Novel genes and sex differences in COVID-19 severity.

Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10-8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10-22 and P = 8.1 × 10-12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10-8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10-8) and ARHGAP33 (P = 1.3 × 10-8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10-8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.

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.

Flexible multiplex PCR to detect SARS-CoV-2, coronavirus OC43 and influenza A virus in nasopharyngeal swab samples.

INTRODUCTION: Quantitative reverse transcription PCR (RT-qPCR) is the leading tool to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Given that it will almost certainly continue to coexist with other respiratory viruses in the coming years, our study aimed to design a multiplex PCR system not affected by supplier outages and with reduced cost compared to the existing commercially available kits. METHODS AND RESULTS: In this study, combinations of four primers/probe sets were used to construct a flexible RT-qPCR assay which is capable of discriminating between SARS-CoV-2 and the seasonal human coronavirus HCoV-OC43, or even influenza A virus. Additionally, the human RPP30 gene was used as an internal control. To demonstrate the robustness of the assay, it was applied to a collection of 150 clinical samples. The results showed 100% sensitivity and specificity compared to the automatized system used at the hospital and were better when indeterminate samples were analysed. CONCLUSIONS: This study provides an efficient method for the simultaneous detection of SARS-CoV-2, HCoV-OC43 and influenza A virus, and its efficacy has been tested on clinical samples showing outstanding results. SIGNIFICANCE AND IMPACT OF THE STUDY: The multiplex RT-qPCR design offers an accessible and economical alternative to commercial detection kits for hospitals and laboratories with limited economic resources or facing situations of supply shortage.

[Effectiveness of the vagino-rectal exudate self-sampling for prenatal screening of Streptococcus agalactiae infection. GALL study]. / Efectividad de la autotoma del exudado vaginorrectal para el cribado prenatal de la infección por Streptococcus agalactiae. Estudio GALL.

OBJETIVE: To evaluate the effectiveness of vagino-rectal swab autotomy for prenatal screening for GBS infection and to identify the barriers and facilitators encountered by the pregnant woman for this intervention. DESIGN: Cross-sectional study of diagnostic tests. PARTICIPANTS AND SITE: A total of 213 pregnant women who attended the primary care midwife's office in 6 health centers of the Basque Health Service/Osakidetza in Bizkaia, who met the inclusion criteria and agreed to participate in the study, participated in the study. MAIN MEASUREMENTS: The result of the vagino-rectal culture obtained by the pregnant woman was compared with the result of the vagino-rectal culture taken by the midwife in consultation on the same day, and the barriers and facilitators encountered by the women in the self-test were collected. RESULTS: Self-testing as a test for GBS was found to have a sensitivity of 93.3% (95% CI 78.7-98.2), a specificity of 99.4% (95% CI 96.5-99.9), a positive predictive value of 96% (95% CI 82.8-99.4) and a negative predictive value of 98.8% (95% CI 95.6-99.7). 27.3% of respondents encountered some difficulty in the collection, only 4.8% did not feel qualified, 84.2% felt comfortable, 99.5% considered the information provided to be adequate and complete, 94.7% did not find the steps to follow complicated, and 96% were satisfied with the study. CONCLUSIONS: Self-collection of vagino-rectal exudate for GBS detection has proved to be valid and reliable, which would make it possible to offer this option to pregnant women in the systematic screening for GBS infection.

Facilitators and barriers to participation in population-based colorectal cancer screening programme from the perspective of healthcare professionals: Qualitative research study.

OBJECTIVE: High participation determines the success of colorectal cancer screening programmes in reducing incidence and mortality. The factors that determine participation must be studied from the perspective of professionals that implement the programme. The aim was to identify factors that facilitate or hinder the participation of the invited people in the bowel cancer screening programme of the Basque Country (Spain) from professional's perspective. METHODS: Qualitative design based on individual interviews and focus groups. Thirty-eight primary care professionals who implement the programme participated (administrative staff, nurses and general practitioners). Thematic analysis was performed. RESULTS: Professionals show high satisfaction with the programme, and they believe firmly in its benefits. Facilitators for participation include professionals' commitment to the programme, their previous positive experiences, their optimistic attitude towards the prognosis of cancer and their trust in the health system and accessibility. Barriers include invitees' lack of independence to make decisions, fear of a positive test result and patient vulnerability and labour mobility of the health professionals. CONCLUSIONS: Professionals show a high degree of involvement and identify primary care is an appropriate place to carry out disease prevention. They identify the closeness to patients, the personal attitude and the characteristics of the health system as key factors that influence participation.

