Severity of COVID-19 cases in the months of predominance of the Alpha and Delta variants.

New SARS-CoV-2 may pose problems in controlling the COVID-19 pandemic for public health. We aimed to assess and compare the symptoms and severity of cases due to the Alpha and Delta variant dominance periods, taking into account the effect of COVID-19 vaccination. A prospective epidemiological study of SARS-CoV-2 in Lleida was made to determine differences between Alpha and Delta variants periods. We assessed symptoms, specific comorbidities, sociodemographic information and vaccination status. Bivariate and logistic regression analyses were used to estimate the adjusted odds ratio (aOR) and 95% confidence intervals (CI) to investigate the relationship between symptoms and severity and the variants. Alpha variant period compared to the Delta showed an increased risk of ICU admission (aOR 2.0; 95% CI 1.2-2.3) and death (aOR 2.6; 95% CI 1.8-3.9) and cases were associated with people aged > 85 years (aOR 2.1; 95% CI 1.7-2.6) and partially vaccinated (aOR 5.6; 95% CI 3.2-9.9) and unvaccinated people (aOR 27.8; 95% CI 19.7-40.5). Fever, cough and vomiting were significantly associated with the Alpha variant compared to the Delta (aOR 1.6 (95% CI 1.5-1.7), 2.0 (95% CI 1.9-2.2) and 2.5 (95% CI 2.2-2.9, respectively). Our results show that the severity and profile of clinical symptoms varied according to the variant. The risk of ICU admission and death was higher in the Alpha period compared to the Delta as it affected the elderly and cases were less vaccinated.

[The experience of medical students as peer tutors]. / Rol de tutor par: experiencia de estudiantes de medicina.

BACKGROUND: Peer tutoring is a process of accompaniment carried out by a student with certain features and skills, whose objective is to support and guide, academically and emotionally, other students who may require it. AIM: To assess the experience of medical students who played the role of peer tutor. MATERIAL AND METHODS: We carried out semi-structured in-depth interviews, with prior informed consent, to a non-probabilistic and intentional sample of six students who performed the role of peer tutor, during 2017 and 2018. The data analysis followed the scheme of constant comparison and progressive reduction in a manual way, according to the comparative method, guaranteeing scientific rigor, maintaining criteria of credibility, dependence, confirmability, and transferability. RESULTS: The first level identified 234 units of meaning that originated in the third level, two qualitative domains, oriented to the contribution of peer tutors derived from their experience to strengthen both the process of peer tutor training and the management of peer tutoring. CONCLUSIONS: Peer tutoring as a teaching-learning strategy contributes to the development of generic competences and metacognitive skills, generating high levels of personal satisfaction and identification their teaching role.

Risk factors and comorbidities associated with severe aortic stenosis: A case-control study.

BACKGROUND AND OBJECTIVE: Aortic stricture (AS) is one of the most prevalent cardiovascular diseases in individuals 65 years of age or older. A number of epidemiological studies have suggested that certain cardiovascular risk factors (CRFs) and comorbidities could be associated with AS. The aim of this study was to evaluate the association between CRFs and comorbidities and severe symptomatic AS in individuals 65 years of age or older in a Spanish healthcare region. PATIENTS AND METHODS: We conducted an epidemiological case-control study from a single primary care centre. We collected information on exposure to CRFs and comorbidities and determined their association with AS, employing adjusted odds ratios (OR) and multiple logistic regression models. RESULTS: The study included 102 cases (mean age, 77.6 years) and 221 controls (mean age, 75.5 years). The CRFs significantly associated with severe symptomatic AS were hypercholesterolaemia (OR, 2.67; p < .001), tobacco use (OR, 2.60; p < .001), hypertension (OR, 2.41; p = .010) and low HDL cholesterol readings (OR, 2.20; p = .007). The comorbidities significantly associated with severe symptomatic AS were carotid stenosis (OR, 14.5; p = .017), stroke (OR, 4.14; p = .024), chronic renal failure (OR, 3.78; p < .001) and low haemoglobin levels (OR, 0.76; p < .001). CONCLUSIONS: Hypercholesterolaemia, tobacco use, arterial hypertension and low HDL cholesterol levels are the CRFs with a greater risk of severe AS. Furthermore, this disease is associated with a number of comorbidities (chronic renal failure, stroke, carotid stenosis and low haemoglobin levels), which could be markers of AS.

