Hypochlorous acid in a double formulation (liquid plus gel) is a key prognostic factor for healing and absence of infection in chronic ulcers. A nonrandomized concurrent treatment study.

Background and Aims: Diverse protocols prevent infection and/or improve ulcer epithelialization. The existing protocols tend to antagonize the risk factors that promote the chronicity of this type of wound. Hypochlorous acid (HOCl) is used to treat ulcers and wounds because of its antiseptic and noncytotoxic properties. Its liquid form is effective but has little residual effect, while in gel it has more residual power. Methods: An experimental nonrandomized study has been carried out treating 346 chronic ulcers of various etiologies in 220 patients. Ulcer outcomes were originally classified as: "complete healing," "incomplete healing without infection," and "incomplete healing with infection." Various antiseptic solutions were used as ulcers cleaning solutions: liquid HOCl, gel HOCl, polymeric biguanide, or chlorhexidine. Only one was applied to the lesion as monotherapy. But, in other cases, we used a combined HOCl (liquid then gel: bitherapy). Bivariate (Chi-square and variance tests) and multivariate studies (logistic regression) evaluated associations of ulcer characteristics and mono or bitherapy outcomes. Results: Four factors reduce the probability of complete ulcer healing: patient age (odds ratio [OR]: 0.97); weeks of ulcer evolution (OR: 0.99); poor granulation on admission (OR: 0.35); and need for antibiotic therapy (OR: 0.41). One factor favored healing: combined HOCl therapy with liquid plus gel (OR: 4.8). Infections were associated with longer times of evolution (OR: 1.002) and bad odor of the ulcer on admission (OR: 14), but bitreatment with HOCl reduced the risk of infection (OR: 0.3). Conclusion: A double HOCl formulation (liquid plus gel) reduces the probability of poor healing and infection, in chronic ulcers of various etiologies.

Targeting shared molecular etiologies to accelerate drug development for rare diseases.

Rare diseases affect over 400 million people worldwide and less than 5% of rare diseases have an approved treatment. Fortunately, the number of underlying disease etiologies is far less than the number of diseases, because many rare diseases share a common molecular etiology. Moreover, many of these shared molecular etiologies are therapeutically actionable. Grouping rare disease patients for clinical trials based on the underlying molecular etiology, rather than the traditional, symptom-based definition of disease, has the potential to greatly increase the number of patients gaining access to clinical trials. Basket clinical trials based on a shared molecular drug target have become common in the field of oncology and have been accepted by regulatory agencies as a basis for drug approvals. Implementation of basket clinical trials in the field of rare diseases is seen by multiple stakeholders-patients, researchers, clinicians, industry, regulators, and funders-as a solution to accelerate the identification of new therapies and address patient's unmet needs.

Co-infections, comorbidities, and alcohol or other substances abuses in chronic hepatitis C-related hospitalisations in Spain / Coinfecciones, comorbilidades y abuso de alcohol u otras sustancias en las hospitalizaciones por hepatitis C crónica en España

Background: The Strategic Plan for Tackling Hepatitis C launched in 2015 in Spain has led to an important nationwide decrease in hepatitis C related hospitalisation rates. However, patients’ infection progression during decades could increase their health status complexity and challenge patient's prognosis after hepatitis C eradication. Methods: We carried out an observational retrospective study evaluating the prevalence of the main co-infections, comorbidities (risk factors and extrahepatic manifestations), and alcohol or other substances abuses in chronic hepatitis C related hospitalised patients in Spain. Data were obtained from the National Hospitalisation Registry discharges from January 1st of 2012 to December 31st of 2019. Results: Between 2012 and 2019 there were 356,197 chronic hepatitis C-related hospitalisations. In-hospital deaths occurred in 11,558 (4.6%) non-advanced liver disease and in 10,873 (10.4%) advanced liver disease-related hospitalisations. Compared to 2012–2015, in 2016–2019 the proportion of hospitalisations related to non-advanced liver disease increased from 69.4% to 72.4%, while the advanced disease-related hospitalisations decreased from 30.6% to 27.6% (P<.001). In spite of the decrease in severe cases among hospitalisations, all comorbidities evaluated, and alcohol abuse increased in 2016–2019 compared to 2012–2015, while co-infections and other substances abuses decreased in the same period.In the latest period (2016–2019): 28,679 (18.3%) of the hospitalised patients had a HIV, 6928 (4.4%) a hepatitis B, and 972 (.6%) a tuberculosis co-infection. Most frequent comorbidities were diabetes (N=33,622; 21.5%); moderate to severe renal disease (N=28,042; 17.9%), chronic obstructive pulmonary disease and asthma (N=25,559; 16.3%), and malignant neoplasms (excluding hepatocellular carcinoma) (N=19,873; 12.7%).(AU)

