Incidence and severity of pertussis hospitalisations in infants aged less than 1 year in 37 hospitals of six EU/EEA countries, results of PERTINENT sentinel pilot surveillance system, December 2015 to December 2018.

IntroductionPERTINENT is a pilot active surveillance system of infants hospitalised with pertussis in six European Union/European Economic Area countries (37 hospitals, seven sites).AimThis observational study aimed to estimate annual pertussis incidence per site from 2016 to 2018 and respective trends between 2017 and 2018. Pertussis cases were described, including their severity.MethodsWe developed a generic protocol and laboratory guidelines to harmonise practices across sites. Cases were hospitalised infants testing positive for Bordetella pertussis by PCR or culture. Sites collected demographic, clinical, laboratory data, vaccination status, and risk/protective factors. We estimated sites' annual incidences by dividing case numbers by the catchment populations.ResultsFrom December 2015 to December 2018, we identified 469 cases (247 males; 53%). The median age, birthweight and gestational age were 2.5 months (range: 0-11.6; interquartile range (IQR): 2.5), 3,280 g (range: 700-4,925; IQR: 720) and 39 weeks (range: 25-42; IQR: 2), respectively. Thirty cases (6%) had atypical presentation either with cough or cyanosis only or with absence of pertussis-like symptoms. Of 330 cases with information, 83 (25%) were admitted to intensive care units including five deceased infants too young to be vaccinated. Incidence rate ratios between 2018 and 2017 were 1.43 in Czech Republic (p = 0.468), 0.25 in Catalonia (p = 0.002), 0.71 in France (p = 0.034), 0.14 in Ireland (p = 0.002), 0.63 in Italy (p = 0.053), 0.21 in Navarra (p = 0.148) and zero in Norway.ConclusionsIncidence appeared to decrease between 2017 and 2018 in all but one site. Enhanced surveillance of hospitalised pertussis in Europe is essential to monitor pertussis epidemiology and disease burden.

Azithromycin to Prevent Pertussis in Household Contacts, Catalonia and Navarre, Spain, 2012-2013.

We retrospectively assessed the effectiveness of azithromycin in preventing transmission of pertussis to a patient's household contacts. We also considered the duration between symptom onset in the primary patient and azithromycin administration. We categorized contacts into 4 groups: those treated within <7 days, 8-14 days, 15-21 days, and >21 days after illness onset in the primary patient. We studied 476 primary index patients and their 1,975 household contacts, of whom 4.5% were later identified as having pertussis. When contacts started chemoprophylaxis within <21 days after the primary patient's symptom onset, the treatment was 43.9% effective. Chemoprophylaxis started >14 days after primary patient's symptom onset was less effective. We recommend that contacts of persons with pertussis begin chemoprophylaxis within <14 days after primary patient's symptom onset.

Hepatitis A surveillance: sensitivity of two information sources.

BACKGROUND: The frequency of mild forms of hepatitis A, especially in children, could lead to underreporting. The objective of the study was to investigate the sensitivity of two surveillance systems, mandatory Statutory Disease Reports and the Microbiological Reporting System of Catalonia, using capture-recapture techniques. METHODS: The study was conducted in Catalonia between 2011 and 2015. Hepatitis A cases reported to two independent surveillance systems were included: Statutory Disease Reports (SDR) and Microbiological Reporting System of Catalonia (MRS). The variables collected were: age, sex, year of declaration, size of municipality (< 10,000 and ≥ 10,000), country of birth (Spain or abroad), reporting centre (primary care/hospital) and notification method (electronic or paper). The capture-recapture analysis and the estimate of 95% confidence intervals were made using the Chapman formula for comparison of two sources, both for the estimate of the total number of cases and the stratification according to variables. Multinomial logistic regression was performed to obtain an adjusted estimate. RESULTS: The SDR had a greater overall sensitivity than the MRS (48.8%; 43.5-55.6 vs. 19.3%; 17.2-21.9). In cases aged < 15 years the sensitivity of both systems was higher (76.6%; 72.7-81 vs. 25.2%; 20.9-29.5) than in cases aged > 15 years (25.5%; 22.8-28.3 vs. 12.1%; 10-14.2). For those born in Spain, the sensitivity was 57.2% (49.6-67.4) in the SDR and 27.1% (23.5-31.9) in the MRS, lower than that for foreign-born patients (58%; 51.2-66.8 vs. 49.1%; 43.4-56.6). In electronically-reported cases, the sensitivity was much higher in the SDR than in the MRS (47.2%; 42.3-52.1 vs. 9.4%; 6.5-12.3). No differences were observed according to sex, size of municipality, and year of declaration or reporting centre. The estimated total number of cases using the Chapman formula was very similar to the adjusted estimate (1121; 985-1258 vs. 1120; 876-1525), indicating the robustness of the results. CONCLUSIONS: The sensitivity of the SDR was greater than that of MRS, especially in patients aged < 15 years, although for patients born abroad the difference in sensitivity was lower. Reinforced surveillance combining the SDR and MRS improves the efficiency in the detection of cases.