Rol de tutor par: experiencia de estudiantes de medicina / The experience of medical students as peer tutors

Background: Peer tutoring is a process of accompaniment carried out by a student with certain features and skills, whose objective is to support and guide, academically and emotionally, other students who may require it. Aim: To assess the experience of medical students who played the role of peer tutor. Material and Methods: We carried out semi-structured in-depth interviews, with prior informed consent, to a non-probabilistic and intentional sample of six students who performed the role of peer tutor, during 2017 and 2018. The data analysis followed the scheme of constant comparison and progressive reduction in a manual way, according to the comparative method, guaranteeing scientific rigor, maintaining criteria of credibility, dependence, confirmability, and transferability. Results: The first level identified 234 units of meaning that originated in the third level, two qualitative domains, oriented to the contribution of peer tutors derived from their experience to strengthen both the process of peer tutor training and the management of peer tutoring. Conclusions: Peer tutoring as a teaching-learning strategy contributes to the development of generic competences and metacognitive skills, generating high levels of personal satisfaction and identification their teaching role.

Guidelines on controlling latent tuberculosis infection to support tuberculosis elimination.

OBJECTIVES: Latent TB infection (LTBI) affects 25% of the world's population. As long as this reservoir exists, the elimination of TB will not be feasible. The Assembly of the World Health Organization adopted the "Global End TB" strategy for the elimination of TB in 2014. The objective of this review is to present strategies for risk groups that are candidates for the detection and treatment of LTBI. MATERIAL AND METHOD: There is sufficient evidence of screening in: immunocompromised people (HIV-infected, biological therapies, alternative renal therapy, organ transplantation), recent immigrants, inmates in prison, people injecting drugs and homeless people, and workers from at-risk settings. Tests to diagnose LTBI include tuberculin skin test (TST) and gamma release assay interferon (IGRA). There is no reference test and the choice of one or the other will depend on logistical considerations, such as avoiding injection (TST) or not needing a second visit (IGRA). Treatment of LTBI is based on the use of isoniazide and rifampicin in short period of 3 or 4 months, using associations of rifampicin and isoniazide or rifampicin alone. DISCUSSION: Given the estimated high prevalence of LTBI, renewed efforts are required to reduce the number of people with LTBI that includes a registration and monitoring system to observer progress, increased testing, and the use of short treatment guidelines.

Genome-wide expression changes induced by bisphenol A, F and S in human stem cell derived hepatocyte-like cells.

The debate about possible adverse effects of bisphenol A (BPA) has been ongoing for decades. Bisphenol F (BPF) and S (BPS) have been suggested as "safer" alternatives. In the present study we used hepatocyte-like cells (HLCs) derived from the human embryonic stem cell lines Man12 and H9 to compare the three bisphenol derivatives. Stem cell-derived progenitors were produced using an established system and were exposed to BPA, BPF and BPS for 8 days during their transition to HLCs. Subsequently, we examined cell viability, inhibition of cytochrome P450 (CYP) activity, and genome-wide RNA profiles. Sub-cytotoxic, inhibitory concentrations (IC50) of CYP3A were 20, 9.5 and 25 µM for BPA, BPF and BPS in Man12 derived HLCs, respectively. The corresponding concentrations for H9-derived HLCs were 19, 29 and 31 µM. These IC50 concentrations were used to study global expression changes in this in vitro study and are higher than unconjugated BPA in serum of the general population. A large overlap of up- as well as downregulated genes induced by the three bisphenol derivatives was seen. This is at least 28-fold higher compared to randomly expected gene expression changes. Moreover, highly significant correlations of expression changes induced by the three bisphenol derivatives were obtained in pairwise comparisons. Dysregulated genes were associated with reduced metabolic function, cellular differentiation, embryonic development, cell survival and apoptosis. In conclusion, no major differences in cytochrome inhibitory activities of BPA, BPF and BPS were observed and gene expression changes showed a high degree of similarity.

