Trends in incidence rates of head and neck squamous cell carcinomas overall and by potential relatedness to human papillomavirus, Costa Rica 2006 to 2015.

In Costa Rica (CR), only one report on head and neck cancer (HNC) incidence trends (1985-2007) has been published and no investigations on the epidemiology of potentially human papillomavirus (HPV)-related and HPV-unrelated HNCs have been done. We examined the age-standardized incidence rates (IRs) and trends of head and neck squamous cell carcinomas (HNSCC) and compared incidence trends of potentially HPV-related and HPV-unrelated HNSCCs. We obtained all available HNC cases for the period 2006-2015 from the Costa Rican National Cancer Registry of Tumors and the population estimates from the Costa Rican National Institute of Statistics and Census. The analysis was restricted to invasive HNSCCs (n = 1577). IRs and incidence rate ratios were calculated using SEER*Stat software and were age-standardized for the 2010 Costa Rican population. Joinpoint regression analysis program was used to calculate trends and annual percent changes (APCs) in rates. For all HNSCCs, the age-standardized IR was 34.0/million person-years; 95% CI 32.4, 35.8. There was a significant decline in the incidence of nasopharyngeal cancer (APC: -5.9% per year; 95% CI -10.8, -0.7) and laryngeal cancer (APC: -5.4% per year; -9.2, 1.5). The incidence trends for hypopharyngeal, oropharyngeal and oral cavity cancers each remained stable over time. HNSCCs were categorized by their potential relatedness to HPV infection. Though the APCs were not statistically significant, IRs of potentially HPV-related HNSCCs trended upward, while HPV-unrelated HNSCCs trended downward. HNSCCs are uncommon in CR and decreased over time. We observed a divergent pattern of decreasing HPV-unrelated with increasing HPV-related HNSCCs that should be further informed by HPV genotyping tumor samples.

Prevalencia y determinantes de la infección por virus de papiloma humano en mujeres jóvenes de Guanacaste y Puntarenas, Costa Rica, 2004-2005.

OBJETIVO: Estimar la prevalencia e identificar determinantes de la infección por el virus del papiloma humano (VPH) en mujeres jóvenes (18-25 años). Material y métodos. Se analizaron datos de 5 871 mujeres sexualmente activas a quienes se les realizó una entrevista y toma de muestras cervicouterinas para detección de VPH y citología durante la visita de reclutamiento del Ensayo de Vacunación contra VPH16/18 en Costa Rica. Se calculó la prevalencia total para cualquier tipo de VPH y tipos oncogénicos, no oncogénicos y específicos, con intervalos de confianza al 95% (IC95%). Se utilizó regresión logística múltiple paso-a-paso para identificar determinantes asociados con la infección. RESULTADOS: La prevalencia total de VPH fue 50.0% (IC95% 48.8,51.3) y por tipos oncogénicos fue 33.8% (IC95% 32.6,35.0). El VPH-16 fue el tipo más prevalente (8.3%, IC95% 7.6,9.0). Los determinantes asociados con un alto riesgo de infección prevalente por VPH oncogénicos fueron no estar casada/unión libre, >1 compañero sexual, infección concomitante por Chlamydia trachomatis, y entre aquéllas con un único compañero sexual en su vida, un compañero con antecedente de múltiples compañeras sexuales. Conclusión. Se confirma la asociación de las infecciones por VPH oncogénicos con el comportamiento sexual de la mujer y se destacan los comportamientos del compañero sexual.

Precancerous cervical lesions caused by non-vaccine-preventable HPV types after vaccination with the bivalent AS04-adjuvanted HPV vaccine: an analysis of the long-term follow-up study from the randomised Costa Rica HPV Vaccine Trial.