Cell-based product classification procedure: What can be done differently to improve decisions on borderline products?

In June 2015, European Medicines Agency/Committee for Advanced Therapies (CAT) released the new version of the reflection paper on classification of advanced therapy medicinal products (ATMPs) established to address questions of borderline cases in which classification of a product based on genes, cells or tissues is unclear. The paper shows CAT's understanding of substantial manipulation and essential function(s) criteria that define the legal scope of cell-based medicinal products. This article aims to define the authors' viewpoint on the reflection paper. ATMP classification has intrinsic weaknesses derived from the lack of clarity of the evolving concepts of substantial manipulation and essential function(s) as stated in the EU Regulation, leading to the risk of differing interpretations and misclassification. This might result in the broadening of ATMP scope at the expense of other products such as cell/tissue transplants and blood products, or even putting some present and future clinical practice at risk of being classified as ATMP. Because of the major organizational, economic and regulatory implications of product classification, we advocate for increased interaction between CAT and competent authorities (CAs) for medicines, blood and blood components and tissues and cells or for the creation of working groups including representatives of all parties as recently suggested by several CAs.

Factors influencing the spread of pertussis in households: a prospective study, Catalonia and Navarre, Spain, 2012 to 2013.

We aimed to investigate transmission rates of pertussis in household contacts of cases and factors associated with transmission. A prospective epidemiological study was conducted in 2012 and 2013 to determine the incidence of pertussis among household contacts of reported cases in Catalonia and Navarre, Spain. An epidemiological survey was completed for each case and contact, who were followed for 28 days to determine the source of infection (primary case) and detect the occurrence of secondary cases. Odds ratios (ORs) were used to estimate the effectiveness of vaccination and chemoprophylaxis in preventing new cases, using the formula (1 - OR) × 100. For the 688 primary cases, a total of 2,852 contacts were recorded. The household transmission rate was 16.1% (459/2,852) and rose according to the age (> 18 years) and lack of immunisation of the primary cases, and also the age (0-18 years), family relationship (siblings and children), lack of vaccination and chemoprophylaxis of contacts. Pertussis vaccine effectiveness in preventing new cases was 65.0% (95% confidence interval (CI): 11.6 to 86.2) for full vaccination (≥ 4 doses) and 59.7% (95% CI: -6.8 to 84.8) for incomplete vaccination (< 4 doses). The effectiveness of chemoprophylaxis was 62.1% (95% CI: 40.3 to 75.9). To reduce household transmission, contacts should be investigated to detect further cases and to administer chemoprophylaxis. The current vaccination status of cases and contacts can reduce household transmission.

Geographical differences in whooping cough in Catalonia, Spain, from 1990 to 2010.

BACKGROUND: Whooping cough is a communicable disease whose incidence has increased in recent years in some countries with vaccination. Since 1981, in Catalonia (Spain), cases must be reported to the Public Health Department. In 1997, surveillance changed from aggregated counts to individual report and the surveillance system was improved after 2002. Catalan public health is universal with equal coverage geographically. The aim of this study was to determine whether there are differences in whooping cough incidence in rural and urban counties. METHODS: Cases in 1990-2010 were classified as rural or urban. Incidences and risk ratios (RR) between urban and rural counties and 95% CI were calculated. Associations between rural and urban counties and structural changes during the study period were analysed. RESULTS: Twelve years of the whole study period showed differences in incidence between rural and urban counties. The incidence was higher in urban counties in seven years and rural counties in five years. There was a positive association of whooping cough incidence in rural and urban counties in four-week periods. Structural changes were detected in the following four-week periods: 4th in 1993, 7th in 1996 and 3rd 2005 in rural counties and 5th 1993, 9th in 1996 and 8th in 2007 in urban counties. CONCLUSIONS: Differences in whooping cough between rural and urban counties were found. In most years, the incidence was higher in urban than in rural counties. Rural and urban counties show similar cyclic behaviour when four-week periods were considered.

