Early Epidemiological Assessment of the Virulence of Emerging Infectious Diseases: A Case Study of an Influenza Pandemic

Background: The case fatality ratio (CFR), the ratio of deaths from an infectious disease to the number of cases, provides an assessment of virulence. Calculation of the ratio of the cumulative number of deaths to cases during the course of an epidemic tends to result in a biased CFR. The present study develops a simple method to obtain an unbiased estimate of confirmed CFR (cCFR), using only the confirmed cases as the denominator, at an early stage of epidemic, even when there have been only a few deaths. Methodology/Principal Findings: Our method adjusts the biased cCFR by a factor of underestimation which is informed by the time from symptom onset to death. We first examine the approach by analyzing an outbreak of severe acute respiratory syndrome in Hong Kong (2003) with known unbiased cCFR estimate, and then investigate published epidemiological datasets of novel swine-origin influenza A (H1N1) virus infection in the USA and Canada (2009). Because observation of a few deaths alone does not permit estimating the distribution of the time from onset to death, the uncertainty is addressed by means of sensitivity analysis. The maximum likelihood estimate of the unbiased cCFR for influenza may lie in the range of 0.16-4.48% within the assumed parameter space for a factor of underestimation. The estimates for influenza suggest that the virulence is comparable to the early estimate in Mexico. Even when there have been no deaths, our model permits estimating a conservative upper bound of the cCFR. Conclusions: Although one has to keep in mind that the cCFR for an entire population is vulnerable to its variations among sub-populations and underdiagnosis, our method is useful for assessing virulence at the early stage of an epidemic and for informing policy makers and the public. © 2009 Nishiura et al.published_or_final_versio

On epidemic modeling in real time: An application to the 2009 Novel A (H1N1) influenza outbreak in Canada

<p>Abstract</p> <p>Background</p> <p>Management of emerging infectious diseases such as the 2009 influenza pandemic A (H1N1) poses great challenges for real-time mathematical modeling of disease transmission due to limited information on disease natural history and epidemiology, stochastic variation in the course of epidemics, and changing case definitions and surveillance practices.</p> <p>Findings</p> <p>The Richards model and its variants are used to fit the cumulative epidemic curve for laboratory-confirmed pandemic H1N1 (pH1N1) infections in Canada, made available by the Public Health Agency of Canada (PHAC). The model is used to obtain estimates for turning points in the initial outbreak, the basic reproductive number (R₀), and for expected final outbreak size in the absence of interventions. Confirmed case data were used to construct a best-fit 2-phase model with three turning points. R₀was estimated to be 1.30 (95% CI 1.12-1.47) for the first phase (April 1 to May 4) and 1.35 (95% CI 1.16-1.54) for the second phase (May 4 to June 19). Hospitalization data were also used to fit a 1-phase model with R₀= 1.35 (1.20-1.49) and a single turning point of June 11.</p> <p>Conclusions</p> <p>Application of the Richards model to Canadian pH1N1 data shows that detection of turning points is affected by the quality of data available at the time of data usage. Using a Richards model, robust estimates of R₀were obtained approximately one month after the initial outbreak in the case of 2009 A (H1N1) in Canada.</p

Optimizing imaging in suspected appendicitis (OPTIMAP-study): A multicenter diagnostic accuracy study of MRI in patients with suspected acute appendicitis. Study Protocol

<p>Abstract</p> <p>Background</p> <p>In patients with clinically suspected appendicitis, imaging is needed to substantiate the clinical diagnosis. Imaging accuracy of ultrasonography (US) is suboptimal, while the most accurate technique (CT) is associated with cancer related deaths through exposure to ionizing radiation. MRI is a potential replacement, without associated ionizing radiation and no need for contrast medium administration. If MRI is proven to be sufficiently accurate, it could be introduced in the diagnostic pathway of patients with suspected appendicitis, increasing diagnostic accuracy and improving clinical outcomes, without the risk of radiation induced cancer or iodinated contrast medium-related drawbacks. The multicenter OPTIMAP study was designed to estimate the diagnostic accuracy of MRI in patients with suspected acute appendicitis in the general population.</p> <p>Methods/Design</p> <p>Eligible for this study are consecutive patients presenting with clinically suspected appendicitis at the emergency department in six centers. All patients will undergo imaging according to the Dutch guideline for acute appendicitis: initial ultrasonography in all and subsequent CT whenever US does not confirm acute appendicitis. Then MRI is performed in all patients, but the results are not used for patient management. A final diagnosis assigned by an expert panel, based on all available information including 3-months follow-up, except MRI findings, is used as the reference standard in estimating accuracy. We will calculate the sensitivity, specificity, predictive values and inter-observer agreement of MRI, and aim to include 230 patients. Patient acceptance and total imaging costs will also be evaluated.</p> <p>Discussion</p> <p>If MRI is found to be sufficiently accurate, it could replace CT in some or all patients. This will limit or obviate the ionizing radiation exposure associated risk of cancer induction and contrast medium induced nephropathy with CT, preventing the burden and the direct and indirect costs associated with treatment. Based on the high intrinsic contrast resolution of MRI, one might envision higher accuracy rates for MRI than for CT. If so, MRI could further decrease the number of unnecessary appendectomies and the number of missed appendicitis cases.</p> <p>Trial registration</p> <p><b>NTR2148</b></p