Risk factors and comorbidities associated with severe aortic stenosis: a case-control study. / Factores de riesgo y comorbilidades asociadas a la estenosis aórtica grave: estudio de casos y controles.

BACKGROUND AND OBJECTIVE: Aortic stricture (AS) is one of the most prevalent cardiovascular diseases in individuals 65 years of age or older. A number of epidemiological studies have suggested that certain cardiovascular risk factors (CRFs) and comorbidities could be associated with AS. The aim of this study was to evaluate the association between CRFs and comorbidities and severe symptomatic AS in individuals 65 years of age or older in a Spanish healthcare region. PATIENTS AND METHODS: We conducted an epidemiological case-control study from a single primary care centre. We collected information on exposure to CRFs and comorbidities and determined their association with AS, employing adjusted odds ratios (OR) and multiple logistic regression models. RESULTS: The study included 102 cases (mean age, 77.6 years) and 221 controls (mean age, 75.5 years). The CRFs significantly associated with severe symptomatic AS were hypercholesterolaemia (OR, 2.67; p<.001), tobacco use (OR, 2.60; p<.001), hypertension (OR, 2.41; p=.010) and low HDL cholesterol readings (OR, 2.20; p=.007). The comorbidities significantly associated with severe symptomatic AS were carotid stenosis (OR, 14.5; p=.017), stroke (OR, 4.14; p=.024), chronic renal failure (OR, 3.78; p<.001) and low haemoglobin levels (OR, 0.76; p<.001). CONCLUSIONS: Hypercholesterolaemia, tobacco use, arterial hypertension and low HDL cholesterol levels are the CRFs with a greater risk of severe AS. Furthermore, this disease is associated with a number of comorbidities (chronic renal failure, stroke, carotid stenosis and low haemoglobin levels), which could be markers of AS.

Hospital-acquired influenza infections detected by a surveillance system over six seasons, from 2010/2011 to 2015/2016.

BACKGROUND: In addition to outbreaks of nosocomial influenza, sporadic nosocomial influenza infections also occur but are generally not reported in the literature. This study aimed to determine the epidemiologic characteristics of cases of nosocomial influenza compared with the remaining severe cases of severe influenza in acute hospitals in Catalonia (Spain) which were identified by surveillance. METHODS: An observational case-case epidemiological study was carried out in patients aged ≥18 years from Catalan 12 hospitals between 2010 and 2016. For each laboratory-confirmed influenza case (nosocomial or not) we collected demographic, virological and clinical characteristics. We defined patients with nosocomial influenza as those admitted to a hospital for a reason other than acute respiratory infection in whom ILI symptoms developed ≥48 h after admission and influenza virus infection was confirmed using RT-PCR. Mixed-effects regression was used to estimate the crude and adjusted OR. RESULTS: One thousand seven hundred twenty-two hospitalized patients with severe laboratory-confirmed influenza virus infection were included: 96 (5.6%) were classified as nosocomial influenza and more frequently had > 14 days of hospital stay (42.7% vs. 27.7%, P < .001) and higher mortality (18.8% vs. 12.6%, P < .02). The variables associated with nosocomial influenza cases in acute-care hospital settings were chronic renal disease (aOR 2.44 95% CI 1.44-4.15) and immunodeficiency (aOR 1.79 95% CI 1.04-3.06). CONCLUSIONS: Nosocomial infections are a recurring problem associated with high rates of chronic diseases and death. These findings underline the need for adherence to infection control guidelines.

[Comorbidity in mental health in patients diagnosed with chronic obstructive pulmonary disease]. / La comorbilidad en salud mental en los pacientes diagnosticados de enfermedad pulmonar obstructiva crónica.

