Epidemiology and Trends of Sepsis in Young Adults Aged 20-44 Years: A Nationwide Population-Based Study

BACKGROUND: While sepsis may have especially marked impacts in young adults, there is limited population-based information on its epidemiology and trends. METHODS: Population-based longitudinal study on sepsis in adults aged 20-44 years using the 2006-2015 Spanish national hospital discharge database. Cases are identified by an ICD-9-CM coding strategy. Primary endpoints are incidence and in-hospital mortality. Trends are assessed for annual percentage change (AAPC) in rates using Joinpoint regression models. RESULTS: 28,351 cases are identified, representing 3.06‱ of all-cause hospitalisations and a crude incidence of 16.4 cases/100,000 population aged 20-44. The mean age is 36 years, 58% of cases are men, and around 60% have associated comorbidities. Seen in one third of cases, the source of infection is respiratory. Single organ dysfunction is recorded in 45% of cases. In-hospital mortality is 24% and associated with age, comorbidity and extent of organ dysfunction. Incidence rates increase over time in women (AAPC: 3.8% (95% CI: 2.1, 5.5)), whereas case-fatality decline with an overall AAPC of -5.9% (95% CI -6.6, -5.2). Our results indicate that sepsis is common in young adults and associated with high in-hospital mortality, though it shows a decreasing trend. The substantial increase in incidence rates in women needs further research.This research was supported by the Carlos III Health Institute (grant number PI14/00081).S

The impact of dementia on hospital outcomes for elderly patients with sepsis: A population-based study

BACKGROUND: Prior studies have suggested that dementia adversely influences clinical outcomes and increases resource utilization in patients hospitalized for acute diseases. However, there is limited population-data information on the impact of dementia among elderly hospitalized patients with sepsis. METHODS: From the 2009-2011 National Hospital Discharge Database we identified hospitalizations in adults aged ≥65 years. Using ICD9-CM codes, we selected sepsis cases, divided them into two cohorts (with and without dementia) and compared both groups with respect to organ dysfunction, in-hospital mortality and the use of hospital resources. We estimated the impact of dementia on these primary endpoints through multivariate regression models. RESULTS: Of the 148 293 episodes of sepsis identified, 16 829 (11.3%) had diagnoses of dementia. Compared to their dementia-free counterparts, they were more predominantly female and older, had a lower burden of comorbidities and were more frequently admitted due to a principal diagnosis of sepsis. The dementia cohort showed a lower risk of organ dysfunction (adjusted OR: 0.84, 95% Confidence Interval [CI]: 0.81, 0.87) but higher in-hospital mortality (adjusted OR: 1.32, 95% [CI]: 1.27, 1.37). The impact of dementia on mortality was higher in the cases of younger age, without comorbidities and without organ dysfunction. The cases with dementia also had a lower length of stay (-3.87 days, 95% [CI]: -4.21, -3.54) and lower mean hospital costs (-3040€, 95% [CI]: -3279, -2800). CONCLUSIONS: This nationwide population-based study shows that dementia is present in a substantial proportion of adults ≥65s hospitalized with sepsis, and while the condition does seem to come with a lower risk of organ dysfunction, it exerts a negative influence on in-hospital mortality and acts as an independent mortality predictor. Furthermore, it is significantly associated with shorter length of stay and lower hospital costs.This work was supported by a grant from Instituto de Salud Carlos III (grant number: PI09/0597)S

Effect of dementia on the incidence, short-term outcomes, and resource utilization of invasive mechanical ventilation in the elderly: a nationwide population-based study