Antecedentes: El Plan Estratégico para el Abordaje de la Hepatitis C lanzado en España en 2015ha supuesto una importante disminución a nivel nacional de las tasas de hospitalización relacionadas con la hepatitis C. Sin embargo, la progresión de la infección en los pacientes durante décadas podría aumentar la complejidad de su estado de salud y desafiar el pronóstico del paciente después de la erradicación de la hepatitis C. Métodos: Se realizó un estudio observacional retrospectivo evaluando la prevalencia de las principales coinfecciones, comorbilidades (factores de riesgo y manifestaciones extrahepáticas) y abuso de alcohol u otras sustancias en pacientes hospitalizados relacionados con hepatitis C crónica en España. Los datos se obtuvieron del Registro de altas hospitalarias entre el 1 de enero de 2012 y el 31 de diciembre de 2019. Resultados: Entre 2012 y 2019 hubo 356.197 hospitalizaciones relacionadas con hepatitis C crónica y se registraron 11.558 (4,6%) muertes intrahospitalarias relacionadas con hospitalizaciones por enfermedad hepática no avanzada y 10.873 (10,4%) por enfermedad hepática avanzada. En comparación con 2012-2015, en 2016-2019 la proporción de hospitalizaciones relacionadas con enfermedad no avanzada aumentó del 69,4% al 72,4%, mientras que las relacionadas con enfermedad avanzada disminuyeron del 30,6% al 27,6% (P <0,001). A pesar de la disminución de casos graves entre las hospitalizaciones, todas las comorbilidades evaluadas y el abuso de alcohol aumentaron en 2016-2019 en comparación con 2012-2015, mientras que las coinfecciones y el abuso de otras sustancias disminuyeron en el mismo período. En el último período (2016-2019): 28.679 (18,3%) de los pacientes hospitalizados tenían VIH, 6928 (4,4%) hepatitis B y 972 (0,6%) coinfección tuberculosa. (AU)

The impact of toxic oil syndrome on physical and psychological health status using the HAQ and the PHQ-9 questionnaires.

BACKGROUND: Toxic oil syndrome (TOS) is a multisystemic disease due to a massive intoxication. To evaluate physical and mental health of TOS patients, we used the Health Assessment Questionnaire (HAQ) and the Patient Health Questionnaire-9 (PHQ-9). Additionally, we correlated both questionnaires with the results of the Short Form-36v2 (SF-36v2) Health Survey obtained in the same patients' sample. METHODS: 895 TOS patients who participated in the prior SF-36v2 study were invited to participate. We described patients' demographic and clinical characteristics, HAQ and PHQ-9 results. HAQ and PHQ-9 scores were correlated to the standardised SF-36v2 results obtained in our previous study. RESULTS: In total, 828 (92.5%) TOS annual follow-up and HAQ and 810 (90.5%) PHQ-9 valid questionnaires were analysed. Participants' average age was 65.4 (Standard Deviation (SD): 13.4), 521 (62.9%) were women, 725 (87.6%) reported having at least other chronic disease and 789 (95.3%) an additional TOS-related health problem. Average scores were 0.91 (SD: 0.83) for HAQ, 35.8 (SD: 10.1) for PCS and 37.8 (SD: 11.6) for MCS. Overall, 467 (57.7%) participants had moderate/severe depression (PHQ-9 ≥ 10), but only 229 (49.6%) of them reported having a depression diagnosis. Correlation between questionnaires was very strong for HAQ and physical function SF-36v2 dimension and moderate/fair for the rest of combinations. CONCLUSIONS: TOS cohort presented low/very low health status measured with SF-36v2, moderate difficulties in performing daily activities according to HAQ, and a high prevalence of major depression measured with PHQ-9. High proportion of undiagnosed depression was detected, proving PHQ-9 useful in terms of detecting and promoting depression diagnosis in the cohort.

Co-infections, comorbidities, and alcohol or other substances abuses in chronic hepatitis C-related hospitalisations in Spain.

BACKGROUND: The Strategic Plan for Tackling Hepatitis C launched in 2015 in Spain has led to an important nationwide decrease in hepatitis C related hospitalisation rates. However, patients' infection progression during decades could increase their health status complexity and challenge patient's prognosis after hepatitis C eradication. METHODS: We carried out an observational retrospective study evaluating the prevalence of the main co-infections, comorbidities (risk factors and extrahepatic manifestations), and alcohol or other substances abuses in chronic hepatitis C related hospitalised patients in Spain. Data were obtained from the National Hospitalisation Registry discharges from January 1st of 2012 to December 31st of 2019. RESULTS: Between 2012 and 2019 there were 356,197 chronic hepatitis C-related hospitalisations. In-hospital deaths occurred in 11,558 (4.6%) non-advanced liver disease and in 10,873 (10.4%) advanced liver disease-related hospitalisations. Compared to 2012-2015, in 2016-2019 the proportion of hospitalisations related to non-advanced liver disease increased from 69.4% to 72.4%, while the advanced disease-related hospitalisations decreased from 30.6% to 27.6% (P<.001). In spite of the decrease in severe cases among hospitalisations, all comorbidities evaluated, and alcohol abuse increased in 2016-2019 compared to 2012-2015, while co-infections and other substances abuses decreased in the same period. In the latest period (2016-2019): 28,679 (18.3%) of the hospitalised patients had a HIV, 6928 (4.4%) a hepatitis B, and 972 (.6%) a tuberculosis co-infection. Most frequent comorbidities were diabetes (N=33,622; 21.5%); moderate to severe renal disease (N=28,042; 17.9%), chronic obstructive pulmonary disease and asthma (N=25,559; 16.3%), and malignant neoplasms (excluding hepatocellular carcinoma) (N=19,873; 12.7%). Alcohol or substances abuse was reported in 48,506 (31.0%) hospitalisations: 30,782 (19.7%) with alcohol; 29,388 (18.8%) with other substances; and 11,664 (7.5%) with both, alcohol and other substances, abuses. CONCLUSIONS: Despite the reduction in advanced liver disease hepatitis C-related hospitalisations due to prioritisation of treatment to the more severe cases, high and increasing prevalence of comorbidities and risks factors among hepatitis C-related hospitalisations have been found.