BACKGROUND: In women vaccinated against human papillomavirus (HPV), reductions in cervical disease and related procedures results in more women having intact transformation zones, potentially increasing the risk of cervical lesions caused by non-vaccine-preventable HPV types, a phenomenon termed clinical unmasking. We aimed to evaluate HPV vaccine efficacy against cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and cervical intraepithelial neoplasia grade 3 or worse (CIN3+) attributed to non-preventable HPV types in the long-term follow-up phase of the Costa Rica HPV Vaccine Trial (CVT). METHODS: CVT was a randomised, double-blind, community-based trial done in Costa Rica. Eligible participants were women aged 18-25 years who were in general good health. Participants were randomly assigned (1:1) to receive an HPV 16 and 18 AS04-adjuvanted vaccine or control hepatitis A vaccine, using a blocked randomisation method (permuted block sizes of 14, 16, and 18). Vaccines in both groups were administered intramuscularly with 0·5 mL doses at 0, 1, and 6 months. Masking of vaccine allocation was maintained throughout the 4-year randomised trial phase, after which participants in the hepatitis A virus vaccine control group were provided the HPV vaccine and exited the study; a screening-only, unvaccinated control group was enrolled. The unvaccinated control group and HPV vaccine group were followed up for 7 years, during which treatment allocation was not masked. One of the prespecified primary endpoints for the long-term follow-up phase was precancers associated with HPV types not prevented by the vaccine, defined as histologically confirmed incident CIN2+ events or CIN3+ events attributed to any HPV type except HPV 16, 18, 31, 33, and 45. Our primary analytical period was years 7-11. Primary analyses were in all participants with at least one follow-up visit and excluded participants with a previous endpoint (ie, modified intention-to-treat cohort). Safety endpoints have been reported elsewhere. This trial is registered with ClinicalTrials.gov, NCT00128661 and NCT00867464. The randomised, masked trial phase is completed; an unmasked subset of women in the HPV-vaccinated group is under active investigation. FINDINGS: Between June 28, 2004, and Dec 21, 2005, 7466 participants were enrolled (HPV vaccine group n=3727 and hepatitis A virus vaccine control group n=3739). Between March 30, 2009, and July 5, 2012, 2836 women enrolled in the new unvaccinated control group. The primary analytical cohort (years 7 to 11) included 2767 participants in the HPV vaccine group and 2563 in the unvaccinated group for the CIN2+ events endpoint assessment and 2826 participants in the HPV vaccine group and 2592 in the unvaccinated control group for the CIN3+ events endpoint assessment. Median follow-up during years 7 to 11 for women included for the CIN2+ events analysis was 52·8 months (IQR 44·0 to 60·7) for the HPV vaccine group and 49·8 months (42·0 to 56·9) for the unvaccinated control group. During years 7 to 11, clinical unmasking was observed with a negative vaccine efficacy against CIN2+ events attributed to non-preventable HPV types (-71·2% [95% CI -164·0 to -12·5]), with 9·2 (95% CI 2·1 to 15·6) additional CIN2+ events attributed to non-preventable HPV types per 1000 HPV-vaccinated participants versus HPV-unvaccinated participants. 27·0 (95% CI 14·2 to 39·9) fewer CIN2+ events irrespective of HPV type per 1000 vaccinated participants were observed during 11 years of follow-up. Vaccine efficacy against CIN3+ events attributed to non-preventable HPV types during years 7 to 11 was -135·0% (95% CI -329·8 to -33·5), with 8·3 (3·0 to 12·8) additional CIN3+ events attributed to non-preventable HPV types per 1000 vaccinated participants versus unvaccinated participants. INTERPRETATION: Higher rates of CIN2+ events and CIN3+ events due to non-preventable HPV types in vaccinated versus unvaccinated participants suggests clinical unmasking could attenuate long-term reductions in high-grade disease following successful implementation of HPV vaccination programmes in screened populations. Importantly, the net benefit of vaccination remains considerable; therefore, HPV vaccination should still be prioritised as primary prevention for cervical cancer. FUNDING: National Cancer Institute and National Institutes of Health Office of Research on Women's Health. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Analysis of cervical HPV infections among unvaccinated young adult women to inform vaccine strategies in this age group: the Costa Rica HPV Vaccine Trial.

