Considerations for Research Funders and Managers to Facilitate the Translation of Scientific Knowledge into Practice.

Research funders and managers can play a critical role in supporting the translation of knowledge into action by facilitating the brokering of knowledge and partnerships. We use semi-structured interviews with a research funding agency, the Australian Centre for International Agricultural Research (ACIAR), to explore (i) ways that funders can facilitate knowledge brokering, the (ii) barriers to, and (iii) enablers for, facilitating knowledge brokering, and (iv) the individual skills and attributes for research program funders and managers to be effective brokers. Based on these findings, we generate three considerations for research funders elsewhere, in particular R4D funders, seeking to build capacity for knowledge brokering: (i) formalise the process and practice, (ii) develop shared language and understanding, and (iii) build individual competencies and capabilities. Our findings complement the existing literature with a context specific analysis of how research funders can facilitate knowledge brokering, and by identifying the barriers and enablers in doing so.

A seroprevalence study to determine the frequency of hantavirus infection in people exposed to wild and pet fancy rats in England.

Recent cases of acute kidney injury due to Seoul hantavirus infection from exposure to wild or pet fancy rats suggest this infection is increasing in prevalence in the UK. We conducted a seroprevalence study in England to estimate cumulative exposure in at-risk groups with contact with domesticated and wild rats to assess risk and inform public health advice. From October 2013 to June 2014, 844 individual blood samples were collected. Hantavirus seroprevalence amongst the pet fancy rat owner group was 34.1% (95% CI 23·9-45·7%) compared with 3·3% (95% CI 1·6-6·0) in a baseline control group, 2·4% in those with occupational exposure to pet fancy rats (95% CI 0·6-5·9) and 1·7% with occupational exposure to wild rats (95% CI 0·2-5·9). Variation in seroprevalence across groups with different exposure suggests that occupational exposure to pet and wild rats carries a very low risk, if any. However incidence of hantavirus infection among pet fancy rat owners/breeders, whether asymptomatic, undiagnosed mild viral illness or more severe disease may be very common and public health advice needs to be targeted to this at-risk group.

Q fever through consumption of unpasteurised milk and milk products - a risk profile and exposure assessment.

Q fever is a zoonotic disease caused by the bacterium Coxiella burnetii which is endemic in cattle, sheep and goats in much of the world, including the United Kingdom (UK). There is some epidemiological evidence that a small proportion of cases in the developed world may arise from consumption of unpasteurised milk with less evidence for milk products such as cheese. Long maturation at low pH may give some inactivation in hard cheese, and viable C. burnetii are rarely detected in unpasteurised cheese compared to unpasteurised milk. Simulations presented here predict that the probability of exposure per person to one or more C. burnetii through the daily cumulative consumption of raw milk in the UK is 0·4203. For those positive exposures, the average level of exposure predicted is high at 1266 guinea pig intraperitoneal infectious dose 50% units (GP_IP_ID50 ) per person per day. However, in the absence of human dose-response data, the case is made that the GP_IP_ID50 unit represents a very low risk through the oral route. The available evidence suggests that the risks from C. burnetii through consumption of unpasteurised milk and milk products (including cheese) are not negligible but they are lower in comparison to transmission via inhalation of aerosols from parturient products and livestock contact.

Falls and fractures 2 years after acute stroke: the North Dublin Population Stroke Study.

BACKGROUND: Stroke patients are at increased risk of falls and fractures. The aim of this study was to determine the rate, predictors and consequences of falls within 2 years after stroke in a prospective population-based study in North Dublin, Ireland. DESIGN: Prospective population-based cohort study. SUBJECTS: 567 adults aged >18 years from the North Dublin Population Stroke Study. METHODS: Participants were enrolled from an Irish urban population of 294,592 individuals, according to recommended criteria. Patients were followed for 2 years. Outcome measures included death, modified Rankin Scale (mRS), fall and fracture rate. RESULTS: At 2 years, 23.5% (124/522) had fallen at least once since their stroke, 14.2% (74/522) had 2 or more falls and 5.4% (28/522) had a fracture. Of 332 survivors at 2 years, 107 (32.2%) had fallen, of whom 60.7% (65/107) had 2 or more falls and 23.4% (25/107) had fractured. In a multivariable model controlling for age and gender, independent risk factors for falling within the first 2 years of stroke included use of alpha-blocker medications for treatment of hypertension (P = 0.02). When mobility measured at Day 90 was included in the model, patients who were mobility impaired (mRS 2-3) were at the highest risk of falling within 2 years of stroke [odds ratio (OR) 2.30, P = 0.003] and those functionally dependent (mRS 4-5) displayed intermediate risk (OR 2.02, P = 0.03) when compared with independently mobile patients. CONCLUSION: Greater attention to falls risk, fall prevention strategies and bone health in the stroke population are required.