Toxic oil syndrome: health-related quality-of-life assessment using the SF-36 Health Survey.

BACKGROUND: Toxic oil syndrome (TOS) is a multisystemic disease due to a massive intoxication that occurred in Spain in 1981 affecting >20 000 persons. This study aims to evaluate the quality of life of the survivors' cohort after 38 years of follow-up using the Short Form 36 (SF-36) Health Survey. METHODS: One thousand patients were selected among the 14 084 alive TOS cohort members in 2018 using a stratified random sampling method. Stratification was performed by the 2017 self-rated health status reported by patients. SF-36 results were compared directly and as standardized (T scores) with the Spanish-population reference values. Relationship between self-rated health status and SF-36 results was assessed. RESULTS: Overall, 900 cohort members participated and 895 valid responses were included in the study. Participants' average age was 65.2 (standard deviation: 13.8) years and 563 (62.9%) participants were women. Participants' distribution by self-rated health status was: 219 (24.5%) good/very good, 415 (46.4%) fair and 261 (29.1%) poor/very poor. Quality of life was below the Spanish-population reference in 84% of the TOS patients (87.2% for women and 78.6% for men) for the Physical Component Summary (PCS) and in 75.4% (81.7% for women and 64.8% for men) for the Mental Component Summary (MCS). PCS and MCS scores decreased similarly for both sexes with worse self-rated health. CONCLUSIONS: Very low quality of life and self-rated health, especially for women, were found in the total TOS participants that can be extrapolated to the TOS survivors' cohort. The TOS cohort still requires standardization of care with integral plans around the country.

Reduction in hepatitis C-related hospitalizations after the implementation of the Strategic Plan for Tackling Hepatitis C in the Spanish National Health System: regional level differences.

This work evaluates the potential impact at territorial level of the Strategic Plan for Tackling Hepatitis C in the Spanish National Health System on hepatitis C virus (HCV)-associated hospitalizations. Chronic HCV-related hospitalization discharges from 2014 to 2018 were obtained from the National Registry of Hospitalisations. A descriptive analysis of the hospitalizations was performed for all chronic, advanced liver disease and non-advanced liver disease. Hospitalization rates were calculated at national and regional level. Year 2015 and period 2016-2018 hospitalization rates were compared to 2014 hospitalization rates using a Poisson model. Municipal standardized hospitalization rates ratios adjusted by age-group were calculated for 2016-2018 period (2014 hospitalization rates as reference). From 2014 to 2018, there were 22,352 chronic HCV-related hospitalizations. In-hospital fatality rate was 4.3% for non-advanced liver disease and 11.7% for advanced liver disease patients. National hospitalization rate decreased 22% (95% CI: 21%-22%), 16% (95% CI: 15%-17%) and 34% (95% CI: 33%-35%) in 2016-2018 compared to 2014 for all chronic, non-advanced and advanced liver disease, respectively. During 2016-2018 period, 11/19 Spanish regions achieved >20% decrease in the hospitalization rates (p < .001) for non-advanced liver disease and 19/19 (except Melilla, the rest with p < .001) for advanced liver disease. At municipal level, 84.8% and 90.2% municipalities had <20% of chronic HCV-related hospitalization need compared to 2014 adjusted by age-group. Based on the data analysed, a high impact on reducing chronic HCV-associated hospitalizations have been achieved after the implementation of the Strategic Plan for Tackling Hepatitis C in the Spanish National Health System. However, small differences between regions and rural/urban areas were noticed.

Hepatitis C and hepatitis C-related advanced liver disease hospitalisation trends before and after the Strategic Plan for Tackling Hepatitis C in the National Health System.

