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.

Acute respiratory infection rates in primary care anticipate ICU bed occupancy during COVID-19 waves.

BACKGROUND: Bed occupancy in the ICU is a major constraint to in-patient care during COVID-19 pandemic. Diagnoses of acute respiratory infection (ARI) by general practitioners have not previously been investigated as an early warning indicator of ICU occupancy. METHODS: A population-based central health care system registry in the autonomous community of Catalonia, Spain, was used to analyze all diagnoses of ARI related to COVID-19 established by general practitioners and the number of occupied ICU beds in all hospitals from Catalonia between March 26, 2020 and January 20, 2021. The primary outcome was the cross-correlation between the series of COVID-19-related ARI cases and ICU bed occupancy taking into account the effect of bank holidays and weekends. Recalculations were later implemented until March 27, 2022. FINDINGS: Weekly average incidence of ARI diagnoses increased from 252.7 per 100,000 in August, 2020 to 496.5 in October, 2020 (294.2 in November, 2020), while the average number of ICU beds occupied by COVID-19-infected patients rose from 1.7 per 100,000 to 3.5 in the same period (6.9 in November, 2020). The incidence of ARI detected in the primary care setting anticipated hospital occupancy of ICUs, with a maximum correlation of 17.3 days in advance (95% confidence interval 15.9 to 18.9). INTERPRETATION: COVID-19-related ARI cases may be a novel warning sign of ICU occupancy with a delay of over two weeks, a latency window period for establishing restrictions on social contacts and mobility to mitigate the propagation of COVID-19. Monitoring ARI cases would enable immediate adoption of measures to prevent ICU saturation in future waves.

[Relationship between psychosocial risks exposure and health: a cohort study using the COPSOQ-Istas21]. / Relación entre exposición a riesgos psicosociales y salud: un estudio de cohorte mediante el COPSOQ-Istas21.

OBJECTIVE: To estimate the prospective relationships between exposure to psychosocial risks dimensions included in the COPSOQ-Istas21 and the deterioration of general and mental health and sleep problems among workers residing in Spain. METHOD: Cohort whose baseline corresponds to the 2016 Psychosocial Risks Survey with a new measurement after one year. RESULTS: Social capital and interpersonal relations and leadership dimensions, as well as work̶life conflict, were related to all health variables. Dimensions of work organization and job contents did it especially with the mental health, the quantitative demands with the general health and the emotional ones with the mental health. The dimensions related to job insecurity did not show relationships with health. CONCLUSIONS: The results obtained reinforce the role of the COPSOQ-Istas21 as a useful instrument for the evaluation and prevention of psychosocial risks at work.

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 ).

New statistical model for misreported data with application to current public health challenges.

The main goal of this work is to present a new model able to deal with potentially misreported continuous time series. The proposed model is able to handle the autocorrelation structure in continuous time series data, which might be partially or totally underreported or overreported. Its performance is illustrated through a comprehensive simulation study considering several autocorrelation structures and three real data applications on human papillomavirus incidence in Girona (Catalonia, Spain) and Covid-19 incidence in two regions with very different circumstances: the early days of the epidemic in the Chinese region of Heilongjiang and the most current data from Catalonia.

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.

SARS-CoV-2 transmission in students of public schools of Catalonia (Spain) after a month of reopening.

