A stepped wedge cluster randomized control trial of dried blood spot testing to improve the uptake of hepatitis C antibody testing within UK prisons

Background: The prevalence of hepatitis C (HCV) is elevated within prison populations, yet diagnosis in prisons remains low. Dried blood spot testing (DBST) is a simple procedure for the detection of HCV antibodies; its impact on testing in the prison context is unknown. Methods: We carried out a stepped-wedge cluster-randomized control trial of DBST for HCV among prisoners within five male prisons and one female prison. Each prison was a separate cluster. The order in which the intervention (training in use of DBST for HCV testing and logistic support) was introduced was randomized across clusters. The outcome measure was the HCV testing rate by prison. Imputation analysis was carried out to account for missing data. Planned and actual intervention times differed in some prisons; data were thus analysed by intention to treat (ITT) and by observed step times. Results: There was insufficient evidence of an effect of the intervention on testing rate using either the ITT intervention time (OR: 0.84; 95% CI: 0.68�1.03; P = 0.088) or using the actual intervention time (OR: 0.86; 95% CI: 0.71�1.06; P = 0.153). This was confirmed by the pooled results of five imputed data sets. Conclusions: DBST as a stand-alone intervention was insufficient to increase HCV diagnosis within the UK prison setting. Factors such as staff training and allocation of staff time for regular clinics are key to improving service delivery. We demonstrate that prisons can conduct rigorous studies of new interventions, but data collection can be problematic. Trial registration: International Standard Randomized Controlled Trial Number Register (ISRCTN number ISRCTN05628482)

Prevalence of liver fluke (Fasciola hepatica) in wild Red Deer (Cervus elaphus): coproantigen ELISA is a practicable alternative to faecal egg counting for surveillance in remote populations

Red deer (Cervus elaphus) are hosts of liver fluke (Fasciola hepatica); yet, prevalence is rarely quantified in wild populations. Testing fresh samples from remote regions by faecal examination (FE) can be logistically challenging; hence, we appraise frozen storage and the use of a coproantigen ELISA (cELISA) for F. hepatica surveillance. We also present cELISA surveillance data for red deer from the Highlands of Scotland. Diagnoses in faecal samples (207 frozen, 146 fresh) were compared using a cELISA and by FE. For each storage method (frozen or fresh), agreement between the two diagnostics was estimated at individual and population levels, where population prevalence was stratified into cohorts (e.g., by sampling location). To approximate sensitivity and specificity, 65 post-slaughter whole liver examinations were used as a reference. At the individual level, FE and cELISA diagnoses agreed moderately (κfrozen = 0.46; κfresh = 0.51), a likely reflection of their underlying principles. At the population level, FE and cELISA cohort prevalence correlated strongly (Pearson’s R = 0.89, p < 0.0001), reflecting good agreement on relative differences between cohort prevalence. In frozen samples, prevalence by cELISA exceeded FE overall (42.8% vs. 25.8%) and in 9/12 cohorts, alluding to differences in sensitivity; though, in fresh samples, no significant difference was found. In 959 deer tested by cELISA across the Scottish Highlands, infection prevalence ranged from 9.6% to 53% by sampling location. We highlight two key advantages of cELISA over FE: i) the ability to store samples long term (frozen) without apparent loss in diagnostic power; and ii) reduced labour and the ability to process large batches. Further evaluation of cELISA sensitivity in red deer, where a range of fluke burdens can be obtained, is desirable. In the interim, the cELISA is a practicable diagnostic for F. hepatica surveillance in red deer, and its application here has revealed considerable geographic, temporal, sex and age related differences in F. hepatica prevalence in wild Scottish Highland red deer

Ecological interpretations of nitrogen isotope ratios of terrestrial plants and soils

Background Knowledge of biological and climatic controls in terrestrial nitrogen (N) cycling within and across ecosystems is central to understanding global patterns of key ecosystem processes. The ratios of 15N:14N in plants and soils have been used as indirect indices of N cycling parameters, yet our understanding of controls over N isotope ratios in plants and soils is still developing. Scope In this review, we provide background on the main processes that affect plant and soil N isotope ratios. In a similar manner to partitioning the roles of state factors and interactive controls in determining ecosystem traits, we review N isotopes patterns in plants and soils across a number of proximal factors that influence ecosystem properties as well as mechanisms that affect these patterns. Lastly, some remaining questions that would improve our understanding of N isotopes in terrestrial ecosystems are highlighted. Conclusion Compared to a decade ago, the global patterns of plant and soil N isotope ratios are more resolved. Additionally, we better understand how plant and soil N isotope ratios are affected by such factors as mycorrhizal fungi, climate, and microbial processing. A comprehensive understanding of the N cycle that ascribes different degrees of isotopic fractionation for each step under different conditions is closer to being realized, but a number of process-level questions still remain

Intervention Now to Eliminate Repeat Unintended Pregnancy in Teenagers (INTERUPT): a systematic review of intervention effectiveness and cost-effectiveness, and qualitative and realist synthesis of implementation factors and user engagement.