Risk factors for severe complications of colonoscopy in screening programs.

Severe complications (SC) in colonoscopy represent the most important adverse effect of colorectal cancer screening programs (CRCSP). The objective is to evaluate the risk factors for SC in colonoscopy indicated after a positive fecal occult blood test in population-based CRCSP. The SC (n = 161) identified from 48,730 diagnostic colonoscopies performed in a cohort of all the women and men invited from 2000 to 2012 in 6 CRCSP in Spain. A total of 318 controls were selected, matched for age, sex and period when the colonoscopy was performed. Conditional logistic regression models were estimated. The analysis was performed separately in groups: immediate-SC (same day of the colonoscopy); late-SC (between 1 and 30 days after); perforation; and bleeding events. SC occurred in 3.30‰ of colonoscopies. Prior colon disease showed a higher risk of SC (OR = 4.87). Regular antiplatelet treatment conferred a higher risk of overall SC (OR = 2.80) and late-SC (OR = 9.26), as did regular anticoagulant therapy (OR = 3.47, OR = 7.36). A history of pelvic-surgery or abdominal-radiotherapy was a risk factor for overall SC (OR = 5.03), immediate-SC (OR = 8.49), late-SC (OR = 4.65) and perforation (OR = 21.59). A finding of adenoma or cancer also showed a higher risk of overall SC (OR = 8.71), immediate-SC (OR = 12.67), late-SC (OR = 4.08), perforation (OR = 4.69) and bleeding (OR = 17.02). The risk of SC doesn't vary depending on the type of preparation or type of anesthesia. Knowing the clinical history of patients such as regular previous medication and history of surgery or radiotherapy, as well as the severity of the findings during the colonoscopy process could help to focus prevention measures in order to minimize SC in CRCSP.

International Epidemiological Differences in Acute Poisonings in Pediatric Emergency Departments.

BACKGROUND AND OBJECTIVE: Identifying international differences in the epidemiology of acute poisonings in children may help in improving prevention. We sought to evaluate the international epidemiological differences in acute poisonings in children presenting to emergency departments (EDs) from 8 different global regions. METHODS: This was an international multicenter cross-sectional prospective study including children younger than 18 years with acute poisonings presenting to 105 EDs in 20 countries was conducted. Data collection started at each ED between January and September 2013, and continued for 1 year. RESULTS: During the study period, we registered 363,245 pediatric ED presentations, of which 1727 were for poisoning (0.47%; 95% confidence interval, 0.45%-0.50%), with a significant variation in incidence between the regions. Full data were obtained for 1688 presentations. Most poisonings (1361 [80.6%]) occurred at home with either ingestion (1504 [89.0%]) or inhalation of the toxin (126 [7.6%]). Nonintentional exposures accounted for 1157 poisonings (68.5%; mainly in South America and Eastern Mediterranean region), with therapeutic drugs (494 [42.7%]), household products (310 [26.8%]), and pesticides (59 [5.1%]) being the most common toxins. Suicide attempts accounted for 233 exposures (13.8%; mainly in the Western Pacific region and North America), with therapeutic drugs (214 [91.8%], mainly psychotropics and acetaminophen) being the most common toxins. Significant differences between regions were found in both types of poisonings. Recreational poisonings were more common in Europe and Western Pacific region. No patient died. CONCLUSIONS: There are substantial epidemiological differences in acute poisonings among children in different countries and regions of the globe. International best practices need to be identified for prevention of acute poisonings in childhood.

Quality indicators and patient satisfaction in colonoscopy. / Indicadores de calidad y satisfacción de los pacientes en la colonoscopia.