INTRODUCTION: Human papillomavirus (HPV) vaccines protect against incident HPV infections, which cause cervical cancer. OBJECTIVES: We estimated the prevalence and incidence of HPV infections in young adult women to understand the impact of an HPV vaccination programme in this population. METHODS: We collected cervical specimens from 6322 unvaccinated women, aged 18-37 years, who participated in the Costa Rica Vaccine Trial and its long-term follow-up. Women were followed for (median) 4.8 years and had (median) 4.0 study visits. Cervical specimens were tested for the presence/absence of 25 HPV genotypes. For each age band, we estimated the percentage of women with 1+ prevalent or 1+ incident HPV infections using generalised estimating equations. We also estimated the prevalence and incidence of HPV as a function of time since first sexual intercourse (FSI). RESULTS: The model estimated HPV incident infections peaked at 28.0% (95% CI 25.3% to 30.9%) at age 20 years then steadily declined to 11.8% (95% CI 7.6% to 17.8%) at age 37 years. Incident oncogenic HPV infections (HPV16/18/31/33/35/39/45/51/52/56/58/59) peaked and then declined from 20.3% (95% CI 17.9% to 22.9%) to 7.7% (95% CI 4.4% to 13.1%); HPV16/18 declined from 6.4% (95% CI 5.1% to 8.1%) to 1.1% (95% CI 0.33% to 3.6%) and HPV31/33/45/52/58 declined from 11.0% (95% CI 9.3% to 13.1%) to 4.5% (95% CI 2.2% to 8.9%) over the same ages. The percentage of women with 1+ incident HPV of any, oncogenic, non-oncogenic and vaccine-preventable (HPV16/18, HPV31/33/45, HPV31/33/45/52/58, and HPV6/11) types peaked <1 year after FSI and steadily declined with increasing time since FSI (p for trends <0.001). We observed similar patterns for model estimated HPV prevalences. CONCLUSION: Young adult women may benefit from HPV vaccination if newly acquired vaccine-preventable oncogenic infections lead to cervical precancer and cancer. HPV vaccination targeting this population may provide additional opportunities for primary prevention. TRIAL REGISTRATION NUMBER: NCT00128661.

Risk Factors for Non-Human Papillomavirus (HPV) Type 16/18 Cervical Infections and Associated Lesions Among HPV DNA-Negative Women Vaccinated Against HPV-16/18 in the Costa Rica Vaccine Trial.

BACKGROUND: Factors that lead human papillomavirus (HPV) infections to persist and progress to cancer are not fully understood. We evaluated co-factors for acquisition, persistence, and progression of non-HPV-16/18 infections among HPV-vaccinated women. METHODS: We analyzed 2153 women aged 18-25 years randomized to the HPV-vaccine arm of the Costa Rica HPV Vaccine Trial. Women were HPV DNA negative for all types at baseline and followed for approximately 11 years. Generalized estimating equation methods were used to account for correlated observations. Time-dependent factors evaluated were age, sexual behavior, marital status, hormonally related factors, number of full-term pregnancies (FTPs), smoking behavior, and baseline body mass index. RESULTS: A total of 1777 incident oncogenic non-HPV-16/18 infections were detected in 12 292 visits (average, 0.14 infections/visit). Age and sexual behavior-related variables were associated with oncogenic non-HPV-16/18 acquisition. Twenty-six percent of incident infections persisted for ≥1 year. None of the factors evaluated were statistically associated with persistence of oncogenic non-HPV-16/18 infections. Risk of progression to Cervical Intraepithelial Neoplasia grade 2 or worst (CIN2+) increased with increasing age (P for trend = .001), injectable contraceptive use (relative risk, 2.61 [95% confidence interval, 1.19-5.73] ever vs never), and increasing FTPs (P for trend = .034). CONCLUSIONS: In a cohort of HPV-16/18-vaccinated women, age and sexual behavior variables are associated with acquisition of oncogenic non-HPV-16/18 infections; no notable factors are associated with persistence of acquired infections; and age, parity, and hormonally related exposures are associated with progression to CIN2+.

