Estimated Covid-19 burden in Spain: ARCH underreported non-stationary time series.

BACKGROUND: The problem of dealing with misreported data is very common in a wide range of contexts for different reasons. The current situation caused by the Covid-19 worldwide pandemic is a clear example, where the data provided by official sources were not always reliable due to data collection issues and to the high proportion of asymptomatic cases. In this work, a flexible framework is proposed, with the objective of quantifying the severity of misreporting in a time series and reconstructing the most likely evolution of the process. METHODS: The performance of Bayesian Synthetic Likelihood to estimate the parameters of a model based on AutoRegressive Conditional Heteroskedastic time series capable of dealing with misreported information and to reconstruct the most likely evolution of the phenomenon is assessed through a comprehensive simulation study and illustrated by reconstructing the weekly Covid-19 incidence in each Spanish Autonomous Community. RESULTS: Only around 51% of the Covid-19 cases in the period 2020/02/23-2022/02/27 were reported in Spain, showing relevant differences in the severity of underreporting across the regions. CONCLUSIONS: The proposed methodology provides public health decision-makers with a valuable tool in order to improve the assessment of a disease evolution under different scenarios.

Left-censored recurrent event analysis in epidemiological studies: a proposal for when the number of previous episodes is unknown.

BACKGROUND: When dealing with recurrent events in observational studies it is common to include subjects who became at risk before follow-up. This phenomenon is known as left censoring, and simply ignoring these prior episodes can lead to biased and inefficient estimates. We aimed to propose a statistical method that performs well in this setting. METHODS: Our proposal was based on the use of models with specific baseline hazards. In this, the number of prior episodes were imputed when unknown and stratified according to whether the subject had been at risk of presenting the event before t = 0. A frailty term was also used. Two formulations were used for this "Specific Hazard Frailty Model Imputed" based on the "counting process" and "gap time." Performance was then examined in different scenarios through a comprehensive simulation study. RESULTS: The proposed method performed well even when the percentage of subjects at risk before follow-up was very high. Biases were often below 10% and coverages were around 95%, being somewhat conservative. The gap time approach performed better with constant baseline hazards, whereas the counting process performed better with non-constant baseline hazards. CONCLUSIONS: The use of common baseline methods is not advised when knowledge of prior episodes experienced by a participant is lacking. The approach in this study performed acceptably in most scenarios in which it was evaluated and should be considered an alternative in this context. It has been made freely available to interested researchers as R package miRecSurv.

Analysis of zero inflated dichotomous variables from a Bayesian perspective: application to occupational health.

BACKGROUND: Zero-inflated models are generally aimed to addressing the problem that arises from having two different sources that generate the zero values observed in a distribution. In practice, this is due to the fact that the population studied actually consists of two subpopulations: one in which the value zero is by default (structural zero) and the other is circumstantial (sample zero). METHODS: This work proposes a new methodology to fit zero inflated Bernoulli data from a Bayesian approach, able to distinguish between two potential sources of zeros (structural and non-structural). RESULTS: The proposed methodology performance has been evaluated through a comprehensive simulation study, and it has been compiled as an R package freely available to the community. Its usage is illustrated by means of a real example from the field of occupational health as the phenomenon of sickness presenteeism, in which it is reasonable to think that some individuals will never be at risk of suffering it because they have not been sick in the period of study (structural zeros). Without separating structural and non-structural zeros one would be studying jointly the general health status and the presenteeism itself, and therefore obtaining potentially biased estimates as the phenomenon is being implicitly underestimated by diluting it into the general health status. CONCLUSIONS: The proposed methodology is able to distinguish two different sources of zeros (structural and non-structural) from dichotomous data with or without covariates in a Bayesian framework, and has been made available to any interested researcher in the form of the bayesZIB R package ( https://cran.r-project.org/package=bayesZIB ).

Quantifying the under-reporting of uncorrelated longitudal data: the genital warts example.

