Qualitative Subgenomic RNA to Monitor the Response to Remdesivir in Hospitalized Patients With Coronavirus Disease 2019: Impact on the Length of Hospital Stay and Mortality.

BACKGROUND: There is no reliable microbiological marker to guide the indication and the response to antiviral treatment in patients with coronavirus disease 2019 (COVID-19). We aimed to evaluate the dynamics of subgenomic RNA (sgRNA) in patients with COVID-19 before and after receiving treatment with remdesivir. METHODS: We included consecutive patients admitted for COVID-19 who received remdesivir according to our institutional protocol and accepted to participate in the study. A nasopharyngeal swab for quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was collected at baseline and after 3 and 5 days of treatment with remdesivir. Genomic and sgRNA were analyzed in those samples and main comorbidities and evolution were collected for the analyses. The main outcomes were early discharge (≤10 days) and 30-day mortality. RESULTS: A total of 117 patients were included in the study, of whom 24 had a negative sgRNA at baseline, with 62.5% (15/24) receiving early discharge (≤10 days) and no deaths in this group. From the 93 remaining patients, 62 had a negative sgRNA at day 5 with 37/62 (59.6%) with early discharge and a mortality rate of 4.8% (3/62). In the subgroup of 31 patients with positive sgRNA after 5 days of remdesivir, the early discharge rate was 29% (9/31) and the mortality rate was 16.1% (5/31). In multivariable analyses, the variables associated with early discharge were negative sgRNA at day 3 and not needing treatment with corticosteroids or intensive care unit admission. CONCLUSIONS: Qualitative sgRNA could help in monitoring the virological response in patients who receive remdesivir. Further studies are needed to confirm these findings.

HPV Vaccination in Women with Cervical Intraepithelial Neoplasia Undergoing Excisional Treatment: Insights into Unsolved Questions.

Several questions regarding the role of vaccination in women treated for high-grade cervical intraepithelial lesion (HSIL) have not been clarified. One of the main queries is whether the time at which the vaccine is administered (before or after treatment) influences the protection against post-treatment HSIL. A second unanswered question is whether the vaccine has any effect in women with persistent HPV after treatment. We aimed to address these questions in a study of 398 women undergoing excisional treatment from July 2016 to December 2019. Vaccination was funded and offered to all women undergoing treatment. A total of 306 women (76.9%) accepted HPV vaccination (vaccinated group): 113 (36.9%) received the first dose before excision and 193 (63.1%) after the procedure. A total of 92 women (23.1%) refused the vaccine (non-vaccinated group). Women vaccinated before treatment showed a lower rate of post-treatment HSIL compared with non-vaccinated women (0.9% vs. 6.5%; p = 0.047). Among women with persistent HPV infection after treatment, those who had received the vaccine showed a lower prevalence of post-treatment HSIL than non-vaccinated women (2.6% vs. 10.5%; p = 0.043). In conclusion, this study shows that HPV vaccination before treatment reduces the prevalence of post-treatment HSIL and suggests that vaccination might even benefit women with persistent HPV after treatment.

Immunogenicity and reactogenicity of BNT162b2 booster in ChAdOx1-S-primed participants (CombiVacS): a multicentre, open-label, randomised, controlled, phase 2 trial.