BACKGROUND: Though the prevalence of dementia among hospitalized patients is increasing, there is limited population data in Europe about the use of life-support measures such as invasive mechanical ventilation in these patients. Our objective is to assess whether dementia influences the incidence, outcomes, and hospital resource use in elderly patients undergoing mechanical ventilation. METHODS: Using ICD-9-CM codes, all hospitalizations involving invasive mechanical ventilation in adults aged ≥ 65 years were identified in the Spanish national hospital discharge database covering the period 2000-2013. The cases identified were stratified into two cohorts (patients with or without dementia) in which main outcome measures were compared. The impact of dementia on in-hospital mortality and hospital resource use were assessed through multivariable models. Trends were assessed through joinpoint regression analysis and results expressed as average annual percentage change. RESULTS: Of the 259,623 cases identified, 5770 (2.2%) had been assigned codes for dementia. Cases with dementia were older, had a lower Charlson comorbidity score, and less frequently received prolonged mechanical ventilation or were assigned a surgical DRG. Circulatory disease was the most common main diagnosis in both cohorts. No significant impact of dementia was observed on in-hospital mortality (adjusted OR 1.04, [95% CI] 0.98, 1.09). In the cohort with dementia, the incidence of mechanical ventilation underwent an average annual increase over time of 5.39% (95% CI 4.0, 6.7) while this rate was 1.62% (95% CI 0.9, 2.4) in cases without dementia. However, unlike this cohort, mortality in cases with dementia did not significantly decline over time. Geometric mean hospital cost and stay were lower among cases with than without dementia (- 14% [95% CI - 12%, - 15%] and - 12% [95% CI, - 9%, - 14%], respectively), and these differences increased over time. CONCLUSION: This nationwide population-based study suggests no impact of dementia on in-hospital mortality in elderly patients undergoing invasive mechanical ventilation. However, dementia is significantly associated with shorter stay and hospital costs. Our data also identifies a recent marked increase in the use of this life-support measure in elderly patients with dementia and that this increase is much greater than that observed in elderly individuals without dementia.This research was supported by the Instituto de Salud Carlos III (grant number PI14/00081). The funding source has no role in the design and conduct of the study, the analysis and interpretation of data, or in the writing of the manuscript.S

Suicidal and accidental drug poisoning mortality among older adults and working-age individuals in Spain between 2000 and 2018

Background: Although medication poisoning in older adults is considered an increasingly important, but preventable cause of death, it has received relatively little attention. We explored recent trends and correlates of suicidal and accidental fatal drug poisonings among older and working-age individuals using nationwide data from Spain. Methods: We identified all 15,353 fatal drug poisonings involving decedents aged ≥15 years in Spain between 2000 and 2018 and divided them by age into older adults (≥65 years) and working-age (15-64 years) individuals. For each age group, we analyzed time trends in suicidal and accidental fatal drug poisoning rates (overall and by ICD-10 drug categories) using joinpoint regressions. To understand the specific drugs classified as "Non-psychotropic/non-specified", we used 2018 data including substance-specific ICD-10 supplementary codes. We explored relevant sociodemographic correlates of suicidal and accidental fatal poisoning rates using multivariable negative binomial regressions. Results: Between 2000 and 2018, suicidal fatal poisonings increased faster among older (from 0.19 to 0.63 per 100,000 - average annual change: 7.7%) than working-age individuals (from 0.40 to 0.72 per 100,000 - average annual change: 3.8%). Accidental fatal poisonings increased among older adults (from 0.25 to 2.67 per 100,000 - average annual change: 16.2%) but decreased among working-age counterparts (from 2.38 to 1.42 per 100,000 - average annual change: - 1.9%). Anticoagulants and cardiac-stimulants glycosides accounted for 70% of the 223 accidental fatal poisonings due to non-psychotropic/non-specified drugs registered among older adults in 2018. Roles of gender and urban dwelling in suicidal and accidental poisonings were heterogeneous across age groups. Conclusion: Increases in suicidal drug poisonings were faster among older than working-age individuals. Accidental fatal poisonings increased only among older adults. Our findings that (i) sociodemographic correlates were heterogeneous across age groups and (ii) anticoagulant and cardiac-stimulant glycosides were particularly salient drivers of accidental poisonings among older adults have implications for prevention.This study was supported by the Instituto de Salud Carlos III (grant number PI19CIII/00037). The funders had neither role in study design, data collection, analysis, decision to publish, nor preparation of the manuscript.S

Role of Foreign-Born Status on Suicide Mortality in Spain Between 2000 and 2019: An Age-Period-Cohort Analysis