INTRODUCTION: This work evaluates the burden and trends of hepatitis C virus (HCV)-associated hospitalisations in Spain before and after the implementation of the Strategic Plan for Tackling Hepatitis C in the National Health System in 2015. METHODS: HCV-related hospitalisation discharges from 2005 to 2017 were obtained from the National Registry of Hospitalisations. A descriptive analysis of the hospitalisations was performed. RESULTS: From 2005 to 2017, there were 674 067 HCV-related hospitalisations: 1.2%, 29.9%, 63.9% and 5% of them due to acute, carriers, chronic and unspecified hepatitis C. Average age of the patients was 57.7 years (SD: 16.4), average hospital stay was 9.1 days (SD: 12.2) and intra-hospital case-fatality rate was 6.5%. Hospitalisation rates decreased notably (P < 0.05) in 2016-2017 compared to 2005-2015 for all [hospitalisation rate ratio (HRR): 0.77], males (HRR: 0.80), females (HRR: 0.74), chronic hepatitis C (HRR: 0.84), non-advanced liver disease (N-AdLD) (HRR: 0.80) and AdLD (HRR: 0.73). Acute HCV (HRR: 0.54) and carriers (HRR: 0.49) show decreases in 2016-2017 vs. 2005-2015, although their rates started to decrease in 2008/2009. Unspecified HCV hospitalisation rates increased (P < 0.05) in 2016-2017 (HRR: 2.02) vs. 2005-2015. From 2015 to 2017, cost per patient increased from 5981 euros to 6349 euros, but overall cost decreased, as hospitalisations rates decreased from 302 to 264 million euros. DISCUSSION: HCV-related hospitalisation rates decreased notably in 2016 and 2017 after the strategic plan for tackling hepatitis C was launched. Although cost per AdLD patient increased in 2016 and 2017, globally costs were reduced around 35 million euros per year.

Risk Minimisation Evaluation with Process Indicators and Behavioural or Health Outcomes in Europe: Systematic Review.

BACKGROUND: European Pharmacovigilance regulatory guidance recommends the evaluation of additional risk minimisation measures (aRMMs) with process indicators and outcomes. Evaluation of both measures within the same evaluation helps to establish the relationship between the implementation of aRMMs (across process indicators) and the impact on drug safety-related outcomes. The term risk minimisation evaluation (RMEv) was used to describe a study or group of studies that assesses the effectiveness of aRMMs for one specific product. OBJECTIVES: The objective of this systematic review was to describe the characteristics and results of RMEv that include both process indicators and outcomes as well as those of studies that conform the RMEv in Europe. METHODS: We conducted a systematic search in the European Union Register of Post-Authorization Studies, PubMed and grey literature (Google and abstracts of the International Conference on Pharmacoepidemiology and Therapeutic Risk Management) to identify studies that assessed the effectiveness of aRMMs including at least one European country, from 1 January, 2011 to 12 October, 2019. Identified studies linked to one product were considered part of the product RMEv. Only RMEv that included both process indicators and outcomes (behavioural and/or health/safety outcomes) were eligible. Data were abstracted from reports, manuscripts and abstracts. RESULTS: Eighteen of 102 (18%) RMEv had both process indicators and outcomes, and were included in this review. Of the 18 RMEv, ten consisted of one study only, five of two studies, and three of three or more studies. A total of 30 studies were included within the 18 RMEv. The designs of the studies were: 19 (63%) cross-sectional surveys (47% targeted patients and 89% healthcare professionals), 17 (57%) retrospective studies (47% using pre/post approach) and 3 (10%) prospective studies. Nineteen studies included process indicators that were receipt (n = 14), use (n = 12), knowledge (n = 17) and self-reported behaviour (n = 15). Regarding outcomes, 67% of the 18 RMEv evaluated behavioural outcomes and 50% health/safety outcomes. Three of the 18 RMEv evaluated both behavioural and health/safety outcomes. For five RMEv, correlations between process indicators and outcomes were performed, two at the patient level. Results were available for 14 of the 18 RMEv. In healthcare professional surveys, the median percentage was 57% for receipt, 92% for reading, 80% for use, 77% for knowledge and 74% for behaviour. In patient surveys, the median percentage was 56% for receipt, 87% for reading, 65% for use, 47% for knowledge and 69% for behaviour. Knowledge was better in healthcare professionals than patients (p < 0.05). Of the three RMEv with a correlation analysis, only one found a positive trend for a lower occurrence of outcomes as process indicators improved, though this was not statistically significant. CONCLUSIONS: A minority of RMEv assessed both process indicators and outcomes. More RMEv require approaches that correlate process indicators and outcomes at the patient level to evaluate more comprehensively the implementation of aRMMs.

Linking process indicators and clinical/safety outcomes to assess the effectiveness of abatacept (ORENCIA) patient alert cards in patients with rheumatoid arthritis.

PURPOSE: Patient alert cards (PACs) for abatacept (ORENCIA) inform patients and healthcare professionals (HCPs) about the risk of infections and allergic reactions. The study evaluates the effectiveness of the PACs in rheumatoid arthritis patients and HCPs, using process indicators (awareness, receipt, utility, knowledge, behaviour) and outcomes. METHODS: Surveys of patients and HCPs in five European countries. A retrospective chart review permitted linking clinical and safety outcomes with survey responses. RESULTS: Data on 190 patients and 79 HCPs (50 physicians and 29 nurses) were analysed. Sixty percent of patients were aware of the PAC, of whom 95% had received it. Knowledge of risk of infection was higher among patients who had received the PAC vs those who had not (64% vs 46%; P = .013). Infections leading to hospitalisation increased with decreasing patient survey global scores: scores of ≥67%, 34%-67% and ≤ 33% were associated with hospitalisation rates of 2.5%, 5.2% and 8.4%, respectively (P = .4). Among HCPs 90% were aware and 68% had accessed the PAC. More nurses than physicians were aware (93% vs 88%), had accessed (78% vs 74%), read (90% vs 59%), distributed (81% vs 66%) and explained the content (94% vs 43%) of the PAC. Knowledge of risk of infection was higher among HCPs who had (91%) vs those who had not (73%) accessed the PAC (P = .053). CONCLUSIONS: PACs were effective in improving knowledge of key safety messages in patients and HCPs. This novel study design bridges the gap of linking process indicators with outcomes in the same patients, thereby strengthening the clinical relevance of patient surveys.

