Enclosing a pen to improve response rate to postal questionnaire: an embedded randomised controlled trial

Background: Poor response to questionnaires collecting outcome data in randomised controlled trials (RCTs) can affect the validity of trial results. The aim of this study within a trial (SWAT) was to evaluate the effectiveness of including a pen with a follow-up postal questionnaire on response rate. Methods: A two-armed RCT was embedded within SSHeW (Stopping Slips among Healthcare Workers), a trial of slip-resistant footwear to reduce slips in NHS staff. Participants were randomised 1:1 to receive a pen or no pen with their follow-up questionnaire. The primary outcome was the proportion of participants who returned the questionnaire. Secondary outcomes were: time to response, completeness of response, and whether a postal reminder notice was required. Data were analysed using logistic regression, linear regression and Cox proportional hazards regression. Results: Overall, 1466 SSHEW trial participants were randomised into the SWAT. In total, 13 withdrew from the host trial before they were due to be sent their follow-up questionnaire, 728 participants received a pen with their questionnaire, and 725 did not receive a pen. A questionnaire was returned from 67.7% of the pen group and 64.7% of the group who did not receive a pen. There was no significant difference in return rates between the two groups (OR 1.15, 95% CI 0.92 to 1.43, p=0.22), nor level of completeness of the questionnaires (AMD -0.01, 95% CI 0.06 to 0.05, p=0.77). There was weak evidence of a reduction in the proportion of participants requiring a reminder and in time to response in the pen group. Conclusion: Inclusion of a pen with the follow-up postal questionnaire sent to participants in the SSHeW trial did not statistically significantly increase the response rate. These results add to the body of evidence around improving response rates in trials. Trial registration: ISRCTN 33051393 (for SSHEW). Registered on 14/03/2017

Herpesvirus skin disease in free-living common frogs Rana temporaria in Great Britain

Infectious disease is a significant driver of global amphibian declines, yet despite this, relatively little is known about the range of pathogens that affect free-living amphibians. Recent detection of the tentatively named Ranid herpesvirus 3 (RHV3), associated with skin disease in free-living common frogs Rana temporaria in Switzerland, helps to address this paucity in knowledge, but the geographic distribution and epidemiology of the pathogen remains unclear. Syndromic surveillance for ranid herpesvirus skin disease was undertaken throughout Great Britain (GB), January 2014 to December 2016. Reports of common frogs with macroscopic skin lesions with a characteristic grey appearance were solicited from members of the public. Post-mortem examination was conducted on one affected frog found dead in 2015 at a site in England. In addition, archived samples from an incident involving common frogs in England in 1997 with similar macroscopic lesions were further investigated. Transmission electron microscopy identified herpes-like virions in skin lesions from both the 1997 and 2015 incidents. RHV3, or RHV3-like virus, was detected in skin lesions from the 2015 case by PCR and sequencing. Our findings indicate that herpesvirus skin disease is endemic in common frogs in GB, with widespread distribution at apparently low prevalence. Further research into the role of host immunity, virus latency and the significance of infection to host survival is required to better understand the epidemiology and impact of cutaneous herpesvirus infections in amphibian populations

The thoughtful self

The relationship between a concept in the external world (e.g., the self), and its representation in cognition

Death and Emergency Readmission of Infants Discharged After Interventions for Congenital Heart Disease: A National Study of 7643 Infants to Inform Service Improvement.