BACKGROUND: To date, no immunological data on COVID-19 heterologous vaccination schedules in humans have been reported. We assessed the immunogenicity and reactogenicity of BNT162b2 (Comirnaty, BioNTech, Mainz, Germany) administered as second dose in participants primed with ChAdOx1-S (Vaxzevria, AstraZeneca, Oxford, UK). METHODS: We did a phase 2, open-label, randomised, controlled trial on adults aged 18-60 years, vaccinated with a single dose of ChAdOx1-S 8-12 weeks before screening, and no history of SARS-CoV-2 infection. Participants were randomly assigned (2:1) to receive either BNT162b2 (0·3 mL) via a single intramuscular injection (intervention group) or continue observation (control group). The primary outcome was 14-day immunogenicity, measured by immunoassays for SARS-CoV-2 trimeric spike protein and receptor binding domain (RBD). Antibody functionality was assessed using a pseudovirus neutralisation assay, and cellular immune response using an interferon-γ immunoassay. The safety outcome was 7-day reactogenicity, measured as solicited local and systemic adverse events. The primary analysis included all participants who received at least one dose of BNT162b2 and who had at least one efficacy evaluation after baseline. The safety analysis included all participants who received BNT162b2. This study is registered with EudraCT (2021-001978-37) and ClinicalTrials.gov (NCT04860739), and is ongoing. FINDINGS: Between April 24 and 30, 2021, 676 individuals were enrolled and randomly assigned to either the intervention group (n=450) or control group (n=226) at five university hospitals in Spain (mean age 44 years [SD 9]; 382 [57%] women and 294 [43%] men). 663 (98%) participants (n=441 intervention, n=222 control) completed the study up to day 14. In the intervention group, geometric mean titres of RBD antibodies increased from 71·46 BAU/mL (95% CI 59·84-85·33) at baseline to 7756·68 BAU/mL (7371·53-8161·96) at day 14 (p<0·0001). IgG against trimeric spike protein increased from 98·40 BAU/mL (95% CI 85·69-112·99) to 3684·87 BAU/mL (3429·87-3958·83). The interventional:control ratio was 77·69 (95% CI 59·57-101·32) for RBD protein and 36·41 (29·31-45·23) for trimeric spike protein IgG. Reactions were mild (n=1210 [68%]) or moderate (n=530 [30%]), with injection site pain (n=395 [88%]), induration (n=159 [35%]), headache (n=199 [44%]), and myalgia (n=194 [43%]) the most commonly reported adverse events. No serious adverse events were reported. INTERPRETATION: BNT162b2 given as a second dose in individuals prime vaccinated with ChAdOx1-S induced a robust immune response, with an acceptable and manageable reactogenicity profile. FUNDING: Instituto de Salud Carlos III. TRANSLATIONS: For the French and Spanish translations of the abstract see Supplementary Materials section.

Incidence and Impact of COVID-19 in MS: A Survey From a Barcelona MS Unit.

OBJECTIVE: To investigate the incidence of coronavirus disease 2019 (COVID-19) in a single-center cohort of patients with MS and to explore the contribution of their comorbidities and therapies to the outcome. METHODS: A cross-sectional mixed-method study was conducted involving an email-based, self-administered questionnaire sent on May 21, 2020, to 586 patients with MS followed at the MS Unit of Hospital Clinic, University of Barcelona, along with telephone interview, and review of electronic medical records until June 18, 2020. The cumulative incidence of confirmed COVID-19 (positive PCR or antibody test) and all COVID-19 cases (confirmed and suspected) from the start of the pandemic was compared with the population estimates for Barcelona. RESULTS: A total of 407 patients (69.5%) completed the survey. Most of the responders (67%) were female. The responders had a median age of 48 years (range 19-86), relapsing-remitting disease (84%), at least 1 comorbidity (45%), and were on disease-modifying therapy (DMT; 74.7%). COVID-19 was confirmed in 5 patients (1.2%) and suspected in 46 (11.3%). The cumulative incidence of confirmed COVID-19 cases was similar to that of the general population but was almost 2-fold higher when all cases were considered (p < 0.001). Six patients (11.7%) were hospitalized, of which 5 had good recovery and 1 died. Hospitalized patients were more frequently male, had diabetes and had progressive forms of MS (p < 0.05). DMT was not associated with the risk of infection or the outcome. CONCLUSIONS: In the studied MS cohort, the incidence of COVID-19 was higher than that of the general population; however, most patients did not require hospitalization and had a good outcome despite the frequent presence of comorbidities and treatment with DMT.

Influencia de la vía diagnóstica en la clínica y el uso de terapias no convencionales en mujeres con cáncer de mama de la cohorte DAMA / Influence of diagnostic pathway on clinical and non-conventional therapies use in women with breast cancer of the cohort DAMA