Impacto de la vacuna triple vírica sobre la incidencia de la parotiditis en la Comunidad de Madrid y evaluación de la efectividad de la cepa Jeryl-Lynn entre 1998 y 2016 / Impact of the MMR vaccine on the incidence of mumps in the Community of Madrid and evaluation of the effectiveness of the Jeryl-Lynn strain. Years 1998-2016

Introducción y objetivo: La parotiditis se caracteriza por la inflamación de la glándula parótida y fiebre, y es prevenible mediante vacunación con triple vírica (TV). El objetivo es evaluar el impacto y la efectividad vacunal (EV). Material y métodos: Se seleccionaron los casos notificados al Sistema de Enfermedades de Declaración Obligatoria entre 1998 y 2016. La EV se calculó en cohortes vacunadas con 2 dosis de Jeryl-Lynn, y el impacto comparando las incidencias por edad y por cohortes Rubini (1995-1998) y Jeryl-Lynn (1999-2002) en los periodos 1998-2004, 2005-2009 y 2010-2015. Las estimaciones por grupo de edad y período se compararon con las del período anterior y las estimaciones por cohortes se compararon entre sí dentro de cada período mediante razones de incidencia (RI) empleando modelos de Poisson. La EV se estimó empleando el método de cribado mediante modelos de regresión logística. Resultados: Se notificaron 13.816 casos. La incidencia en 2005-2009 fue superior a la de 1998-2004 (RI: 1,46; IC 95%: 1,40-1,53), y en 2010-2015 se mantuvo estable (RI: 0,99; IC 95%: 0,95-1,03). La incidencia anual media de las cohortes Rubini fue de 69,43 casos por 100.000 habitantes y la de las cohortes Jeryl-Lynn de 32,24. La RI fue de 0,25 (IC 95%: 0,22-0,29), 0,55 (IC 95%: 0,49-0,61) y 0,88 (IC 95%: 0,76-1,00) para cada periodo, respectivamente. Se incluyeron 2.574 casos en el estudio de EV. La EV disminuyó con el tiempo al alcanzar valores no significativos tras 7 años de seguimiento (EV: 55%; IC 95%: 82 a -12%). Conclusiones: El comportamiento de la parotiditis se caracteriza por presentar fluctuaciones, cambios en la presentación etaria y una disminución de la EV

Introduction: Mumps is characterised by parotid inflammation and fever and is preventable by vaccination with MMR vaccine. The objective of the study is to assess the impact and effectiveness of the vaccine. Material and methods: Cases notified to the Notifiable Disease System between 1998 and 2016 were used for the study. The vaccine effectiveness (VE) was calculated in cohorts vaccinated with two doses of Jeryl-Lynn, and the impact was calculated by comparing incidences by age and by Rubini (1995-1998) and Jeryl-Lynn (1999-2002) cohorts during the periods 1998-2004, 2005-2009 and 2010-2015. The incidences for age group and period were compared with the previous period and the incidences for cohorts were compared within a period with incidence ratios (IR) using Poisson models. The VE was estimated using the screening method using logistic regression models. Results: 13,816 cases were reported. The incidence in 2005-2009 was higher than in 1998-2004 (IR: 1.46, 95% CI: 1.40-1.53), and it remained stable in 2010-2015 (IR: 0.99, 95% CI: 0.95-1.03). The average incidence rate of the Rubini cohort was 69.43 and the Jeryl-Lynn cohort was 32.24. The IR was 0.25 (95% CI: 0.22-0.29), 0.55 (95% CI: 0.49-0.61) and 0.88 (95% CI: 0.76-1.00) for each period respectively. 2,574 cases were included in the VE study. EV decreased over time reaching not significant values after seven years of follow-up (VE: 55%, 95% CI: 82 to -12%). Conclusions: Parotiditis behavior is characterised by fluctuations, changes in presentation and a decrease in VE

Are risk minimization measures for approved drugs in Europe effective? A systematic review.