OBJECTIVE: Anxiety and depression play an important role in chronic obstructive pulmonary disease, although there are a limited number of studies that have attempted to determine their relationship with exacerbations, and even less have tried to quantify the number of associated exacerbations. The aim of this study was to determine the risk of exacerbations associated with anxiety and depression in patients diagnosed with chronic obstructive pulmonary disease. MATERIAL AND METHODS: A prospective cohort study was conducted that analysed the factors associated with exacerbations in 512 patients over a 2-year period. The exacerbations that required antibiotics and/or systemic corticosteroids were defined as moderate, and those that required hospital admission, as severe. The Hospital Anxiety and Depression Scale was applied to each patient, and the number of exacerbations during follow-up were quantified. RESULTS: The prevalence of anxiety/depression at the beginning of the study was 15.6%. During the 2 years of follow-up, the mean number of exacerbations was 2.21. The patients that also had anxiety/depression at the beginning of the study had a higher mean number of exacerbations (2.8; P=.001). Anxiety/depression was associated with an increased number of moderate-severe exacerbations in the adjusted analysis (IRRa=1.48). The other risk factors associated with a higher mean number of exacerbations were, a history of a previous severe exacerbation (IRRa=1.50; obesity (IRRa=1.27); overweight (IRRa=1.23); FEV1 ≤ 77% (IRRa=0.84); and more dyspnoea (IRRa=1.14). CONCLUSIONS: Patients with anxiety/depression have a greater number of exacerbations, and have a 48% higher risk of suffering an exacerbation compared to those with chronic obstructive pulmonary disease with no anxiety/depression.

Phage cocktail SalmoFREE® reduces Salmonella on a commercial broiler farm.

According to the World Health Organization, Salmonella is one of the most important zoonotic foodborne pathogens. Poultry products are thought to be the main source of Salmonella, which means that it is necessary to control Salmonella at the pre-harvest stage. Bacteriophages, acting as host-specific parasites of bacterial cells, represent one of the alternatives to antibiotics that can contribute to food safety and security. The present study evaluated the effectiveness of the bacteriophage cocktail SalmoFREE® to control Salmonella on a commercial broiler farm. We assessed the relationship between the use of SalmoFREE® and productivity parameters (feed conversion, weight gain, homogeneity). Two field trials (trial 1 n = 34,986; trial 2 n = 34,680) were carried out under commercial rearing conditions on a Colombian broiler farm with a record of Salmonella presence. Each trial comprised 2 control chicken houses and 2 experimental ones. SalmoFREE® and a control suspension were delivered in the drinking water at 3 time points in the production cycle, and the presence of Salmonella was assessed in cloacal swabs the day before and after the treatments. Results revealed that SalmoFREE® controls the incidence of Salmonella and does not affect the animals nor the production parameters, demonstrating its efficacy and innocuity at the production scale. We detected phage-specific genes in samples of total DNA extracted from ceca after the treatment with SalmoFREE®, and tested for the appearance of cocktail-resistant Salmonella, which showed to be an uncommon event. These results contribute relevant information to the adoption of phage therapy as an alternative to growth-promoter antibiotics on poultry farms.

Effectiveness of antiviral treatment in preventing death in severe hospitalised influenza cases over six seasons.

We investigated the predictors of neuraminidase inhibitor (NAI) treatment in severe hospitalised influenza cases and the association between antiviral treatment and mortality. An observational epidemiological study was carried out in Catalonia (Spain) during 2010-2016 in patients aged ⩾18 years. Severe hospitalised cases of laboratory-confirmed influenza requiring hospitalisation were included. We collected demographic, virological and clinical characteristics. Mixed-effects logistic regression was used to estimate crude and adjusted odds ratio (aOR). We included 1727 hospitalised patients, of whom 1577 (91.3%) received NAI. Receiving NAI ⩽48 h after onset of clinical symptoms (aOR 0.37, 95% confidence interval (CI) 0.22-0.63), ⩽3 days (aOR 0.49, 95% CI 0.30-0.79) and ⩽5 days (aOR 0.50, 95% CI 0.32-0.79) was associated with a reduction in deaths. In patients admitted to the intensive care unit (ICU) (595; 34.5%), treatment ⩽48 h (aOR 0.32, 95% CI 0.14-0.74), ⩽3 days (aOR 0.44, 95% CI 0.20-0.97) and ⩽5 days (aOR 0.45, 95% CI 0.22-0.96) was associated with a reduction in deaths. Receiving treatment >5 days after onset of clinical symptoms was not associated with the reduction in deaths in hospitalised patients or those admitted to the ICU. NAI treatment of hospitalised patients with severe confirmed influenza was effective in avoiding death, mainly when administered ⩽48 h after symptom onset, but also when no more than 5 days had elapsed.