Objectives: To examine recent age-period-cohort effects on suicide among foreign-born individuals, a particularly vulnerable sociodemographic group in Spain. Methods: Using 2000-2019 mortality data from Spain's National Institute of Statistics, we estimated age-period-cohort effects on suicide mortality, stratified by foreign-born status (native- vs. foreign-born) and, among the foreign-born, by Spanish citizenship status, a proxy for greater socioeconomic stability. Results: Annual suicide mortality rates were lower among foreign- than native-born individuals. There was heterogeneity in age-period-cohort effects between study groups. After 2010, suicide mortality increased markedly among the foreign-born-especially for female cohorts born around 1950, and slightly among native-born women-especially among female cohorts born after the 1960s. Among native-born men, suicide increased linearly with age and remained stable over time. Increases in suicide among the foreign-born were driven by increases among individuals without Spanish citizenship-especially among cohorts born after 1975. Conclusion: After 2010, suicide in Spain increased markedly among foreign-born individuals and slightly among native-born women, suggesting an association between the downstream effects of the 2008 economic recession and increases in suicide mortality among socioeconomically vulnerable populations.This work was supported by the National Institute of Mental Health (Grant number R01-MH121410) and the Instituto de Salud Carlos III (Grant number FIS PI19CIII/00037). The funders had no role in the conception, design, or execution of the study.S

Clustering of unhealthy lifestyle behaviors, self-rated health and disability

The main objective was to identify sociodemographic characteristics of the population at risk for a greater clustering of unhealthy behaviors and to evaluate the association of such clustering with self-rated health status and disability. Data come from the 2017 Spanish National Health Survey with a sample of 21,947 participants of 15 years of age or older. Based on tobacco consumption, risk drinking, unbalanced diet, sedentarism, and body mass index <18.5/≥25 we created two indicators of risk factor clustering: 1) Number of unhealthy behaviors (0-5); and 2) Unhealthy lifestyle index (score: 0-15). Self-rated health was dichotomized into "optimal" and "suboptimal," and disability was classified as "no disability," "mild," and "severe" based on the Global Activity Limitation Index (GALI). We estimated prevalence ratios (PR) adjusted for covariates using generalized linear models using the clustering count variable, and dose-response curves using the unhealthy lifestyle index. Most participants (77.4%) reported 2 or more risk factors, with men, middle-age individuals, and those with low socioeconomic status being more likely to do so. Compared to those with 0-1 risk factors, the PR for suboptimal health was 1.26 (95% CI:1.18-1.34) for those reporting 2-3 factors, reaching 1.43 (95% CI:1.31-1.55) for 4-5 factors. The PR for severe activity limitation was 1.66 (95% CI:1.35-2.03) for those reporting 2-3 factors and 2.06 (95% CI:1.59-2.67) for 4-5 factors. The prevalence of both health indicators increased in a non-linear fashion as the unhealthy lifestyle index score increased, increasing rapidly up to 5 points, slowing down between 5 and 10 points, and plateauing afterwards.This work was supported by the Institute of Health Carlos III, Ministry of Science and Innovation [grant number PI19CIII/00021.N

Meta-analysis of percutaneous radiofrequency ablation versus ethanol injection in hepatocellular carcinoma