OBJETIVO: Describir y analizar, según la vía diagnóstica, las características de los tumores de cáncer de mama. Se analizan los efectos adversos de los tratamientos recibidos y la utilización de terapias no convencionales para paliarlos. MÉTODO: Diseño descriptivo anidado en cohorte mixta (Cohorte DAMA). La variable dependiente fue la vía diagnóstica del cáncer de mama. Las variables independientes fueron la edad, el índice de masa corporal, la clase social, con renta familiar disponible, el tipo de tumor, el grado histológico, el estadio tumoral, las recidivas, el tratamiento, los efectos adversos de los tratamientos y las terapias no convencionales. Se realizaron análisis descriptivos bivariados y se ajustaron modelos de regresión univariados y multivariados, y se hicieron representaciones gráficas de la frecuentación de terapias no convencionales. RESULTADOS: Existen diferencias en las características de los tumores y en el impacto de los efectos adversos derivados de los tratamientos. Las pacientes diagnosticadas por cribado fueron de mayor edad y de clase social alta, presentaron un mayor porcentaje de tumores de grado I histológico, estadios iniciales, menos recidivas y efectos adversos debidos al tratamiento, aunque este no fuera distinto en el grupo de cribado respecto al resto. También hubo un menor uso de terapias no convencionales. CONCLUSIONES: Los resultados indican que la implantación de programas de cribado aumenta la posibilidad de detectar tumores en etapas iniciales y con terapias con menos efectos adversos; en consecuencia, con menor necesidad de recurrir a terapias no convencionales

OBJECTIVE: To describe and analyze the characteristics of breast cancer tumours according to the diagnostic pathway. We analyse the adverse effects of the treatments and the use of unconventional therapies in order to alleviate them. METHOD: Descriptive design nested in a mixed cohort (Cohort DAMA). The dependent variable was the route to diagnosis of breast cancer. The independent variables were age, body mass index, social class, disposable family income, type of tumour, histological degree, tumour stage, recurrences, treatment, adverse effects derived from treatments and unconventional therapies. Bivariate descriptive analyses were performed and univariate and multivariate regression models were adjusted; and graphic representations of the unconventional therapies. RESULTS: There are differences in the characteristics of the tumours, and the impact of the adverse effects derived from the treatments. The patients diagnosed by screening were older, from a high social class, had a higher percentage of tumours of grade I differentiation, initial stages, fewer recurrences and fewer adverse effects due to treatment, although this was not different in the screening group compared to the rest. There was also less use of unconventional therapies. CONCLUSIONS: The results indicate that the implementation of screening programmes increases the possibility of detecting tumours in initial stages and with therapies with fewer adverse effects. As a result, there is less need to resort to unconventional therapies

[Influence of diagnostic pathway on clinical and non-conventional therapies use in women with breast cancer of the cohort DAMA]. / Influencia de la vía diagnóstica en la clínica y el uso de terapias no convencionales en mujeres con cáncer de mama de la cohorte DAMA.

OBJECTIVE: To describe and analyze the characteristics of breast cancer tumours according to the diagnostic pathway. We analyse the adverse effects of the treatments and the use of unconventional therapies in order to alleviate them. METHOD: Descriptive design nested in a mixed cohort (Cohort DAMA). The dependent variable was the route to diagnosis of breast cancer. The independent variables were age, body mass index, social class, disposable family income, type of tumour, histological degree, tumour stage, recurrences, treatment, adverse effects derived from treatments and unconventional therapies. Bivariate descriptive analyses were performed and univariate and multivariate regression models were adjusted; and graphic representations of the unconventional therapies. RESULTS: There are differences in the characteristics of the tumours, and the impact of the adverse effects derived from the treatments. The patients diagnosed by screening were older, from a high social class, had a higher percentage of tumours of grade I differentiation, initial stages, fewer recurrences and fewer adverse effects due to treatment, although this was not different in the screening group compared to the rest. There was also less use of unconventional therapies. CONCLUSIONS: The results indicate that the implementation of screening programmes increases the possibility of detecting tumours in initial stages and with therapies with fewer adverse effects. As a result, there is less need to resort to unconventional therapies.

