Using e-mail recruitment and an online questionnaire to establish effect size: A worked example

Background\ud Sample size calculations require effect size estimations. Sometimes, effect size estimations and standard deviation may not be readily available, particularly if efficacy is unknown because the intervention is new or developing, or the trial targets a new population. In such cases, one way to estimate the effect size is to gather expert opinion. This paper reports the use of a simple strategy to gather expert opinion to estimate a suitable effect size to use in a sample size calculation.\ud \ud Methods\ud Researchers involved in the design and analysis of clinical trials were identified at the University of Birmingham and via the MRC Hubs for Trials Methodology Research. An email invited them to participate.\ud \ud An online questionnaire was developed using the free online tool 'Survey Monkey©'. The questionnaire described an intervention, an electronic participant information sheet (e-PIS), which may increase recruitment rates to a trial. Respondents were asked how much they would need to see recruitment rates increased by, based on 90%. 70%, 50% and 30% baseline rates, (in a hypothetical study) before they would consider using an e-PIS in their research.\ud \ud Analyses comprised simple descriptive statistics.\ud \ud Results\ud The invitation to participate was sent to 122 people; 7 responded to say they were not involved in trial design and could not complete the questionnaire, 64 attempted it, 26 failed to complete it. Thirty-eight people completed the questionnaire and were included in the analysis (response rate 33%; 38/115). Of those who completed the questionnaire 44.7% (17/38) were at the academic grade of research fellow 26.3% (10/38) senior research fellow, and 28.9% (11/38) professor. Dependent upon the baseline recruitment rates presented in the questionnaire, participants wanted recruitment rate to increase from 6.9% to 28.9% before they would consider using the intervention.\ud \ud Conclusions\ud This paper has shown that in situations where effect size estimations cannot be collected from previous research, opinions from researchers and trialists can be quickly and easily collected by conducting a simple study using email recruitment and an online questionnaire. The results collected from the survey were successfully used in sample size calculations for a PhD research study protocol.\ud \u

Characteristics of outdoor falls among older people: A qualitative study

Background Falls are a major threat to older people’s health and wellbeing. Approximately half of falls occur in outdoor environments but little is known about the circumstances in which they occur. We conducted a qualitative study to explore older people’s experiences of outdoor falls to develop understanding of how they may be prevented. Methods We conducted nine focus groups across the UK (England, Wales, and Scotland). Our sample was from urban and rural settings and different environmental landscapes. Participants were aged 65+ and had at least one outdoor fall in the past year. We analysed the data using framework and content analyses. Results Forty-four adults aged 65 – 92 took part and reported their experience of 88 outdoor falls. Outdoor falls occurred in a variety of contexts, though reports suggested the following scenarios may have been more frequent: when crossing a road, in a familiar area, when bystanders were around, and with an unreported or unknown attribution. Most frequently, falls resulted in either minor or moderate injury, feeling embarrassed at the time of the fall, and anxiety about falling again. Ten falls resulted in fracture, but no strong pattern emerged in regard to the contexts of these falls. Anxiety about falling again appeared more prevalent among those that fell in urban settings and who made more visits into their neighbourhood in a typical week. Conclusions This exploratory study has highlighted several aspects of the outdoor environment that may represent risk factors for outdoor falls and associated fear of falling. Health professionals are recommended to consider outdoor environments as well as the home setting when working to prevent falls and increase mobility among older people

Trends in anemia management in US hemodialysis patients 2004-2010.

BACKGROUND: There have been major changes in the management of anemia in US hemodialysis patients in recent years. We sought to determine the influence of clinical trial results, safety regulations, and changes in reimbursement policy on practice. METHODS: We examined indicators of anemia management among incident and prevalent hemodialysis patients from a medium-sized dialysis provider over three time periods: (1) 2004 to 2006 (2) 2007 to 2009, and (3) 2010. Trends across the three time periods were compared using generalized estimating equations. RESULTS: Prior to 2007, the median proportion of patients with monthly hemoglobin >12 g/dL for patients on dialysis 0 to 3, 4 to 6 and 7 to 18 months, respectively, was 42%, 55% and 46% declined to 41%, 54%, and 40% after 2007, and declined more sharply in 2010 to 34%, 41%, and 30%. Median weekly Epoeitin alpha doses over the same periods were 18,000, 12,400, and 9,100 units before 2007; remained relatively unchanged from 2007 to 2009; and decreased sharply in the patients 3-6 and 6-18 months on dialysis to 10,200 and 7,800 units, respectively in 2010. Iron doses, serum ferritin, and transferrin saturation levels increased over time with more pronounced increases in 2010. CONCLUSION: Modest changes in anemia management occurred between 2007 and 2009, followed by more dramatic changes in 2010. Studies are needed to examine the effects of declining erythropoietin use and hemoglobin levels and increasing intravenous iron use on quality of life, transplantation rates, infection rates and survival