Histological assessment of nanostructured fibrin-agarose skin substitutes grafted in burnt patients. A time-course study.

A previously developed fibrin-agarose skin model-UGRSKIN-showed promising clinical results in severely burnt patients. To determine the histological parameters associated to the biocompatibility and therapeutic effects of this model, we carried out a comprehensive structural and ultrastructural study of UGRSKIN grafted in severely burnt patients after 3 months of follow-up. The grafted epidermis was analogue to native human skin from day 30th onward, revealing well-structured strata with well-differentiated keratinocytes expressing CK5, CK8, CK10, claudin, plakoglobin, filaggrin, and involucrin in a similar way to controls, suggesting that the epidermis was able to mature and differentiate very early. Melanocytes and Langerhans cells were found from day 30th onward, together with a basement membrane, abundant hemidesmosomes and lack of rete ridges. At the dermal layer, we found an interface between the grafted skin and the host tissue at day 30th, which tended to disappear with time. The grafted superficial dermis showed a progressive increase in properly-oriented collagen fibers, elastic fibers and proteoglycans, including decorin, similarly to control dermis at day 60-90th of in vivo follow-up. Blood vessels determined by CD31 and SMA expression were more abundant in grafted skin than controls, whereas lymphatic vessels were more abundant at day 90th. These results contribute to shed light on the histological parameters associated to biocompatibility and therapeutic effect of the UGRSKIN model grafted in patients and demonstrate that the bioengineered skin grafted in patients is able to mature and differentiate very early at the epithelial level and after 60-90 days at the dermal level.

Use of the socio-ecological model to explore trusted sources of COVID-19 information in Black and Latinx communities in Michigan.

BACKGROUND: Identifying trusted sources of health information and exploring what makes these sources trustworthy is an important aspect of public health. This exploration requires embracing the cultural differences in minoritized communities, which are often treated as homogeneous. This qualitative study identifies and analyze the sources of trusted COVID-19 information among Black and Latinx communities in Michigan and assesses the rationale underlying this trust. METHODS: Interviews were conducted with 24 Black and 16 Latinx participants (n = 40) in four Michigan counties significantly impacted by COVID-19. The socio-ecological model was applied as an analytical framework for understanding the entities considered trusted sources of information. Within each level of the model, the dimensions of trustworthiness most salient for participants were identified. RESULTS: We found that sources of information came from all levels of the model, including interpersonal (COVID-19 survivors, church representatives, friends, relatives), organizational (employers, healthcare providers, traditional news reports), social media (hybrid source), community (members and groups), and public policy (county health department, federal and state government). Furthermore, participants determined whether they could trust information about COVID-19 by cross-referencing multiple resources. We identified competence, confidence, communication, and system trust as the dimensions of trustworthiness most often reported by participants. CONCLUSIONS: Our research suggests public health communications should engage in cross-referencing practices, providing information from sources at all levels of interaction, cultural competency, and awareness of historical/structural inequities. These efforts would be further strengthened by attending to needs for both factual information as well as care and personal connection.

Progress and harmonization of gene editing to treat human diseases: Proceeding of COST Action CA21113 GenE-HumDi.

The European Cooperation in Science and Technology (COST) is an intergovernmental organization dedicated to funding and coordinating scientific and technological research in Europe, fostering collaboration among researchers and institutions across countries. Recently, COST Action funded the "Genome Editing to treat Human Diseases" (GenE-HumDi) network, uniting various stakeholders such as pharmaceutical companies, academic institutions, regulatory agencies, biotech firms, and patient advocacy groups. GenE-HumDi's primary objective is to expedite the application of genome editing for therapeutic purposes in treating human diseases. To achieve this goal, GenE-HumDi is organized in several working groups, each focusing on specific aspects. These groups aim to enhance genome editing technologies, assess delivery systems, address safety concerns, promote clinical translation, and develop regulatory guidelines. The network seeks to establish standard procedures and guidelines for these areas to standardize scientific practices and facilitate knowledge sharing. Furthermore, GenE-HumDi aims to communicate its findings to the public in accessible yet rigorous language, emphasizing genome editing's potential to revolutionize the treatment of many human diseases. The inaugural GenE-HumDi meeting, held in Granada, Spain, in March 2023, featured presentations from experts in the field, discussing recent breakthroughs in delivery methods, safety measures, clinical translation, and regulatory aspects related to gene editing.