Impacto de una intervención de Atención Primaria en el programa de detección precoz de cáncer colorrectal / Impact of a Primary Care intervention on the colorectal cancer early detection programme

Objetivo: Evaluar la efectividad de una entrevista telefónica realizada por profesionales de Atención Primaria en personas no participantes en la primera ronda del Programa de detección precoz de cáncer colorrectal (PDPCCR), en el área básica de salud (ABS) urbana Guineueta de Barcelona (España). Pacientes y métodos: Un grupo de profesionales de Atención Primaria del ABS Guineueta contactó, mediante un protocolo de llamadas telefónicas estandarizadas, con personas que no atendieron la invitación a participar en la primera ronda del PDPCCR. Se analiza el impacto de esta intervención en la tasa de participación y las enfermedades detectadas. Resultados: Se realizaron 3.327 llamadas telefónicas a 2.343 personas. Tras la intervención, la tasa de participación fue del 54,9%, lo que supone un incremento del 5,7% con respecto a la participación del protocolo habitual del programa (49,2%). Se han diagnosticado 5 cánceres, 2 neoplasias de riesgo alto y 8 lesiones de riesgo bajo e intermedio. En promedio, han sido necesarias 9 llamadas para conseguir la aceptación de una persona adicional. Discusión: La intervención telefónica de los profesionales de Atención Primaria ha aumentado de forma significativa la tasa de participación de la población y la detección de neoplasias con respecto al protocolo habitual del PDPCCR

Aim: To assess the effectiveness of a telephonic interview performed by primary care professionals among non-participants in the first round of the colorectal cancer early detection programme in the basic urban health area Guineueta in Barcelona, Spain. Patients and methods: The Primary Healthcare Team of La Guineueta contacted people who did not respond to the invitation to the first round of the colorectal cancer early detection programme using a standardised telephone call protocol. We analysed the impact of the intervention based on participation and diagnosed disease. Results: We made 3,327 phone calls to 2,343 people. After the intervention the participation rate was 54.9%, which meant an increase of 5.7% with respect to the participation in the usual protocol for the programme (49.2%). The intervention allowed 5cancers, 2high-risk neoplasms and 8low- and intermediate-risk lesions to be diagnosed. An average of 9phone calls was necessary to achieve the participation of one additional person. Discussion: The telephonic intervention performed by primary care professionals has significantly increased the population participation rate and the detection of neoplasms with respect to the usual colorectal cancer early detection programme protocol

Impact of a Primary Care intervention on the colorectal cancer early detection programme. / Impacto de una intervención de Atención Primaria en el programa de detección precoz de cáncer colorrectal.

AIM: To assess the effectiveness of a telephonic interview performed by primary care professionals among non-participants in the first round of the colorectal cancer early detection programme in the basic urban health area Guineueta in Barcelona, Spain. PATIENTS AND METHODS: The Primary Healthcare Team of La Guineueta contacted people who did not respond to the invitation to the first round of the colorectal cancer early detection programme using a standardised telephone call protocol. We analysed the impact of the intervention based on participation and diagnosed disease. RESULTS: We made 3,327 phone calls to 2,343 people. After the intervention the participation rate was 54.9%, which meant an increase of 5.7% with respect to the participation in the usual protocol for the programme (49.2%). The intervention allowed 5cancers, 2high-risk neoplasms and 8low- and intermediate-risk lesions to be diagnosed. An average of 9phone calls was necessary to achieve the participation of one additional person. DISCUSSION: The telephonic intervention performed by primary care professionals has significantly increased the population participation rate and the detection of neoplasms with respect to the usual colorectal cancer early detection programme protocol.

La vacunación de la gripe en el personal sanitario: auctoritas y potestas / Influenza vaccination in health-care workers: Auctoritas and potestas

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Changes in FIT values below the threshold of positivity and short-term risk of advanced colorectal neoplasia: Results from a population-based cancer screening program.

INTRODUCTION: Increased values in the fecal immunochemical test (FIT) are correlated with increasingly severe colorectal neoplasia, but little attention has been given to FIT values below the cut-off point (negative FIT, nFIT). We analysed the relationship between the concentrations of two consecutive nFIT and the risk of following screen-detected advanced neoplasia and interval cancer (IC) in a population-based colorectal cancer screening program. METHODS: FIT results were categorised into non-detectable nFIT (0-3.8 µg haemoglobin/g feces), low nFIT (3.9-9.9) and high nFIT (10.0-19.9). Multivariable adjusted logistic regression was used to estimate the odds ratios (OR) of advanced neoplasia and IC with the nFIT results in the first two screens. RESULTS: More than 90% of the 42,524 persons had non-detectable nFIT in the first and second screen; 4.5% and 5.8% had a low nFIT, respectively, and 2.2% and 2.9% had a high nFIT. The probability of testing positive and being diagnosed of advanced neoplasia or IC rose with increasing values of nFIT. Compared with those with two non-detectable nFIT results, the highest OR were found among those who had two high nFIT results (OR 21.75; 95% confidence interval: 12.44, 38.04) and those with one low nFIT and one high nFIT (ORs around 20). CONCLUSIONS: Participants with nFIT results above the detection limit of the test had an increased risk of advanced neoplasia and IC in subsequent participations. This information could be used in the design of personalised screening strategies.

