Calibration of individual-based models to epidemiological data : a systematic review

Individual-based models (IBMs) informing public health policy should be calibrated to data and provide estimates of uncertainty. Two main components of model-calibration methods are the parameter-search strategy and the goodness-of-fit (GOF) measure; many options exist for each of these. This review provides an overview of calibration methods used in IBMs modelling infectious disease spread. We identified articles on PubMed employing simulation-based methods to calibrate IBMs informing public health policy in HIV, tuberculosis, and malaria epidemiology published between 1 January 2013 and 31 December 2018. Articles were included if models stored individual-specific information, and calibration involved comparing model output to population-level targets. We extracted information on parameter-search strategies, GOF measures, and model validation. The PubMed search identified 653 candidate articles, of which 84 met the review criteria. Of the included articles, 40 (48%) combined a quantitative GOF measure with an algorithmic parameter-search strategy–either an optimisation algorithm (14/40) or a sampling algorithm (26/40). These 40 articles varied widely in their choices of parameter-search strategies and GOF measures. For the remaining 44 (52%) articles, the parameter-search strategy could either not be identified (32/44) or was described as an informal, non-reproducible method (12/44). Of these 44 articles, the majority (25/44) were unclear about the GOF measure used; of the rest, only five quantitatively evaluated GOF. Only a minority of the included articles, 14 (17%) provided a rationale for their choice of model-calibration method. Model validation was reported in 31 (37%) articles. Reporting on calibration methods is far from optimal in epidemiological modelling studies of HIV, malaria and TB transmission dynamics. The adoption of better documented, algorithmic calibration methods could improve both reproducibility and the quality of inference in model-based epidemiology. There is a need for research comparing the performance of calibration methods to inform decisions about the parameter-search strategies and GOF measures

Calibration of individual-based models to epidemiological data: A systematic review.

Individual-based models (IBMs) informing public health policy should be calibrated to data and provide estimates of uncertainty. Two main components of model-calibration methods are the parameter-search strategy and the goodness-of-fit (GOF) measure; many options exist for each of these. This review provides an overview of calibration methods used in IBMs modelling infectious disease spread. We identified articles on PubMed employing simulation-based methods to calibrate IBMs informing public health policy in HIV, tuberculosis, and malaria epidemiology published between 1 January 2013 and 31 December 2018. Articles were included if models stored individual-specific information, and calibration involved comparing model output to population-level targets. We extracted information on parameter-search strategies, GOF measures, and model validation. The PubMed search identified 653 candidate articles, of which 84 met the review criteria. Of the included articles, 40 (48%) combined a quantitative GOF measure with an algorithmic parameter-search strategy-either an optimisation algorithm (14/40) or a sampling algorithm (26/40). These 40 articles varied widely in their choices of parameter-search strategies and GOF measures. For the remaining 44 (52%) articles, the parameter-search strategy could either not be identified (32/44) or was described as an informal, non-reproducible method (12/44). Of these 44 articles, the majority (25/44) were unclear about the GOF measure used; of the rest, only five quantitatively evaluated GOF. Only a minority of the included articles, 14 (17%) provided a rationale for their choice of model-calibration method. Model validation was reported in 31 (37%) articles. Reporting on calibration methods is far from optimal in epidemiological modelling studies of HIV, malaria and TB transmission dynamics. The adoption of better documented, algorithmic calibration methods could improve both reproducibility and the quality of inference in model-based epidemiology. There is a need for research comparing the performance of calibration methods to inform decisions about the parameter-search strategies and GOF measures

The Impact of Rubella Vaccine Introduction on Rubella Infection and Congenital Rubella Syndrome: A Systematic Review of Mathematical Modelling Studies