Objectives: The effectiveness of risk minimization measures (RMMs) requires evaluation. This study aims to evaluate the results of cross-sectional surveys assessing the effectiveness of RMMs in Europe (EU RM Surveys) and review the regulatory consequences. Methods: The authors searched for study reports and manuscripts of completed EU RM surveys in the EU PAS Register, MEDLINE, and Google between 01/2011 and 01/2018. Regulatory responses were extracted from Assessment Reports. Random effects models to combine proportions were used. Results: Twenty-four EU RM surveys were identified. Twenty-three studies targeted health-care professionals (HCPs). The pre-specified sample size was reached in 52% of studies. HCP participation was 5% defined as completers/invited and 89% for completers/eligible. Receipt of materials was recalled by 60% of HCPs and 77% of items scored knowledge >60%. Eight studies targeted patients/caregivers. The pre-specified sample size was reached in only two. Participation was 93%, defined as completers/eligible. Materials were received by 50-80% of patients and read by over 90%. Patients only scored knowledge >60% in 38% of items. Further action was requested by regulators in 59% of studies. Conclusion: Surveys are necessary to evaluate many RMMs. Challenges remain in the design, conduct, and reporting of these studies which may benefit from the use of standard definitions and further guidance on reporting. EU PAS Register: http://www.encepp.eu/encepp/viewResource.htm?id=23435.

Impact of the MMR vaccine on the incidence of mumps in the Community of Madrid and evaluation of the effectiveness of the Jeryl-Lynn strain. Years 1998-2016. / Impacto de la vacuna triple vírica sobre la incidencia de la parotiditis en la Comunidad de Madrid y evaluación de la efectividad de la cepa Jeryl-Lynn entre 1998 y 2016.

INTRODUCTION: Mumps is characterised by parotid inflammation and fever and is preventable by vaccination with MMR vaccine. The objective of the study is to assess the impact and effectiveness of the vaccine. MATERIAL AND METHODS: Cases notified to the Notifiable Disease System between 1998 and 2016 were used for the study. The vaccine effectiveness (VE) was calculated in cohorts vaccinated with two doses of Jeryl-Lynn, and the impact was calculated by comparing incidences by age and by Rubini (1995-1998) and Jeryl-Lynn (1999-2002) cohorts during the periods 1998-2004, 2005-2009 and 2010-2015. The incidences for age group and period were compared with the previous period and the incidences for cohorts were compared within a period with incidence ratios (IR) using Poisson models. The VE was estimated using the screening method using logistic regression models. RESULTS: 13,816 cases were reported. The incidence in 2005-2009 was higher than in 1998-2004 (IR: 1.46, 95% CI: 1.40-1.53), and it remained stable in 2010-2015 (IR: 0.99, 95% CI: 0.95-1.03). The average incidence rate of the Rubini cohort was 69.43 and the Jeryl-Lynn cohort was 32.24. The IR was 0.25 (95% CI: 0.22-0.29), 0.55 (95% CI: 0.49-0.61) and 0.88 (95% CI: 0.76-1.00) for each period respectively. 2,574 cases were included in the VE study. EV decreased over time reaching not significant values after seven years of follow-up (VE: 55%, 95% CI: 82 to -12%). CONCLUSIONS: Parotiditis behavior is characterised by fluctuations, changes in presentation and a decrease in VE.

Salmonella Surveillance Systems in Swine and Humans in Spain: A Review.

Non-typhoid salmonellosis is a common and problematic foodborne zoonotic disease in which pork and pork products can be an important potential source of infection. To prevent this disease, important efforts to monitor the situation in the main source, livestock, are conducted in most developed countries. In the European Union, European Food Safety Agency (EFSA) and European Center for Disease Control (ECDC) compile information at the member-state level, even though important differences in production systems and surveillance systems exist. Here, Salmonella surveillance systems in one of the main sources of foodborne salmonellosis, swine, and humans in Spain were reviewed to identify potential gaps and discuss potential ways of integration under a "One-Health" approach. Despite the extensive information generated through the surveillance activities, source attribution can be only routinely performed through ad-hoc outbreak investigations, and national reports on human outbreaks do not provide sufficiently detailed information to gain a better understanding of the epidemiology of the pathogen. Human and animal monitoring of Salmonella would benefit from a better exchange of information and collaboration. Analysis of spatio-temporal trends in livestock and humans could help to identify likely sources of infection and to target surveillance efforts in areas with higher prevalence or where specific strains are found.

Non-Typhi, non-Paratyphi Salmonella-related hospitalisations in Spain: trends, clinical aspects, risk factors for worse prognosis and hospital costs.