INTRODUCTION: SARS-CoV-2 transmission within schools and its contribution to community transmission are still a matter of debate. METHODS: A retrospective cohort study in all public schools in Catalonia was conducted using publicly available data assessing the association between the number of reported SARS-CoV-2 cases among students and staff in weeks 1-2 (Sept 14-27th, 2020) of the academic year with school SARS-CoV-2 incidence among students in weeks 4-5. A multilevel Poisson regression model adjusted for the community incidence in the corresponding basic health area (BHA) and the type of school (primary or secondary), with random effects at the sanitary region and BHA levels, was performed. RESULTS: A total of 2184 public schools opened on September 14th with 778,715 students. Multivariate analysis showed a significant association between the total number of SARS-CoV-2 cases in a centre in weeks 1-2 and the SARS-CoV-2 school incidence among students in weeks 4-5 (Risk Ratio (RR) 1.074, 95% CI 1.044-1.105, p-value <0.001). The adjusted BHA incidence in the first two weeks was associated with school incidence in weeks 4-5 (RR 1.002, 95% CI 1.002-1.003, p-value <0.001). Secondary schools showed an increased incidence in weeks 4 and 5 (RR primary vs secondary 1.709 95% CI 1.599-1.897, p-value <0.001). CONCLUSIONS: Safety measures adopted by schools were not enough to stop related-to-school transmission in students and could be improved. The safest way to keep schools open is to reduce community transmission down to a minimum.

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.

Analysis of the impact of lockdown on the reproduction number of the SARS-Cov-2 in Spain.

OBJECTIVE: The late 2019 COVID-19 outbreak has put the health systems of many countries to the limit of their capacity. The most affected European countries are, so far, Italy and Spain. In both countries (and others), the authorities decreed a lockdown, with local specificities. The objective of this work is to evaluate the impact of the measures undertaken in Spain to deal with the pandemic. METHOD: We estimated the number of cases and the impact of lockdown on the reproducibility number based on the hospitalization reports up to April 15th 2020. RESULTS: The estimated number of cases shows a sharp increase until the lockdown, followed by a slowing down and then a decrease after full quarantine was implemented. Differences in the basic reproduction ratio are also significant, dropping from 5.89 (95% confidence interval [95%CI]: 5.46-7.09) before the lockdown to 0.48 (95%CI: 0.15-1.17) afterwards. CONCLUSIONS: Handling a pandemic like COVID-19 is complex and requires quick decision making. The large differences found in the speed of propagation of the disease show us that being able to implement interventions at the earliest stage is crucial to minimise the impact of a potential infectious threat. Our work also stresses the importance of reliable up to date epidemiological data in order to accurately assess the impact of Public Health policies on viral outbreak.

Transcranial Direct Current Stimulation and Visual Illusion Effect According to Sensory Phenotypes in Patients With Spinal Cord Injury and Neuropathic Pain.

Treatment of neuropathic pain (NP) in patients with spinal cord injury (SCI) remains a major challenge. The aim of the present study is to investigate if the effect of transcranial direct current stimulation combined with visual illusion, following a previously published protocol, has differential effects on pain-related sensory symptoms according to sensory phenotypes profiles. One hundred and thirty SCI patients with NP participated in this open-label trial. Sixty-five patients were given a daily 20-minutes combined treatment of transcranial direct current stimulation and visual illusion for 2 weeks. Sixty-five patients served as a control group. Clinical assessment was performed before and 2 weeks later, by using Neuropathic Pain Symptom Inventory (NPSI), Brief Pain Inventory, and Patient Health Questionnaire-9. There was significant improvement in the combined treatment group according to NPSI, Brief Pain Inventory, and Patient Health Questionnaire-9, but no changes in the control group. Following a cluster analysis of NPSI items at baseline assessment, 5 subgroups of patients with different pain-related characteristics were identified among the treated group, although differences between clusters were not significant. There was also improvement in mood, sleep quality, and enjoyment of life in the treated group. Despite a reduction of NP with the combined treatment, the analysis of sensory phenotype pain profiles does not provide a predictive value regarding the analgesic results of this combined neuromodulatory treatment. PERSPECTIVE: In this article we confirm the analgesic effect of a combined neuromodulatory therapy, transcranial direct current stimulation associated with visual illusion in patients with NP after an SCI. We have identified 5 clusters of NP with distinct sensory phenotypes, but there was not any specific sensory phenotype cluster that significantly responded to the combined therapy better than the other.

Decision-making in HIV clinical trials: a study with patients enrolled in antiretroviral trials.