Introduction: Rubella vaccines have been used to prevent rubella and congenital rubella syndrome (CRS) in several World Health Organization (WHO) regions. Mathematical modelling studies have simulated introduction of rubella-containing vaccines (RCVs), and their results have been used to inform rubella introduction strategies in several countries. This systematic review aimed to synthesize the evidence from mathematical models regarding the impact of introducing RCVs. Methods: We registered the review in the international prospective register of systematic reviews (PROSPERO) with registration number CRD42020192638. Systematic review methods for classical epidemiological studies and reporting guidelines were followed as far as possible. A comprehensive search strategy was used to identify published and unpublished studies with no language restrictions. We included deterministic and stochastic models that simulated RCV introduction into the public sector vaccination schedule, with a time horizon of at least five years. Models focused only on estimating epidemiological parameters were excluded. Outcomes of interest were time to rubella and CRS elimination, trends in incidence of rubella and CRS, number of vaccinated individuals per CRS case averted, and cost-effectiveness of vaccine introduction strategies. The methodological quality of included studies was assessed using a modified risk of bias tool, and a qualitative narrative was provided, given that data synthesis was not feasible. Results: Seven studies were included from a total of 1393 records retrieved. The methodological quality was scored high for six studies and very high for one study. Quantitative data synthesis was not possible, because only one study reported point estimates and uncertainty intervals for the outcomes. All seven included studies presented trends in rubella incidence, six studies reported trends in CRS incidence, two studies reported the number vaccinated individuals per CRS case averted, and two studies reported an economic evaluation measure. Time to CRS elimination and time to rubella elimination were not reported by any of the included studies. Reported trends in CRS incidence showed elimination within five years of RCV introduction with scenarios involving mass vaccination of older children in addition to routine infant vaccination. CRS incidence was higher with RCV introduction than without RCV when public vaccine coverage was lower than 50% or only private sector vaccination was implemented. Although vaccination of children at a given age achieved slower declines in CRS incidence compared to mass campaigns targeting a wide age range, this approach resulted in the lowest number of vaccinated individuals per CRS case averted. Conclusion and recommendations: We were unable to conduct data synthesis of included studies due to discrepancies in outcome reporting. However, qualitative assessment of results of individual studies suggests that vaccination of infants should be combined with vaccination of older children to achieve rapid elimination of CRS. Better outcomes are obtained when rubella vaccination is introduced into public vaccination schedules at coverage figures of 80%, as recommended by WHO, or higher. Guidelines for reporting of outcomes in mathematical modelling studies and the conduct of systematic reviews of mathematical modelling studies are required

The Impact of Rubella Vaccine Introduction on Rubella Infection and Congenital Rubella Syndrome: A Systematic Review of Mathematical Modelling Studies

Introduction: Rubella vaccines have been used to prevent rubella and congenital rubella syndrome (CRS) in several World Health Organization (WHO) regions. Mathematical modelling studies have simulated introduction of rubella-containing vaccines (RCVs), and their results have been used to inform rubella introduction strategies in several countries. This systematic review aimed to synthesize the evidence from mathematical models regarding the impact of introducing RCVs. Methods: We registered the review in the international prospective register of systematic reviews (PROSPERO) with registration number CRD42020192638. Systematic review methods for classical epidemiological studies and reporting guidelines were followed as far as possible. A comprehensive search strategy was used to identify published and unpublished studies with no language restrictions. We included deterministic and stochastic models that simulated RCV introduction into the public sector vaccination schedule, with a time horizon of at least five years. Models focused only on estimating epidemiological parameters were excluded. Outcomes of interest were time to rubella and CRS elimination, trends in incidence of rubella and CRS, number of vaccinated individuals per CRS case averted, and cost-effectiveness of vaccine introduction strategies. The methodological quality of included studies was assessed using a modified risk of bias tool, and a qualitative narrative was provided, given that data synthesis was not feasible. Results: Seven studies were included from a total of 1393 records retrieved. The methodological quality was scored high for six studies and very high for one study. Quantitative data synthesis was not possible, because only one study reported point estimates and uncertainty intervals for the outcomes. All seven included studies presented trends in rubella incidence, six studies reported trends in CRS incidence, two studies reported the number vaccinated individuals per CRS case averted, and two studies reported an economic evaluation measure. Time to CRS elimination and time to rubella elimination were not reported by any of the included studies. Reported trends in CRS incidence showed elimination within five years of RCV introduction with scenarios involving mass vaccination of older children in addition to routine infant vaccination. CRS incidence was higher with RCV introduction than without RCV when public vaccine coverage was lower than 50% or only private sector vaccination was implemented. Although vaccination of children at a given age achieved slower declines in CRS incidence compared to mass campaigns targeting a wide age range, this approach resulted in the lowest number of vaccinated individuals per CRS case averted. Conclusion and recommendations: We were unable to conduct data synthesis of included studies due to discrepancies in outcome reporting. However, qualitative assessment of results of individual studies suggests that vaccination of infants should be combined with vaccination of older children to achieve rapid elimination of CRS. Better outcomes are obtained when rubella vaccination is introduced into public vaccination schedules at coverage figures of 80%, as recommended by WHO, or higher. Guidelines for reporting of outcomes in mathematical modelling studies and the conduct of systematic reviews of mathematical modelling studies are required

Deep learning approaches to landmark detection in tsetse wing images.