Global patterns and trends in colorectal cancer incidence and mortality.

OBJECTIVE: The global burden of colorectal cancer (CRC) is expected to increase by 60% to more than 2.2 million new cases and 1.1 million deaths by 2030. In this study, we aim to describe the recent CRC incidence and mortality patterns and trends linking the findings to the prospects of reducing the burden through cancer prevention and care. DESIGN: Estimates of sex-specific CRC incidence and mortality rates in 2012 were extracted from the GLOBOCAN database. Temporal patterns were assessed for 37 countries using data from Cancer Incidence in Five Continents (CI5) volumes I-X and the WHO mortality database. Trends were assessed via the annual percentage change using joinpoint regression and discussed in relation to human development levels. RESULTS: CRC incidence and mortality rates vary up to 10-fold worldwide, with distinct gradients across human development levels, pointing towards widening disparities and an increasing burden in countries in transition. Generally, CRC incidence and mortality rates are still rising rapidly in many low-income and middle-income countries; stabilising or decreasing trends tend to be seen in highly developed countries where rates remain among the highest in the world. CONCLUSIONS: Patterns and trends in CRC incidence and mortality correlate with present human development levels and their incremental changes might reflect the adoption of more western lifestyles. Targeted resource-dependent interventions, including primary prevention in low-income, supplemented with early detection in high-income settings, are needed to reduce the number of patients with CRC in future decades.

Assays for the determination of the activity of DNA nucleases based on the fluorometric properties of the YOYO dye.

Here we characterize the fluorescence of the YOYO dye as a tool for studying DNA-protein interactions in real time and present two continuous YOYO-based assays for sensitively monitoring the kinetics of DNA digestion by λ-exonuclease and the endonuclease EcoRV. The described assays rely on the different fluorescence intensities between single- and double-stranded DNA-YOYO complexes, allowing straightforward determination of nuclease activity and quantitative determination of reaction products. The assays were also employed to assess the effect of single-stranded DNA-binding proteins on the λ-exonuclease reaction kinetics, showing that the extreme thermostable single-stranded DNA-binding protein (ET-SSB) significantly reduced the reaction rate, while the recombination protein A (RecA) displayed no effect.

Social gradient and rural-urban disparities in cancer mortality in Costa Rica.

INTRODUCTION: Data on social inequalities in cancer mortality are sparse, especially in low- and middle-income countries. We aimed to analyze the socioeconomic inequalities in cancer mortality in Costa Rica between 2010 and 2018. METHODS: We linked 9-years of data from the National Electoral Rolls, National Birth Index and National Death Index to classify deaths due to cancer and socioeconomic characteristics of the district of residence, as measured by levels of urbanicity and wealth. We analyzed the fifteen most frequent cancer sites in Costa Rica among the 2.7 million inhabitants aged 20 years and older. We used a parametric survival model based on a Gompertz distribution. RESULTS: Compared to urban areas, mixed and rural area residents had lower mortality from pancreas, lung, breast, prostate, kidney, and bladder cancers, and higher mortality from stomach cancer. Mortality from stomach, lung and cervical cancer was higher, and mortality from colorectal cancer, non-Hodgkin lymphoma and leukemia was lower in the most disadvantaged districts, compared to the wealthiest ones. CONCLUSION: We observed marked disparities in cancer mortality in Costa Rica in particular from infection- and lifestyle- related cancers. There are important opportunities to reduce disparities in cancer mortality by targeting cancer prevention, early detection and opportune treatment, mainly in urban and disadvantaged districts.

A surveillance study of cancer incidence and mortality among young adults in Costa Rica.

