Effectiveness of a Meningococcal Group B Vaccine (4CMenB) in Children.

BACKGROUND: In September 2015, the four-component, protein-based meningococcal serogroup B vaccine (4CMenB; Bexsero) became available for private purchase in Spain. METHODS: We conducted a nationwide matched case-control study to assess the effectiveness of 4CMenB in preventing invasive meningococcal disease in children. The study included all laboratory-confirmed cases of invasive meningococcal disease in children younger than 60 months of age between October 5, 2015, and October 6, 2019, in Spain. Each case patient was matched with four controls according to date of birth and province. 4CMenB vaccination status of the case patients and controls was compared with the use of multivariate conditional logistic regression. RESULTS: We compared 306 case patients (243 [79.4%] with serogroup B disease) with 1224 controls. A total of 35 case patients (11.4%) and 298 controls (24.3%) had received at least one dose of 4CMenB. The effectiveness of complete vaccination with 4CMenB (defined as receipt of at least 2 doses, administered in accordance with the manufacturer's recommendations) was 76% (95% confidence interval [CI], 57 to 87) against invasive meningococcal disease caused by any serogroup, and partial vaccination was 54% (95% CI, 18 to 74) effective. Complete vaccination resulted in an effectiveness of 71% (95% CI, 45 to 85) against meningococcal serogroup B disease. Vaccine effectiveness with at least one dose of 4CMenB was 64% (95% CI, 41 to 78) against serogroup B disease and 82% (95% CI, 21 to 96) against non-serogroup B disease. With the use of the genetic Meningococcal Antigen Typing System, serogroup B strains that were expected to be covered by 4CMenB were detected in 44 case patients, none of whom had been vaccinated. CONCLUSIONS: Complete vaccination with 4CMenB was found to be effective in preventing invasive disease by serogroup B and non-serogroup B meningococci in children younger than 5 years of age.

Long COVID 12 months after discharge: persistent symptoms in patients hospitalised due to COVID-19 and patients hospitalised due to other causes-a multicentre cohort study.

BACKGROUND: Long-term-specific sequelae or persistent symptoms (SPS) after hospitalisation due to COVID-19 are not known. The aim of this study was to explore the presence of SPS 12 months after discharge in survivors hospitalised due to COVID-19 and compare it with survivors hospitalised due to other causes. METHODS: Prospective cohort study, the Andalusian Cohort of Hospitalised patients for COVID-19 (ANCOHVID study), conducted in 4 hospitals and 29 primary care centres in Andalusia, Spain. The sample was composed of 906 adult patients; 453 patients hospitalised due to COVID-19 (exposed) and 453 hospitalised due to other causes (non-exposed) from March 1 to April 15, 2020, and discharged alive. The main outcomes were (1) the prevalence of SPS at 12 months after discharge and (2) the incidence of SPS after discharge. Outcome data at 12 months were compared between the exposed and non-exposed cohorts. Risk ratios were calculated, and bivariate analyses were performed. RESULTS: A total of 163 (36.1%) and 160 (35.3%) patients of the exposed and non-exposed cohorts, respectively, showed at least one SPS at 12 months after discharge. The SPS with higher prevalence in the subgroup of patients hospitalised due to COVID-19 12 months after discharge were persistent pharyngeal symptoms (p<0.001), neurological SPS (p=0.049), confusion or memory loss (p=0.043), thrombotic events (p=0.025) and anxiety (p=0.046). The incidence of SPS was higher for the exposed cohort regarding pharyngeal symptoms (risk ratio, 8.00; 95% CI, 1.85 to 36.12), confusion or memory loss (risk ratio, 3.50; 95% CI, 1.16 to 10.55) and anxiety symptoms (risk ratio, 2.36; 95% CI, 1.28 to 4.34). CONCLUSIONS: There was a similar frequency of long-term SPS after discharge at 12 months, regardless of the cause of admission (COVID-19 or other causes). Nevertheless, some symptoms that were found to be more associated with COVID-19, such as memory loss or anxiety, merit further investigation. These results should guide future follow-up of COVID-19 patients after hospital discharge.

Socioeconomic differences in COVID-19 infection, hospitalisation and mortality in urban areas in a region in the South of Europe.