This study reviews non-typhoid Salmonella (NTS)-related hospitalisations at National level in Spain between 2010 and 2015. NTS hospitalisations were obtained from the National Registry of Hospitalisations. A descriptive analysis of the hospitalisations was performed, including hospitalisation rates (HR) and case-fatality rates (CFR%) calculation. For those with NTS as Main Diagnosis logistic regression were used to estimate the relationship between the different factors and death outcome. 21,660 registered NTS-related hospitalisations were described (88.8% with Salmonella coded as Main Diagnosis). Average HR2010-2015 was 7.7 (range, 7.3 to 8.1) hospitalisations/100,000 population. Those with NTS infections as Secondary Diagnosis were on average (p < 0.001) older (47.9 vs. 36.5 years), presented worse Charlson Comorbidity Index (2.1 vs. 1.2), higher CFR% (4.8% vs. 0.7%), spent more days hospitalised (15.1 vs. 5.8 days), and generated more costs (6173 vs. 4272 euros/per hospitalisation) than those with NTS as Main Diagnosis. For those with NTS as Main Diagnosis increased risk of death was related to being > 64 years old (OR = 20.99; p < 0.001); presenting septicaemia (OR = 15.82; p < 0.001) or localised infections (OR = 3.98; p = 0.061); Charlson Comorbidity Index > 3 (OR = 4.57; p < 0.001); a non-HIV co-infection (OR = 1.80; p = 0.013); other risk factors (OR = 5.70; p < 0.001); bowel perforation (OR = 70.30; p < 0.001); or acute renal failure (OR = 1.95; p = 0.001). In those with Salmonella as Main Diagnosis, among all complications, bowel perforation presented the strongest association with death outcome. Clinical practice guidelines can help to identify patients at risk of bowel perforation to reduce the fatality of the disease.

Effectiveness and impact of a single-dose vaccine against chickenpox in the community of Madrid between 2001 and 2015.

BACKGROUND: Chickenpox is a contagious airborne disease. Immunization by varicella vaccine is an effective preventive measure. The objective of this study is to evaluate the impact and effectiveness of a single-dose vaccination against chickenpox at 15 months of age. METHODS: Observational study based on data from the Epidemiological Surveillance System of the Autonomous Community of Madrid from 2001 to 2015. The years were grouped into 4 periods according to epidemic cycles and vaccination schedule: 2001-06, 2007-10, 2011-13 and 2014-15. The impact was calculated as Relative Risk (RR) between the incidence of chickenpox in children between 15 months and 13 years of age between 2011-13 and 2001-06 through Poisson regression using notifications made to the Diseases of Compulsory Declaration (DCD) system, the Sentinel Physicians Network (SPN) and hospital discharge records noted as Minimum Basic Data Set (MBDS). The vaccine effectiveness (VE) was calculated using the screening method and a 1:2 case-control study paired by age and paediatrician in population from 15 months to 13 years and between 2007 and 2015 using SPN source data. RESULTS: The RR2011-13/2001-06 using data from the DCD was 0.14 (95% CI: 0.14 to 0.15), 0.07 (95% CI: 0.06 to 0.08) from SPN and 0.17 (95% CI: 0.15 to 0.20) from MBDS. A total of 338 cases were included in the VE screening obtaining an overall of 76.7% (IC 95%: 71.9 to 80.7%). For a case-control study, 120 cases and 247 controls were recruited obtaining a VE of 92.4% (IC 95%: 80.8 to 97.0%). CONCLUSIONS: The single-dose vaccination against chickenpox at 15 months of age has high impact and effectiveness.

[Epidemiology of childhood tuberculosis in Spain: 2005-2009]. / Epidemiología de la tuberculosis pediátrica en España, 2005-2009.

BACKGROUND: European recent data about paediatric tuberculosis point out the importance of evaluate the trends of the disease to study the recent transmission, as well as the necessity of improving the microbiological diagnosis in paediatric cases. The aim of this paper is to study the epidemiology and trend evolution of paediatric tuberculosis in Spain during the period 2005-2009 and to establish the epidemiological differences between adult and paediatric tuberculosis. METHODS: Data reported to the National Surveillance Net (Red Nacional de Vigilancia Epidemiológica) in Spain was checked. Lineal regression was developed to establish the trend of the disease in all, adult and paediatric cases. Bivariate and multivariate logistic regression was used to compare paediatric and adult cases reported in 2009 and estimate the influence of different factors in the development of the disease. RESULTS: A total 39775, 2690 paediatrics (6.76%) cases of tuberculosis were reported during 2005-2009 period. Paediatric tuberculosis rates showed a slight increasing tendency (y=0.15x+7.8), while adult rates decrease during the period (y=-0.28x+20.2). In 2009, rates were 8.1 and 18.3 cases/100,000 inhab. for children and adults respectively. Paediatric cases presented higher proportion of pulmonary locations (84% vs. 76% in adults) and lower percentages of cases confirmed by culture (51% vs. 82% in adults) and of cases in non-Spanish population (25% vs. 34%). CONCLUSIONS: Paediatric tuberculosis rates showed a slight increasing tendency, while global and adult rates decrease slightly during the period. Tuberculosis disease shows different epidemiology in children and adults, what it is important to take into account to design public heh interventions.