Short- and long-term outcomes for patients with variceal haemorrhage in a tertiary hospital.

BACKGROUND/AIM: To determine short- and long-term outcomes among a cohort of patients with variceal haemorrhage at a tertiary referral centre, and to determine the predictive value of the model for end-stage liver disease (MELD) score for mortality in these patients. METHODS: Prospective database hospital audit that captured patients who presented with or were transferred with variceal haemorrhage between 2004 and 2008, and a retrospective review of long-term outcomes. Patients who presented to or were transferred to John Hunter Hospital, a tertiary referral hospital, with confirmed variceal bleeding were included. The main outcome measures were in-hospital, 6 weeks and end-of-audit mortality. We also recorded cause, location and degree of planning surrounding the deaths in this patient group. We analysed the MELD score for patients with complete survival data. RESULTS: We recorded 93 episodes of variceal haemorrhage from 78 unique patients during the initial study period. The in-hospital mortality, 6 weeks mortality and end-of-audit mortality were 2.6, 9.0 and 59, respectively, and median survival time was 3.2 years (95% confidence interval 0.0, 6.1). The most frequent cause of death was related to complications of end-stage liver disease at 74%, followed by variceal bleeding (19%) and unknown (6%). A Cox proportional hazard model showed that the risk of mortality is increased by 1.06 (1.01-1.11) for each unit increase in MELD score. CONCLUSIONS: Short-term outcomes for patients with variceal bleeding continue to improve, but long-term prognosis remains guarded and should prompt further emphasis on advanced care planning to optimise patient care.

Blood transfusion: old blood, new blood or no blood.

Vigorous blood transfusion has long been regarded as having an essential role in the management of acute gastrointestinal haemorrhage. Two new studies, one a nationwide audit of acute gastrointestinal haemorrhage in the UK and another, a complex physiological study of stored blood from the USA, offer new insights.

Bleeding peptic ulcer: characteristics and outcomes in Newcastle, NSW.

BACKGROUND: Peptic ulcer disease risk factors have changed, as has the impact of treatment on morbidity and mortality. Recent data on clinical presentation and outcome are sparse in Australia. AIM: To determine the characteristics and outcome of patients presenting with a bleeding peptic ulcer to a tertiary referral centre. METHODS: We evaluated patients diagnosed with peptic ulcer bleeding between 2004 and 2008 at a tertiary referral hospital. Variables assessed included demographic data, comorbidities, medication use and Rockall score. Outcomes of interest were the time to endoscopy, peptic ulcer treatment, transfusion requirements, urgent surgery and survival. RESULTS: Peptic ulcers were confirmed in 265 patients (55% male), of which 145 were gastric and 119 duodenal. The mean age was 71 years. On admission 38% of patients had haemodynamic instability and 92% had one or more comorbidity. Consumption of ulcerogenic medications at the time of admission was frequent (non-steroidal anti-inflammatory drugs (NSAIDs) 22%, aspirin 41%, clopidogrel or warfarin 10%) and proton pump inhibitors infrequent (15%). A gastroenterologist managed all patients according to their usual practice. Only a minority of patients received over three units of packed red cells. Few patients were referred for surgery (3%) or died (3%), but both events were significantly higher for the duodenal ulcer group. CONCLUSION: The characteristics and outcomes in patients with peptic ulcer bleeding have changed. Peptic ulcer disease remains a public health problem with modifiable risk factors, such as Helicobacter pylori infection and NSAIDs, which should be targeted to reduce the burden of illness.

Obesity, overeating, and rapid gastric emptying in rats with ventromedial hypothalamic lesions.