INTRODUCTION: Colonoscopy is the diagnostic/therapeutic confirmation test for colorectal cancer. The monitoring of the experience of people who have undergone the test is interesting to improve the quality of the colonoscopy. The aim of the project was to study factors affecting patients' experience and their relationship with the quality indicators of the Clinical Practice Guidelines. PATIENTS AND METHODS: An observational cross-sectional study was conducted, including quality and experience indicators (adapted mGHAA-9 questionnaire and clinical history) in a sample of 432 participants aged between 40- and 75-years-old who had undergone a colonoscopy in 2015. Univariate and multivariate analysis with multiple logistic regression. RESULTS: Satisfaction was associated in the multivariate analysis with evaluating the waiting time for the colonoscopy as short (OR=3.80) (1.76-10.90, 95% CI),>55-years-old (OR=2.60) (1.19-5.68, 95% CI), rating the experience with the preparation positively (OR=7.34) (3.15-17.09, 95% CI), not reporting pain or discomfort during the procedure (OR=3.71) (1.03-13.40, 95% CI) (P=.006) and being examined in a tertiary hospital (OR=2.81) (1.17-6.72; 95% CI) (P=.020). DISCUSSION: The mGHAA-9 questionnaire adapted to Spanish is useful to evaluate patient experience factors. There are aspects to improve in terms of waiting time, colon cleansing, satisfaction with preparation and post-colonoscopy problems. Interventions should be implemented to enhance patient experience and colonoscopy quality.

Pilot Clinical Trial of High-Flow Oxygen Therapy in Children with Asthma in the Emergency Service.

OBJECTIVES: To assess the efficacy of high-flow nasal cannula (HFNC) oxygen therapy and safety in children with asthma and moderate respiratory failure in the emergency department (ED). STUDY DESIGN: This was a prospective randomized pilot trial of children (aged 1-14 years) presenting to a tertiary academic pediatric ED with moderate-to-severe asthma exacerbations between September 2012 and December 2015. Patients with a pulmonary score (PS) ≥6 or oxygen saturation <94% with a face mask despite initial treatment (salbutamol/ipratropium bromide and corticosteroids) were randomized to HFNC or to conventional oxygen therapy. Pharmacologic treatment was at the discretion of attending physicians. The primary outcome was a decrease in PS ≥2 in the first 2 hours. Secondary outcomes included disposition, length of stay, and need for additional therapies. RESULTS: We randomly allocated 62 children to receive either HFNC (n = 30) or standard oxygen therapy (n = 32). Baseline patient characteristics were similar in the 2 groups. At 2 hours after the start of therapy, PS had decreased by ≥2 points in 16 patients in the HFNC group (53%) compared with 9 controls (28%) (P = .01). Between-group differences in disposition, length of stay, and need for additional therapies were not significant. No side effects were reported. CONCLUSION: HFNC appears to be superior to conventional oxygen therapy for reducing respiratory distress within the first 2 hours of treatment in children with moderate-to-severe asthma exacerbation refractory to first-line treatment. Further studies are needed to demonstrate its overall efficacy in the management of asthma and respiratory failure in the ED. TRIAL REGISTRATION: EudraCT: 2012-001771-36.

Cost-effectiveness and budget impact analyses of a colorectal cancer screening programme in a high adenoma prevalence scenario using MISCAN-Colon microsimulation model.

BACKGROUND: The Basque Colorectal Cancer Screening Programme began in 2009 and the implementation has been complete since 2013. Faecal immunological testing was used for screening in individuals between 50 and 69 years old. Colorectal Cancer in Basque country is characterized by unusual epidemiological features given that Colorectal Cancer incidence is similar to other European countries while adenoma prevalence is higher. The object of our study was to economically evaluate the programme via cost-effectiveness and budget impact analyses with microsimulation models. METHODS: We applied the Microsimulation Screening Analysis (MISCAN)-Colon model to predict trends in Colorectal Cancer incidence and mortality and to quantify the short- and long-term effects and costs of the Basque Colorectal Cancer Screening Programme. The model was calibrated to the Basque demographics in 2008 and age-specific Colorectal Cancer incidence data in the Basque Cancer Registry from 2005 to 2008 before the screening begun. The model was also calibrated to the high adenoma prevalence observed for the Basque population in a previously published study. The multi-cohort approach used in the model included all the cohorts in the programme during 30 years of implementation, with lifetime follow-up. Unit costs were obtained from the Basque Health Service and both cost-effectiveness analysis and budget impact analysis were carried out. RESULTS: The goodness-of-fit of the model adaptation to observed programme data was evidence of validation. In the cost-effectiveness analysis, the savings from treatment were larger than the added costs due to screening. Thus, the Basque programme was dominant compared to no screening, as life expectancy increased by 29.3 days per person. The savings in the budget analysis appeared 10 years after the complete implementation of the programme. The average annual budget was €73.4 million from year 2023 onwards. CONCLUSIONS: This economic evaluation showed a screening intervention with a major health gain that also produced net savings when a long follow-up was used to capture the late economic benefit. The number of colonoscopies required was high but remain within the capacity of the Basque Health Service. So far in Europe, no other population Colorectal Cancer screening programme has been evaluated by budget impact analysis.