Statistical process control of mortality series in the Australian and New Zealand Intensive Care Society (ANZICS) adult patient database: implications of the data generating process

for the ANZICS Centre for Outcome and Resource Evaluation (CORE) of the Australian and New Zealand Intensive Care Society (ANZICS)BACKGROUND Statistical process control (SPC), an industrial sphere initiative, has recently been applied in health care and public health surveillance. SPC methods assume independent observations and process autocorrelation has been associated with increase in false alarm frequency. METHODS Monthly mean raw mortality (at hospital discharge) time series, 1995–2009, at the individual Intensive Care unit (ICU) level, were generated from the Australia and New Zealand Intensive Care Society adult patient database. Evidence for series (i) autocorrelation and seasonality was demonstrated using (partial)-autocorrelation ((P)ACF) function displays and classical series decomposition and (ii) “in-control” status was sought using risk-adjusted (RA) exponentially weighted moving average (EWMA) control limits (3 sigma). Risk adjustment was achieved using a random coefficient (intercept as ICU site and slope as APACHE III score) logistic regression model, generating an expected mortality series. Application of time-series to an exemplar complete ICU series (1995-(end)2009) was via Box-Jenkins methodology: autoregressive moving average (ARMA) and (G)ARCH ((Generalised) Autoregressive Conditional Heteroscedasticity) models, the latter addressing volatility of the series variance. RESULTS The overall data set, 1995-2009, consisted of 491324 records from 137 ICU sites; average raw mortality was 14.07%; average(SD) raw and expected mortalities ranged from 0.012(0.113) and 0.013(0.045) to 0.296(0.457) and 0.278(0.247) respectively. For the raw mortality series: 71 sites had continuous data for assessment up to or beyond lag ₄₀ and 35% had autocorrelation through to lag ₄₀; and of 36 sites with continuous data for ≥ 72 months, all demonstrated marked seasonality. Similar numbers and percentages were seen with the expected series. Out-of-control signalling was evident for the raw mortality series with respect to RA-EWMA control limits; a seasonal ARMA model, with GARCH effects, displayed white-noise residuals which were in-control with respect to EWMA control limits and one-step prediction error limits (3SE). The expected series was modelled with a multiplicative seasonal autoregressive model. CONCLUSIONS The data generating process of monthly raw mortality series at the ICU level displayed autocorrelation, seasonality and volatility. False-positive signalling of the raw mortality series was evident with respect to RA-EWMA control limits. A time series approach using residual control charts resolved these issues.John L Moran, Patricia J Solomo

Envelope Determinants of Equine Lentiviral Vaccine Protection

Lentiviral envelope (Env) antigenic variation and associated immune evasion present major obstacles to vaccine development. The concept that Env is a critical determinant for vaccine efficacy is well accepted, however defined correlates of protection associated with Env variation have yet to be determined. We reported an attenuated equine infectious anemia virus (EIAV) vaccine study that directly examined the effect of lentiviral Env sequence variation on vaccine efficacy. The study identified a significant, inverse, linear correlation between vaccine efficacy and increasing divergence of the challenge virus Env gp90 protein compared to the vaccine virus gp90. The report demonstrated approximately 100% protection of immunized ponies from disease after challenge by virus with a homologous gp90 (EV0), and roughly 40% protection against challenge by virus (EV13) with a gp90 13% divergent from the vaccine strain. In the current study we examine whether the protection observed when challenging with the EV0 strain could be conferred to animals via chimeric challenge viruses between the EV0 and EV13 strains, allowing for mapping of protection to specific Env sequences. Viruses containing the EV13 proviral backbone and selected domains of the EV0 gp90 were constructed and in vitro and in vivo infectivity examined. Vaccine efficacy studies indicated that homology between the vaccine strain gp90 and the N-terminus of the challenge strain gp90 was capable of inducing immunity that resulted in significantly lower levels of post-challenge virus and significantly delayed the onset of disease. However, a homologous N-terminal region alone inserted in the EV13 backbone could not impart the 100% protection observed with the EV0 strain. Data presented here denote the complicated and potentially contradictory relationship between in vitro virulence and in vivo pathogenicity. The study highlights the importance of structural conformation for immunogens and emphasizes the need for antibody binding, not neutralizing, assays that correlate with vaccine protection. © 2013 Craigo et al