Measurements confirm the quantitative theoretical prediction that the autonomic nonendocrine abnormality of rapid daytime gastric emptying is the major primary cause of the obesity resulting from ventromedial hypothalamic lesions in rats. Therapy for obesity could include slowing of stomach emptying.

Increased number of community-living older adults attending an emergency department with falls and fractures: North Dublin experience.

BACKGROUND: The number of attendances to emergency department (ED) due to falls and fractures increases as the population ages. The community-based falls prevention strategy may reduce the number of falls requiring medical attention. AIM: Our aim was to determine the changes over time in community-living older adults on the number of attendances to an urban ED over a 5 year period. METHODS: Community-living adults aged ≥65 years from a catchment attending with falls and fractures to an ED in 2010 and 2014 were identified through an electronic patient record. The age, gender and patient-related outcome (admit, discharge with and without follow-up, died in department) were collected. Patient-related outcome was compared by age group. RESULTS: There were 477 and 772 attendances with falls and fractures in 2010 and 2014, respectively. Between 3 and 7% were repeat attendees. Compared with 2010, in 2014, there were more women attendees; the proportion of patients aged ≥80 years were higher, more likely to be admitted and discharged without follow-up. Patients aged 85+ were six times more likely to require admission compared with under 75's. CONCLUSION: With the rapidly ageing population in North Dublin, there is an urgent need to prioritise comprehensive assessment and provide a coordinated falls programme when older adults present to ED to reduce the risk of future falls and injuries.

Personal view: crystalloid transfusion in acute gastrointestinal haemorrhage: is it beneficial? An historical perspective.

The conventional management of acute gastrointestinal haemorrhage mandates early repletion of blood volume with crystalloids and blood, as part of the initial management, where there is evidence of hypovolaemia. Meanwhile there is a major trend towards a restrained use of fluid to raise blood pressure to near normal for the bleeding patient in trauma and similar emergencies. This divergence of view requires analysis. An Ovid/MEDLINE, Google and extensive literature search focused on the resuscitation and transfusion of bleeding trauma patients was performed. In addition to clear evidence from animal experiments that early restoration of blood volume perpetuates bleeding, there is considerable evidence in humans - both in war and civilian life - that rapid crystalloid infusion is harmful. I also report a personal series of benefit from restricted transfusion in acute upper gastrointestinal haemorrhage in humans. Given the lack of evidence of benefit for rapid blood volume repletion in acute gastrointestinal haemorrhage, there is need for controlled studies of the most appropriate approach to crystalloid transfusion in acute gastrointestinal bleeding.

Estimating bias in derived body mass index in the Maternity Experiences Survey. / Estimation du biais lié à l'indice de masse corporelle utilisé dans l'Enquête canadienne sur l'expérience de la maternité.

INTRODUCTION: The objective of this study was to assess bias in the body mass index (BMI) measure in the Canadian Maternity Experiences Survey (MES) and possible implications of bias on the relationship between BMI and selected pregnancy outcomes. METHODS: We assessed BMI classification based on self-reported versus measured values. We used a random sample of 6175 women from the MES, which derived BMI from self-reported height and weight, and a random sample of 259 women who had previously given birth from the Canadian Health Measures Survey (CHMS), which derived BMI from self-reported and measured height and weight. Two correction equations were applied to self-reported based BMI, and the impact of these corrections on associations between BMI and caesarean section, small-for-gestational age (SGA) and large-for-gestational age (LGA) births was studied. RESULTS: Overall, 86.9% of the CHMS subsample was classified into the same BMI category based on self-reported versus measured data. However, misclassification had a substantial effect on the proportion of women in underweight and obese BMI categories. For example, 14.5% versus 20.8% of women were classified as obese based on self-reported data versus measured data. Corrections improved estimates of obesity prevalence, but over- and underestimated other BMI categories. Corrections had nonsignificant effects on the associations between BMI and SGA, LGA, and caesarean section. CONCLUSION: While there was high concordance in BMI classification based on selfreported versus measured height and weight, bias in self-reported based measures may slightly over- or underestimate the risks associated with a particular BMI class. However, the general trend in associations is unaffected.