BACKGROUND: To analyse differences in confirmed cases, hospitalisations and deaths due to COVID-19 related to census section socioeconomic variables.  METHODS: Ecological study in the 12 largest municipalities in Andalusia (Spain) during the first three epidemic waves of the COVID-19 (02/26/20-03/31/21), covering 2,246 census sections (unit of analysis) and 3,027,000 inhabitants. Incidence was calculated, standardised by age and sex, for infection, hospitalisation and deaths based on average gross income per household (AGI) for the census tracts in each urban area. Association studied using a Poisson Bayesian regression model with random effects for spatial smoothing. RESULTS: There were 140,743 cases of COVID-19, of which 12,585 were hospitalised and 2,255 died. 95.2% of cases were attributed to the second and third waves, which were jointly analysed. We observed a protective effect of income for infection in 3/12 cities. Almeria had the largest protective effect (smoothed relative risk (SRR) = 0.84 (0.75-0.94 CI 95%). This relationship reappeared with greater magnitude in 10/12 cities for hospitalisation, lowest risk in Algeciras SRR = 0.41 (0.29-0.56). The pattern was repeated for deaths in all urban areas and reached statistical significance in 8 cities. Lowest risk in Dos Hermanas SRR = 0.35 (0.15-0.81). CONCLUSIONS: Income inequalities by geographical area were found in the incidence of COVID-19. The strengths of the association increased when analysing the severe outcomes of hospitalisations and, above all, deaths.

Listeriosis outbreak caused by contaminated stuffed pork, Andalusia, Spain, July to October 2019.

Between 1 July and 26 October 2019 in Andalusia, Spain, a large outbreak with 207 confirmed cases of listeriosis was identified. Confirmed cases had a median age of 44 years (range: 0-94) and 114 were women (55.1%). Most cases (n = 154) had mild gastroenteritis, 141 (68.1%) required hospitalisation and three died; five of 34 pregnant women had a miscarriage. The median incubation period was 1 day (range: 0-30), and was significantly shorter in cases presenting with gastroenteritis compared to those presenting without gastroenteritis (1 day vs. 3 days, respectively, p value < 0.001). Stuffed pork, a ready-to-eat product consumed unheated, from a single producer contaminated with Listeria monocytogenes ST388 was identified as the source of infection. The outbreak strain was identified in 189 human samples and 87 non-human (82 food and 5 environmental) samples. Notification of new cases declined abruptly after control measures were implemented. These included contaminated food recall, protocols for clinical management of suspected cases and for post-exposure prophylaxis in pregnant women and communication campaigns with concise messages to the population through social media. Given that there were 3,059 probable cases, this was the largest L. monocytogenes outbreak ever reported in Europe.

Sequelae, persistent symptomatology and outcomes after COVID-19 hospitalization: the ANCOHVID multicentre 6-month follow-up study.

BACKGROUND: Long-term effects of COVID-19, also called Long COVID, affect more than 10% of patients. The most severe cases (i.e. those requiring hospitalization) present a higher frequency of sequelae, but detailed information on these effects is still lacking. The objective of this study is to identify and quantify the frequency and outcomes associated with the presence of sequelae or persistent symptomatology (SPS) during the 6 months after discharge for COVID-19. METHODS: Retrospective observational 6-month follow-up study conducted in four hospitals of Spain. A cohort of all 969 patients who were hospitalized with PCR-confirmed SARS-CoV-2 from March 1 to April 15, 2020, was included. We collected all the SPS during the 6 months after discharge reported by patients during follow-up from primary care records. Cluster analyses were performed to validate the measures. The main outcome measures were return to the Emergency Services, hospital readmission and post-discharge death. Surviving patients' outcomes were collected through clinical histories and primary care reports. Multiple logistic regression models were applied. RESULTS: The 797 (82.2%) patients who survived constituted the sample followed, while the rest died from COVID-19. The mean age was 63.0 years, 53.7% of them were men and 509 (63.9%) reported some sequelae during the first 6 months after discharge. These sequelae were very diverse, but the most frequent were respiratory (42.0%), systemic (36.1%), neurological (20.8%), mental health (12.2%) and infectious (7.9%) SPS, with some differences by sex. Women presented higher frequencies of headache and mental health SPS, among others. A total of 160 (20.1%) patients returned to the Emergency Services, 35 (4.4%) required hospital readmission and 8 (1.0%) died during follow-up. The main factors independently associated with the return to Emergency Services were persistent fever, dermatological SPS, arrythmia or palpitations, thoracic pain and pneumonia. CONCLUSIONS: COVID-19 cases requiring hospitalization during the first wave of the pandemic developed a significant range of mid- to long-term SPS. A detailed list of symptoms and outcomes is provided in this multicentre study. Identification of possible factors associated with these SPS could be useful to optimize preventive follow-up strategies in primary care for the coming months of the pandemic.

