Do delays in data availability limit the implementation of near real-time vaccine safety surveillance using the Clinical Practice Research Datalink?

Near real-time vaccine safety surveillance (NRTVSS) using electronic health records has been used to detect timely vaccine safety signals. Trial implementation of NRTVSS using the Clinical Practice Research Datalink (CPRD) has shown that there is limited power to detect safety signals for rare events. Delays in recording outcomes and receiving data influence the power and timeliness to identify a signal. Our work aimed to compare how different sources of delays influence power and expected time to signal to implement NRTVSS using CPRD. We studied seasonal influenza vaccine/Guillain-Barré syndrome and performed power and expected time to signal calculations for the 2013-2014/2014-2015 seasons. We used the Poisson-based maximised sequential probability ratio test, which compares observed-to-expected events. For each study season, we obtained an average Guillain-Barré syndrome/seizures age-sex-adjusted rate from the 5 previous seasons and then used this rate to calculate the expected number of events, assuming a 42-day risk-window. Calculations were performed for detecting rate ratios of 1.5 to 10. We compared power and timeliness considering combinations of the presence/absence of delays in recording outcomes and in receiving data. The R-package Sequential was used. In general, there was ≥80% power to detect increases in risk of ≥4 at the end of the season. Assuming absence of delays slightly improved power (a maximum increase of 4%) but did not noticeably reduce time to detect a signal. Removing delays in data availability is insufficient to significantly improve the performance of a NRTVSS system using CPRD. Expansion of CPRD data is required. KEY POINTS The Clinical Practice Research Datalink (CPRD) can be used to implement near real-time vaccine safety surveillance, but there is limited power to detect signals for rare outcomes. Delays in recording outcomes and in receiving data might limit power and timeliness of a system. We assessed the influence of these sources of delays to inform data providers of the steps required to improve a system using CPRD data. Removing delays in recording outcomes and receiving data is unlikely to significantly improve the performance of a system using CPRD data. Expansion of the data available is needed

Moving from evidence-based medicine to evidence-based health.

While evidence-based medicine (EBM) has advanced medical practice, the health care system has been inconsistent in translating EBM into improvements in health. Disparities in health and health care play out through patients' limited ability to incorporate the advances of EBM into their daily lives. Assisting patients to self-manage their chronic conditions and paying attention to unhealthy community factors could be added to EBM to create a broader paradigm of evidence-based health. A perspective of evidence-based health may encourage physicians to consider their role in upstream efforts to combat socially patterned chronic disease

New web-based applications for mechanistic case diagramming

The goal of mechanistic case diagraming (MCD) is to provide students with more in-depth understanding of cause and effect relationships and basic mechanistic pathways in medicine. This will enable them to better explain how observed clinical findings develop from preceding pathogenic and pathophysiological events. The pedagogic function of MCD is in relating risk factors, disease entities and morphology, signs and symptoms, and test and procedure findings in a specific case scenario with etiologic pathogenic and pathophysiological sequences within a flow diagram. In this paper, we describe the addition of automation and predetermined lists to further develop the original concept of MCD as described by Engelberg in 1992 and Guerrero in 2001. We demonstrate that with these modifications, MCD is effective and efficient in small group case-based teaching for second-year medical students (ratings of ~3.4 on a 4.0 scale). There was also a significant correlation with other measures of competency, with a ‘true’ score correlation of 0.54. A traditional calculation of reliability showed promising results (α =0.47) within a low stakes, ungraded environment. Further, we have demonstrated MCD's potential for use in independent learning and TBL. Future studies are needed to evaluate MCD's potential for use in medium stakes assessment or self-paced independent learning and assessment. MCD may be especially relevant in returning students to the application of basic medical science mechanisms in the clinical years

Trends in the burden of varicella in UK general practice.

Childhood varicella vaccination has not yet been introduced in the UK. To inform decision-making about future vaccine programmes, data on the burden of varicella in general practice over a 10-year period (01/01/2005-31/12/2014) was calculated by age and ethnicity, using anonymised data from >8 million individuals in the Clinical Practice Research Datalink. Varicella consultations peaked at 20 603 in 2007, then decreased annually in all age groups to 11 243 in 2014. Each year, consultation rates were common among infants, were highest among 1-3 year olds (61·2 consultations/1000 person-years in 2007, 39·7/1000 person-years in 2014) and then fell with increasing age to <1·0/1000 person-years at ages ⩾20 years. Varicella acquisition appeared to be delayed in some ethnic groups, with lower consultation rates for children aged <3 years but increased rates for older children and adults aged ⩽40 years among those of black African, Afro-Caribbean, South Asian or other Asian ethnicity. Decreasing general practice consultation rates over time could reflect changes in healthcare utilisation, with patients seeking care in alternative settings such as Accident and Emergency Departments, although current data prevent full assessment of this. Availability of data on varicella diagnoses across all health settings would enable estimation of the total healthcare burden due to varicella and the cost-effectiveness of introducing varicella vaccination

The changing epidemiology of varicella and herpes zoster in Hong Kong before universal varicella vaccination in 2014.

