Climate Variability and Ross River Virus Transmission in Townsville Region, Australia 1985 to 1996

Background How climate variability affects the transmission of infectious diseases at a regional level remains unclear. In this paper, we assessed the impact of climate variation on the Ross River virus (RRv) transmission in the Townsville region, Queensland, north-east Australia. Methods Population-based information was obtained on monthly variations in RRv cases, climatic factors, sea level, and population growth between 1985 and 1996. Cross-correlations were computed for a series of associations between climate variables (rainfall, maximum temperature, minimum temperature, relative humidity and high tide) and the monthly incidence of RRv disease over a range of time lags. The impact of climate variability on RRv transmission was assessed using the seasonal auto-regressive integrated moving average (SARIMA) model. Results There were significant correlations of the monthly incidence of RRv to rainfall, maximum temperature, minimum temperature and relative humidity, all at a lag of 2 months, and high tide in the current month. The results of SARIMA models show that monthly average rainfall (β=0.0012, p=0.04) and high tide (β=0.0262, p=0.01) were significantly associated with RRv transmission, although temperature and relative humidity did not seem to have played an important role in the Townsville region. Conclusions Rainfall, and high tide were likely to be key determinants of RRv transmission in the Townsville region

blandaltman: A command to create variants of Bland–Altman plots

Bland–Altman plots can be useful in paired data settings such as measurement-method comparison studies. A Bland–Altman plot has differences, percentage differences, or ratios on the y axis and a mean of the data pairs on the x axis, with 95% limits of agreement indicating the central 95% range of differences, percentage differences, or ratios. This range can vary with the mean. We introduce the community-contributed blandaltman command, which uniquely in Stata can 1) create Bland–Altman plots featuring ratios in addition to differences and percentage differences, 2) allow the limits of agreement for ratios and percentage differences to vary as a function of the mean, and 3) add confidence intervals, prediction intervals, and tolerance intervals to the plots

Case-finding of dementia in general practice and effects of subsequent collaborative care; design of a cluster RCT

<p>Abstract</p> <p>Background</p> <p>In the primary care setting, dementia is often diagnosed relatively late in the disease process. Case finding and proactive collaborative care may have beneficial effects on both patient and informal caregiver by clarifying the cause of cognitive decline and changed behaviour and by enabling support, care planning and access to services.</p> <p>We aim to improve the recognition and diagnosis of individuals with dementia in general practice. In addition to this diagnostic aim, the effects of case finding and subsequent care on the mental health of individuals with dementia and the mental health of their informal carers are explored.</p> <p>Methods and design</p> <p>Design: cluster randomised controlled trial with process evaluation.</p> <p>Participants: 162 individuals ≥ 65 years, in 15 primary care practices, in whom GPs suspect cognitive impairment, but without a dementia diagnosis.</p> <p>Intervention; case finding and collaborative care: 2 trained practice nurses (PNs) invite all patients with suspected cognitive impairment for a brief functional and cognitive screening. If the cognitive tests are supportive of cognitive impairment, individuals are referred to their GP for further evaluation. If dementia is diagnosed, a comprehensive geriatric assessment takes place to identify other relevant geriatric problems that need to be addressed. Furthermore, the team of GP and PN provide information and support.</p> <p>Control: GPs provide care and diagnosis as usual.</p> <p>Main study parameters: after 12 months both groups are compared on: 1) incident dementia (and MCI) diagnoses and 2) patient and caregiver quality of life (QoL-AD; EQ5D) and mental health (MH5; GHQ 12) and caregiver competence to care (SSCQ). The process evaluation concerns facilitating and impeding factors to the implementation of this intervention. These factors are assessed on the care provider level, the care recipient level and on the organisational level.</p> <p>Discussion</p> <p>This study will provide insight into the diagnostic yield and the clinical effects of case finding and collaborative care for individuals with suspected cognitive impairment, compared to usual care. A process evaluation will give insight into the feasibility of this intervention.</p> <p>The first results are expected in the course of 2013.</p> <p>Trial registration</p> <p>NTR3389</p

Reduced red blood cell deformability in Plasmodium knowlesi malaria

The simian parasite Plasmodium knowlesi can cause severe and fatal human malaria. However, little is known about the pathogenesis of this disease. In falciparum malaria, reduced red blood cell deformability (RBC-D) contributes to microvascular obstruction and impaired organ perfusion. In P knowlesi infection, impaired microcirculatory flow has been observed in Macaca mulatta (rhesus macaques), unnatural hosts who develop severe and fatal disease. However, RBC-D has not been measured in human infection or in the natural host M fascicularis (long-tailed macaques). Using ektacytometry, we measured RBC-D in adults with severe and non-severe knowlesi and falciparum malaria and in healthy controls. In addition, we used micropipette aspiration to determine the relative stiffness of infected RBCs (iRBCs) and uninfected RBCs (uRBCs) in P knowlesi-infected humans and M fascicularis Ektacytometry demonstrated that RBC-D overall was reduced in human knowlesi malaria in proportion to disease severity, and in severe knowlesi malaria, it was comparable to that of severe falciparum malaria. RBC-D correlated inversely with parasitemia and lactate in knowlesi malaria and HRP2 in falciparum malaria, and it correlated with hemoglobin nadir in knowlesi malaria. Micropipette aspiration confirmed that in humans, P knowlesi infection increased stiffness of both iRBCs and uRBCs, with the latter mostly the result of echinocytosis. In contrast, in the natural host M fascicularis, echinocyte formation was not observed, and the RBC-D of uRBCs was unaffected. In unnatural primate hosts of P knowlesi, including humans, reduced deformability of iRBCs and uRBCs may represent a key pathogenic mechanism leading to microvascular accumulation, impaired organ perfusion, and anemia