INTRODUCTION: Cette étude visait à évaluer le biais dans la mesure de l'indice de masse corporelle (IMC) dans l'Enquête canadienne sur l'expérience de la maternité (ECEM) ainsi que les répercussions possibles de ce biais sur l'association entre l'IMC et certaines issues de grossesse. MÉTHODOLOGIE: Nous avons évalué la répartition des valeurs de l'IMC en comparant des données autodéclarées et des données mesurées. Nous avons utilisé un échantillon aléatoire de 6 175 participantes à l'ECEM dont l'IMC avait été calculé d'après la taille et le poids autodéclarés et un échantillon aléatoire de 259 participantes à l'Enquête canadienne sur les mesures de santé (ECMS) ayant déjà accouché et dont l'IMC avait été calculé d'après la taille et le poids autodéclarés et mesurés. Nous avons appliqué deux équations de correction à l'IMC fondé sur des valeurs autodéclarées, et nous avons examiné l'impact de ces corrections sur les associations entre l'IMC et un accouchement par césarienne, un faible poids pour l'âge gestationnel (FPAG) et un poids élevé pour l'âge gestationnel (PEAG). RÉSULTATS: Dans l'ensemble, 86,9 % des femmes du sous-échantillon de l'ECMS appartenaient à la même catégorie d'IMC lorsque ses valeurs étaient autodéclarées et lorsqu'elles étaient mesurées. Cependant, les différences de répartition ont eu un effet considérable sur la proportion de femmes des catégories de poids insuffisant et d'obésité. Par exemple, le pourcentage de femmes classées comme obèses était de 14,5 % avec les données autodéclarées contre 20,8 % avec les données mesurées. Les corrections ont permis d'améliorer les estimations de la prévalence de l'obésité, mais ont surestimé ou sous-estimé les autres catégories d'IMC. Les corrections ont eu un effet non significatif sur les associations entre l'IMC et l'accouchement par césarienne, le FPAG et le PEAG. CONCLUSION: Bien que la concordance pour la répartition des valeurs de l'IMC entre la taille et le poids autodéclarés et la taille et le poids mesurés soit élevée, il existe un biais dans les mesures fondées sur les valeurs autodéclarées susceptible d'entraîner de légères surestimations ou sous-estimations des risques associés à une catégorie d'IMC donnée. La tendance générale des associations reste néanmoins inchangée.

Impact of season, weekends and bank holidays on emergency department transfers of nursing home residents.

BACKGROUND: For urgent, unexpected clinical events, nursing home (NH) residents are transferred to the acute hospital emergency department (ED). A previous study showed that a third of transfers occurred during working hours. AIMS: Our aims were to profile a one-year NH transfers to the ED and to examine the re-presentation, patient-oriented outcome and the impact of season, weekends and bank holidays on NH transfers. METHODS: All NH transfers from a catchment to an ED over one year were identified using electronic patient record. Age, gender, reason for presentation, patient-oriented outcome and date and time of presentation were recorded. Representation and the interval between transfers were calculated. Number of transfers was calculated for season, weekdays/weekends and bank holidays. Student t test, Chi-square statistics and one-way ANOVA were used. Significance was set at 0.05. RESULTS: There were 802 transfers from 465 NH residents over a year; 501 (62.5 %) resulted in admissions, 189 (40.6 %) residents represent to the service and 80 episodes occurred within a fortnight of the last attendance. The highest transfers occurred in May (2.81 patients/day), during working hours and on Wednesdays and Thursdays (>2.5 transfers/day). 'Unwell adult' and 'falls' were the two commonest reasons for presentation. CONCLUSIONS: Our study showed that NH transfers occurred mainly within working hours and during weekdays. Insights into the transfer pattern and the reasons for NH patients to utilise ED will facilitate improved design and operation of the department by creating care pathways for these patients.

Ambulatory blood pressure monitoring.