BACKGROUND: Percutaneous radiofrequency ablation (RFA) has gained popularity in the treatment of hepatocellular carcinoma (HCC). However, its role versus other conventional minimally invasive therapies is still a matter of debate. The purpose of this work is to analyse the efficacy and safety of RFA versus that of ethanol injection (PEI), the percutaneous standard approach to treat nonsurgical HCC. METHODS: Systematic review and meta-analysis of randomised or quasi-randomised controlled trials published up to August 2008 in PubMed, ISI Web of Science and The Cochrane Library. Overall survival, local recurrence rate and adverse effects were considered as primary outcomes. Studies were critically appraised and estimates of effect were calculated according to the random-effects model. Inconsistency across studies was evaluated using the I2 statistic. Sensitivity analyses were conducted to explore statistical heterogeneity. RESULTS: Six studies were eligible. The studies reported data on 396 patients treated by RFA and 391 treated by PEI. In general, subjects were in Child-Pugh class A (74%) and had unresectable HCC (mean size 2.5 cm). Mean follow-up was 25 +/- 11 months. The survival rate showed a significant benefit for RFA over PEI at one, two, three and four years. The advantage in survival increased with time with Relative Risk values of: 1.28 (95%CI:1.12-1.45) and 1.24 (95%CI:1.05-1.48) for RFA versus PEI at 3- and 4-years respectively. Likewise, RFA achieved significantly lower rates of local recurrence (RR: 0.37, 95%CI: 0.23-0.59). The overall rate of adverse events was higher with RFA (RR:2.55, 95%CI: 1.8-3.6) yet no significant differences were found concerning major complications (RR:1.85, 95%CI: 0.68-5.01). There was not enough evidence supporting a better cost-effectiveness ratio for RFA compared to PEI. CONCLUSION: Available evidence from adequate quality controlled studies support the superiority of RFA versus PEI, in terms of better survival and local control of the disease, for the treatment of patients with relatively preserved liver function and early-stage non-surgical HCC. However, the higher rate of adverse events displayed is something that will have to be tested with appropriate weighting of the possible benefits in each individual case. Overall cost-effectiveness of RFA needs further evaluation.This study was commissioned by the Health Technology Assessment Programme on behalf of the Ministry of Health & Consumer Affairs and was partially funded by the Spanish National I+D Program Ministry of Science & Technology (to C Bouza, Z Saz and JM Amate, grant SEC 2001-0138 and PI08/90612). The funding body had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.S

Survival Patterns of Human Prion Diseases in Spain, 1998-2018: Clinical Phenotypes and Etiological Clues

Background: Human transmissible spongiform encephalopathies (TSEs) are a group of fatal neurodegenerative disorders of short duration. There are few studies on TSE survival. This study sought to analyze the survival and related factors of a TSE patient cohort, based on a nationwide surveillance system in Spain. Methods: Survival analyses were performed on 1,530 cases diagnosed across the period 1998–2018 in Spain. We calculated median survival times and plotted survival curves using the Kaplan–Meier method for all cases and for sporadic TSE (sTSE) and genetic TSE (gTSE). Crude and adjusted Cox proportional hazard models were used to identify variables associated with shorter survival. Findings: Median age at onset decreased from the sporadic forms to gTSE and, lastly, to acquired TSE. Overall median and interquartile range (IQR) survival time was 5.2 (IQR, 3.0–11.7) months and 4.9 (IQR, 2.8–10.8) months in sporadic cases and 9 (IQR, 4.9 to over 12) months in genetic cases, p < 0.001. Male sex, older age at onset, presence of 14-3-3 protein, typical MRI, and MM and VV polymorphisms at codon 129 were associated with shorter survival. gTSE showed higher survival in crude comparisons but not after adjustment. Interpretation: TSE survival in Spain replicates both the magnitude of that shown and the TSE entity-specific population patterns observed in Western countries but differs from features described in Asian populations, such as the Japanese. The reduction in differences in survival between gTSE and sTSE on adjusting for covariates and international patterns might support the view that gTSE and sTSE share causal and pathophysiological features.This work was basically funded by the Spain’s Ministry of Health and the Carlos III Health Institute (research grant no. PI08/0139) and Consortium for Biomedical Research in Neurodegenerative Diseases (CIBERNED) networks (QLRG3-CT-2002-81223). Role of funders: The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

Effectiveness and safety of glimepiride and iDPP4, associated with metformin in second line pharmacotherapy of type 2 diabetes mellitus: systematic review and meta-analysis