Factors related to the participation and detection of lesions in colorectal cancer screening programme-based faecal immunochemical test.

Background: The overall aim of this study was to describe trends in participation rates and detection of lesions in a colorectal cancer (CRC) screening programme, during three rounds, using faecal immunochemical test (FIT). Methods: National registers were used to collect data on invitations for CRC screening in the Basque Country (Spain) from 2009 to 2014. Information about participation, age, gender and lesions in each round were collected. Results: A total of 961.533 individuals were included in the analysis; respectively, 584.950, 298.143 and 78.440 in the first, second and third rounds. The average participation rate was 68.4% (66.8, 70.4 and 72.3%, respectively by round; P < 0.001) and the positivity rate was 6.3% (7, 5.5 and 5.4%, respectively by round; P < 0.001). The participation rate increased significantly with age and was found to be higher in women versus men. A total of 15.144 advanced adenomas and 2.131 CRCs were diagnosed, leading to a detection rate of 23.9 and 3.4‰, respectively. Regarding gender, men had the highest rates in all periods and rounds. The detection rate of advanced neoplasia was lower in the regular when compared with irregular paricipants. Conclusions: In a CRC screening, this organization obtained high FIT participation rates. Older participants and women were associated with a higher participation. The detection rate of lesions was higher in men, independent on age and round.

Outpatient management of children at low risk for bacterial meningitis.

OBJECTIVE: To determine the outcome of children aged 2-14 years with cerebrospinal fluid (CSF) pleocytosis and at very low risk for bacterial meningitis managed as outpatients without antibiotics. METHODS: Multicentre, prospective, observational study conducted at nine Spanish paediatric EDs. Patients were diagnosed with meningitis based on clinical suspicion of meningitis and CSF pleocytosis when evaluated in the ED. Children between 2 and 14 years of age with pleocytosis and very low-risk criteria for bacterial meningitis (well appearing, Bacterial Meningitis Score (BMS)=0, procalcitonin (PCT)<0.5 ng/mL and observation without deterioration for less than 24 hours in the ED) were treated as outpatients without antibiotics pending CSF cultures. The primary composite outcome was a final diagnosis of bacterial meningitis or return to the ED for clinical deterioration. RESULTS: Of 182 children between 2 and 14 years old diagnosed with meningitis, 56 met the very low-risk criteria and 45 were managed as outpatients. None was diagnosed with bacterial meningitis or returned due to clinical deterioration. Another 31 patients with BMS=1 (due to a peripheral absolute neutrophil count (ANC)>10 000/mm3) and PCT <0.5 ng/mL were managed as outpatients, diagnosed with aseptic meningitis and did well. BMS using PCT had the same sensitivity but greater specificity than classic BMS. CONCLUSIONS: This set of low-risk criteria appears safe for the outpatient management without antibiotics of children with CSF pleocytosis. Larger studies are needed to evaluate the predictive values of replacing peripheral ANC with PCT in the BMS.

Randomized Trial of Dexamethasone Versus Prednisone for Children with Acute Asthma Exacerbations.

OBJECTIVE: To determine whether 2 doses of dexamethasone is as effective as 5 days of prednisolone/prednisone therapy in improving symptoms and quality of life of children with asthma exacerbations admitted to the emergency department (ED). STUDY DESIGN: We conducted a randomized, noninferiority trial including patients aged 1-14 years who presented to the ED with acute asthma to compare the efficacy of 2 doses of dexamethasone (0.6 mg/kg/dose, experimental treatment) vs a 5-day course of prednisolone/prednisone (1.5 mg/kg/d, followed by 1 mg/kg/d on days 2-5, conventional treatment). Two follow-up telephone interviews were completed at 7 and 15 days. The primary outcome measures were the percentage of patients with asthma symptoms and quality of life at day 7. Secondary outcomes were unscheduled returns, admissions, adherence, and vomiting. RESULTS: During the study period, 710 children who met the inclusion criteria were invited to participate and 590 agreed. Primary outcome data were available in 557 patients. At day 7, experimental and conventional groups did not show differences related to persistence of symptoms (56.6%, 95% CI 50.6-62.6 vs 58.3%, 95% CI 52.3-64.2, respectively), quality of life score (80.0 vs 77.7, not significant [ns]), admission rate (23.9% vs 21.7%, ns), unscheduled ED return visits (4.6% vs 3.3%, ns), and vomiting (2.1% vs 4.4%, ns). Adherence was greater in the dexamethasone group (99.3% vs 96.0%, P < .05). CONCLUSION: Two doses of dexamethasone may be an effective alternative to a 5-day course of prednisone/prednisolone for asthma exacerbations, as measured by persistence of symptoms and quality of life at day 7. CLINICAL TRIAL REGISTRATION: clinicaltrialsregister.eu: 2013-003145-42.