BACKGROUND: Unintended repeat conceptions can result in emotional, psychological and educational harm to young women, often with enduring implications for their life chances. This study aimed to identify which young women are at the greatest risk of repeat unintended pregnancies; which interventions are effective and cost-effective; and what are the barriers to and facilitators for the uptake of these interventions. METHODS: We conducted a mixed-methods systematic review which included meta-analysis, framework synthesis and application of realist principles, with stakeholder input and service user feedback to address this. We searched 20 electronic databases, including MEDLINE, Excerpta Medica database, Applied Social Sciences Index and Abstracts and Research Papers in Economics, to cover a broad range of health, social science, health economics and grey literature sources. Searches were conducted between May 2013 and June 2014 and updated in August 2015. RESULTS: Twelve randomised controlled trials (RCTs), two quasi-RCTs, 10 qualitative studies and 53 other quantitative studies were identified. The RCTs evaluated psychosocial interventions and an emergency contraception programme. The primary outcome was repeat conception rate: the event rate was 132 of 308 (43%) in the intervention group versus 140 of 289 (48%) for the control group, with a non-significant risk ratio (RR) of 0.92 [95% confidence interval (CI) 0.78-1.08]. Four studies reported subsequent birth rates: 29 of 237 (12%) events for the intervention arm versus 46 out of 224 (21%) for the control arm, with an RR of 0.60 (95% CI 0.39-0.93). Many repeat conceptions occurred in the context of poverty, low expectations and aspirations and negligible opportunities. Qualitative and realist evidence highlighted the importance of context, motivation, future planning and giving young women a central and active role in the development of new interventions. CONCLUSIONS: Little or no evidence for the effectiveness or cost-effectiveness of any of the interventions to reduce repeat pregnancy in young women was found. Qualitative and realist evidence helped to explain gaps in intervention design that should be addressed. More theory-based, rigorously evaluated programmes need to be developed to reduce unintended repeat pregnancy in young women. TRIAL REGISTRATION: PROSPERO, CRD42012003168 . Cochrane registration number: i = fertility/0068

Intervention Now To Eliminate Repeat Unintended Pregnancy in Teenagers (INTERUPT): a systematic review of intervention effectiveness and cost-effectiveness, qualitative and realist synthesis of implementation factors and user engagement

Background The UK has the highest rate of teenage pregnancies in Western Europe, a fifth are repeat pregnancies. Unintended conceptions can result in emotional, psychological and educational harm to teenage girls, often with enduring implications for their life chances. Babies of teenage mothers have increased mortality in their first year and increased risk of poverty, educational underachievement and unemployment later in life, with associated societal costs. Methods and analysis We will conduct a streamed, mixed-methods systematic review to find and evaluate interventions designed to reduce repeat unintended teen pregnancies. Our aims are to identify Who is at greater risk of repeat unintended pregnancies? Which interventions are effective, cost-effective, how they work, in what setting and for whom? What are the barriers and facilitators to intervention uptake? Traditional electronic database searches will be augmented by targeted searches for evidence ‘clusters’ and guided by an advisory group of experts and stakeholders. To address the topic's inherent complexities, we will use a highly structured, innovative and iterative approach combining methodological techniques tailored to each stream of evidence. Quantitative data will be synthesised with reference to Cochrane guidelines for public health interventions. Qualitative evidence addressing facilitators and barriers to the uptake of interventions, experience and acceptability of interventions will be synthesised thematically. We will apply the principles of realist synthesis to uncover theories and mechanisms underpinning interventions. We will conduct an integration and overarching narrative of findings authenticated by client group feedback. Ethics and dissemination We will publish the complete review in ‘Health Technology Assessment’ and sections in specialist peer-reviewed journals. We will present at national and international conferences in the fields of public health, reproductive medicine and review methodology. Findings will be fed back to service users and practitioners via workshops run by the partner collaborators

Centennial-scale reductions in nitrogen availability in temperate forests of the United States

Forests cover 30% of the terrestrial Earth surface and are a major component of the global carbon (C) cycle. Humans have doubled the amount of global reactive nitrogen (N), increasing deposition of N onto forests worldwide. However, other global changes—especially climate change and elevated atmospheric carbon dioxide concentrations—are increasing demand for N, the element limiting primary productivity in temperate forests, which could be reducing N availability. To determine the long-term, integrated effects of global changes on forest N cycling, we measured stable N isotopes in wood, a proxy for N supply relative to demand, on large spatial and temporal scales across the continental U.S.A. Here, we show that forest N availability has generally declined across much of the U.S. since at least 1850 C.E. with cool, wet forests demonstrating the greatest declines. Across sites, recent trajectories of N availability were independent of recent atmospheric N deposition rates, implying a minor role for modern N deposition on the trajectory of N status of North American forests. Our results demonstrate that current trends of global changes are likely to be consistent with forest oligotrophication into theforeseeable future, further constraining forest C fixation and potentially storage

HCV treatment rates and sustained viral response among people who inject drugs in seven UK sites: real world results and modelling of treatment impact.