Epidemiology of NMOSD in Catalonia: Influence of the new 2015 criteria in incidence and prevalence estimates.

BACKGROUND: Population-based studies on neuromyelitis optica spectrum disorders (NMOSD) are limited, and it is unclear whether the rates have changed with the implementation of the new 2015 criteria. OBJECTIVES: To estimate the incidence and prevalence of NMOSD in Catalonia (Spain), using both the 2006 and the 2015 criteria. METHODS: In this clinic-based retrospective study, patients diagnosed with NMOSD between 2006 and 2015 were identified using multiple sources, including direct contact to all Catalan hospitals, identification of cases through the Catalan Health Surveillance System, and registry of antibodies to aquaporin-4 (AQP4-IgG) and myelin oligodendrocyte glycoprotein (MOG-IgG) in a reference laboratory. The incidence rate was calculated for the period 1 January 2006-1 January 2016 and prevalence for the date 1 January 2016. RESULTS: We identified 74 patients (by the 2015 criteria). Most patients were Caucasian (81%), and female (76%) with a median age at disease onset of 42 years (range, 10-76 years). In total, 54 (73%) patients were positive for AQP4-IgG, 11 (15%) double-seronegative, and 9 (12%) MOG-IgG-positive. Rates of incidence and prevalence (0.63/1,000,000 person-years and 0.89/100,000, respectively) were 1.5-fold higher than those reported by the 2006 criteria. Lowest rates were seen in children and elder people and highest in women and middle-aged people (40-59 years). The female predominance was lost in incident AQP4-IgG-seronegative children and AQP4-IgG-positive elder people. MOG-IgG and double-seronegativity contributed similarly but did not influence the long-term outcome. CONCLUSION: The new criteria increase the estimates, but NMOSD remains as a rare disease. The differences in age- and sex-specific estimates highlight the importance of the serologic classification.

Chronic proton pump inhibition therapy in the diagnostic accuracy of serum pepsinogen I and gastrin concentrations to identify pernicious anaemia.

BACKGROUND: Chronic use of proton pump inhibitors (PPIs) leads to increases in gastrin and pepsinogen-I serum concentrations. AIM: To asses if chronic treatment with PPIs has an effect on serum gastrin and pepsinogen-I concentrations for the diagnosis of pernicious anaemia (PA). MATERIALS AND METHODS: Serum gastrin and pepsinogen-I were measured in 38 patients with PA and 74 without PA (controls); 17/38 PA patients and 36/74 controls were treated with PPIs. Receiver Operating Curves (ROC) were used to compare diagnostic accuracy of gastrin and pepsinogen-I for PA in patients under chronic treatment with PPIs and in untreated patients. RESULTS: PPI treatment increased pepsinogen-I in patients and in controls, while gastrin increased only in controls. In untreated patients, a pepsinogen-I <8.3ng/mL had 95.2% sensitivity and 100% specificity, whereas a gastrin >115pg/mL had 100% sensitivity and 92.11% specificity for PA diagnosis. In PPI-treated patients, a pepsinogen I<24.1ng/mL had a lower sensitivity (82.4%) but retained 100% specificity, however the best cut-off point for gastrin, 610pg/mL, had a very low sensitivity (58%). CONCLUSIONS: PPI chronic treatment decreased the diagnostic accuracy for the studied biomarkers, particularly of gastrin. In PPI-treated patients, serum pepsinogen-I concentrations >24.1ng/mL allowed rejecting a PA diagnosis with 100% specificity.

Immunogenicity and immunization costs of adjuvanted versus non-adjuvanted hepatitis B vaccine in chronic kidney disease patients.