Objective: Our review analyses the studies that have specifically compared the association iDPP4/metformin with glimepiride/metformin, both in second line pharmacotherapy of type 2 diabetes mellitus (DM2). Methods: Systematic literature review with a meta-analysis of clinical trials comparing glimepiride with any iDPP4, both used together with metformin as a second line treatment of DM2. The effectiveness variables used were as follows: %HbA1c variation, fasting plasma glucose variation, patients achieving the therapeutic objective of HbA1c <7%, treatment dropouts due to lack of effectiveness and rescue treatments needed. The safety variables included were as follows: weight variation at the end of treatment; presentation of any type of adverse event; presentation of serious adverse events; patients who experienced any type of hypoglycaemia; patients who experienced severe hypoglycaemia; treatments suspended due to adverse effects; and deaths for any reason. Results: Four studies met the inclusion criteria. The group treated with glimepiride showed better results in all effectiveness variables. Regarding safety variables, the main differences observed were in the greater number of cases with hypoglycaemia in the group treated with glimepiride, and the serious adverse events or treatment discontinuations due to these which occurred in slightly over 2% more cases in this group compared to the iDPP4 group. The remaining adverse events, including mortality, did not show any differences between both groups. The variation in the weight difference between groups (2.1 kg) is not considered clinically relevant. Conclusions: A greater effectiveness is seen in the glimepiride/metformin association, which should not be diminished by slight differences in adverse effects, with absence of severe hypoglycaemia in over 98% of patients under treatment. The association of glimepiride/metformin, both due to cost as well as effectiveness and safety, may be the preferential treatment for most DM2 patients, and it offers a potential advantage in refractory hyperglycemic populations, tolerant to treatment.S

Mortalidad por causas esternas en España

En España se producen unas 14.000 muertes anuales por causas externas. Según datos de Eurostat 1, en el trienio 2008-2010 España tenía en hombres las tasas ajustadas de mortalidad por causas externas más bajas de los países de la Unión Europea, incluidos los de la Asociación Europea de Libre Comercio (EFTA), y en mujeres sólo Grecia presentaba tasas más bajas. La mortalidad mayor por estas causas se encontraba en Lituania, con unas tasas que para uno y otro sexo cuadruplicaban a las españolas, seguida de Letonia y Estonia. Al hablar de mortalidad por causas externas nos referimos a la que tiene su origen en accidentes, violencia, acontecimientos ambientales, envenenamientos y otros efectos adversos, tal como se recoge en el Capítulo XX de la décima revisión de la Clasificación Internacional de Enfermedades (CIE) y en los códigos «E» de revisiones anteriores 2. Cuando se produce un fallecimiento que obedezca o se sospeche que pueda ser debido a alguna de estas situaciones, es preceptiva la intervención judicial y la práctica de autopsia medicolegal para determinar la causa y circunstancias de la muerte 3, 4. El secretario judicial es el responsable, a partir del informe forense, de cumplimentar el Boletín Estadístico de Defunción Judicial (BEDJ) 5 (hasta 2009 era el documento MNP-52), que es el documento con finalidad estadística a partir del que se selecciona la causa básica de defunción que se codifica de acuerdo con la CIE vigente para la elaboración, por parte del Instituto Nacional de Estadística (INE), de la Estadística de Defunciones según la Causa de Muerte 6. En estos casos se considera como causa básica de defunción el acontecimiento que origina las lesiones que conducen a la muerte, siguiendo las normas de la Organización Mundial de la Salud. Dentro de este grupo tenemos una variedad de causas que de acuerdo con la CIE se pueden clasificar en intencionales (suicidio y homicidio), no intencionales (accidentes, ya sean de tráfico o de cualquier otro tipo, incluyendo las causas de iatrogenia) y de intención indeterminada. Los accidentes laborales mortales no se pueden diferenciar por la configuración de las CIE. Según las fuentes específicas, la mortalidad por accidentes laborales de causa traumática vendría a suponer alrededor de un 11% de todas las defunciones de causa externa no intencional en las edades productivas 7, 8. Las causas de intención indeterminada en España supusieron en el período 2007-2011 solo un 0,6% de todas las externas, porcentaje muy inferior al de otros países. Así, en la unión europea, como media en el trienio 2008-2010 significaron el 5,1%, aunque con grandes variaciones, presentando los porcentajes más bajos los países mediterráneos, y los más altos los del este y, principalmente y a bastante distancia, Portugal (25%) 9. En algunos países, una mayoría de fallecimientos así clasificados responden a la sospecha de que pueda tratarse de algunas causas como homicidio y principalmente suicidio, pero cuya intencionalidad no queda absolutamente clara.N