OBJECTIVE: To explore the decisional process of people living with human immunodeficiency virus (HIV) currently enrolled in antiretroviral clinical trials. METHOD: Cross-sectional retrospective study. Outcome variables were reasons to participate, perceived decisional role (Control Preference Scale), the Decisional Conflict Scale and the Decisional Regret Scale. Descriptive statistics were calculated, and associations among these variables and with sociodemographic and clinical characteristics were analyzed with non-parametric techniques. RESULTS: Main reasons to participate were gratitude towards Fundación Huesped (47%), the doctor's recommendation (32%), and perceived difficulty to access treatment in a public hospital (28%). Most patients thought that they made their decision alone (54.8%) or collaboratively with the physician (43%). Decisional conflict was low, with only some conflict in the support subscale (median=16.67). Education was the only significant correlate of the total decisional conflict score (higher in less educated patients; p=0.018), whereas education, recent diagnosis, living alone, lower age, being man and doctor's recommendation to go to Fundación Huésped related to higher conflict in different subscales. Nobody regretted to participate. CONCLUSIONS: The decision making regarding participation in HIV trials, from the perspective of participants, was made respecting their autonomy and with very low decisional conflict. Currently, patients show no signs of regret. However, even in this favorable context, results highlight the necessity of enhancing the decision support in more vulnerable patients (e.g., less educated, recently diagnosed or with less social support), thus warranting equity in the quality of the decision making process.

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.

Estimating the real burden of disease under a pandemic situation: The SARS-CoV2 case.

The present paper introduces a new model used to study and analyse the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) epidemic-reported-data from Spain. This is a Hidden Markov Model whose hidden layer is a regeneration process with Poisson immigration, Po-INAR(1), together with a mechanism that allows the estimation of the under-reporting in non-stationary count time series. A novelty of the model is that the expectation of the unobserved process's innovations is a time-dependent function defined in such a way that information about the spread of an epidemic, as modelled through a Susceptible-Infectious-Removed dynamical system, is incorporated into the model. In addition, the parameter controlling the intensity of the under-reporting is also made to vary with time to adjust to possible seasonality or trend in the data. Maximum likelihood methods are used to estimate the parameters of the model.

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.

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.

Cervical cancer prevention in Morocco: a model-based cost-effectiveness analysis.

Objective: Cervical cancer is a huge public health issue in Morocco which represents the second most frequent and fatal cancer among women. Countries that have not yet introduced the HPV vaccine could benefit greatly, but before implementation it is necessary to perform country-specific economic assessments that include current screening practices. Methods: A Markov model was developed to simulate the natural history of HPV and cervical cancer so as to calculate the long-term health benefits and costs of HPV vaccination and current screening by visual inspection with acetic acid (VIA). Starting from a previous transition probability matrix used for a model from Spain, the present model was calibrated to cervical cancer incidence from Morocco. Cost survey data was used to estimate the cost of screening and clinical procedures from the public healthcare perspective. Incremental cost-effectiveness ratios were calculated as 2018US$ per additional year of life saved (YLS) and both costs and health outcomes were discounted at 3%. Results: The expected reduction in lifetime risk of cervical cancer for current screening would be 14% at a cost of US$551/YLS compared with no intervention, assuming VIA every 3 years in women aged 30-49 at 10% coverage. HPV vaccination of pre-adolescent girls at 70% coverage would reduce the lifetime risk of cervical cancer by 62% at a cost of US$1,150/YLS, compared with no intervention. When implementing HPV vaccination in combination with current screening, vaccination would be dominated, and the combined strategy would provide a 69% reduction at a cost of US$2,843/YLS, compared with screening alone. Current screening would be dominated by vaccination when screening coverage is higher than 15%, whereas the combined strategy rapidly exceeds US$4,000/YLS. Conclusions: HPV vaccination could be highly effective and cost-effective in Morocco. Current screening would be good value for money compared with no intervention, but scaling-up screening coverage would make it inefficient compared with vaccination.