BACKGROUND: Genital warts are a common and highly contagious sexually transmitted disease. They have a large economic burden and affect several aspects of quality of life. Incidence data underestimate the real occurrence of genital warts because this infection is often under-reported, mostly due to their specific characteristics such as the asymptomatic course. METHODS: Genital warts cases for the analysis were obtained from the Catalan public health system database (SIDIAP) for the period 2009-2016. People under 15 and over 94 years old were excluded from the analysis as the incidence of genital warts in this population is negligible. This work introduces a time series model based on a mixture of two distributions, capable of detecting the presence of under-reporting in the data. In order to identify potential differences in the magnitude of the under-reporting issue depending on sex and age, these covariates were included in the model. RESULTS: This work shows that only about 80% in average of genital warts incidence in Catalunya in the period 2009-2016 was registered, although the frequency of under-reporting has been decreasing over the study period. It can also be seen that this issue has a deeper impact on women over 30 years old. CONCLUSIONS: Although this study shows that the quality of the registered data has improved over the considered period of time, the Catalan public health system is underestimating genital warts real burden in almost 10,000 cases, around 23% of the registered cases. The total annual cost is underestimated in about 10 million Euros respect the 54 million Euros annually devoted to genital warts in Catalunya, representing 0.4% of the total budget.

Persistent inequality: evolution of psychosocial exposures at work among the salaried population in Spain between 2005 and 2016.

PURPOSE: To assess the prevalence of poor mental health and of exposure to psychosocial risks among the working population in Spain in 2005, 2010 and 2016; to analyse the associations between workplace psychosocial exposures and mental health problems according to gender and occupation. METHODS: Three representative samples of the Spanish working population were analysed, in 2005 (n = 7,023), 2010 (n = 4,979), and 2016 (n = 1,807). Prevalence ratios between mental health and the five dimensions - job demands, job control, social support, employment insecurity and insecurity over working conditions-were estimated using multilevel mixed-effects Poisson regressions. All the analyses were separated by gender and occupation. RESULTS: In 2016, there were improvements in job control, job demands and social support, and deteriorations in employment insecurity and insecurity over working conditions. The risk of poor mental health among manual workers rose if they were exposed to high demands, low social support and high employment insecurity; among non-manual workers, the risk increased if they were exposed to high demands, low control, low social support and high insecurity over working conditions. There were no differences according to gender. CONCLUSION: The new findings shed light on the evolution of the working conditions and health of the wage-earning population in Spain over the last 11 years. The stratification by gender and occupational group is relevant, since it allows a detailed analysis of the social disparities in the associations between psychosocial risks and mental health. The most vulnerable groups can be identified and preventive measures developed at source.

Cumulated burden of COVID-19 in Spain from a Bayesian perspective.

BACKGROUND: The main goal of this work is to estimate the actual number of cases of COVID-19 in Spain in the period 31 January 2020 to 01 June 2020 by Autonomous Communities. Based on these estimates, this work allows us to accurately re-estimate the lethality of the disease in Spain, taking into account unreported cases. METHODS: A hierarchical Bayesian model recently proposed in the literature has been adapted to model the actual number of COVID-19 cases in Spain. RESULTS: The results of this work show that the real load of COVID-19 in Spain in the period considered is well above the data registered by the public health system. Specifically, the model estimates show that, cumulatively until 1 June 2020, there were 2 425 930 cases of COVID-19 in Spain with characteristics similar to those reported (95% credibility interval: 2 148 261-2 813 864), from which were actually registered only 518 664. CONCLUSIONS: Considering the results obtained from the second wave of the Spanish seroprevalence study, which estimates 2 350 324 cases of COVID-19 produced in Spain, in the period of time considered, it can be seen that the estimates provided by the model are quite good. This work clearly shows the key importance of having good quality data to optimize decision-making in the critical context of dealing with a pandemic.

Online Cost-Effectiveness ANalysis (OCEAN): a user-friendly interface to conduct cost-effectiveness analyses for cervical cancer.