The impact of immigration and vaccination in reducing the incidence of hepatitis B in Catalonia (Spain).

BACKGROUND: The Hepatitis B virus (HBV) infection is a major cause of liver disease and liver cancer worldwide according to the World Health Organization. Following acute HBV infection, 1-5% of infected healthy adults and up to 90% of infected infants become chronic carriers and have an increased risk of cirrhosis and primary hepatocellular carcinoma. The aim of this study was to investigate the relationship between the reduction in acute hepatitis B incidence and the universal vaccination programme in preadolescents in Catalonia (Spain), taking population changes into account, and to construct a model to forecast the future incidence of cases that permits the best preventive strategy to be adopted. METHODS: Reported acute hepatitis B incidence in Catalonia according to age, gender, vaccination coverage, percentage of immigrants and the year of report of cases was analysed. A statistical analysis was made using three models: generalized linear models (GLM) with Poisson or negative binomial distribution and a generalized additive model (GAM). RESULTS: The higher the vaccination coverage, the lower the reported incidence of hepatitis B (p <0.01). In groups with vaccination coverage > 70%, the reduction in incidence was 2-fold higher than in groups with a coverage <70% (p <0.01). The increase in incidence was significantly-higher in groups with a high percentage of immigrants and more than 15% (p <0.01) in immigrant males of working age (19-49 years). CONCLUSIONS: The results of the adjusted models in this study confirm that the global incidence of hepatitis B has declined in Catalonia after the introduction of the universal preadolescent vaccination programme, but the incidence increased in male immigrants of working age. Given the potential severity of hepatitis B for the health of individuals and for the community, universal vaccination programmes should continue and programmes in risk groups, especially immigrants, should be strengthened.

High Influenza Vaccine Effectiveness and Absence of Increased Influenza-like-Illness Epidemic Activity in the 2021-2022 Influenza Season in Catalonia (Spain) Based on Surveillance Data Collected by Sentinel Pharmacies.

Influenza surveillance and influenza vaccination are the key activities for preventing and controlling influenza epidemics. The study assessed the influenza surveillance and influenza vaccination data obtained from sentinel pharmacies of Catalonia, Spain, in the 2021-2022 influenza season. The sentinel pharmacies were selected from all community pharmacies to report all influenza-like illness (ILI) cases detected during the 2021-2022 influenza season and collect influenza surveillance and influenza vaccination data. The ILI cases were identified based on European Centre for Disease Control (ECDC) criteria. The moving epidemic method (MEM) was used to assess the ILI epidemic activity. The screening method was used to assess influenza vaccination effectiveness in patients aged 65-or-more years old. The sentinel pharmacies reported 212 ILI cases with a negative COVID-19 test and a total number of 412 ILI cases. An absence of increased ILI epidemic activity was observed in the 2021-2022 influenza season based on two criteria: (1) Number of ILI cases reported per week in the 2021-2022 influenza season significantly lower than the MEM-based epidemic threshold. (2) Mean number of ILI cases reported per week in the 2021-2022 influenza season significantly lower than during the ILI/influenza epidemic periods detected from 2017 to 2020 using the same methodology. Influenza vaccination was effective in preventing ILI among patients aged 65-or-more-years old. The absence of the influenza epidemic during the 2021-2022 influenza season could be explained by influenza vaccination and COVID-19 prevention measures (wearing face masks, social distancing). The sentinel pharmacies provided influenza surveillance data not provided by traditional influenza surveillance systems.

Estimation of the incidence of invasive meningococcal disease using a capture-recapture model based on two independent surveillance systems in Catalonia, Spain.