Background: There has been an increase in certain cancers among young adults (YA) aged 20-39, particularly in Latin America. This is the first study to examine cancer incidence and mortality in YA in Costa Rica, focusing on sex-specific patterns. Methods: Invasive cancer cases (excluding non-melanoma skin cancer) in YA from 2006 to 2015 were obtained from the Costa Rican National Registry of Tumors. Utilising SEER∗Stat software, age-standardized incidence rates (IRs) and incidence rate ratios (IRRs) were calculated. Trends and annual percent changes (APCs) in IRs were estimated using the Joinpoint regression analysis program. Cancer deaths from 2000 to 2021 were obtained from the Costa Rican National Institute of Statistics and Census. Age-standardised mortality rates were calculated using STATA®17. Findings: YA comprised 10.7% of all invasive cancer cases diagnosed from 2006 to 2015. The age-standardized incidence rate (ASIR) of invasive cancer in YA was 50.9/100,000 person-years. The ASIR was twofold higher for females compared to males (IRR = 2.03, 95% CI:1.94, 2.13). This difference increased with age, peaking in the 35-39-year age group (IRR = 2.84, 95% CI:2.62, 3.10). Thyroid, breast, and cervical cancer were the most common in females. Testicular cancer was the most common in males. Leading causes of cancer-related deaths included cervical and breast cancer in females and stomach and brain/nervous system cancer in males. Interpretation: The study highlights sex-specific patterns in cancer incidence and mortality among YA in Costa Rica to increase understanding and improve cancer outcomes in this age group. Funding: This study was funded by the Intramural Research Program of the National Cancer Institute.

Global evaluation of lineage-specific human papillomavirus capsid antigenicity using antibodies elicited by natural infection.

Human Papillomavirus (HPV) type variants have been classified into lineages and sublineages based upon their whole genome sequence. Here we have examined the specificity of antibodies generated following natural infection with lineage variants of oncogenic types (HPV16, 18, 31, 33, 45, 52 and 58) by testing serum samples assembled from existing archives from women residing in Africa, The Americas, Asia or Europe against representative lineage-specific pseudoviruses for each genotype. We have subjected the resulting neutralizing antibody data to antigenic clustering methods and created relational antigenic profiles for each genotype to inform the delineation of lineage-specific serotypes. For most genotypes, there was evidence of differential recognition of lineage-specific antigens and in some cases of a sufficient magnitude to suggest that some lineages should be considered antigenically distinct within their respective genotypes. These data provide compelling evidence for a degree of lineage specificity within the humoral immune response following natural infection with oncogenic HPV.

State-of-the-Science of human papillomavirus vaccination in women with human immunodeficiency Virus: Summary of a scientific workshop.

The burden of cervical cancer is disproportionately distributed globally, with the vast majority of cases occurring in low- and middle-income countries. Women with human immunodeficiency virus (HIV) (WWH) are at increased risk of human papillomavirus (HPV) infection and cervical cancer as compared to HIV-negative individuals. HPV vaccination remains a priority in regions with a high burden of cervical cancer and high HIV prevalence. With HPV vaccines becoming more accessible, optimal use beyond the initial World Health Organization-recommended target population of 9 to 14-year-old girls is an important question. In March 2022, a group of experts in epidemiology, immunology, and vaccinology convened to discuss the state-of-the-science of HPV vaccination in WWH. This report summarizes the proceedings: review of HIV epidemiology and its intersection with cervical cancer burden, immunology, HPV vaccination including reduced-dose schedules and experience with other vaccines in people with HIV (PWH), HPV vaccination strategies and knowledge gaps, and outstanding research questions. Studies of HPV vaccine effectiveness among WWH, including duration of protection, are limited. Until data from ongoing research is available, the current recommendation for WWH remains for a multi-dose HPV vaccination regimen. A focus of the discussion included the potential impact of HIV acquisition following HPV vaccination. With no data currently existing for HPV vaccines and limited information from non-HPV vaccines, this question requires further research. Implementation research on optimal HPV vaccine delivery approaches for WWH and other priority populations is also urgently needed.