BACKGROUND: Most cost-effectiveness analyses in the context of cervical cancer prevention involve the use of mathematical models to simulate HPV infection, cervical disease and prevention strategies. However, it is common for professionals who would need to perform these analyses to not be familiar with the models. This work introduces the Online Cost-Effectiveness ANalysis tool, featuring an easy-to-use web interface providing health professionals, researchers and decision makers involved in cervical cancer prevention programmes with a useful instrument to conduct complex cost-effectiveness analyses, which are becoming an essential tool as an approach for supporting decision-making that involves important trade-offs. RESULTS: The users can run cost-effectiveness evaluations of cervical cancer prevention strategies without deep knowledge of the underlying mathematical model or any programming language, obtaining the most relevant costs and health outcomes in a user-friendly format. The results provided by the tool are consistent with the existing literature. CONCLUSIONS: Having such a tool will be an asset to the cervical cancer prevention community, providing researchers with an easy-to-use instrument to conduct cost-effectiveness analyses.

Hepatic accumulation of S-adenosylmethionine in hamsters with non-alcoholic fatty liver disease associated with metabolic syndrome under selenium and vitamin E deficiency.

Progression of non-alcoholic fatty liver disease (NAFLD) in the context of metabolic syndrome (MetS) is only partially explored due to the lack of preclinical models. In order to study the alterations in hepatic metabolism that accompany this condition, we developed a model of MetS accompanied by the onset of steatohepatitis (NASH) by challenging golden hamsters with a high-fat diet low in vitamin E and selenium (HFD), since combined deficiency results in hepatic necroinflammation in rodents. Metabolomics and transcriptomics integrated analyses of livers revealed an unexpected accumulation of hepatic S-Adenosylmethionine (SAM) when compared with healthy livers likely due to diminished methylation reactions and repression of GNMT. SAM plays a key role in the maintenance of cellular homeostasis and cell cycle control. In agreement, analysis of over-represented transcription factors revealed a central role of c-myc and c-Jun pathways accompanied by negative correlations between SAM concentration, MYC expression and AMPK phosphorylation. These findings point to a drift of cell cycle control toward senescence in livers of HFD animals, which could explain the onset of NASH in this model. In contrast, hamsters with NAFLD induced by a conventional high-fat diet did not show SAM accumulation, suggesting a key role of selenium and vitamin E in SAM homeostasis. In conclusion, our results suggest that progression of NAFLD in the context of MetS can take place even in a situation of hepatic SAM excess and that selenium and vitamin E status might be considered in current therapies against NASH based on SAM supplementation.

Untangling serially dependent underreported count data for gender-based violence.

Underreporting in gender-based violence data is a worldwide problem leading to the underestimation of the magnitude of this social and public health concern. This problem deteriorates the data quality, providing poor and biased results that lead society to misunderstand the actual scope of this domestic violence issue. The present work proposes time series models for underreported counts based on a latent integer autoregressive of order 1 time series with Poisson distributed innovations and a latent underreporting binary state, that is, a first-order Markov chain. Relevant theoretical properties of the models are derived, and the moment-based and maximum-based methods are presented for parameter estimation. The new time series models are applied to the quarterly complaints of domestic violence against women recorded in some judicial districts of Galicia (Spain) between 2007 and 2017. The models allow quantifying the degree of underreporting. A comprehensive discussion is presented, studying how the frequency and intensity of underreporting in this public health concern are related to some interesting socioeconomic and health indicators of the provinces of Galicia (Spain).

Sickness presenteeism: Are we sure about what we are studying? A research based on a literature review and an empirical illustration.

