Gaps in the evidence for treatment decisions in cystic fibrosis: a systematic review

Introduction:Cystic fibrosis (CF) is a multisystem disorder. Treatment is complex and evidence for treatment decisions may be absent. Characterising gaps in the research evidence will highlight treatment uncertainties and help prioritise research questions. We systematically identified the evidence gaps for treatment decisions in CF.Methods: We searched for systematic reviews and guidelines on treatment interventions in CF. Two researchers identified eligible reviews with arbitration from a third. Using a structured framework, we extracted and characterised evidence gaps.Results: There were 73 reviews and 21 guidelines that met our inclusion criteria. From these, we identified 148 evidence gaps across a range of treatment areas. We found 111 evidence gaps through systematic reviews and a further 37 from guidelines. The reason for an evidence gap could only be reliably characterised for systematic reviews. In most cases, there was more than one explanation—most commonly few or no trials (97/111 evidence gaps). Other important factors leading to evidence gaps were small sample size (49/111), inadequate duration of follow-up (38/111) or intervention (37/111) and factors relating to outcomes (35/111). Evidence gaps from both systematic reviews and guidelines fell into the following categories: Respiratory (91); Gastrointestinal (20); PhysiotherapyandExercise (16); Musculoskeletal (6); Endocrine (4); Basic defect of CF (8); Psychosocial (2); Ears, Nose and Throat (1).Conclusions: We have compiled an up-to-date list of treatment uncertainties in CF and the reasons for these uncertainties. These can be used as a resource to aid researchers and funders when planning future trials.PROSPERO registration number: Pre-results; CRD42015030111

Long term drought and warming alter soil bacterial and fungal communities in an upland heathland

The response of soil microbial communities to a changing climate will impact global biogeochemical cycles, potentially leading to positive and negative feedbacks. However, our understanding of how soil microbial communities respond to climate change and the implications of these changes for future soil function is limited. Here, we assess the response of soil bacterial and fungal communities to long-term experimental climate change in a heathland organo-mineral soil. We analysed microbial communities using Illumina sequencing of the 16S rRNA gene and ITS2 region at two depths, from plots undergoing 4 and 18 years of in situ summer drought or warming. We also assessed the colonisation of Calluna vulgaris roots by ericoid and dark septate endophytic (DSE) fungi using microscopy after 16 years of climate treatment. We found significant changes in both the bacterial and fungal communities in response to drought and warming, likely mediated by changes in soil pH and electrical conductivity. Changes in the microbial communities were more pronounced after a longer period of climate manipulation. Additionally, the subsoil communities of the long-term warmed plots became similar to the topsoil. Ericoid mycorrhizal colonisation decreased with depth while DSEs increased; however, these trends with depth were removed by warming. We largely ascribe the observed changes in microbial communities to shifts in plant cover and subsequent feedback on soil physicochemical properties, especially pH. Our results demonstrate the importance of considering changes in soil microbial responses to climate change across different soil depths and after extended periods of time

Joining the conspiracy? Negotiating ethics and emotions in researching (around) AIDS in southern Africa

AIDS is an emotive subject, particularly in southern Africa. Among those who have been directly affected by the disease, or who perceive themselves to be personally at risk, talking about AIDS inevitably arouses strong emotions - amongst them fear, distress, loss and anger. Conventionally, human geography research has avoided engagement with such emotions. Although the ideal of the detached observer has been roundly critiqued, the emphasis in methodological literature on 'doing no harm' has led even qualitative researchers to avoid difficult emotional encounters. Nonetheless, research is inevitably shaped by emotions, not least those of the researchers themselves. In this paper, we examine the role of emotions in the research process through our experiences of researching the lives of 'Young AIDS migrants' in Malawi and Lesotho. We explore how the context of the research gave rise to the production of particular emotions, and how, in response, we shaped the research, presenting a research agenda focused more on migration than AIDS. This example reveals a tension between universalised ethics expressed through ethical research guidelines that demand informed consent, and ethics of care, sensitive to emotional context. It also demonstrates how dualistic distinctions between reason and emotion, justice and care, global and local are unhelpful in interpreting the ethics of research practice

Does increased atmospheric resolution improve seasonal climate predictions?

We assess the impact of atmospheric horizontal resolution on the prediction skill and fidelity of seasonal forecasts. We show the response to an increase of atmospheric resolution from 0.8 to 0.3⁰ horizontal grid spacing in parallel ensembles of forecasts. Changes in the prediction skill of major modes of tropical El Nino Southern Oscillation (ENSO) and extratropical North Atlantic Oscillation (NAO) variability are small and not detected and there is no discernible impact on the weak signal-to-noise ratio in seasonal predictions of the winter NAO at this range of resolutions. Although studies have shown improvements in the simulation of tropical cyclones as model resolution is increased, we find little impact on seasonal prediction skill of either their numbers or intensity. Over this range of resolutions it appears that the benefit of increasing atmospheric resolution to seasonal climate predictions is minimal. However, at yet finer scales there appears to be increased eddy feedback which could strengthen weak signals in predictions of the NAO. Until prediction systems can be run operationally at these scales, it may be better to use additional computing resources for other enhancements such as increased ensemble size, for which there is a clear benefit in extratropical seasonal prediction skill

Financial incentives for quitting smoking in pregnancy : Are they cost-effective?

AIMS: To evaluate whether adding financial incentives to usual care is cost-effective in encouraging pregnant women to quit tobacco smoking, compared with usual care alone. DESIGN: Cost-effectiveness analysis (CEA) and cost-utility analysis (CUA) from a health-care provider's perspective, embedded in the Smoking Cessation in Pregnancy Incentives Trial (CPIT III). Long-term analyses were conducted from the same perspective, using an existing Markov model over a life-time horizon. SETTING: Seven maternity smoking cessation sites in Scotland, England and Northern Ireland in the United Kingdom. PARTICIPANTS: In the short-term analysis, CPIT III participants were assessed: women 16 years or older, self-reporting as smokers, fewer than 24 weeks pregnant and English-speaking (n = 944). The same population was used for the life-time analysis, plus their infants. MEASUREMENTS: Costs included financial incentive vouchers and postage, cessation support and nicotine replacement therapy and neonatal stays. The outcome measure was a biochemically verified quit rate for the CEA and quality-adjusted life-years (QALYs) for CUA. Costs are presented in 2020 GBP sterling (£). Data for the life-time analysis came from the trial and were combined with data from published literature embedded in the model, reporting incremental cost per quitter and QALY. A 3.5% discount rate was applied. FINDINGS: The short-term incremental cost per quitter was £4400 and cost per QALY was £150 000. Results of sensitivity analyses confirmed these results. The long-term analysis combined costs and outcomes for mother and infants; results showed a cost saving of £37 [95% confidence interval (CI]) = £35-106] and increase in QALYs of 0.171 (95% CI = 0.124-0.229). These findings indicate that, over a life-time, financial incentives are cost-saving and improve health outcomes. CONCLUSIONS: In the United Kingdom, offering up to £400 financial incentives, in addition to usual care, to support pregnant women to stop smoking appears to be highly cost-effective over a life-time for mother and infants