OBJECTIVES: Invasive meningococcal disease (IMD) is an urgent notifiable disease and its early notification is essential to prevent cases. The objective of the study was to assess the sensitivity of two independent surveillance systems and to estimate the incidence of IMD. DESIGN: We used capture-recapture model based on two independent surveillance systems, the statutory disease reporting (SDR) system and the microbiological reporting system (MRS) of the Public Health Agency of Catalonia, between 2011 and 2015. The capture-recapture analysis and 95% CIs were calculated using the Chapman formula. Multivariate vector generalised linear model was performed for adjusted estimation. MEASURES: The variables collected were age, sex, year of report, size of municipality (<10 000 and ≥10 000), clinical form, death, serogroup, country of birth and type of reporting centre (private and public). RESULTS: The sensitivity of the two combined surveillance systems was 88.5% (85.0-92.0). SDR had greater sensitivity than the MRS (67.9%; 62.7-73.1 vs 64.7%; 59.4-70.0). In 2014-2015, the sensitivity of both systems was higher (80.6%; 73.2-87.9 vs 73.4%; 65.2-81.6) than in 2011-2013 (59.3%; 52.6-66.0 vs 58.3%; 51.6-65.1). In private centres, the sensitivity was higher for SDR than for MRS (100%; 100-100 vs 4.8%; -4.4-13.9). The adjusted estimate of IMD cases was lower than that obtained using the Chapman formula (279; 266-296 vs 313; 295-330). The estimated adjusted incidence of IMD was 0.7/100 000 persons-year. CONCLUSIONS: The sensitivity of enhanced surveillance through the combination of two complementary sources was higher than for the sources individually. Factors associated with under-reporting in different systems should be analysed to improve IMD surveillance.

Hepatitis A outbreaks in the vaccination era in Catalonia, Spain.

Hepatitis A outbreaks have a major impact on public health services and involve case investigation and intervention measures to susceptible contacts. At the end of 1998 a universal vaccination program with a combined hepatitis A+B vaccine was started in Catalonia (Spain) in 12-years-old preadolescents. The objective of this study was to compare the characteristics of hepatitis A outbreaks in the periods before and after the introduction of the preadolescent vaccination program and to estimate the preventable fraction of cases associated to outbreaks. The incidence rates of outbreaks, cases and hospitalization associated with each outbreak were calculated. Two periods were considered: before (1991-1998) and after (2000-2007) the introduction of mass vaccination. The preventable fraction and 95% confidence intervals (CI) of cases associated with outbreaks was calculated. The rate of associated cases with outbreaks was higher in the period before the vaccination program than in the post vaccination period (1.53 per 100,000 person-year vs 1.12 ; p< 0.001), but the rate of hospitalization was greater in the period after the introduction of vaccination program than in the period previous to vaccination (0.70 per million persons-year vs 0.08; p< 0.001). The preventable fraction of cases associated to outbreaks was 19.6%(95%CI 6.7-32.5) in the 0-4 years group and 16.7% (95% CI 6.0-27.5) in the 5-14 years group, but the highest figure (38.6%; 95%CI 21.3-55.9) was observed in the 15-24 years age group. The estimated proportion of cases associated with outbreaks that would theoretically have been prevented with the vaccination program suggests that substantial benefits have been obtained in Catalonia in people aged less than 25 years.

Effectiveness of maternal pertussis vaccination in protecting newborn: A matched case-control study.

INTRODUCTION: The objective was to estimate the effectiveness of maternal pertussis vaccination in protecting infants aged < 2 months. METHODS: We performed a case-control study. Laboratory-confirmed cases aged <8 weeks at disease onset were identified and 2-4 matched-controls born within ± 15 days of the case were included. Information was obtained from healthcare providers and maternal interviews. Odds ratios (OR) were calculated using multivariable conditional logistic regression. Vaccine effectiveness (VE) was estimated as (1 - OR) × 100%. RESULTS: 47 cases and 124 controls were studied. The mean age (in days) (39.8 ± 12.7 vs. 40.8 ± 13.2), weeks of gestation (38.8 vs. 39.1, p = 0.43) and mean birth weight (3.309 vs. 3.253 kg, p = 0.55) were comparable between cases and controls. Mothers of cases were less frequently vaccinated in the third trimester (59.6% vs. 83.9%, p <0.001). The VE of maternal vaccination in pregnancy was 88.0% (95%CI 53.8% -96.5%), and was slightly higher in those vaccinated before the 32nd week of gestation (88.5% vs 87.8%). CONCLUSION: Pertussis vaccination in pregnancy is very effective in reducing pertussis in children aged < 2 months. Vaccination before and after the 32nd week of pregnancy are equally effective in reducing the risk of pertussis.

[Evaluation of mass vaccination programmes: the experience of Hepatitis A in Catalonia]. / Evaluación del impacto de los programas de vacunación masiva: la experiencia de la hepatitis A en Cataluña.