Epidemiología de la tuberculosis pediátrica en España, 2005-2009 / Epidemiology of childhood tuberculosis in Spain: 2005-2009

Fundamentos: Los últimos datos europeos sobre tuberculosis pediátrica señalan la utilidad de evaluar las tendencias para estudiar la transmisión así como la necesidad de mejorar el diagnóstico microbiológico en estas edades. El objetivo es estudiar la epidemiología de la tuberculosis pediátrica en España, su evolución durante el periodo 2005- 2009, y las diferencias respecto con la epidemiología de los adultos. Métodos: Se utilizaron los datos de la declaración individualizada de tuberculosis a la Red Nacional de Vigilancia Epidemiológica en 2005-2009. Se estudió la tendencia de las tasas en niños y adultos mediante modelos de regresión lineal. Para estudiar los riesgos asociados a la tuberculosis en niños en relación a la de los adultos, se realizó un análisis bivariado y otro multivariado por regresión logística, empleando los datos de 2009. Resultados: En el periodo de estudio se declararon 39.775 casos de tuberculosis, 2.690 de ellos pediátricos (6,76%). La tendencia en las tasas de tuberculosis fue ascendente para la edad pediátrica (y=0,15x+7,8) y descendente para los adultos (y=-0,28x+20,2). En 2009 las tasas fueron 8,1 casos/100.000 en niños y 18,3/100.000 en adultos. Se encontró en niños una mayor proporción de localizaciones pulmonares (84% frente a 76%), menor porcentaje de confirmaciones por cultivo (51% frente a 82%) y de casos extranjeros (25% frente a 34%). Conclusiones: En el periodo de estudio las tasas de tuberculosis pediátrica mostraron una tendencia ligeramente ascendente, mientras que las tasas globales y en adultos la tuvieron descendente . La tuberculosis muestra escenarios diferentes en niños y adultos, lo que hay que tener en cuenta para dirigir las acciones de salud pública(AU)

Background: European recent data about paediatric tuberculosis point out the importance of evaluate the trends of the disease to study the recent transmission, as well as the necessity of improving the microbiological diagnosis in paediatric cases. The aim of this paper is to study the epidemiology and trend evolution of paediatric tuberculosis in Spain during the period 2005-2009 and to establish the epidemiological differences between adult and paediatric tuberculosis. Methods: Data reported to the National Surveillance Net (Red Nacional de Vigilancia Epidemiológica) in Spain was checked. Lineal regression was developed to establish the trend of the disease in all, adult and paediatric cases. Bivariate and multivariate logistic regression was used to compare paediatric and adult cases reported in 2009 and estimate the influence of different factors in the development of the disease. Results: A total 39775, 2690 paediatrics (6.76%) cases of tuberculosis were reported during 2005-2009 period. Paediatric tuberculosis rates showed a slight increasing tendency (y=0.15x+7.8), while adult rates decrease during the period (y=-0.28x+20.2). In 2009, rates were 8.1 and 18.3 cases/100,000 inhab. for children and adults respectively. Paediatric cases presented higher proportion of pulmonary locations (84% vs. 76% in adults) and lower percentages of cases confirmed by culture (51% vs. 82% in adults) and of cases in non-Spanish population (25% vs. 34%). Conclusions: Paediatric tuberculosis rates showed a slight increasing tendency, while global and adult rates decrease slightly during the period. Tuberculosis disease shows different epidemiology in children and adults, what it is important to take into account to design public health interventions(AU)

Evaluation of mammographic density patterns: reproducibility and concordance among scales.

BACKGROUND: Increased mammographic breast density is a moderate risk factor for breast cancer. Different scales have been proposed for classifying mammographic density. This study sought to assess intra-rater agreement for the most widely used scales (Wolfe, Tabár, BI-RADS and Boyd) and compare them in terms of classifying mammograms as high- or low-density. METHODS: The study covered 3572 mammograms drawn from women included in the DDM-Spain study, carried-out in seven Spanish Autonomous Regions. Each mammogram was read by an expert radiologist and classified using the Wolfe, Tabár, BI-RADS and Boyd scales. In addition, 375 mammograms randomly selected were read a second time to estimate intra-rater agreement for each scale using the kappa statistic. Owing to the ordinal nature of the scales, weighted kappa was computed. The entire set of mammograms (3572) was used to calculate agreement among the different scales in classifying high/low-density patterns, with the kappa statistic being computed on a pair-wise basis. High density was defined as follows: percentage of dense tissue greater than 50% for the Boyd, "heterogeneously dense and extremely dense" categories for the BI-RADS, categories P2 and DY for the Wolfe, and categories IV and V for the Tabár scales. RESULTS: There was good agreement between the first and second reading, with weighted kappa values of 0.84 for Wolfe, 0.71 for Tabár, 0.90 for BI-RADS, and 0.92 for Boyd scale. Furthermore, there was substantial agreement among the different scales in classifying high- versus low-density patterns. Agreement was almost perfect between the quantitative scales, Boyd and BI-RADS, and good for those based on the observed pattern, i.e., Tabár and Wolfe (kappa 0.81). Agreement was lower when comparing a pattern-based (Wolfe or Tabár) versus a quantitative-based (BI-RADS or Boyd) scale. Moreover, the Wolfe and Tabár scales classified more mammograms in the high-risk group, 46.61 and 37.32% respectively, while this percentage was lower for the quantitative scales (21.89% for BI-RADS and 21.86% for Boyd). CONCLUSIONS: Visual scales of mammographic density show a high reproducibility when appropriate training is provided. Their ability to distinguish between high and low risk render them useful for routine use by breast cancer screening programs. Quantitative-based scales are more specific than pattern-based scales in classifying populations in the high-risk group.