BACKGROUND: There has been an increasing interest in studying sickness presenteeism (SP). An ever-increasing amount of scientific literature is published using this term, yet there appears to be considerable heterogeneity in how it is assessed, which could result in substantial differences in the definition and interpretation of the phenomenon really being studied. We aim to discuss what really is being studied, depending on how the phenomenon is operationalized, measured, and analyzed. METHODS: A study based on a literature review and an empirical illustration using data of the third Spanish Psychosocial Risks Survey (2016). RESULTS: Differences are observed based on the population in which SP is measured, the cut-off points used to define a worker as presenteeist, the reasons for an SP episode and even an analysis of the phenomenon treated as a count or as a dichotomous. CONCLUSIONS: Without being completely exclusive, it seems that restricting the population of analysis to only those workers who consider that they should not have gone to work due to their health, and/or establishing low cut-off points to define someone as presenteeist, would more clearly delimit the study of SP to the exercise of a right to sick leave. In contrast, working with the entire population or using high cut-off points appears to relate the study of SP more with health status and less with the exercise of rights. On the other hand, taking the reasons for SP into account would probably help to improve interpretation of the phenomenon.

Cost-Effectiveness of the EdAl (Educació en Alimentació) Program: A Primary School-Based Study to Prevent Childhood Obesity.

BACKGROUND: The cost-effectiveness of childhood obesity prevention interventions is critical for their sustained implementation. This study evaluated the cost-effectiveness of the Educació en Alimentació (EdAl) program, a school-based intervention for reducing obesity. METHODS: Total EdAl program implementation costs and per-child costs were estimated. Cost-effectiveness, defined using the incremental cost-effectiveness ratio (ICER), was estimated as the difference between the intervention and control group costs divided by the obesity-related outcome effects for boys (avoided cases of obesity, obesity prevalence, body mass index [BMI], and BMI z-score units) for each group. As a significant difference (4.39%) in the reduction of obesity prevalence between the intervention and control groups was observed for boys in the EdAl program, the data were calculated only for boys. RESULTS: The intervention cost was 24,246.53 € for 1,550 children (15.64 €/child/3 years) or 5.21 €/child/year. The ICERs/boy were 968.66 € to avoid one case of obesity, 3.6 € to reduce the obesity prevalence by 1%, 44.68 € to decrease BMI by one unit, and 65.16 € to reduce the BMI z-score by one unit. CONCLUSIONS: The cost of reducing the obesity prevalence in boys by 4.39% was 5.21 €/child/year, half the cost proposed by the Spanish Health Ministry, indicating that the EdAl program is cost-effective.

Gay Circuit Parties in Barcelona and Their Impact on Gonorrhea Incidence.

This study explored the role of circuit parties on the incidence of gonorrhea among men who have sex with men (MSM) in Barcelona (Spain). Specifically, it aimed to detect cyclic peaks in the number of reported diagnoses of gonorrhea after gay circuit parties. We analyzed monthly cases of gonorrhea reported from January 2007 through December 2016 after the main annual gay circuit parties in Barcelona. We used the integer autoregressive model for time series with discrete values. The performance of the model was tested in heterosexual men and women, in whom the circuit parties could be expected to have no impact. A sensitivity analysis was conducted, changing post-event diagnosis windows to 1 week later/1 week before. In the study period, a total of 4182 of gonorrhea cases were detected, of which 74.8% (n = 2181) occurred in men who identified themselves as MSM. The average annual increase in gonorrhea cases reported among MSM was 32.57%. In an independent analysis of each gay circuit party, cases increased significantly in two of them. The results were also similar for same-sex practices among men only. On controlling for the increasing trend over the study period and the seasonal effect, an average of 1.16 gonorrhea cases in MSM (95% CI: 0.68, 1.64) were attributable to the celebration of one of the gay circuit parties considered. During the expected outbreak, an average of 13 gonorrhea cases were detected and between 5 and 13% were attributable to one of the circuit parties. In view of these findings, participants should consider seeking advice from their healthcare provider and practice safer sex using condoms to prevent sexually transmitted infections. Local public health services should be reinforced to ensure care for participants during and after gay circuit parties. More research is needed to design and implement preventive programs.

Follow-up of a healthy lifestyle education program (the EdAl study): four years after cessation of randomized controlled trial intervention.

