External validation, update and development of prediction models for pre-eclampsia using an Individual Participant Data (IPD) meta-analysis: the International Prediction of Pregnancy Complication Network (IPPIC pre-eclampsia) protocol.

Background: Pre-eclampsia, a condition with raised blood pressure and proteinuria is associated with an increased risk of maternal and offspring mortality and morbidity. Early identification of mothers at risk is needed to target management. Methods/design: We aim to systematically review the existing literature to identify prediction models for pre-eclampsia. We have established the International Prediction of Pregnancy Complication Network (IPPIC), made up of 72 researchers from 21 countries who have carried out relevant primary studies or have access to existing registry databases, and collectively possess data from more than two million patients. We will use the individual participant data (IPD) from these studies to externally validate these existing prediction models and summarise model performance across studies using random-effects meta-analysis for any, late (after 34 weeks) and early (before 34 weeks) onset pre-eclampsia. If none of the models perform well, we will recalibrate (update), or develop and validate new prediction models using the IPD. We will assess the differential accuracy of the models in various settings and subgroups according to the risk status. We will also validate or develop prediction models based on clinical characteristics only; clinical and biochemical markers; clinical and ultrasound parameters; and clinical, biochemical and ultrasound tests. Discussion: Numerous systematic reviews with aggregate data meta-analysis have evaluated various risk factors separately or in combination for predicting pre-eclampsia, but these are affected by many limitations. Our large-scale collaborative IPD approach encourages consensus towards well developed, and validated prognostic models, rather than a number of competing non-validated ones. The large sample size from our IPD will also allow development and validation of multivariable prediction model for the relatively rare outcome of early onset pre-eclampsia. Trial registration: The project was registered on Prospero on the 27 November 2015 with ID: CRD42015029349

East London’s Homeless: a retrospective review of an eye clinic for homeless people

Background There is very little published work on the visual needs of homeless people. This paper is the first study to investigate the visual needs of homeless people in the UK. Although similar work has been done in other countries, this study is unique because the United Kingdom is the only country with a National Health Service which provides free healthcare at the point of access. This study analysed the refractive status of the sample used, determined the demographics of homeless people seeking eye care and established if there is a need for community eye health with access to free spectacle correction in East London. Methods This retrospective case study analysed the clinical records of 1,141 homeless people using the Vision Care for Homeless People services at one of their clinics in East London. All eye examinations were carried out by qualified optometrists and, where appropriate, spectacles were dispensed to patients. Data captured included age, gender, ethnicity and refractive error. Results were analysed using two-sample t-tests with Excel and Minitab. Results Demographics of age, gender and ethnicity are described. Spherical equivalents (SE) were calculated from prescription data available for 841 clinic users. Emmetropia was defined as SE–0.50DS to +1DS, myopia as SE  +1DS. The majority of clinic users were male (79.2 %, n = 923). Approximately 80 % (n = 583) of clinic users were white, 10 % (n = 72) were ‘black’, 4 % (n = 29) ‘Asian’ and the remaining 5.6 % (n = 40) were of ‘mixed ethnicity’ and ‘other’ groups. The mean age of females attending the clinic was significantly lower than that of males (45.9 years, SD = 13.8 vs’ 48.4 years, SD = 11.8) when analysed using a two-sample t-test (t (317) = 2.44, p = 0.02). One third of service users were aged between 50–59 years. Myopia and hyperopia prevalence rates were 37.0 % and 21.0 % respectively. A total of 34.8 % of homeless people were found to have uncorrected refractive error, and required spectacle correction. Conclusions This study has identified a high proportion of uncorrected refractive error in this sample and therefore a need for regular eye examinations and provision of refractive correction for homeless people

Moving interdisciplinary science forward: integrating participatory modelling with mathematical modelling of zoonotic disease in Africa

This review outlines the benefits of using multiple approaches to improve model design and facilitate multidisciplinary research into infectious diseases, as well as showing and proposing practical examples of effective integration. It looks particularly at the benefits of using participatory research in conjunction with traditional modelling methods to potentially improve disease research, control and management. Integrated approaches can lead to more realistic mathematical models which in turn can assist with making policy decisions that reduce disease and benefit local people. The emergence, risk, spread and control of diseases are affected by many complex bio-physical, environmental and socio-economic factors. These include climate and environmental change, land-use variation, changes in population and people’s behaviour. The evidence base for this scoping review comes from the work of a consortium, with the aim of integrating modelling approaches traditionally used in epidemiological, ecological and development research. A total of five examples of the impacts of participatory research on the choice of model structure are presented. Example 1 focused on using participatory research as a tool to structure a model. Example 2 looks at identifying the most relevant parameters of the system. Example 3 concentrates on identifying the most relevant regime of the system (e.g., temporal stability or otherwise), Example 4 examines the feedbacks from mathematical models to guide participatory research and Example 5 goes beyond the so-far described two-way interplay between participatory and mathematical approaches to look at the integration of multiple methods and frameworks. This scoping review describes examples of best practice in the use of participatory methods, illustrating their potential to overcome disciplinary hurdles and promote multidisciplinary collaboration, with the aim of making models and their predictions more useful for decision-making and policy formulation

Teacher led school-based surveillance can allow accurate tracking of emerging infectious diseases - evidence from serial cross-sectional surveys of febrile respiratory illness during the H1N1 2009 influenza pandemic in Singapore

10.1186/1471-2334-12-336BMC Infectious Diseases12-BIDM

Minimum sample size for external validation of a clinical prediction model with a binary outcome