Hepatitis B virus (HBV) vaccination is recommended for all susceptible chronic pre-hemodialysis and hemodialysis patients. This study assessed the immunogenicity of HBV vaccines (adjuvanted and non-adjuvanted) in chronic kidney disease patients vaccinated at the Hospital Clinic of Barcelona (Spain) between January 2007 and July 2012. In addition, the costs for the health system were evaluated accor-ding to the proportion of vaccine responders after receiving either vaccine. Patients receiving 3 doses of hepatitis B adjuvanted vaccine were 3 times more likely to seroconvert than patients immunized with non-adjuvanted vaccines, OR 3.56 (95% CI 1.84-6.85). This resulted in fewer patients requiring a second course of HBV vaccination and fewer outpatient visits, saving more than €9,500 per 100 patients. The higher immunogenicity of the adjuvanted HBV vaccine would counterbalance the lower costs associated with the non-adjuvanted vaccine.

Sistema de autodeclaración de acontecimientos adversos y cobertura de vacunación antigripal en profesionales sanitarios en un hospital universitario de tercer nivel / Adverse events self-declaration system and influenza vaccination coverage of healthcare workers in a tertiary hospital

Introducción: Durante la campaña de vacunación antigripal 2011-2012 establecimos un sistema de autodeclaración de acontecimientos adversos (AA) en el personal sanitario (PS). El objetivo de este estudio es describir la población vacunada y analizar la cobertura de vacunación y los AA autodeclarados tras la vacunación voluntaria del PS frente a la gripe en un hospital universitario de tercer nivel en Barcelona. Métodos: Estudio observacional. Para el cálculo de la cobertura de vacunación se utilizó el registro de vacunación de profesionales sanitarios del hospital. Los AA se recogieron mediante una encuesta voluntaria, anónima y autoadministrada durante la campaña de vacunación antigripal 2011-2012, y se analizaron mediante regresión logística. Se construyó un modelo de regresión logística para determinar los factores que predisponen a declarar AA. Resultados: La campaña alcanzó una cobertura de vacunación antigripal del 30,5% (n = 1.507/4.944) del PS. De los vacunados, el 23,8% (n = 358) respondieron la encuesta de AA autodeclarados. El 52,0% (n = 186) de los que respondieron a la encuesta declaró haber presentado algún tipo de AA. De estos, el 75,3% (n = 140) refirió signos y síntomas locales tras la vacunación, el 9,7% (n = 18), signos y síntomas sistémicos, y el 15,1% (n = 28), síntomas tanto locales como sistémicos. No se declaró ningún AA grave. Ser mujer y tener menos de 35 años se asoció a declarar algún tipo de AA. Conclusiones: El sistema de autodeclaración no registró AA graves en el PS, suponiendo una oportunidad para aumentar la confianza del PS en la vacuna antigripal (AU)

Introduction: During the influenza vaccination campaign 2011-2012 we established a self-declaration system of adverse events (AEs) in healthcare workers (HCW). The aim of this study is to describe the vaccinated population and analyse vaccination coverage and self-declared AEs after the voluntary flu vaccination in a university hospital in Barcelona. Methods: Observational study. We used the HCW immunization record to calculate the vaccination coverage. We collected AEs using a voluntary, anonymous, self-administered survey during the 2011-2012 flu vaccination campaign. We performed a logistic regression model to determine the associated factors to declare AEs. Results: The influenza vaccination coverage in HCW was 30.5% (n = 1,507/4,944). We received completed surveys from 358 vaccinated HCW (23.8% of all vaccinated). We registered AEs in 186 respondents to the survey (52.0% of all respondents). Of these, 75.3% (n = 140) reported local symptoms after the flu vaccination, 9.7% (n = 18) reported systemic symptoms and 15.1% (n = 28) both local and systemic symptoms. No serious AEs were self-reported. Female sex and aged under 35 were both factors associated with declaring AEs. Conclusions: Our self-reporting system did not register serious AEs in HCW, resulting in an opportunity to improve HCW trust in flu vaccination (AU)

[Adverse events self-declaration system and influenza vaccination coverage of healthcare workers in a tertiary hospital]. / Sistema de autodeclaración de acontecimientos adversos y cobertura de vacunación antigripal en profesionales sanitarios en un hospital universitario de tercer nivel.