The role of undergraduate medical students training in respect for patient confidentiality.

BACKGROUND: Encouraging professional integrity is vital for providing a standard of excellence in quality medical care and education and in promoting a culture of respect and responsibility. The primary objective of this work consisted of studying the relationship of medical students to the right to patient privacy in Spain, specifically by analysing the conditions for accessing patient clinical histories (CHs). METHODS: A cross-sectional study was conducted based on a questionnaire sent by e-mail to final-year students at 41 Spanish universities. It had 14 multiple choice and closed questions framed in 3 large blocks. The first question addressed basic general knowledge issues on the right to privacy and the obligation for confidentiality. The two remaining blocks were made up of questions directed towards evaluating the frequency with which certain requirements and action steps related to students attending patients were performed and regarding the guarantees associated with accessing and handling patient CHs both on paper and in the Electronic Medical Record. RESULTS: A total of 245 valid replies were considered. A total of 67.8 % of participants were women, with an average age of 24.05 ± 3.49 years. Up to 90.6 % were aware that confidentiality affected the data in CHs, although 43.3 % possessed non-anonymized photocopies of patient clinical reports outside the healthcare context, and only 49.8 % of the students were always adequately identified. A total of 59.2 % accessed patient CHs on some occasions by using passwords belonging to healthcare professionals, 77.2 % of them did not have the patients' express consent, and 71.9 % accessed a CH that was not anonymised. CONCLUSIONS: The role of healthcare institutions and universities is considered to be fundamental in implementing educational measures regarding the risks and ethical and legal problems arising from the use of CHs among professionals and students. A thorough study of medical ethics is needed through the analysis of clinical cases and direct exposure to situations in which the patient's confidentiality is questioned.

Risk Factors for Multidrug-Resistant Gram-Negative Bacteria Carriage upon Admission to the Intensive Care Unit.

Multidrug-resistant Gram-negative bacteria (MDR-GNB) are microorganisms that have acquired resistance to extended-spectrum antibacterials and constitute an emerging threat to public health. Although carriers are an important source of transmission in healthcare settings, data about risk factors for MDR-GNB carriage are limited. Therefore, we aimed to identify risk factors for MDR-GNB carriage upon intensive care unit (ICU) admission and to optimise screening strategies. We conducted a case-control study. Admissions of adult patients to the ICU of a 1000-bed hospital during a year were included. We collected sociodemographic, clinical and microbiological data and performed a multivariate logistic regression model. A total of 1342 patients resulted in 1476 episodes of ICU admission, 91 (6.2%) of whom harboured MDR-GNB (38.5% women; median age 63.9 years). The most frequently isolated pathogens were Escherichia coli (57%) and Klebsiella pneumoniae (16%). The most frequent resistance mechanism was production of extended-spectrum beta lactamases. MDR-GNB carriage was associated to liver cirrhosis (OR 6.54, 95% CI 2.17-19.17), previous MDR-GNB carriage (OR 5.34, 1.55-16.60), digestive surgery (OR 2.83, 1.29-5.89) and length of hospital stay (OR 1.01 per day, 1.00-1.03). Several risk factors for MDR-GNB carriage upon admission to a high-risk setting were identified; the main comorbidity was liver cirrhosis.

Impact of the COVID-19 Pandemic on Palliative Care in Cancer Patients in Spain.

BACKGROUND: The COVID-19 pandemic outbreak has severely affected healthcare organizations worldwide, and the provision of palliative care (PC) to cancer patients has been no exception. The aim of this paper was to analyse the levels of health care provided by the Clinical Management Unit for PC in Córdoba (Spain) for cancer patients. METHOD: a retrospective cohort study was conducted. It analyzed the PC internal management database including all cancer patients treated in the period of 2018-2021. RESULTS: 1967 cases were studied. There was a drop in cancer cases (p = 0.008), deaths at the PC hospital (p < 0.001), and referrals from primary care (p < 0.001). However, there was a rise in highly complex clinical situations (p = 0.020) and in ECOG performance status scores of 3-4 (p < 0.001). The pandemic was not shown to be a risk factor for survival in the PC program (0.99 [0.82-1.20]; p = 0.931). However, being female (p = 0.005), being older and having a high Karnofsky Performance Status (KPS) score (p < 0.001) could be indicators of a longer stay. CONCLUSION: The COVID-19 pandemic has presented a challenge in the management of patients requiring PC and has highlighted the urgent needs of the healthcare system if it is to continue providing a level of care which meets the needs of patients and their families.