Non-invasive measurement of blood pressure in ambulatory humans began in the 1960s. Ambulatory devices have been modified over the years and are now pocket-sized, with almost noiseless pumps. Their accuracy must be validated by independent laboratories using a standardised protocol. Twenty-four-hour ambulatory monitoring offers considerable advantages over conventional measurement, including avoidance of error associated with conventional measurement, elimination of white-coat effect and the provision of a series of blood pressure readings over the time period rather than a one-off measurement. In clinical practice, 24-hr monitoring provides valuable assistance in both the diagnosis and treatment of hypertension, in particular, in the selection of drug and dosage regimen. In the research setting, 24-hr monitoring plays an important role in establishing dose-response relationships and the duration of action of new drugs. It also has a role in the design of antihypertensive trials by ensuring that those with white-coat hypertension are excluded and by reducing the number of subjects necessary for recruitment. Although 24-hr ambulatory blood pressure is a better predictor of target organ damage, definitive evidence as to whether it is a better predictor of prognosis in hypertension awaits the results of longitudinal studies, which are now underway.

Systematic review: the liver in coeliac disease.

BACKGROUND: For over a decade isolated reports have noted liver histology and biochemistry changes in patients with coeliac disease. The prevalence and response to treatment is clinically important. AIM: To outline the frequency and significance of liver abnormalities in coeliac disease. METHODS: A Medline search using Ovid-Coeliac/Coeliac (exp) and liver disease (exp) was completed of English references published during 1966-June 2003. Bibliographic references and other appropriate sources were also searched. RESULTS: Six studies reported liver biochemistry in 591 patients; 248 patients had abnormal results. Elevated transaminases were the most frequently reported abnormality. A gluten-free diet produced resolution of elevated transaminases in 115 of 130 patients. There was a greater than expected association with primary biliary cirrhosis and advanced liver disease. CONCLUSIONS: Mildly abnormal liver biochemistry is frequent in untreated coeliac disease and may provide a key to the diagnosis. Routine investigations for undiagnosed liver disease should include tissue transglutaminase testing. Left untreated, coeliac-induced hepatitis may rarely progress to end-stage liver disease. Primary biliary cirrhosis is clearly linked to coeliac disease. The full story of these linkages is yet to be written.

The interrelationship between chloride ions and endothelium on alpha(1)-adrenoceptor-mediated contractions in aortic rings from Dahl normotensive and hypertensive rats.

OBJECTIVES: The effects of chloride-free buffer in the absence or presence of the nitric oxide synthase inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME), or chloride channel antagonist, indanyloxyacetic acid 94 (IAA-94) on alpha(1)-adrenoceptor mediated contractions were investigated in aortic rings from Dahl salt-resistant normotensive (SRN) and salt-sensitive hypertensive (SSH) rats on a 4% salt diet. METHODS: Systolic and diastolic blood pressure were measured via intra-arterial catheters under halothane anesthesia. Subsequently, the aorta was removed and cirazoline-induced contractions were recorded in normal Krebs and chloride-free buffer using ring preparation. Guanosine 3',5'-cyclic monophosphate (cyclic GMP) content of aortic rings was also determined by scintillation proximity assay kits. RESULTS: Systolic and diastolic blood pressure of SSH (180/130+/-1/1, mean+/-S.E.; n=14) were significantly higher than those of SRN (101/76+/-1/1, mean+/-S.E.; n=14) 7 weeks after they were placed on a salt diet. While the presence of L-NAME failed to have any impact on cirazoline-induced contractions in aortic rings from SSH rats, it significantly accentuated the effects of cirazoline in tissues from SRN rats. On the other hand, IAA-94 was able to inhibit cirazoline-mediated contractions in aortic rings from both SRN and SSH rats. The removal of chloride ions potentiated contractions produced by cirazoline in tissues from SRN but not SSH rats. Moreover, cirazoline-evoked responses in tissues from SRN were not further accentuated by the inclusion of L-NAME in chloride-free buffer. Cirazoline-mediated contractions in tissues from SSH rats were not influenced by absence of chloride ions, and the presence of L-NAME. It was also apparent that the inclusion of IAA-94 in absence of chloride ions did not prevent the potentiation of responses to cirazoline. Removal of chloride ions did not significantly decrease basal cyclic GMP levels in aortic rings from either strain. CONCLUSIONS: Basal release of nitric oxide seems to make a greater contribution in the suppression of cirazoline-evoked contractions in vessels from SRN as opposed to SSH rats. Chloride channels appear to contribute to cirazoline-evoked contractions in normal Krebs but not in chloride-free buffer.