INTRODUCTION: During the influenza vaccination campaign 2011-2012 we established a self-declaration system of adverse events (AEs) in healthcare workers (HCW). The aim of this study is to describe the vaccinated population and analyse vaccination coverage and self-declared AEs after the voluntary flu vaccination in a university hospital in Barcelona. METHODS: Observational study. We used the HCW immunization record to calculate the vaccination coverage. We collected AEs using a voluntary, anonymous, self-administered survey during the 2011-2012 flu vaccination campaign. We performed a logistic regression model to determine the associated factors to declare AEs. RESULTS: The influenza vaccination coverage in HCW was 30.5% (n=1,507/4,944). We received completed surveys from 358 vaccinated HCW (23.8% of all vaccinated). We registered AEs in 186 respondents to the survey (52.0% of all respondents). Of these, 75.3% (n=140) reported local symptoms after the flu vaccination, 9.7% (n=18) reported systemic symptoms and 15.1% (n=28) both local and systemic symptoms. No serious AEs were self-reported. Female sex and aged under 35 were both factors associated with declaring AEs. CONCLUSIONS: Our self-reporting system did not register serious AEs in HCW, resulting in an opportunity to improve HCW trust in flu vaccination.

Sodium interference in the determination of urinary aldosterone.

OBJECTIVES: Primary hyperaldosteronism (PHA) is one of the most common endocrine forms of secondary hypertension. Among the most used confirmatory tests for PHA is urinary aldosterone determination after oral sodium loading test. The primary aim of our study was to investigate if sodium concentrations interfere with urinary aldosterone in an automated competitive immunoassay (Liaison®) as well as to verify the manufacturer's specifications. DESIGN AND METHODS: 24-hr urine samples were collected and stored frozen until assayed. Two pools at low and high aldosterone concentrations were prepared. Verification of performance for precision was tested according to Clinical and Laboratory Standards Institute (CLSI) document EP15-A2 and interference with increasing concentrations of NaCl according to CLSI EP7-A2. RESULTS: The assay met the quality specifications according to optimal biological variation. Our results show that sodium concentrations up to 200mmol/L do not interfere on urinary aldosterone quantification, but sodium concentrations above 486mmol/L negatively interfere with the test. CONCLUSIONS: The Liaison® automated method is useful for aldosterone determination in the PHA confirmatory test, but interferences with NaCl may occur. It is therefore recommended to determine urinary NaCl before measuring urinary aldosterone to avoid falsely low results.

Disminución de la respuesta eritropoyética en pacientes con anorexia nerviosa y anemia / Blunted erythropoietic response in the anemia of anorexia nervosa

Fundamento y objetivo: La causa o causas de la anemia que acompaña a la anorexia nerviosa (AN) no ha sido establecida, pero no parece relacionarse con deficiencias nutricionales ni cambios medulares. El objetivo de este trabajo fue evaluar la producción de eritropoyetina (EPO) en respuesta a la anemia en un pequeño grupo de pacientes con AN y anemia. Pacientes y métodos: Los niveles de EPO en muestras de suero de 41 mujeres con AN (11 con anemia y 30 sin alteraciones en los parámetros de la serie eritroide) se compararon con la respuesta observada en un grupo de pacientes de peso normal con anemia. Resultados: Las concentraciones de EPO en pacientes con AN anémicas fueron mayores que en las no anémicas: 20,63 mU/ml (4,04 a 28,46) frente a 8,7 mU/ml (3,9 a 20,93), p = 0,0088, pero el aumento de EPO fue menor de lo esperado (27,85 mU/ml [17,7 a 118,9]), p = 0,014. La correlación entre el IMC y la diferencia entre la EPO y la EPO esperada es inversa. Conclusiones: Una producción inadecuada de EPO puede explicar en parte la anemia en la AN. Son necesarios más estudios para investigar la causa de esta respuesta (AU)