Global health education: a pilot in trans-disciplinary, digital instruction

Background: The development of new global health academic programs provides unique opportunities to create innovative educational approaches within and across universities. Recent evidence suggests that digital media technologies may provide feasible and cost-effective alternatives to traditional classroom instruction; yet, many emerging global health academic programs lag behind in the utilization of modern technologies. Objective: We created an inter-departmental University of Southern California (USC) collaboration to develop and implement a course focused on digital media and global health. Design: Course curriculum was based on core tenants of modern education: multi-disciplinary, technologically advanced, learner-centered, and professional application of knowledge. Student and university evaluations were reviewed to qualitatively assess course satisfaction and educational outcomes. Results: &#x2018;New Media for Global Health&#x2019; ran for 18 weeks in the Spring 2012 semester with N=41 students (56.1% global health and 43.9% digital studies students). The course resulted in a number of high quality global health-related digital media products available at http://iml420.wordpress.com/. Challenges confronted at USC included administrative challenges related to co-teaching and frustration from students conditioned to a rigid system of teacher-led learning within a specific discipline. Quantitative and qualitative course evaluations reflected positive feedback for the course instructors and mixed reviews for the organization of the course. Conclusion: The development of innovative educational programs in global health requires on-going experimentation and information sharing across departments and universities. Digital media technologies may have implications for future efforts to improve global health education

Using patient management as a surrogate for patient health outcomes in diagnostic test evaluation

<p>Abstract</p> <p>Background</p> <p>Before a new test is introduced in clinical practice, evidence is needed to demonstrate that its use will lead to improvements in patient health outcomes. Studies reporting test accuracy may not be sufficient, and clinical trials of tests that measure patient health outcomes are rarely feasible. Therefore, the consequences of testing on patient management are often investigated as an intermediate step in the pathway. There is a lack of guidance on the interpretation of this evidence, and patient management studies often neglect a discussion of the limitations of measuring patient management as a surrogate for health outcomes.</p> <p>Methods</p> <p>We discuss the rationale for measuring patient management, describe the common study designs and provide guidance about how this evidence should be reported.</p> <p>Results</p> <p>Interpretation of patient management studies relies on the condition that patient management is a valid surrogate for downstream patient benefits. This condition presupposes two critical assumptions: the test improves diagnostic accuracy; and the measured changes in patient management improve patient health outcomes. The validity of this evidence depends on the certainty around these critical assumptions and the ability of the study design to minimise bias. Three common designs are test RCTs that measure patient management as a primary endpoint, diagnostic before-after studies that compare planned patient management before and after testing, and accuracy studies that are extended to report on the actual treatment or further tests received following a positive and negative test result.</p> <p>Conclusions</p> <p>Patient management can be measured as a surrogate outcome for test evaluation if its limitations are recognised. The potential consequences of a positive and negative test result on patient management should be pre-specified and the potential patient benefits of these management changes clearly stated. Randomised comparisons will provide higher quality evidence about differences in patient management using the new test than observational studies. Regardless of the study design used, the critical assumption that patient management is a valid surrogate for downstream patient benefits or harms must be discussed in these studies.</p

A Situational Alignment Framework for PACS

This paper reports the outcomes of a study on an integrated situational alignment framework for picture archiving and communication systems (PACS) labeled as PISA. Following the design research cycle, complementary validation methods and pilot cases were used to assess the proposed framework and its operationalized survey. In this paper, the authors outline (a) the process of the framework’ development, (b) the validation process with its underlying iterative steps, (c) the outcomes of pilot cases, and (d) improvement opportunities to refine and further validate the PISA framework. Results of this study support empirical application of the framework to hospital enterprises in order to gain insights into their PACS maturity and alignment. We argue that the framework can be applied as a valuable tool for assessments, monitoring and benchmarking purposes and strategic PACS planning

Designing programmes of physical activity through sport: Learning from a widening participation intervention, 'City of Football'

Background: Implementation profoundly influences how well new audiences engage with sport-based physical activity programmes. Recognising that effective implementation relies on concurrently generating supportive contexts, systems and networks for the least engaged ‘target’ groups; this paper aims to address what underpins children’s (non) engagement with football-based physical activity. Methods: An observational research design, using a non-probability sample of N=594 primary and secondary schoolchildren assessed outcomes of a three-year ‘City of Football’ (CoF) programme. Pupils self-reported football participation, personal friendship networks and exposure to six concurrent sources of influence (SoI). A 2-step hierarchical cluster analysis and univariate analyses assessed between-cluster differences. Results: Girls played football least regularly (χ2 [4] = 86.722, p = 0.000). Overall, participation was significantly associated with personal networks engaged in football. Boys’ personal networks were more stable and structurally effective. Football participation was also positively and linearly association with SoI scores. Girls and pupils with no personal networks around football reported the lowest SoI scores. Three clusters emerged, dominated by social network influences. The Traditional Market (n=157, 27.7%) comprised 81.7% boys; they regularly played football, had the most effective network structure and scored highly across all six domains of SoI. The Sporadically Engaging Socialisers (n=190, 33.5%) comprised 52.9% girls who rarely played football, reported low SoI scores and an inferior network structure. In the Disconnected cluster (n=220, 38.8%), 59.3% were non-footballing girls who reported the lowest motivation and ability SoI scores; and no personal networks engaged in football. Conclusions: This study reveals new insights about the primacy of social network effects for engaging children in football-based physical activity programmes. With little or no attention to these social-oriented issues, such interventions will struggle to attract ‘target’ children, but will readily engage already well-connected, experienced football-playing boys. The challenge for drawing non-footballing children into football-based interventions lies with engaging children – especially girls - whose social networks are not football-focused, while they also find football neither personally motivating nor easy to do