BACKGROUND: An important challenge of school-based childhood obesity (OB) intervention programs is understanding the maintenance of the effects after cessation of the intervention to overcome the limitations of follow-up studies. The aim of this study is to verify the sustainability of the benefits achieved at a 4-year follow-up of the post-Educació en Alimentació (EDAl) program intervention cessation by assessing the OB-related outcomes and lifestyles of 13- to 15-year-old adolescents. METHODS: This paper describes a 4-year follow-up study after the cessation of a school-based randomized controlled intervention in adolescents (n = 349, intervention; n = 154, control) with baseline and 4-year follow-up data from high schools in Reus (intervention group), Salou, Cambrils and Vila-seca (control group). The outcomes are body mass index (BMI), BMI z-score, and OB prevalence according to the World Health Organization and International Obesity Task Force criteria and lifestyle data (obtained from questionnaires). RESULTS: Compared with the control girls, the intervention girls showed reduced BMI z-scores (-0.33 units, p < 0.01) from baseline (2007) to the 4-year follow-up post-intervention (2014). Compared with the control boys, the intervention boys showed reduced OB prevalence (-7.7%; p = 0.02). Compared with the control boys, more boys in the intervention group (19% increase; p = 0.059) showed ≥4 h/week after-school physical activity (PA). A decrease in the consumption of dairy products, fruits and fish was observed in both groups. CONCLUSIONS: At the 4-year post-intervention follow-up of the EdAl program, compared with the control groups, girls had lower BMI z-scores and boys had lower OB prevalence from the intervention. The encouragement in after-school PA was long-lasting and maintained after the cessation of the intervention, whereas healthy food habits must be further reinforced in adolescents. TRIAL REGISTRATION: ISRCTN29247645 .

Moving towards an organized cervical cancer screening: costs and impact.

Background: HPV screening has been shown to be more cost-effective than cytology screening under most scenarios. Furthermore, it should be offered only in organized programmes with good quality assurance mechanisms. This study analyses the comparative cost of the current policy of opportunistic cytology screening vs. a hypothetical organized programme based on primary HPV screening. Methods: Total cervical cancer expenditure was defined as the sum of three cost elements: (i) direct (medical and non-medical) costs, obtained from a calibrated Markov model of the natural history of HPV and cervical cancer; (ii) programmatic costs, estimated based on other organized screening programmes; and (iii) indirect costs, extrapolated from previously published data. Results: Organized HPV screening at 5-year intervals costs consistently less across all coverage levels than opportunistic cytology screening at 3-year intervals. The current annual direct medical cost to the public health system of the opportunistic cytology at 40% coverage is estimated at €33.2 per woman screened aged 25-64. Under an organized programme of primary HPV screening at 70% coverage, the cost is estimated to be €18.4 per woman screened aged 25-64. Conclusion: Our study concludes that the economic resources currently devoted to providing opportunistic cytology screening to 40% of the target population at 3-year intervals could be more effectively used to screen 70% of the target population at 5-year intervals by switching to an organized programme based on primary HPV screening. This finding is of relevance to other European countries or regions with similar screening policies and health infrastructures.

Under-reported data analysis with INAR-hidden Markov chains.

In this work, we deal with correlated under-reported data through INAR(1)-hidden Markov chain models. These models are very flexible and can be identified through its autocorrelation function, which has a very simple form. A naïve method of parameter estimation is proposed, jointly with the maximum likelihood method based on a revised version of the forward algorithm. The most-probable unobserved time series is reconstructed by means of the Viterbi algorithm. Several examples of application in the field of public health are discussed illustrating the utility of the models. Copyright © 2016 John Wiley & Sons, Ltd.

Rationale of the Spanish FRAX model in decision-making for predicting osteoporotic fractures: an update of FRIDEX cohort of Spanish women.