Background and objective: The cause of the anemia in anorexia nervosa (AN) has not been fully ascertained. Ferritin, folate and cobalamin values are usually within normal ranges. Anemia does not have a relationship with bone marrow changes and erythropoietin (EPO) levels have not been investigated. The objective of this study was to evaluate the EPO response in a small group of AN patients. Patients and methods: EPO levels were measured in serum samples of 41 female AN patients (11 with anemia, and 30 with normal blood cell count). The adequacy of EPO response was assessed by comparing the increase observed in a group of normal weight patients with anemia. Results: EPO concentrations in anemic AN patients were higher than in non-anemic: 20.63 mU/mL (4.04-28.46) vs 8.7 mU/mL (3.9-20.93), P = .0088, but the increase in EPO was lower than expected (27.85 mU/mL [17.7-118.9]), P = .014. BMI and the difference between actual and expected EPO were inversely correlated. Conclusions: Inadequate EPO response may partly explain anemia in AN, but further studies are necessary (AU)

Controlled human malaria infection by intramuscular and direct venous inoculation of cryopreserved Plasmodium falciparum sporozoites in malaria-naïve volunteers: effect of injection volume and dose on infectivity rates.

BACKGROUND: Controlled human malaria infection (CHMI) by mosquito bite is a powerful tool for evaluation of vaccines and drugs against Plasmodium falciparum malaria. However, only a small number of research centres have the facilities required to perform such studies. CHMI by needle and syringe could help to accelerate the development of anti-malaria interventions by enabling centres worldwide to employ CHMI. METHODS: An open-label CHMI study was performed with aseptic, purified, cryopreserved P. falciparum sporozoites (PfSPZ Challenge) in 36 malaria naïve volunteers. In part A, the effect of the inoculation volume was assessed: 18 participants were injected intramuscularly (IM) with a dose of 2,500 PfSPZ divided into two injections of 10 µL (n = 6), 50 µL (n = 6) or 250 µL (n = 6), respectively. In part B, the injection volume that resulted in highest infectivity rates in part A (10 µL) was used to formulate IM doses of 25,000 PfSPZ (n = 6) and 75,000 PfSPZ (n = 6) divided into two 10-µL injections. Results from a parallel trial led to the decision to add a positive control group (n = 6), each volunteer receiving 3,200 PfSPZ in a single 500-µL injection by direct venous inoculation (DVI). RESULTS: Four/six participants in the 10-µL group, 1/6 in the 50-µL group and 2/6 in the 250-µL group developed parasitaemia. Geometric mean (GM) pre-patent periods were 13.9, 14.0 and 15.0 days, respectively. Six/six (100%) participants developed parasitaemia in the 25,000 and 75,000 PfSPZ IM and 3,200 PfSPZ DVI groups. GM pre-patent periods were 12.2, 11.4 and 11.4 days, respectively. Injection of PfSPZ Challenge was well tolerated and safe in all groups. CONCLUSIONS: IM injection of 75,000 PfSPZ and DVI injection of 3,200 PfSPZ resulted in infection rates and pre-patent periods comparable to the bite of five PfSPZ-infected mosquitoes. Remarkably, it required 23.4-fold more PfSPZ administered IM than DVI to achieve the same parasite kinetics. These results allow for translation of CHMI from research to routine use, and inoculation of PfSPZ by IM and DVI regimens. TRIAL REGISTRATION: ClinicalTrials.gov NCT01771848.

[Blunted erythropoietic response in the anemia of anorexia nervosa]. / Disminución de la respuesta eritropoyética en pacientes con anorexia nerviosa y anemia.

BACKGROUND AND OBJECTIVE: The cause of the anemia in anorexia nervosa (AN) has not been fully ascertained. Ferritin, folate and cobalamin values are usually within normal ranges. Anemia does not have a relationship with bone marrow changes and erythropoietin (EPO) levels have not been investigated. The objective of this study was to evaluate the EPO response in a small group of AN patients. PATIENTS AND METHODS: EPO levels were measured in serum samples of 41 female AN patients (11 with anemia, and 30 with normal blood cell count). The adequacy of EPO response was assessed by comparing the increase observed in a group of normal weight patients with anemia. RESULTS: EPO concentrations in anemic AN patients were higher than in non-anemic: 20.63mU/mL (4.04-28.46) vs 8.7mU/mL (3.9-20.93), P=.0088, but the increase in EPO was lower than expected (27.85mU/mL [17.7-118.9]), P=.014. BMI and the difference between actual and expected EPO were inversely correlated. CONCLUSIONS: Inadequate EPO response may partly explain anemia in AN, but further studies are necessary.