Splanchnic Vein Thrombosis in Inflammatory Bowel Disease: An Observational Study from the ENEIDA Registry and Systematic Review.

BACKGROUND: Thromboembolic events are frequent among patients with inflammatory bowel disease (IBD). However, there is little information on the prevalence, features and outcomes of splanchnic vein thrombosis (SVT) in patients with IBD. AIMS: To describe the clinical features and outcomes of SVT in patients with IBD and to perform a systematic review of these data with published cases and series. METHODS: A retrospective observational study from the Spanish nationwide ENEIDA registry was performed. A systematic search of the literature was performed to identify studies with at least one case of SVT in IBD patients. RESULTS: A new cohort of 49 episodes of SVT from the Eneida registry and 318 IBD patients with IBD identified from the literature review (sixty studies: two multicentre, six single-centre and fifty-two case reports or case series) were analysed. There was a mild predominance of Crohn's disease and the most frequent clinical presentation was abdominal pain with or without fever followed by the incidental finding in cross-sectional imaging techniques. The most frequent SVT location was the main portal trunk in two-thirds of the cases, followed by the superior mesenteric vein. Anticoagulation therapy was prescribed in almost 90% of the cases, with a high rate of radiologic resolution of SVT. Thrombophilic conditions other than IBD itself were found in at least one-fifth of patients. CONCLUSIONS: SVT seems to be a rare (or underdiagnosed) complication in IBD patients. SVT is mostly associated with disease activity and evolves suitably when anticoagulation therapy is started.

HPV16 infection decreases vaccine-induced HPV16 antibody avidity: the CVT trial.

The HPV vaccine has shown sustained efficacy and consistent stabilization of antibody levels, even after a single dose. We defined the HPV16-VLP antibody avidity patterns over 11 years among women who received one- or three doses of the bivalent HPV vaccine in the Costa Rica HPV Vaccine Trial. Absolute HPV16 avidity was lower in women who received one compared to three doses, although the patterns were similar (increased in years 2 and 3 and remained stable over the remaining 8 years). HPV16 avidity among women who were HPV16-seropositive women at HPV vaccination, a marker of natural immune response to HPV16 infection, was significantly lower than those of HPV16-seronegative women, a difference that was more pronounced among one-dose recipients. No differences in HPV16 avidity were observed by HPV18 serostatus at vaccination, confirming the specificity of the findings. Importantly, point estimates for vaccine efficacy against incident, six-month persistent HPV16 infections was similar between women who were HPV16 seronegative and seropositive at the time of initial HPV vaccination for both one-dose and three-dose participants. It is therefore likely that this lower avidity level is still sufficient to enable antibody-mediated protection. It is encouraging for long-term HPV-vaccine protection that HPV16 antibody avidity was maintained for over a decade, even after a single dose.

Rationale and design of a double-blind randomized non-inferiority clinical trial to evaluate one or two doses of vaccine against human papillomavirus including an epidemiologic survey to estimate vaccine efficacy: The Costa Rica ESCUDDO trial.