Trends and risk factors of hepatitis A in Catalonia after the introduction of a hepatitis A+B vaccination programme.

At the end of 1998, universal hepatitis A+B vaccination of 12 year olds was introduced in Catalonia. The aim was to examine trends in hepatitis A during 2005-2015 and assess risk factors by age group. We carried out an observational epidemiological study of the incidence and risk factors of hepatitis A reported to the surveillance system. Information on exposure was recorded for each case for the 2-6 weeks before symptom onset. Spearman's coefficient was used to evaluate the trends of rates. The chi-square test was used to compare categorical. We studied 2621 hepatitis A cases; the age mean was 26.6 years (SD=18.2), and >50% of cases were in the 20-49 years age group. The incidence decreased from 3.28/100 000 in 2005 to 1.50/100 000 in 2015. The rate for women decreased over time (P = .008), but the reduction was not significant in men (P = .234). Men consistently had higher rates than women with the biggest difference being in the 20-34 years age group (rate 8.8 vs 2.8). The greatest risk factor was travel to an endemic country (42.1%) in the 0-19 years age group and male-to-male sexual contact (18.6%) in the 20-49 years age group. The case fatality rate in adults aged >49 years was 0.4%. In conclusion, the vaccination programme of preadolescents resulted in a reduction in hepatitis A cases. However, a significant amount of cases still appear in immigrants and men who have sex with men. Hepatitis A in adults is an emerging health problem that will require new strategies.

A highly transmissible tuberculosis outbreak: the importance of bars.

The transmission of tuberculosis (TB) in bars is difficult to study. The objective was to describe a large TB outbreak in a company's bar and other leisure settings. A descriptive study of a TB outbreak was carried out. Contacts were studied in the index case's workplace bar (five circles of contacts) and other recreational areas (social network of three bars in the index case's neighbourhood). Chest X-rays were recommended to contacts with positive tuberculin skin tests (TST) (⩾5 mm). The risk of latent tuberculosis infection (LTBI) was determined using an adjusted odds ratio. The dose-response relationship was determined using the chi-square test for linear trend. We studied 316 contacts at the index case's workplace and detected five new cases of TB. The prevalence of LTBI was 57·9% (183/316) and was higher in the first circle, 96·0% (24/25), and lower in the fifth, 46·5% (20/43) (P < 0·0001). Among 58 contacts in the three neighbourhood bars, two TB cases were detected and the LTBI prevalence was 51·7% (30/58). Two children of one secondary TB company patient became ill. Bars may be transmission locations for TB and, as they are popular venues for social events, should be considered as potential areas of exposure.

Copy number variants of Ras/MAPK pathway genes in patients with isolated cryptorchidism.

Cryptorchidism is the most common congenital disorder in boys, but the cause for most cases remains unknown. Patients with Noonan Syndrome are characterized by a typical face, growth retardation, congenital heart defects, learning disabilities and cryptorchidism. Copy number variations of Ras/MAPK pathway genes are unusual in patients with several clinical features of Noonan Syndrome; however, they have not been studied in patients with only one feature of this condition, such as cryptorchidism. Our aim was to determine whether patients with isolated cryptorchidism exhibit Ras/MAPK pathway gene copy number variations (CNVs). Fifty-nine patients with isolated cryptorchidism and negative for mutations in genes associated with Noonan Syndrome were recruited. Determination of Ras/MAPK pathway gene CNVs was performed by Comparative Genome Hybridization array. A CNV was identified in two individuals, a ~175 kb microduplication at 3p25.2, partially including RAF1. A similar RAF1 microduplication has been observed in a patient with testicular aplasia. This suggests that some patients with isolated cryptorchidism may harbor Ras/MAPK pathway gene CNVs.

Detection of linezolid resistance due to the optrA gene in Enterococcus faecalis from poultry meat from the American continent (Colombia).