BACKGROUND: The hepatitis A + B vaccination programme of preadolescents was introduced in 1998 in Catalonia. During the following years, one of the main objectives has been to quantify the reduction in the incidence of hepatitis A caused by the vaccination programme. METHODS: A retrospective analysis applying the space-time scan statistic to reported incidence rates of hepatitis A was carried out in the counties of Catalonia from 1992 to 2007. The relative risk (RR) was calculated and the spatial autocorrelation was estimated using Moran's I statistic. RESULTS: Six of the 7 space-time clusters identified by the scan statistic occurred in the pre-vaccine era (1992-1998) and only one in the post-vaccine era (1992-2007). In the first 10 four-weekly periods of the post-vaccine era (1999-2005) there was a significant reduction in the incidence of hepatitis A in Catalonia with respect to the pre-vaccine era (1992-1998) (p<0,01). CONCLUSIONS: Moran's I statistic showed no pattern of global spatial dependence and was useful in detecting local clusters. These results corroborate previous studies that attributed most of the reduction in the incidence of hepatitis A in Catalonia to the effect of vaccination.

Transplant of Tissue-Engineered Artificial Autologous Human Skin in Andalusia: An Example of Coordination and Institutional Collaboration.

A new model of tissue-engineered artificial autologous human skin developed in Andalusia is currently being transplanted into patients suffering from large burns within the Andalusian Public Healthcare System. This product is considered an advanced therapy medicinal product (ATMP) in Europe, and its clinical use implies meeting transplant and medicinal product legal requirements, being the Guidelines of Good Manufacturing Practice for ATMPs of particular importance. The preclinical research and clinical translation of the product have represented a technical, regulatory, and organizational challenge, which has taken 10 years since the first preclinical experiments were designed. Twelve patients with large burns, including 3 pediatric patients, have hitherto received artificial autologous skin grafts with an overall survival rate of 75% and positive clinical, homeostatic, and histologic results. Achieving such a milestone within our Healthcare System was possible through a multidisciplinary approach and the joint efforts of multiple publicly funded institutions and units under the coordination of the Andalusian Initiative for Advanced Therapies. In this article, we present the organizational model set up to facilitate collaboration and logistics among the professionals involved, totaling more than 80 people. The similarities between the tissue-engineered artificial autologous human skin transplant and other organ and tissue transplants, in terms of logistic requirements, reveal how regional and hospital transplant coordination have played a crucial role.

Reduction of Direct Health Costs Associated with Pertussis Vaccination with Acellular Vaccines in Children Aged 0-9 Years with Pertussis in Catalonia (Spain).

OBJECTIVES: The aim of this study was to assess direct health costs in children with pertussis aged 0-9 years who were vaccinated, partially vaccinated, and unvaccinated during childhood, and to assess the association between pertussis costs and pertussis vaccination in Catalonia (Spain) in 2012-2013. METHODS: Direct healthcare costs included pertussis treatment, pertussis detection, and preventive chemotherapy of contacts. Pertussis patients were considered vaccinated when they had received 4-5 doses, and unvaccinated or partially vaccinated when they had received 0-3 doses of vaccine. The Chi square test and the odds ratios were used to compare percentages and the t test was used to compare mean pertussis costs in different groups, considering a p < 0.05 as statistically significant. The correlation between pertussis costs and study variables was assessed using the Spearman's ρ, with a p < 0.05 as statistically significant. Multiple linear regression analysis (IBM-SPSS program) was used to quantify the association of pertussis vaccination and other study variables with pertussis costs. RESULTS: Vaccinated children with pertussis aged 0-9 years had significantly lower odds ratios of hospitalizations (OR 0.02, p < 0.001), laboratory confirmation (OR 0.21, p < 0.001), and severe disease (OR 0.02, p < 0.001) than unvaccinated or partially vaccinated children with pertussis of the same age. Mean direct healthcare costs were significantly lower (p < 0.001) in vaccinated patients (€190.6) than in unvaccinated patients (€3550.8), partially vaccinated patients (€1116.9), and unvaccinated/partially vaccinated patients (€2330). Multivariable linear regression analysis showed that pertussis vaccination with 4-5 doses was associated with a non-significant reduction of pertussis costs of €107.9 per case after taking into account the effect of other study variables, and €200 per case after taking into account pertussis severity. CONCLUSIONS: Direct healthcare costs were lower in children with pertussis aged 0-9 years vaccinated with 4-5 doses of acellular vaccines than in unvaccinated or partially vaccinated children with pertussis of the same age.