Population-based colorectal cancer screening programmes using a faecal immunochemical test: should faecal haemoglobin cut-offs differ by age and sex?

BACKGROUND: The Basque Colorectal Cancer Screening Programme has both high participation rate and high compliance rate of colonoscopy after a positive faecal occult blood test (FIT). Although, colorectal cancer (CRC) screening with biannual (FIT) has shown to reduce CRC mortality, the ultimate effectiveness of the screening programmes depends on the accuracy of FIT and post-FIT colonoscopy, and thus, harms related to false results might not be underestimated. Current CRC screening programmes use a single faecal haemoglobin concentration (f-Hb) cut-off for colonoscopy referral for both sexes and all ages. We aimed to determine optimum f-Hb cut-offs by sex and age without compromising neoplasia detection and interval cancer proportion. METHODS: Prospective cohort study using a single-sample faecal immunochemical test (FIT) on 444,582 invited average-risk subjects aged 50-69 years. A result was considered positive at ≥20 µg Hb/g faeces. Outcome measures were analysed by sex and age for a wide range of f-Hb cut-offs. RESULTS: We analysed 17,387 positive participants in the programme who underwent colonoscopy. Participation rate was 66.5%. Men had a positivity rate for f-Hb of 8.3% and women 4.8% (p < 0.0001). The detection rate for advanced neoplasia (cancer plus advanced adenoma) was 44.0‰ for men and 15.9‰ for women (p < 0.0001). The number of colonoscopies required decreased in both sexes and all age groups through increasing the f-Hb cut-off. However, the loss in CRC detection increased by up to 28.1% in men and 22.9% in women. CRC missed were generally at early stages (Stage I-II: from 70.2% in men to 66.3% in women). CONCLUSIONS: This study provides detailed outcomes in men and women of different ages at a range of f-Hb cut-offs. We found differences in positivity rates, neoplasia detection rate, number needed to screen, and interval cancers in men and women and in younger and older groups. However, there are factors other than sex and age to consider when consideration is given to setting the f-Hb cut-off.

Factors influencing participation in colorectal cancer screening programs in Spain.

To analyze the sociodemographic and organizational factors influencing participation in population-based colorectal cancer screening programs (CRCSP) in Spain, a retrospective study was conducted in a cohort of people invited to participate in the first 3 screening rounds of 6 CRCSP from 2000 to 2012. Mixed logistic regression models were used to analyze the relationship between sociodemographic and organizational factors, such as the type of fecal occult blood test (FOBT) used and the FOBT delivery type. The analysis was performed separately in groups (Initial screening-first invitation, Subsequent invitation for previous never-responders, Subsequent invitation-regular, Subsequent invitation-irregular intervals). The results showed that, in the Initial screening-first invitation group, participation was higher in women than in men in all age groups (OR 1.05 in persons aged 50-59years and OR 1.12 in those aged 60-69years). Participation was also higher when no action was required to receive the FOBT kit, independently of the type of screening (Initial screening-first invitation [OR 2.24], Subsequent invitation for previous never-responders [OR 2.14], Subsequent invitation-regular [OR 2.03], Subsequent invitation-irregular intervals [OR 9.38]) and when quantitative rather than qualitative immunological FOBT (FIT) was offered (Initial screening-first invitation [OR 0.70], Subsequent invitation for previous never-responders [OR 0.12], Subsequent invitation-regular [OR 0.20]) or guaiac testing (Initial screening-first invitation [OR 0.81], Subsequent invitation for previous never-responders [OR 0.88], Subsequent invitation-regular [OR 0.73]). In conclusion, the results of this study show that screening participation could be enhanced by inclusion of the FOBT kit with the screening invitation and the use of the quantitative FIT.