Improvements in hospital-based care have reduced early mortality in congenital heart disease. Later adverse outcomes may be reducible by focusing on care at or after discharge. We aimed to identify risk factors for such events within 1 year of discharge after intervention in infancy and, separately, to identify subgroups that might benefit from different forms of intervention.Cardiac procedures performed in infants between 2005 and 2010 in England and Wales from the UK National Congenital Heart Disease Audit were linked to intensive care records. Among 7976 infants, 333 (4.2%) died before discharge. Of 7643 infants discharged alive, 246 (3.2%) died outside the hospital or after an unplanned readmission to intensive care (risk factors were age, weight-for-age, cardiac procedure, cardiac diagnosis, congenital anomaly, preprocedural clinical deterioration, prematurity, ethnicity, and duration of initial admission; c-statistic 0.78 [0.75-0.82]). Of the 7643, 514 (6.7%) died outside the hospital or had an unplanned intensive care readmission (same risk factors but with neurodevelopmental condition and acquired cardiac diagnosis and without preprocedural deterioration; c-statistic 0.78 [0.75-0.80]). Classification and regression tree analysis were used to identify 6 subgroups stratified by the level (3-24%) and nature of risk for death outside the hospital or unplanned intensive care readmission based on neurodevelopmental condition, cardiac diagnosis, congenital anomaly, and duration of initial admission. An additional 115 patients died after planned intensive care admission (typically following elective surgery).Adverse outcomes in the year after discharge are of similar magnitude to in-hospital mortality, warrant service improvements, and are not confined to diagnostic groups currently targeted with enhanced monitoring

What is stirring in the reservoir? Modelling mechanisms of henipavirus circulation in fruit bat hosts

Pathogen circulation among reservoir hosts is a precondition for zoonotic spillover. Unlike the acute, high morbidity infections typical in spillover hosts, infected reservoir hosts often exhibit low morbidity and mortality. Although it has been proposed that reservoir host infections may be persistent with recurrent episodes of shedding, direct evidence is often lacking. We construct a generalized SEIR (susceptible, exposed, infectious, recovered) framework encompassing 46 sub-models representing the full range of possible transitions among those four states of infection and immunity. We then use likelihood-based methods to fit these models to nine years of longitudinal data on henipavirus serology from a captive colony of Eidolon helvum bats in Ghana. We find that reinfection is necessary to explain observed dynamics; that acute infectious periods may be very short (hours to days); that immunity, if present, lasts about 1–2 years; and that recurring latent infection is likely. Although quantitative inference is sensitive to assumptions about serology, qualitative predictions are robust. Our novel approach helps clarify mechanisms of viral persistence and circulation in wild bats, including estimated ranges for key parameters such as the basic reproduction number and the duration of the infectious period. Our results inform how future field-based and experimental work could differentiate the processes of viral recurrence and reinfection in reservoir hosts. This article is part of the theme issue ‘Dynamic and integrative approaches to understanding pathogen spillover’

Colorectal cancer linkage on chromosomes 4q21, 8q13, 12q24, and 15q22

A substantial proportion of familial colorectal cancer (CRC) is not a consequence of known susceptibility loci, such as mismatch repair (MMR) genes, supporting the existence of additional loci. To identify novel CRC loci, we conducted a genome-wide linkage scan in 356 white families with no evidence of defective MMR (i.e., no loss of tumor expression of MMR proteins, no microsatellite instability (MSI)-high tumors, or no evidence of linkage to MMR genes). Families were ascertained via the Colon Cancer Family Registry multi-site NCI-supported consortium (Colon CFR), the City of Hope Comprehensive Cancer Center, and Memorial University of Newfoundland. A total of 1,612 individuals (average 5.0 per family including 2.2 affected) were genotyped using genome-wide single nucleotide polymorphism linkage arrays; parametric and non-parametric linkage analysis used MERLIN in a priori-defined family groups. Five lod scores greater than 3.0 were observed assuming heterogeneity. The greatest were among families with mean age of diagnosis less than 50 years at 4q21.1 (dominant HLOD = 4.51, α = 0.84, 145.40 cM, rs10518142) and among all families at 12q24.32 (dominant HLOD = 3.60, α = 0.48, 285.15 cM, rs952093). Among families with four or more affected individuals and among clinic-based families, a common peak was observed at 15q22.31 (101.40 cM, rs1477798; dominant HLOD = 3.07, α = 0.29; dominant HLOD = 3.03, α = 0.32, respectively). Analysis of families with only two affected individuals yielded a peak at 8q13.2 (recessive HLOD = 3.02, α = 0.51, 132.52 cM, rs1319036). These previously unreported linkage peaks demonstrate the continued utility of family-based data in complex traits and suggest that new CRC risk alleles remain to be elucidated. © 2012 Cicek et al

Hip fracture risk assessment: Artificial neural network outperforms conditional logistic regression in an age- and sex-matched case control study