Morphometric analysis of wings has been suggested for identifying and controlling isolated populations of tsetse (Glossina spp), vectors of human and animal trypanosomiasis in Africa. Single-wing images were captured from an extensive data set of field-collected tsetse wings of species Glossina pallidipes and G. m. morsitans. Morphometric analysis required locating 11 anatomical landmarks on each wing. The manual location of landmarks is time-consuming, prone to error, and infeasible for large data sets. We developed a two-tier method using deep learning architectures to classify images and make accurate landmark predictions. The first tier used a classification convolutional neural network to remove most wings that were missing landmarks. The second tier provided landmark coordinates for the remaining wings. We compared direct coordinate regression using a convolutional neural network and segmentation using a fully convolutional network for the second tier. For the resulting landmark predictions, we evaluate shape bias using Procrustes analysis. We pay particular attention to consistent labelling to improve model performance. For an image size of 1024 × 1280, data augmentation reduced the mean pixel distance error from 8.3 (95% confidence interval [4.4,10.3]) to 5.34 (95% confidence interval [3.0,7.0]) for the regression model. For the segmentation model, data augmentation did not alter the mean pixel distance error of 3.43 (95% confidence interval [1.9,4.4]). Segmentation had a higher computational complexity and some large outliers. Both models showed minimal shape bias. We deployed the regression model on the complete unannotated data consisting of 14,354 pairs of wing images since this model had a lower computational cost and more stable predictions than the segmentation model. The resulting landmark data set was provided for future morphometric analysis. The methods we have developed could provide a starting point to studying the wings of other insect species. All the code used in this study has been written in Python and open sourced

Roux-Y Gastric Bypass and Sleeve Gastrectomy directly change gut microbiota composition independent of surgery type

Bariatric surgery in morbid obesity, either through sleeve gastrectomy (SG) or Roux-Y gastric bypass (RYGB), leads to sustainable weight loss, improvement of metabolic disorders and changes in intestinal microbiota. Yet, the relationship between changes in gut microbiota, weight loss and surgical procedure remains incompletely understood. We determined temporal changes in microbiota composition in 45 obese patients undergoing crash diet followed by SG (n = 22) or RYGB (n = 23). Intestinal microbiota composition was determined before intervention (baseline, S1), 2 weeks after crash diet (S2), and 1 week (S3), 3 months (S4) and 6 months (S5) after surgery. Relative to S1, the microbial diversity index declined at S2 and S3 (p < 0.05), and gradually returned to baseline levels at S5. Rikenellaceae relative abundance increased and Ruminococcaceae and Streptococcaceae abundance decreased at S2 (p < 0.05). At S3, Bifidobacteriaceae abundance decreased, whereas those of Streptococcaceae and Enterobacteriaceae increased (p < 0.05). Increased weight loss between S3-S5 was not associated with major changes in microbiota composition. No significant differences appeared between both surgical procedures. In conclusion, undergoing a crash diet and bariatric surgery were associated with an immediate but temporary decline in microbial diversity, with immediate and permanent changes in microbiota composition, independent of surgery type

Benzodiazepine-associated delirium in critically ill adults

PURPOSE: The association between benzodiazepine use and delirium risk in the ICU remains unclear. Prior investigations have failed to account for disease severity prior to delirium onset, competing events that may preclude delirium detection, other important delirium risk factors, and an adequate number of patients receiving continuous midazolam. The aim of this study was to address these limitations and evaluate the association between benzodiazepine exposure and ICU delirium occurrence. METHODS: In a cohort of consecutive critically ill adults, daily mental status was classified as either awake without delirium, delirium, or coma. In a first-order Markov model, multinomial logistic regression analysis was used, which considered five possible outcomes the next day (i.e., awake without delirium, delirium, coma, ICU discharge, and death) and 16 delirium-related covariables, to quantify the association between benzodiazepine use and delirium occurrence the following day. RESULTS: Among 1112 patients, 9867 daily transitions occurred. Benzodiazepine administration in an awake patient without delirium was associated with increased risk of delirium the next day [OR 1.04 (per 5 mg of midazolam equivalent administered) 95 % CI 1.02-1.05). When the method of benzodiazepine administration was incorporated in the model, the odds of transitioning to delirium was higher with benzodiazepines given continuously (OR 1.04, 95 % CI 1.03-1.06) compared to benzodiazepines given intermittently (OR 0.97, 95 % CI 0.88-1.05). CONCLUSIONS: After addressing potential methodological limitations of prior studies, we confirm that benzodiazepine administration increases the risk for delirium in critically ill adults but this association seems to be limited to continuous infusion use only