Sex Differences and Predictors of In-Hospital Mortality among Patients with COVID-19: Results from the ANCOHVID Multicentre Study.

Spain is one of the countries most affected by the COVID-19 pandemic. Although risk factors for severe disease are published, sex differences have been widely neglected. In this multicentre study, we aimed to identify predictors of in-hospital mortality in men and women hospitalised with COVID-19. An observational longitudinal study was conducted in the cohort of patients admitted to four hospitals in Andalusia, Spain, from 1 March 2020 to 15 April 2020. Sociodemographic and clinical data were collected from hospital records. The Kaplan-Meier method was used to estimate 30-day survival and multiple Cox regression models were applied. All analyses were stratified by sex. A total of 968 patients were included (54.8% men, median age 67.0 years). In-hospital mortality reached 19.1% in men and 16.0% in women. Factors independently associated with an increased hazard of death were advanced age, higher CURB-65 score and not receiving azithromycin treatment, in both sexes; active cancer and autoimmune disease, in men; cardiovascular disease and chronic lung disease, in women. Disease outcomes and predictors of death differed between sexes. In-hospital mortality was higher in men, but the long-term effects of COVID-19 merit further research. The sex-differential impact of the pandemic should be addressed in public health policies.

[Economic evaluation of the introduction of 4CMenB (Bexsero®) in the national vaccine schedule in Spain]. / Evaluación económica de la inclusión en el calendario vacunal de 4CMenB (Bexsero®) en España.

INTRODUCTION: Bexsero® (4CMenB), meningococcal B vaccine, was licensed in Europe in 2013. In Spain, despite MenB being the most frequent cause of invasive meningococcal disease (IMD), Bexsero® is recommended and financed for patients at increased risk of IMD but is not financed by the NHS in the routine vaccination schedule. OBJECTIVE: to evaluate the cost-utility, epidemiological impact, and total costs of the introduction of 4CMenB into the vaccination schedule to help inform vaccine policy in Spain. METHOD: We adapted a cost-utility analysis, a probabilistic decision-tree, to Spain. A cohort of new-born infants in 2015 was modelled with two dosages, using two different strategies: routine vaccination schedule with 4CMenB and non-vaccination. Costs were measured from a payer perspective and benefits were calculated in quality-adjusted life years (QALYs). A Monte Carlo analysis and 32 scenarios were performed to assess the robustness and the uncertainty of our results. RESULTS: With the 3+1 dosage, routine vaccination prevented 54% of cases and deaths and an incremental cost-utility ratio (ICUR) of 351.389 €/QALY (95% confidence interval [95%CI]: 265,193-538,428) was estimated. The 2+1 dosage prevented 50% of cases and deaths, with an ICUR of 278.556 €/QALY (95%CI: 210,285-430,122). CONCLUSIONS: Given the current incidence of invasive meningococcal disease in Spain and the information available from 4CMenB, our model shows that routine vaccination is not cost-effective at the current price. Only with a vaccine price of 1.45 € for the 3+1 schedule or 3.37 € for the 2+1 schedule could it be recommended based on efficiency criteria.

Knowledge about E-Cigarettes and Tobacco Harm Reduction among Public Health Residents in Europe.

INTRODUCTION: Although electronic cigarettes (e-cigarettes) and other tobacco-related products are becoming widely popular as alternatives to tobacco, little has been published on the knowledge of healthcare workers about their use. Thus, the aim of this study was to elicit the current knowledge and perceptions about e-cigarettes and tobacco harm reduction (THR) among medical residents in public health (MRPH). MATERIAL AND METHODS: A Europe-wide cross-sectional study was carried out amongst MRPH from the countries associated with the European Network of MRPH from April to October 2018 using an online questionnaire. RESULTS: 256 MRPHs agreed to participate in the survey. Approximately half the participants were women (57.4%), with a median age of 30 years, and were mainly Italian (26.7%), Spanish (16.9%) and Portuguese (16.5%). Smoking prevalence was 12.9%. Overall, risk scores significantly differed for each investigated smoking product when compared with e-cigarettes; with tobacco cigarettes and snus perceived as more risky, and nicotine replacement therapy (NRT) and non-NRT oral medications seen as less risky (p < 0.01 for all). Regarding the effects of nicotine on health, the vast majority of MRPHs associated nicotine with all smoking-related diseases. Knowledge of THR was low throughout the whole sample. CONCLUSIONS: European MRPH showed a suboptimal level of knowledge about e-cigarettes and THR. Training programs for public health and preventive medicine trainees should address this gap.

