The NET cluster randomised controlled trial [ACTRN12612001286831]. Study sample: Seventeen EDs were randomised to the control condition and 14 to the intervention. One thousand nine hundred forty-three patients were included in the analysis of clinical practice outcomes (NET sample). A total of 343 patients from 14 control and 10 intervention EDs participated in follow-up interviews and were included in the analysis of patient-reported health outcomes (NET-Plus sample). Outcome measures: Appropriate post-traumatic amnesia (PTA) screening in the ED (primary outcome). Secondary clinical practice outcomes: provision of written information on discharge (INFO) and safe discharge (defined as CT scan appropriately provided plus PTA plus INFO). Secondary patient-reported, post-discharge health outcomes: anxiety (Hospital Anxiety and Depression Scale), post-concussive symptoms (Rivermead), and preference-based health-related quality of life (SF6D). Methods: Trial-based economic evaluations from a health sector perspective, with time horizons set to coincide with the final follow-up for the NET sample (2 months post-intervention) and to 1-month post-discharge for the NET-Plus sample. Results: Intervention and control groups were not significantly different in health service utilisation received in the ED/inpatient ward following the initial mTBI presentation (adjusted mean difference $23.86 per patient; 95$106, $153; p = 0.719) or over the longer follow-up in the NET-plus sample (adjusted mean difference$341.78 per patient; 95%CI − $58,$742; p = 0.094). Savings from lower health service utilisation are therefore unlikely to offset the significantly higher upfront cost of the intervention (mean difference $138.20 per patient; 95$135, $141; p < 0.000). Estimates of the net effect of the intervention on total cost (intervention cost net of health service utilisation) suggest that the intervention entails significantly higher costs than the control condition (adjusted mean difference$169.89 per patient; 95%CI $43,$297, p = 0.009). This effect is larger in absolute magnitude over the longer follow-up in the NET-plus sample (adjusted mean difference $505.06; 95$96, $915; p = 0.016), mostly due to additional health service utilisation. For the primary outcome, the NET intervention is more costly and more effective than passive dissemination; entailing an additional cost of$1246 per additional patient appropriately screened for PTA ($169.89/0.1363; Fieller’s 95$525, $2055). For NET to be considered cost-effective with 95% confidence, decision-makers would need to be willing to trade one quality-adjusted life year (QALY) for 25 additional patients appropriately screened for PTA. While these results reflect our best estimate of cost-effectiveness given the data, it is possible that a NET intervention that has been scaled and streamlined ready for wider roll-out may be more or less cost-effective than the NET intervention as delivered in the trial. CONCLUSION: While the NET intervention does improve the management of mTBI in the ED, it also entails a significant increase in cost and—as delivered in the trial—is unlikely to be cost-effective at currently accepted funding thresholds. There may be a scope for a scaled-up and streamlined NET intervention to achieve a better balance between costs and outcomes. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12612001286831, date registered 12 December 2012

Implementing evidence-based recommended practices for the management of patients with mild traumatic brain injuries in Australian emergency care departments: study protocol for a cluster randomised controlled trial

Background: Mild head injuries commonly present to emergency departments. The challenges facing clinicians in emergency departments include identifying which patients have traumatic brain injury, and which patients can safely be sent home. Traumatic brain injuries may exist with subtle symptoms or signs, but can still lead to adverse outcomes. Despite the existence of several high quality clinical practice guidelines, internationally and in Australia, research shows inconsistent implementation of these recommendations. The aim of this trial is to test the effectiveness of a targeted, theory- and evidence-informed implementation intervention to increase the uptake of three key clinical recommendations regarding the emergency department management of adult patients (18 years of age or older) who present following mild head injuries (concussion), compared with passive dissemination of these recommendations. The primary objective is to establish whether the intervention is effective in increasing the percentage of patients for which appropriate post-traumatic amnesia screening is performed. / Methods/design: The design of this study is a cluster randomised trial. We aim to include 34 Australian 24-hour emergency departments, which will be randomised to an intervention or control group. Control group departments will receive a copy of the most recent Australian evidence-based clinical practice guideline on the acute management of patients with mild head injuries. The intervention group will receive an implementation intervention based on an analysis of influencing factors, which include local stakeholder meetings, identification of nursing and medical opinion leaders in each site, a train-the-trainer day and standardised education and interactive workshops delivered by the opinion leaders during a 3 month period of time. Clinical practice outcomes will be collected retrospectively from medical records by independent chart auditors over the 2 month period following intervention delivery (patient level outcomes). In consenting hospitals, eligible patients will be recruited for a follow-up telephone interview conducted by trained researchers. A cost-effectiveness analysis and process evaluation using mixed-methods will be conducted. Sample size calculations are based on including 30 patients on average per department. Outcome assessors will be blinded to group allocation. / Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12612001286831 (date registered 12 December 2012)