Effectiveness and impact of the hepatitis B vaccination program in preadolescents in Catalonia 21 years after its introduction.

Hepatitis B is a viral disease of global importance. In Catalonia in the 1980s, the seroepidemiological pattern of HBV infection was low-intermediate. In 1990, the Expert Committee on Vaccinations of the Department of Health of the Generalitat of Catalonia evaluated the systematic introduction of hepatitis B vaccination in preadolescents, maintaining the vaccination of risk groups. The objective of this study was to estimate the effectiveness and impact of the systematic hepatitis B vaccination programme in preadolescents in Catalonia 21 years after its introduction. A retrospective cohort study was conducted, comparing the disease incidence in vaccinated and unvaccinated cohorts. Cases of hepatitis B were defined as those reported by the General Subdirectorate of Surveillance and Response to Public Health Emergencies between 2000 and 2014. The incidence rate was 2.5 per 100,000 persons in 1991 and 1.2 per 100,000 persons in 2014, a reduction of 52%. During the study period, 388 cases of hepatitis B infection were notified, of which three were classified as vaccine failures. Vaccine effectiveness was 99.30% (95% CI: 97.83-99.78) and the population prevented fraction in the cohorts of preadolescents studied was 64.56% (95% CI: 60.45-68.66). The effectiveness and impact of the hepatitis B vaccination program in preadolescents in Catalonia is high, with the consequent benefits for the population.

Successful development and clinical translation of a novel anterior lamellar artificial cornea.

Blindness due to corneal diseases is a common pathology affecting up to 23 million individuals worldwide. The tissue-engineered anterior human cornea, which is currently being tested in a Phase I/II clinical trial to treat severe corneal trophic ulcers with preliminary good feasibility and safety results. This bioartificial cornea is based on a nanostructured fibrin-agarose biomaterial containing human allogeneic stromal keratocytes and cornea epithelial cells, mimicking the human native anterior cornea in terms of optical, mechanical, and biological behavior. This product is manufactured as a clinical-grade tissue engineering product, fulfilling European requirements and regulations. The clinical translation process included several phases: an initial in vitro and in vivo preclinical research plan, including preclinical advice from the Spanish Medicines Agency followed by additional preclinical development, the adaptation of the biofabrication protocols to a good manufacturing practice manufacturing process, including all quality controls required, and the design of an advanced therapy clinical trial. The experimental development and successful translation of advanced therapy medicinal products for clinical application has to overcome many obstacles, especially when undertaken by academia or SMEs. We expect that our experience and research strategy may help future researchers to efficiently transfer their preclinical results into the clinical settings.

[Use of Deliberative Dialogues for the Formulation of Recommendations for Clinical Practice Guidelines]. / Utilidad de los diálogos deliberativos para la formulación de recomendaciones de guías de práctica clínica.

This study reports the experience obtained by the National Institute of Health of Peru in the use of deliberative dialogues for the formulation of recommendations as one of the stages of the process of adaptation of evidence-based clinical practice guidelines using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system. Using a multidisciplinary approach, this study describes: 1. the public health problems addressed in the dialogues; 2. the role of the involved parties; 3. the parameters that were considered before and during the discussions; 4. the challenges for optimizing these dialogues and stimulating the interaction between scientific evidence and the added value provided by the involved parties through their experiences, perspectives, and knowledge for the development of recommendations in health.

En el presente artículo se reporta la experiencia obtenida por el Instituto Nacional de Salud de Perú, en la utilidad del desarrollo de diálogos deliberativos para la formulación de recomendaciones, como uno de los componentes del proceso de adaptación de Guías de Práctica Clínica basadas en evidencia, utilizando el sistema GRADE (por sus siglas en ingles: Grading of Recommendations, Assessment, Development and Evaluations). Describe los temas de salud pública que fueron deliberados y la participación de los actores implicados con un enfoque multidisciplinario. Presenta los aspectos que fueron tomados en cuenta de forma previa y durante los diálogos. Finalmente, propone los desafíos que serán abordados en las siguientes experiencias a fin de optimizar estos procesos y colaborar en la interacción entre las evidencias científicas y el valor agregado que otorgan los actores implicados a través de su experiencias, perspectivas y conocimientos para el desarrollo de recomendaciones en salud.