Evaluación económica de la inclusión en el calendario vacunal de 4CMenB (Bexsero(R)) en España / Economic evaluation of the introduction of 4CMenB (Bexsero(R)) in the national vaccine schedule in Spain

INTRODUCCIÓN: Bexsero® (4CMenB), vacuna contra el meningococo B, fue autorizada en Europa en 2013. En España, a pesar de que el meningococo B es la principal causa de enfermedad meningocócica invasiva (EMI), Bexsero® está recomendada y financiada para pacientes con alto riesgo de EMI pero no de forma sistemática en el calendario vacunal del SNS. OBJETIVO: Evaluar el coste-utilidad, el impacto epidemiológico y los costes totales de la introducción de 4CMenB para una política vacunal informada en España. MÉTODO: Se adaptó para España un análisis de coste-utilidad, árbol de decisión probabilístico. Una cohorte de recién nacidos en 2015 fue modelizada con dos posologías mediante dos estrategias: vacunación sistemática con 4CMenB o no vacunación. Los costes se midieron desde la perspectiva del pagador y los beneficios se calcularon en años de vida ajustados por calidad (AVAC). Se realizó un análisis de Monte Carlo y se consideraron 32 escenarios para valorar la robustez y la incertidumbre de los resultados. RESULTADOS: Con la pauta 3+1, la vacunación sistemática previno el 54% de los casos y de las muertes, y se estimó una razón de coste-utilidad incremental (RCUI) de 351.389 €/AVAC (intervalo de confianza del 95% [IC95%]: 265.193-538.428). La pauta 2+1 previno el 50% de los casos y de las muertes, con una RCUI de 278.556 €/AVAC (IC95%: 210.285-430.122). CONCLUSIONES: Dada la incidencia actual de enfermedad meningocócica invasiva en España y la información disponible sobre 4CMenB, nuestro modelo indica que la vacunación sistemática no es coste-efectiva con el actual precio. Solo con un precio de 1,45 € para la pauta 3+1 o de 3,37 € para la pauta 2+1 podría ser recomendada basándose en su eficiencia

INTRODUCTION: Bexsero® (4CMenB), meningococcal B vaccine, was licensed in Europe in 2013. In Spain, despite MenB being the most frequent cause of invasive meningococcal disease (IMD), Bexsero® is recommended and financed for patients at increased risk of IMD but is not financed by the NHS in the routine vaccination schedule. OBJECTIVE: to evaluate the cost-utility, epidemiological impact, and total costs of the introduction of 4CMenB into the vaccination schedule to help inform vaccine policy in Spain. METHOD: We adapted a cost-utility analysis, a probabilistic decision-tree, to Spain. A cohort of new-born infants in 2015 was modelled with two dosages, using two different strategies: routine vaccination schedule with 4CMenB and non-vaccination. Costs were measured from a payer perspective and benefits were calculated in quality-adjusted life years (QALYs). A Monte Carlo analysis and 32 scenarios were performed to assess the robustness and the uncertainty of our results. RESULTS: With the 3+1 dosage, routine vaccination prevented 54% of cases and deaths and an incremental cost-utility ratio (ICUR) of 351.389 €/QALY (95% confidence interval [95%CI]: 265,193-538,428) was estimated. The 2+1 dosage prevented 50% of cases and deaths, with an ICUR of 278.556 €/QALY (95%CI: 210,285-430,122). CONCLUSIONS: Given the current incidence of invasive meningococcal disease in Spain and the information available from 4CMenB, our model shows that routine vaccination is not cost-effective at the current price. Only with a vaccine price of 1.45 € for the 3+1 schedule or 3.37 € for the 2+1 schedule could it be recommended based on efficiency criteria