Incidence of childhood-onset type 1 diabetes in Biscay, Spain, 1990-2013.

OBJECTIVE: To identify the incidence rate (IR) and epidemiologic trends of childhood type 1 diabetes mellitus (T1DM) in children aged 0 to 14-yr-old from 1990 to 2013, in the north of Spain (Biscay). SUBJECTS AND METHODS: A prospective-retrospective study was performed. Capture-recapture method was used: primary cases were ascertained from hospital register and a secondary independent data source was obtained from diabetes associations and public health plan database. Age and sex-standardized incidence rates were calculated using direct method, assuming an equal distribution in each age/sex group. In order to identify and analyse trends the period studied was divided into two (1990-2001 and 2002-2013) 11-year periods. The 95% confidence interval (CI) was estimated assuming the Poisson distribution. RESULTS: A total of 399 new cases were identified throughout the study. Mean age at diagnosis was 8.9 ± 3.7 yr. Completeness of ascertainment was 99.1%. Mean annual age-standardized IR was 10.7 (95% CI: 9.6-11.7). The mean incidence for the 0-4, 5-9 and 10-14 age groups was 5.1, 14.6 and 13.2 per 100,000 children/yr, respectively. The incidence rate trend in the whole group was not statistically significant. In the 10-14 age group we found a yearly average increase (2.5% [CI 95% 0.4-4.6]; P < 0.05) and analysing by sex, this statistically significant incidence trend was observed only in boys. We did not find a seasonal onset pattern. CONCLUSIONS: The IR did not increase in this population during the period studied unlike the results in other Spanish regions and European Countries.

Incidence of advanced neoplasia during surveillance in high- and intermediate-risk groups of the European colorectal cancer screening guidelines.

Background and study aims: The European guidelines for quality assurance in colorectal cancer (CRC) screening have established high-risk (≥ 5 adenomas or an adenoma ≥ 20 mm) and intermediate-risk (3 - 4 adenomas or at least one adenoma 10 - 19 mm in size, or villous histology, or high grade dysplasia) groups with different endoscopic surveillance intervals. The aim of this study was to evaluate the difference in the incidence of advanced neoplasia (advanced adenoma or CRC) between the two risk groups. Patients and methods: This retrospective group study included patients meeting high- or intermediate-risk criteria for adenomas detected in CRC screening programs and the COLONPREV study before European guidelines were adopted in Spain (June 2011) with a 3-year surveillance recommendation according to Spanish guidelines. The primary outcome measure was the incidence of advanced neoplasia in patients undergoing surveillance. The secondary outcome measure was the CRC incidence. We used an adjusted proportional hazards regression model to control confounding variables. Results: The study included 5401 patients (3379 intermediate risk, 2022 high risk). Endoscopic surveillance was performed in 65.5 % of the patients (2.8 ±â€Š1 years). The incidence of advanced neoplasia in the high- and intermediate-risk groups was 16.0 % (59.0 cases/1000 patient-years) and 12.3 % (41.2 cases/1000 patient-years), respectively. The CRC incidence was 0.5 % (1.4 cases/1000 patient-years) and 0.4 % (1 case/1000 patient-years), respectively. The advanced neoplasia and CRC attributable risk to the high risk group was of 3.7 % and 0.1 %, respectively. In the proportional hazards analysis, the risk of advanced neoplasia was greater in the high-risk group (hazard ratio [HR] 1.5, 95 % confidence interval [CI] 1.2 - 1.8), with no significant differences in the CRC incidence (HR 1.6, 95 %CI 0.6 - 3.8). Conclusions: Patients meeting high-risk criteria have a higher incidence of advanced neoplasia during endoscopic surveillance. No differences were found in the CRC incidence at a 3-year surveillance recommendation.

Social inequalities in a population based colorectal cancer screening programme in the Basque Country.