Hepatitis C virus (HCV) antiviral treatment for people who inject drugs (PWID) could prevent onwards transmission and reduce chronic prevalence. We assessed current PWID treatment rates in seven UK settings and projected the potential impact of current and scaled-up treatment on HCV chronic prevalence. Data on number of PWID treated and sustained viral response rates (SVR) were collected from seven UK settings: Bristol (37-48% HCV chronic prevalence among PWID), East London (37-48%), Manchester (48-56%), Nottingham (37-44%), Plymouth (30-37%), Dundee (20-27%) and North Wales (27-33%). A model of HCV transmission among PWID projected the 10-year impact of (i) current treatment rates and SVR (ii) scale-up with interferon-free direct acting antivirals (IFN-free DAAs) with 90% SVR. Treatment rates varied from <5 to over 25 per 1000 PWID. Pooled intention-to-treat SVR for PWID were 45% genotypes 1/4 [95%CI 33-57%] and 61% genotypes 2/3 [95%CI 47-76%]. Projections of chronic HCV prevalence among PWID after 10 years of current levels of treatment overlapped substantially with current HCV prevalence estimates. Scaling-up treatment to 26/1000 PWID annually (achieved already in two sites) with IFN-free DAAs could achieve an observable absolute reduction in HCV chronic prevalence of at least 15% among PWID in all sites and greater than a halving in chronic HCV in Plymouth, Dundee and North Wales within a decade. Current treatment rates among PWID are unlikely to achieve observable reductions in HCV chronic prevalence over the next 10 years. Achievable scale-up, however, could lead to substantial reductions in HCV chronic prevalence

The moisture response of soil heterotrophic respiration: Interaction with soil properties

Soil moisture is of primary importance for predicting the evolution of soil carbon stocks and fluxes, both because it strongly controls organic matter decomposition and because it is predicted to change at global scales in the following decades. However, the soil functions used to model the heterotrophic respiration response to moisture have limited empirical support and introduce an uncertainty of at least 4% in global soil carbon stock predictions by 2100. The necessity of improving the representation of this relationship in models has been highlighted in recent studies. Here we present a data-driven analysis of soil moisture-respiration relations based on 90 soils. With the use of linear models we show how the relationship between soil heterotrophic respiration and different measures of soil moisture is consistently affected by soil properties. The empirical models derived include main effects and moisture interaction effects of soil texture, organic carbon content and bulk density. When compared to other functions currently used in different soil biogeochemical models, we observe that our results can correct biases and reconcile differences within and between such functions. Ultimately, accurate predictions of the response of soil carbon to future climate scenarios will require the integration of soil-dependent moisture-respiration functions coupled with realistic representations of soil water dynamic

The acceptability and feasibility of a brief psychosocial intervention to reduce blood-borne virus risk behaviours among people who inject drugs: A randomised control feasibility trial of a psychosocial intervention (the PROTECT study) versus treatment as usual

Background: While opiate substitution therapy and injecting equipment provision (IEP) have reduced blood-borne viruses (BBV) among people who inject drugs (PWID), some PWID continue to share injecting equipment and acquire BBV. Psychosocial interventions that address risk behaviours could reduce BBV transmission among PWID.Methods: A pragmatic, two-armed randomised controlled, open feasibility study of PWID attending drug treatment or IEP in four UK regions. Ninety-nine PWID were randomly allocated to receive a three-session manualised psychosocial group intervention and BBV transmission information booklet plus treatment as usual (TAU) (n = 52) or information booklet plus TAU (n = 47). The intervention was developed from evidence-based literature, qualitative interviews with PWID, key stakeholder consultations, and expert opinion. Recruitment rates, retention in treatment, follow-up completion rates and health economic data completion measured feasibility.Results: Fifty-six percent (99/176) of eligible PWID were recruited. More participants attended at least one intervention session in London (10/16; 63%) and North Wales (7/13; 54%) than in Glasgow (3/12; 25%) and York (0/11). Participants who attended no sessions (n = 32) compared to those attending at least one (n = 20) session were more likely to be homeless (56 vs 25%, p = 0.044), injected drugs for a greater number of days (median 25 vs 6.5, p = 0.019) and used a greater number of needles from an IEP in the last month (median 31 vs 20, p = 0.056). No adverse events were reported. 45.5% (45/99) were followed up 1 month post-intervention. Feedback forms confirmed that the intervention was acceptable to both intervention facilitators and participants who attended it. Follow-up attendance was associated with fewer days of injecting in the last month (median 14 vs 27, p = 0.030) and fewer injections of cocaine (13 vs 30%, p = 0.063). Analysis of the questionnaires identified several service use questionnaire categories that could be excluded from the assessment battery in a full-randomised controlled trial.Conclusions: Findings should be interpreted with caution due to small sample sizes. A future definitive RCT of the psychosocial intervention is not feasible. The complex needs of some PWID may have limited their engagement in the intervention. More flexible delivery methods may have greater reach