BACKGROUND: The FRAX® tool estimates the risk of a fragility fracture among the population and many countries have been evaluating its performance among their populations since its creation in 2007. The purpose of this study is to update the first FRIDEX cohort analysis comparing FRAX with the bone mineral density (BMD) model, and its predictive abilities. METHODS: The discriminatory ability of the FRAX was assessed using the 'area under curve' of the receiver operating characteristic (AUC-ROC). Predictive ability was assessed by comparing estimated risk fractures with incidence fractures after a 10-year follow up period. RESULTS: One thousand three hundred eight women ≥ 40 and ≤ 90 years followed up during a 10-year period. The AUC for major osteoporotic fractures using FRAX without DXA was 0.686 (95 % CI 0.630-0.742) and using FN T-score of DXA 0.714 (95 % CI 0.661-0.767). Using only the traditional parameters of DXA (FN T-score), the AUC was 0.706 (95 % CI 0.652-0.760). The AUC for hip osteoporotic fracture was 0.883 (95 % CI 0.827-0.938), 0.857 (95 % CI 0.773-0.941), and 0.814 (95 % CI 0.712-0.916) respectively. For major osteoporotic fractures, the overall predictive value using the ratio Observed fractures/Expected fractures calculated with FRAX without T-score of DXA was 2.29 and for hip fractures 2.28 and with the inclusion of the T-score 2.01 and 1.83 respectively. However, for hip fracture in women < 65 years was 1.53 and 1.24 respectively. CONCLUSIONS: The FRAX tool has been found to show a good discriminatory capacity for detecting women at high risk of fragility fracture, and is better for hip fracture than major fracture. The test of sensibility shows that it is, at least, not inferior than when using BMD model alone. The predictive capacity of FRAX tool needs some adjustment. This capacity is better for hip fracture prediction and better for women < 65 years. Further studies in Catalonia and other regions of Spain are needed to fine tune the FRAX tool's predictive capability.

InterCardioRisk: a novel online tool for estimating doses of ionising radiation to occupationally-exposed medical staff and their associated health risks.

Those working in interventional cardiology and related medical procedures are potentially subject to considerable exposure to x-rays. Two types of tissue of particular concern that may receive considerable doses during such procedures are the lens of the eye and the brain. Ocular radiation exposure results in lens changes that, with time, may progress to partial or total lens opacification (cataracts). In the early stages, such opacities do not result in visual disability; the severity of such changes tends to increase progressively with dose and time until vision is impaired and cataract surgery is required. Scattered radiation doses to the eye lens of an interventional cardiologist in typical working conditions can exceed 34 µGy min-1 in high-dose fluoroscopy modes and 3 µGy per image during image acquisition (instantaneous rate values) when radiation protection tools are not used. A causal relation between exposure to ionising radiation and increased risk of brain and central nervous system tumours has been shown in a number of studies. Although absorbed doses to the brain in interventional cardiology procedures are lower than those to the eye lens by a factor between 3.40 and 8.08 according to our simulations, doses to both tissues are among the highest occupational radiation doses documented for medical staff whose work involves exposures to x-rays. We present InterCardioRisk, a tool featuring an easy-to-use web interface that provides a general estimation of both cumulated absorbed doses experienced by medical staff exposed in the interventional cardiology setting and their estimated associated health risks. The tool is available at http://intercardiorisk.creal.cat.

radir package: an R implementation for cytogenetic biodosimetry dose estimation.

The Bayesian framework has been shown to be very useful in cytogenetic dose estimation. This approach allows description of the probability of an event in terms of previous knowledge, e.g. its expectation and/or its uncertainty. A new R package entitled radir (radiation inverse regression) has been implemented with the aim of reproducing a recent Bayesian-type dose estimation methodology. radir adopts the method of dose estimation under the Poisson assumption of the responses (the chromosomal aberrations counts) for the required dose-response curve (typically linear or quadratic). The individual commands are described in detail and relevant examples of the use of the methods and the corresponding radir software tools are given. The suitability of this methodology is highlighted and its application encouraged by providing a user-friendly command-type software interface within the R statistical software (version 3.1.1 or higher), which includes a complete manual.