BACKGROUND: While it is known that a variety of factors (biological, behavioural and interventional) play a major role in the health of individuals and populations, the importance of the role of social determinants is less clear. The effect of social inequality on population-based screening for colorectal cancer (CRC) could limit the value of such programmes. The present study aims to determine whether such inequalities exist. METHODS: Data was obtained from the population-based screening programme administered in the Autonomous Community of the Basque Country, Spain, with a target population aged 50 to 69, first invited to participate between 2009 and 2011. The magnitude of inequality was analysed using the odds ratio (taking the least disadvantaged socioeconomic quintile as the reference population), the population attributable risk and the relative index of inequality, based on the regression, which is the ratio of the rates in the most and least disadvantaged socioeconomic groups. RESULTS: The target population comprised 242,394 people, with the test kit successfully sent to 95.1 % (230,510). The overall response rate was 64.3 % (67.1 in women and 61.4 % men). Among women, the highest participation was in the third quintile (71.5 %) and the lowest in the first - the least disadvantaged (65.7 %). The lowest and highest rates of people with identified lesions were in the second and fourth quintiles (14.7/1000 and 17.0/1000 respectively). Among men, the response rate was lowest in the fifth - most disadvantaged - quintile (60.2 %). The highest rate of identified lesions was in the fifth quintile; 38 % higher than the first (55.7/1000 compared to 41.0/1000). CONCLUSIONS: Sex and socioeconomic group influence the rate of participation in the CRC programme and the rate of lesions found in the participants. Any public health programme is morally and ethically obliged to strive for equity and effectiveness. Improving participation of men and socially disadvantaged groups should be taken in account.

Increased incidence of pediatric type 1 diabetes during the pandemic in Biscay, Spain.

OBJECTIVE: To update the incidence rate (IR) and trends of type 1 diabetes mellitus (T1DM) in children aged 0-14 years from 2003 to 2022, in Biscay, Spain. SUBJECTS AND METHOD: We used the capture-recapture method: primary cases were prospectively extracted from the hospital registry and a secondary independent data source was obtained from diabetes associations and a public health database. The IRs standardized by age and sex were calculated using the direct method, assuming an equal distribution in each age/sex group. The IR occurring during the various COVID-19 waves was compared with the pre-pandemic IR. RESULTS: A total of 378 new cases were identified. The mean age at diagnosis was 9.7 years (5.8-11.9). The completeness of ascertainment was 99.1%. The mean annual age-standardized IR was 12.92 (95%CI, 11.35-13.91). The mean IRs for the 0-4, 5-9, and 10-14 age groups were 7.67, 13.41 and 17.83 cases/100,000 children/year, respectively. The IR trend was statistically significant in the entire group and in the 5-9 year-old group with a mean annual increase of 1.9% (95%CI, 0.1-3.8) and 3.3% (95%CI, 1.002-1.065); p=0.039. The 5-year period analysis confirmed that the increase was significant only in the last 5 years (20%). When 2020-2022 (pandemic) and 2017-2019 (pre-pandemic) periods were compared this difference goes up to 44.5%; p=0.029. CONCLUSIONS: After a long period of stability in the IR of T1DM in children younger than 15 years of age in Biscay, Spain, an increase in recent years has been reported, which is consistent with the SARS-CoV2 pandemic, with the largest increase being reported in the 5-to 9-year-old age group.

CD151 identifies an NK cell subset that is enriched in COVID-19 patients and correlates with disease severity.

Severe coronavirus disease 2019 (COVID-19) often leads to acute respiratory distress syndrome and multi-organ dysfunction, driven by a dysregulated immune response, including a cytokine storm with elevated proinflammatory cytokine levels. Natural killer (NK) cells are part of the innate immune system with a fundamental role in the defense against viral infections. However, during COVID-19 acute infection, they exhibit an altered phenotype and impaired functionality contributing to the immunopathogenesis of the disease. In this work, we have studied a cohort of patients with COVID-19 (ranging from mild to severe) by analyzing IL-15, TGF-ß, PlGF and GDF-15 plasma levels and performing multiparametric flow cytometry studies. Our results revealed that severe COVID-19 patients exhibited high levels of IL-15, PlGF and GDF-15, along with an enrichment of an NK cell subset expressing the CD151 tetraspanin, which correlated with IL-15 plasma levels and disease severity. In patients, these CD151+ NK cells displayed a more activated phenotype characterized by an increased expression of HLA-DR, CD38 and granzyme B, a distinct receptor repertoire, with lower levels of CD160 and CD31 and higher levels of CD55 and, remarkably, a higher expression of tissue-resident markers CD103 and the NK cell decidual marker CD9. Last of all, in individuals with severe disease, we identified an expansion of a CD151brightCD9+ NK cell subset, suggesting that these cells play a specific role in COVID-19. Altogether, our findings suggest that CD151+ NK cells may have a relevant role in COVID-19 immunopathogenesis.