The acceptability and feasibility of using the Adult Social Care Outcomes Toolkit (ASCOT) to inform practice in care homes

Background: The Adult Social Care Outcomes Toolkit (ASCOT) measures social care related quality of life (SCRQoL) and can be used to measure outcomes and demonstrate impact across different social care settings. This exploratory study built on previous work by collecting new inter-rater reliability data on the mixed-methods version of the toolkit and exploring how it might be used to inform practice in four case study homes. Method: We worked with two care home providers to agree an in-depth study collecting SCRQoL data in four case-study homes. Data was collected about residents’ age, ethnicity, cognitive impairment, ability to perform activities of daily living and SCRQoL in the four homes. Feedback sessions with staff and managers were held in the homes two weeks after baseline and follow-up data collected three months later. Interviews with managers explored their views of the feedback and recorded any changes that had been made because of it. Results: Participant recruitment was challenging, despite working in partnership with the homes. Resident response rates ranged from 23 to 54 % with 58 residents from four care homes taking part in the research. 53 % lacked capacity to consent. Inter-rater reliability for the ASCOT ratings of SCRQoL were good at time one (IRR = 0.72) and excellent at time two (IRR = 0.76). During the study, residents’ ability to perform activities of daily living declined significantly (z = -2.67, p < .01), as did their expected needs in the absence of services (z = -2.41, p < .05). Despite these rapid declines in functionings, residents’ current SCRQoL declined slightly but not significantly (Z = -1.49, p = .14). Staff responded positively to the feedback given and managers reported implementing changes in practice because of it. Conclusion: This exploratory study faced many challenges in the recruitment of residents, many of whom were cognitively impaired. Nevertheless, without a mixed-methods approach many of the residents living in the care homes would have been excluded from the research altogether or had their views represented only by a representative or proxy. The value of the mixed-methods toolkit and its potential for use by providers is discussed

Suppressor of cytokine signaling (SOCS)5 ameliorates influenza infection via inhibition of EGFR signaling

© Kedzierski et al. Influenza virus infections have a significant impact on global human health. Individuals with suppressed immunity, or suffering from chronic inflammatory conditions such as COPD, are particularly susceptible to influenza. Here we show that suppressor of cytokine signaling (SOCS) five has a pivotal role in restricting influenza A virus in the airway epithelium, through the regulation of epidermal growth factor receptor (EGFR). Socs5-deficient mice exhibit heightened disease severity, with increased viral titres and weight loss. Socs5 levels were differentially regulated in response to distinct influenza viruses (H1N1, H3N2, H5N1 and H11N9) and were reduced in primary epithelial cells from COPD patients, again correlating with increased susceptibility to influenza. Importantly, restoration of SOCS5 levels restricted influenza virus infection, suggesting that manipulating SOCS5 expression and/or SOCS5 targets might be a novel therapeutic approach to influenza

Cryptic multiple hypotheses testing in linear models: overestimated effect sizes and the winner's curse

Fitting generalised linear models (GLMs) with more than one predictor has become the standard method of analysis in evolutionary and behavioural research. Often, GLMs are used for exploratory data analysis, where one starts with a complex full model including interaction terms and then simplifies by removing non-significant terms. While this approach can be useful, it is problematic if significant effects are interpreted as if they arose from a single a priori hypothesis test. This is because model selection involves cryptic multiple hypothesis testing, a fact that has only rarely been acknowledged or quantified. We show that the probability of finding at least one ‘significant’ effect is high, even if all null hypotheses are true (e.g. 40% when starting with four predictors and their two-way interactions). This probability is close to theoretical expectations when the sample size (N) is large relative to the number of predictors including interactions (k). In contrast, type I error rates strongly exceed even those expectations when model simplification is applied to models that are over-fitted before simplification (low N/k ratio). The increase in false-positive results arises primarily from an overestimation of effect sizes among significant predictors, leading to upward-biased effect sizes that often cannot be reproduced in follow-up studies (‘the winner's curse’). Despite having their own problems, full model tests and P value adjustments can be used as a guide to how frequently type I errors arise by sampling variation alone. We favour the presentation of full models, since they best reflect the range of predictors investigated and ensure a balanced representation also of non-significant results

Improving Pediatric Readiness in General Emergency Departments: A Prospective Interventional Study

OBJECTIVE: To describe the impact of a national interventional collaborative on pediatric readiness within general emergency departments (EDs). STUDY DESIGN: A prospective, multicenter, interventional study measured pediatric readiness in general EDs before and after participation in a pediatric readiness improvement intervention. Pediatric readiness was assessed using the weighted pediatric readiness score (WPRS) on a 100-point scale. The study protocol extended over 6 months and involved 3 phases: (1) a baseline on-site assessment of pediatric readiness and simulated quality of care; (2) pediatric readiness interventions; and (3) a follow-up on-site assessment of WPRS. The intervention phase included a benchmarking performance report, resources toolkits, and ongoing interactions between general EDs and academic medical centers. RESULTS: Thirty-six general EDs were enrolled, and 34 (94%) completed the study. Four EDs (11%) were located in Canada, and the rest were in the US. The mean improvement in WPRS was 16.3 (P < .001) from a baseline of 62.4 (SEM = 2.2) to 78.7 (SEM = 2.1), with significant improvement in the domains of administration/coordination of care; policies, protocol, and procedures; and quality improvement. Six EDs (17%) were fully adherent to the protocol timeline. CONCLUSIONS: Implementing a collaborative intervention model including simulation and quality improvement initiatives is associated with improvement in WPRS when disseminated to a diverse group of general EDs partnering with their regional pediatric academic medical centers. This work provides evidence that innovative collaboration facilitated by academic medical centers can serve as an effective strategy to improve pediatric readiness and processes of care