In Hong Kong, universal varicella vaccination started in July 2014. Before this, children could receive varicella vaccine via the private market. We analysed the epidemiology of varicella and zoster before universal vaccination. We estimated varicella vaccination coverage through surveys in preschool children. We estimated the burden of varicella and zoster with varicella notifications from 1999/00 to 2013/14, Accident and Emergency Department (A&E) attendance and inpatient admissions to public hospitals from 2004/05 to 2013/14. We fitted a catalytic model to serological data on antibodies against varicella-zoster virus to estimate the force of infection. We found that varicella vaccination coverage gradually increased to about 50% before programme inception. In children younger than 5 years, the annual rate of varicella notifications, varicella admission and zoster A&E attendance generally declined. The annual notification, A&E attendance and hospitalisation rate of varicella and zoster generally increased for individuals between 10 and 59 years old. Varicella serology indicated an age shift during the study period towards a higher proportion of infections in slightly older individuals, but the change was most notable before vaccine licensure. In conclusion, we observed a shift in the burden of varicella to slightly older age groups with a corresponding increase in incidence but it cannot necessarily be attributed to private market vaccine coverage alone. Increasing varicella vaccination uptake in the private market might affect varicella transmission and epidemiology, but not to the level of interrupting transmission

Adaptive Evolution of the Myo6 Gene in Old World Fruit Bats (Family: Pteropodidae)

PMCID: PMC3631194This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Healthcare use for acute gastrointestinal illness in two Inuit communities: Rigolet and Iqaluit, Canada

Background. The incidence of self-reported acute gastrointestinal illness (AGI) in Rigolet, Nunatsiavut, and Iqaluit, Nunavut, is higher than reported elsewhere in Canada; as such, understanding AGI-related healthcare use is important for healthcare provision, public health practice and surveillance of AGI. Objectives: This study described symptoms, severity and duration of self-reported AGI in the general population and examined the incidence and factors associated with healthcare utilization for AGI in these 2 Inuit communities. Design: Cross-sectional survey data were analysed using multivariable exact logistic regression to examine factors associated with individuals’ self-reported healthcare and over-the-counter (OTC) medication utilization related to AGI symptoms. Results: In Rigolet, few AGI cases used healthcare services [4.8% (95% CI=1.5-14.4%)]; in Iqaluit, some cases used healthcare services [16.9% (95% CI=11.2-24.7%)]. Missing traditional activities due to AGI (OR=3.8; 95% CI=1.18-12.4) and taking OTC medication for AGI symptoms (OR=3.8; 95% CI=1.2-15.1) were associated with increased odds of using healthcare services in Iqaluit. In both communities, AGI severity and secondary symptoms (extreme tiredness, headache, muscle pains, chills) were significantly associated with increased odds of taking OTC medication. Conclusions: While rates of self-reported AGI were higher in Inuit communities compared to non-Inuit communities in Canada, there were lower rates of AGI-related healthcare use in Inuit communities compared to other regions in Canada. As such, the rates of healthcare use for a given disease can differ between Inuit and non-Inuit communities, and caution should be exercised in making comparisons between Inuit and non-Inuit health outcomes based solely on clinic records and healthcare use

Closed-loop separation control over a sharp edge ramp using Genetic Programming

We experimentally perform open and closed-loop control of a separating turbulent boundary layer downstream from a sharp edge ramp. The turbulent boundary layer just above the separation point has a Reynolds number $Re_{\theta}\approx 3\,500$ based on momentum thickness. The goal of the control is to mitigate separation and early re-attachment. The forcing employs a spanwise array of active vortex generators. The flow state is monitored with skin-friction sensors downstream of the actuators. The feedback control law is obtained using model-free genetic programming control (GPC) (Gautier et al. 2015). The resulting flow is assessed using the momentum coefficient, pressure distribution and skin friction over the ramp and stereo PIV. The PIV yields vector field statistics, e.g. shear layer growth, the backflow area and vortex region. GPC is benchmarked against the best periodic forcing. While open-loop control achieves separation reduction by locking-on the shedding mode, GPC gives rise to similar benefits by accelerating the shear layer growth. Moreover, GPC uses less actuation energy.Comment: 24 pages, 24 figures, submitted to Experiments in Fluid