HPV vaccination of adolescent girls is the most effective measure to prevent cervical cancer. The World Health Organization recommends that adolescent girls receive two doses of vaccine but only a small proportion of girls from regions with the highest disease burden are vaccinated because of cost and logistical considerations. Our Costa Rica HPV Vaccine trial suggested that one dose of the bivalent HPV vaccine provides robust and lasting protection against persistent HPV infections for over a decade. Data from a post-licensure trial of the quadrivalent vaccine in India also suggested that a single dose may be effective in reducing cervical cancer risk. To formally compare one versus two doses of the bivalent and nonavalent HPV vaccines, we implemented a large, randomized, double-blind trial to investigate the non-inferiority of one compared to two vaccine doses in the prevention of new HPV16/18 infections that persist 6 or more months. Bivalent and nonavalent vaccines will be evaluated separately. The trial enrolled and randomized (1:1:1:1 to 1- and 2-dose arms of the bivalent and nonavalent vaccines) 20,330 girls 12 to 16 years old residing in Costa Rica. Trial participants are followed every 6 months for up to 5 years. We also aim to estimate vaccine efficacy by comparing the rates of 6 month persistent infection in unvaccinated women with the rates in the follow-up visits of trial participants. We included one survey of unvaccinated women at the start of the study (N = 4452) and will include another survey concomitant with follow up visits of trial participants at year 4.5 (planned N = 3000). Survey participants attend two visits 6 months appart. Herein, we present the rationale, design, and enrolled study population of the ESCUDDO trial. ClinicalTrials.gov Identifier: NCT03180034.

Nationwide COVID-19-EII Study: Incidence, Environmental Risk Factors and Long-Term Follow-Up of Patients with Inflammatory Bowel Disease and COVID-19 of the ENEIDA Registry.

We aim to describe the incidence and source of contagion of COVID-19 in patients with IBD, as well as the risk factors for a severe course and long-term sequelae. This is a prospective observational study of IBD and COVID-19 included in the ENEIDA registry (53,682 from 73 centres) between March-July 2020 followed-up for 12 months. Results were compared with data of the general population (National Centre of Epidemiology and Catalonia). A total of 482 patients with COVID-19 were identified. Twenty-eight percent were infected in the work environment, and 48% were infected by intrafamilial transmission, despite having good adherence to lockdown. Thirty-five percent required hospitalization, 7.9% had severe COVID-19 and 3.7% died. Similar data were reported in the general population (hospitalisation 19.5%, ICU 2.1% and mortality 4.6%). Factors related to death and severe COVID-19 were being aged ≥ 60 years (OR 7.1, 95% CI: 1.8-27 and 4.5, 95% CI: 1.3-15.9), while having ≥2 comorbidities increased mortality (OR 3.9, 95% CI: 1.3-11.6). None of the drugs for IBD were related to severe COVID-19. Immunosuppression was definitively stopped in 1% of patients at 12 months. The prognosis of COVID-19 in IBD, even in immunosuppressed patients, is similar to that in the general population. Thus, there is no need for more strict protection measures in IBD.

Correction: Chaparro et al. Incidence, Clinical Characteristics and Management of Inflammatory Bowel Disease in Spain: Large-Scale Epidemiological Study. J. Clin. Med. 2021, 10, 2885.

The authors wish to make the following corrections to this paper [...].

Risk Factors for COVID-19 in Inflammatory Bowel Disease: A National, ENEIDA-Based Case-Control Study (COVID-19-EII).

(1) Scant information is available concerning the characteristics that may favour the acquisition of COVID-19 in patients with inflammatory bowel disease (IBD). Therefore, the aim of this study was to assess these differences between infected and noninfected patients with IBD. (2) This nationwide case−control study evaluated patients with inflammatory bowel disease with COVID-19 (cases) and without COVID-19 (controls) during the period March−July 2020 included in the ENEIDA of GETECCU. (3) A total of 496 cases and 964 controls from 73 Spanish centres were included. No differences were found in the basal characteristics between cases and controls. Cases had higher comorbidity Charlson scores (24% vs. 19%; p = 0.02) and occupational risk (28% vs. 10.5%; p < 0.0001) more frequently than did controls. Lockdown was the only protective measure against COVID-19 (50% vs. 70%; p < 0.0001). No differences were found in the use of systemic steroids, immunosuppressants or biologics between cases and controls. Cases were more often treated with 5-aminosalicylates (42% vs. 34%; p = 0.003). Having a moderate Charlson score (OR: 2.7; 95%CI: 1.3−5.9), occupational risk (OR: 2.9; 95%CI: 1.8−4.4) and the use of 5-aminosalicylates (OR: 1.7; 95%CI: 1.2−2.5) were factors for COVID-19. The strict lockdown was the only protective factor (OR: 0.1; 95%CI: 0.09−0.2). (4) Comorbidities and occupational exposure are the most relevant factors for COVID-19 in patients with IBD. The risk of COVID-19 seems not to be increased by immunosuppressants or biologics, with a potential effect of 5-aminosalicylates, which should be investigated further and interpreted with caution.