Climate change adaptation, flood risks and policy coherence in integrated water resources management in England

Integrated water resources management (IWRM) assumes coherence between cognate aspects of water governance at the river basin scale, for example water quality, energy production and agriculture objectives. But critics argue that IWRM is often less ‘integrated’ in practice, raising concerns over inter-sectoral coherence between implementing institutions. One increasingly significant aspect of IWRM is adaptation to climate change-related risks, including threats from flooding, which are particularly salient in England. Although multiple institutional mechanisms exist for flood risk management (FRM), their coherence remains a critical question for national adaptation. This paper therefore (1) maps the multi-level institutional frameworks determining both IWRM and FRM in England; (2) examines their interaction via various inter-institutional coordinating mechanisms; and (3) assesses the degree of coherence. The analysis suggests that cognate EU strategic objectives for flood risk assessment demonstrate relatively high vertical and horizontal coherence with river basin planning. However, there is less coherence with flood risk requirements for land-use planning and national flood protection objectives. Overall, this complex governance arrangement actually demonstrates de-coherence over time due to ongoing institutional fragmentation. Recommendations for increasing IWRM coherence in England or re-coherence based on greater spatial planning and coordination of water-use and land-use strategies are proposed

Internet-based medical education: a realist review of what works, for whom and in what circumstances

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The extraordinary evolutionary history of the reticuloendotheliosis viruses

The reticuloendotheliosis viruses (REVs) comprise several closely related amphotropic retroviruses isolated from birds. These viruses exhibit several highly unusual characteristics that have not so far been adequately explained, including their extremely close relationship to mammalian retroviruses, and their presence as endogenous sequences within the genomes of certain large DNA viruses. We present evidence for an iatrogenic origin of REVs that accounts for these phenomena. Firstly, we identify endogenous retroviral fossils in mammalian genomes that share a unique recombinant structure with REVs—unequivocally demonstrating that REVs derive directly from mammalian retroviruses. Secondly, through sequencing of archived REV isolates, we confirm that contaminated Plasmodium lophurae stocks have been the source of multiple REV outbreaks in experimentally infected birds. Finally, we show that both phylogenetic and historical evidence support a scenario wherein REVs originated as mammalian retroviruses that were accidentally introduced into avian hosts in the late 1930s, during experimental studies of P. lophurae, and subsequently integrated into the fowlpox virus (FWPV) and gallid herpesvirus type 2 (GHV-2) genomes, generating recombinant DNA viruses that now circulate in wild birds and poultry. Our findings provide a novel perspective on the origin and evolution of REV, and indicate that horizontal gene transfer between virus families can expand the impact of iatrogenic transmission events

Postcopulatory sexual selection

The female reproductive tract is where competition between the sperm of different males takes place, aided and abetted by the female herself. Intense postcopulatory sexual selection fosters inter-sexual conflict and drives rapid evolutionary change to generate a startling diversity of morphological, behavioural and physiological adaptations. We identify three main issues that should be resolved to advance our understanding of postcopulatory sexual selection. We need to determine the genetic basis of different male fertility traits and female traits that mediate sperm selection; identify the genes or genomic regions that control these traits; and establish the coevolutionary trajectory of sexes

Multiple viral infections in Agaricus bisporus - characterisation of 18 unique RNA viruses and 8 ORFans identified by deep sequencing

Thirty unique non-host RNAs were sequenced in the cultivated fungus, Agaricus bisporus, comprising 18 viruses each encoding an RdRp domain with an additional 8 ORFans (non-host RNAs with no similarity to known sequences). Two viruses were multipartite with component RNAs showing correlative abundances and common 3′ motifs. The viruses, all positive sense single-stranded, were classified into diverse orders/families. Multiple infections of Agaricus may represent a diverse, dynamic and interactive viral ecosystem with sequence variability ranging over 2 orders of magnitude and evidence of recombination, horizontal gene transfer and variable fragment numbers. Large numbers of viral RNAs were detected in multiple Agaricus samples; up to 24 in samples symptomatic for disease and 8–17 in asymptomatic samples, suggesting adaptive strategies for co-existence. The viral composition of growing cultures was dynamic, with evidence of gains and losses depending on the environment and included new hypothetical viruses when compared with the current transcriptome and EST databases. As the non-cellular transmission of mycoviruses is rare, the founding infections may be ancient, preserved in wild Agaricus populations, which act as reservoirs for subsequent cell-to-cell infection when host populations are expanded massively through fungiculture