In prediction model research, external validation is needed to examine an existing model's performance using data independent to that for model development. Current external validation studies often suffer from small sample sizes and consequently imprecise predictive performance estimates. To address this, we propose how to determine the minimum sample size needed for a new external validation study of a prediction model for a binary outcome. Our calculations aim to precisely estimate calibration (Observed/Expected and calibration slope), discrimination (C-statistic), and clinical utility (net benefit). For each measure, we propose closed-form and iterative solutions for calculating the minimum sample size required. These require specifying: (i) target SEs (confidence interval widths) for each estimate of interest, (ii) the anticipated outcome event proportion in the validation population, (iii) the prediction model's anticipated (mis)calibration and variance of linear predictor values in the validation population, and (iv) potential risk thresholds for clinical decision-making. The calculations can also be used to inform whether the sample size of an existing (already collected) dataset is adequate for external validation. We illustrate our proposal for external validation of a prediction model for mechanical heart valve failure with an expected outcome event proportion of 0.018. Calculations suggest at least 9835 participants (177 events) are required to precisely estimate the calibration and discrimination measures, with this number driven by the calibration slope criterion, which we anticipate will often be the case. Also, 6443 participants (116 events) are required to precisely estimate net benefit at a risk threshold of 8%. Software code is provided.</p

Region-Specific Responses of Adductor Longus Muscle to Gravitational Load-Dependent Activity in Wistar Hannover Rats

Response of adductor longus (AL) muscle to gravitational unloading and reloading was studied. Male Wistar Hannover rats (5-wk old) were hindlimb-unloaded for 16 days with or without 16-day ambulation recovery. The electromyogram (EMG) activity in AL decreased after acute unloading, but that in the rostral region was even elevated during continuous unloading. The EMG levels in the caudal region gradually increased up to 6th day, but decreased again. Approximately 97% of fibers in the caudal region were pure type I at the beginning of experiment. Mean percentage of type I fibers in the rostral region was 61% and that of type I+II and II fiber was 14 and 25%, respectively. The percent type I fibers decreased and de novo appearance of type I+II was noted after unloading. But the fiber phenotype in caudal, not rostral and middle, region was normalized after 16-day ambulation. Pronounced atrophy after unloading and re-growth following ambulation was noted in type I fibers of the caudal region. Sarcomere length in the caudal region was passively shortened during unloading, but that in the rostral region was unchanged or even stretched slightly. Growth-associated increase of myonuclear number seen in the caudal region of control rats was inhibited by unloading. Number of mitotic active satellite cells decreased after unloading only in the caudal region. It was indicated that the responses of fiber properties in AL to unloading and reloading were closely related to the region-specific neural and mechanical activities, being the caudal region more responsive

Economic Analysis of Pandemic Influenza Vaccination Strategies in Singapore

BACKGROUND: All influenza pandemic plans advocate pandemic vaccination. However, few studies have evaluated the cost-effectiveness of different vaccination strategies. This paper compares the economic outcomes of vaccination compared with treatment with antiviral agents alone, in Singapore. METHODOLOGY: We analyzed the economic outcomes of pandemic vaccination (immediate vaccination and vaccine stockpiling) compared with treatment-only in Singapore using a decision-based model to perform cost-benefit and cost-effectiveness analyses. We also explored the annual insurance premium (willingness to pay) depending on the perceived risk of the next pandemic occurring. PRINCIPAL FINDINGS: The treatment-only strategy resulted in 690 deaths, 13,950 hospitalization days, and economic cost of USD$497 million. For immediate vaccination, at vaccine effectiveness of >55%, vaccination was cost-beneficial over treatment-only. Vaccine stockpiling is not cost-effective in most scenarios even with 100% vaccine effectiveness. The annual insurance premium was highest with immediate vaccination, and was lower with increased duration to the next pandemic. The premium was also higher with higher vaccine effectiveness, attack rates, and case-fatality rates. Stockpiling with case-fatality rates of 0.4-0.6% would be cost-beneficial if vaccine effectiveness was >80%; while at case-fatality of >5% stockpiling would be cost-beneficial even if vaccine effectiveness was 20%. High-risk sub-groups warrant higher premiums than low-risk sub-groups. CONCLUSIONS: The actual pandemic vaccine effectiveness and lead time is unknown. Vaccine strategy should be based on perception of severity. Immediate vaccination is most cost-effective, but requires vaccines to be available when required. Vaccine stockpiling as insurance against worst-case scenarios is also cost-effective. Research and development is therefore critical to develop and stockpile cheap, readily available effective vaccines

Population Genetics of Schistosoma japonicum within the Philippines Suggest High Levels of Transmission between Humans and Dogs

Schistosomiasis is a disease caused by parasitic worms known as schistosomes, which infect about 200 million people worldwide. In the Philippines, as in China, the species of schistosome (Schistosoma japonicum) which causes the disease infects not only humans, but also many other species of mammals. In China, bovines are thought to be particularly important for harboring and transmitting S. japonicum, whereas in the Philippines infections in bovines are relatively rare. However, dogs, rats and pigs are often infected with S. japonicum in the Philippines, although the extent to which infections in these animals may give rise to human infections is unclear. To help answer this question, we characterized the genetic variation of the parasite in Samar province of the Philippines, and found that S. japonicum samples from humans, dogs, rats and pigs were genetically very similar, with no significant genetic difference between samples from humans and dogs. This suggests that in the Philippines this parasite is frequently transmitted between different mammalian species, particularly between dogs and humans. Reducing levels of infections in dogs may therefore help to reduce infections in humans. The results also suggest high levels of transmission between geographic areas, thus regional co-ordination of treatment programs is recommended