Immigrant IBD Patients in Spain Are Younger, Have More Extraintestinal Manifestations and Use More Biologics Than Native Patients.

BACKGROUND: Previous studies comparing immigrant ethnic groups and native patients with IBD have yielded clinical and phenotypic differences. To date, no study has focused on the immigrant IBD population in Spain. METHODS: Prospective, observational, multicenter study comparing cohorts of IBD patients from ENEIDA-registry who were born outside Spain with a cohort of native patients. RESULTS: We included 13,524 patients (1,864 immigrant and 11,660 native). The immigrants were younger (45 ± 12 vs. 54 ± 16 years, p < 0.001), had been diagnosed younger (31 ± 12 vs. 36 ± 15 years, p < 0.001), and had a shorter disease duration (14 ± 7 vs. 18 ± 8 years, p < 0.001) than native patients. Family history of IBD (9 vs. 14%, p < 0.001) and smoking (30 vs. 40%, p < 0.001) were more frequent among native patients. The most prevalent ethnic groups among immigrants were Caucasian (41.5%), followed by Latin American (30.8%), Arab (18.3%), and Asian (6.7%). Extraintestinal manifestations, mainly musculoskeletal affections, were more frequent in immigrants (19 vs. 11%, p < 0.001). Use of biologics, mainly anti-TNF, was greater in immigrants (36 vs. 29%, p < 0.001). The risk of having extraintestinal manifestations [OR: 2.23 (1.92-2.58, p < 0.001)] and using biologics [OR: 1.13 (1.0-1.26, p = 0.042)] was independently associated with immigrant status in the multivariate analyses. CONCLUSIONS: Compared with native-born patients, first-generation-immigrant IBD patients in Spain were younger at disease onset and showed an increased risk of having extraintestinal manifestations and using biologics. Our study suggests a featured phenotype of immigrant IBD patients in Spain, and constitutes a new landmark in the epidemiological characterization of immigrant IBD populations in Southern Europe.

Effect of Helicobacter pylori infection on growth velocity of school-age Andean children.

BACKGROUND: Helicobacter pylori infection affects about half of the world's population and is usually acquired in childhood. The infection has been associated with chronic gastritis, peptic ulcer, and stomach cancer in adulthood. Little is known, however, about its consequences on child health. We examined the effect of H. pylori infection on growth among school-age children in the Colombian Andes by comparing growth velocity in the presence and absence of H. pylori infection. METHODS: Children who were 4-8 years old in 2004 were followed up in a community where infected children received anti-H. pylori treatment (n = 165) and a comparison community (n = 161) for a mean of 2.5 years. Anthropometry measurements were made every 3 months and H. pylori status ascertained by urea breath test every 6 months. Growth velocities (cm/month) were compared across person-time with and without infection, using mixed models for repeated measures. RESULTS: In the untreated community, 83% were H. pylori-positive at baseline and 89% were -positive at study end. The corresponding prevalences were 74% and 46%, respectively, in the treated community. Growth velocity in the pretreatment interval was 0.44 (standard deviation [SD] = 0.13) cm/month. Models that adjusted for age, sex, and height estimated that H. pylori-positive children grew on average 0.022 cm/month (95% confidence interval = 0.008 to 0.035) slower than H. pylori-negative children, a result that was not appreciably altered by adjustment for socioenvironmental covariates. CONCLUSIONS: This study suggests that chronic H. pylori infection is accompanied by slowed growth in school-age Andean children.