Copyright @ 2013 Tseng et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background - Osteoporotic hip fractures with a significant morbidity and excess mortality among the elderly have imposed huge health and economic burdens on societies worldwide. In this age- and sex-matched case control study, we examined the risk factors of hip fractures and assessed the fracture risk by conditional logistic regression (CLR) and ensemble artificial neural network (ANN). The performances of these two classifiers were compared. Methods - The study population consisted of 217 pairs (149 women and 68 men) of fractures and controls with an age older than 60 years. All the participants were interviewed with the same standardized questionnaire including questions on 66 risk factors in 12 categories. Univariate CLR analysis was initially conducted to examine the unadjusted odds ratio of all potential risk factors. The significant risk factors were then tested by multivariate analyses. For fracture risk assessment, the participants were randomly divided into modeling and testing datasets for 10-fold cross validation analyses. The predicting models built by CLR and ANN in modeling datasets were applied to testing datasets for generalization study. The performances, including discrimination and calibration, were compared with non-parametric Wilcoxon tests. Results - In univariate CLR analyses, 16 variables achieved significant level, and six of them remained significant in multivariate analyses, including low T score, low BMI, low MMSE score, milk intake, walking difficulty, and significant fall at home. For discrimination, ANN outperformed CLR in both 16- and 6-variable analyses in modeling and testing datasets (p?<?0.005). For calibration, ANN outperformed CLR only in 16-variable analyses in modeling and testing datasets (p?=?0.013 and 0.047, respectively). Conclusions - The risk factors of hip fracture are more personal than environmental. With adequate model construction, ANN may outperform CLR in both discrimination and calibration. ANN seems to have not been developed to its full potential and efforts should be made to improve its performance.National Health Research Institutes in Taiwa

The 10th Biennial Hatter Cardiovascular Institute workshop: cellular protection—evaluating new directions in the setting of myocardial infarction, ischaemic stroke, and cardio-oncology

Due to its poor capacity for regeneration, the heart is particularly sensitive to the loss of contractile cardiomyocytes. The onslaught of damage caused by ischaemia and reperfusion, occurring during an acute myocardial infarction and the subsequent reperfusion therapy, can wipe out upwards of a billion cardiomyocytes. A similar program of cell death can cause the irreversible loss of neurons in ischaemic stroke. Similar pathways of lethal cell injury can contribute to other pathologies such as left ventricular dysfunction and heart failure caused by cancer therapy. Consequently, strategies designed to protect the heart from lethal cell injury have the potential to be applicable across all three pathologies. The investigators meeting at the 10th Hatter Cardiovascular Institute workshop examined the parallels between ST-segment elevation myocardial infarction (STEMI), ischaemic stroke, and other pathologies that cause the loss of cardiomyocytes including cancer therapeutic cardiotoxicity. They examined the prospects for protection by remote ischaemic conditioning (RIC) in each scenario, and evaluated impasses and novel opportunities for cellular protection, with the future landscape for RIC in the clinical setting to be determined by the outcome of the large ERIC-PPCI/CONDI2 study. It was agreed that the way forward must include measures to improve experimental methodologies, such that they better reflect the clinical scenario and to judiciously select combinations of therapies targeting specific pathways of cellular death and injury

An unusual presentation of multiple cavitated lung metastases from colon carcinoma

<p>Abstract</p> <p>Background</p> <p>Consolidation with or without ground-glass opacity is the typical radiologic finding of lung metastases of adenocarcinoma from the gastrointestinal tract. Lung excavated metastases from gastrointestinal carcinoma are very rare.</p> <p>Case presentation</p> <p>The authors describe an unusual presentation of multiple cavitated lung metastases from colon adenocarcinoma and discuss the outcome of a patient. The absence both of symptoms and other disease localizations, the investigations related to different diagnostic hypotheses and the empirical treatments caused a delay in correct diagnosis. Only a transparietal biopsy revealed the neoplastic origin of nodules.</p> <p>Conclusions</p> <p>This report demonstrates that although lung excavated metastases are described in literature, initial failure to reach a diagnosis is common. We would like to alert clinicians and radiologists to the possibility of unusual atypical features of pulmonary metastases from colon adenocarcinoma.</p