Background: Three Enterococcus isolates obtained from retail chicken collected in 2010-11 as part of the Colombian Integrated Program for Antimicrobial Resistance Surveillance (COIPARS) showed reduced susceptibility towards linezolid (MIC 8 mg/L). Objectives: This study aimed at characterizing the isolates resistant to linezolid and detecting the resistance mechanism. Methods: Strains were analysed in 2011-12 without successful detection of the resistance mechanism. All isolates were found negative for the cfr gene and no 23S rRNA mutations were detected. In 2016, with the novel resistance gene optrA being described, the WGS data were re-analysed using in silico genomic tools for confirmation of species, detection of virulence and resistance genes, MLST and SNP analyses and comparison of the genetic environment with the previously published plasmid pE349. Results: : Three Enterococcus faecalis isolates were found positive for the optrA gene encoding resistance to linezolid and phenicols. Additional screening of 37 enterococci strains from the same study did not detect any further positives. Typing showed that two of the isolates belong to ST59, while the last belongs to ST489. All isolates carry genes encoding resistance to macrolide-lincosamide-streptogramin B, tetracycline and phenicols. In addition, the ST489 isolate also carries genes conferring aminoglycoside resistance and is resistant to quinolones, but no plasmid-mediated gene was detected. The optrA gene regions of the three plasmids showed high similarity to the originally reported optrA -carrying plasmid pE349. Conclusions: To the best of our knowledge, this is the first description of the optrA gene in E. faecalis isolated from poultry meat in the Americas.

Effectiveness of acellular pertussis vaccination during childhood (<7 years of age) for preventing pertussis in household contacts 1-9 years old in Catalonia and Navarra (Spain).

Pertussis vaccination with 4-5 doses of acellular vaccines is recommended in Spain to all children at 2 months to 6 years of age. The effectiveness of the acellular pertussis vaccination was assessed in this study by comparing the incidence of secondary pertussis in vaccinated (4-5 doses) and unvaccinated or partially vaccinated (0-3 doses) household contacts 1-9 years old of confirmed cases of pertussis in Spain in 2012-13. Eighty-five percent of contacts had been vaccinated with 4-5 doses of acellular pertussis vaccines. During the 2-year study period, 64 cases of secondary pertussis were detected among 405 household contacts 1-9 years old: 47 among vaccinated and 17 among unvaccinated or partially vaccinated contacts. The effectiveness for preventing secondary pertussis, calculated as 1 minus the relative risk (RR) of secondary pertussis in vaccinated vs. unvaccinated/partially vaccinated contacts, was 50 % [95 % confidence interval (CI): 19-69 %, p < 0.01] when household contacts were vaccinated using DTaP, Tdap, hexavalent or heptavalent vaccines, and it was 51.3 % (95 % CI: 21-70 %, p < 0.01) when they were vaccinated using DTaP or TdaP vaccines. The effectiveness adjusted for age, sex, pertussis chemotherapy and type of household contact was 58.6 % (95 % CI: 17-79 %, p < 0.05) when contacts were vaccinated using available acellular vaccines, and it was 59.6 % (95 % CI: 18-80 %, p < 0.01) when they were vaccinated using DTaP vaccines. Acellular pertussis vaccination during childhood was effective for preventing secondary pertussis in household contacts 1-9 years old of pertussis cases in Catalonia and Navarra, Spain.

Mass carbon monoxide poisoning among television viewers of a football match. / Brote masivo de intoxicación por monóxido de carbono en los telespectadores de un partido de fútbol.

BACKGROUND: The objective was to study a mass carbon monoxide (CO) poisoning and the characteristics of the asymptomatic cases. METHODS: On the 2nd of February, 2015, a group of more than 30 television viewers of a football match contacted the emergency department due to suspected CO poisoning from a butane stove. A visual inspection of the location of the exposure and a descriptive epidemiological study were conducted. Based on the type of variable, the presence of a statistical association was studied with Fisher's exact test or the Kruskal-Wallis test. RESULTS: Thirty-four of the 39 individuals were affected (87.2%). The exposed individuals had a mean age of 43.8 years (SD, 22.1), and 28.2% (11/39) were women. The time of exposure was 52.4min (SD, 21.0), and the mean distance from the oven was 4.2m (SD, 2.5). The most common symptoms were headache (50%), nausea (20.6%), weakness (20.6%) and dizziness (14.7%). The carboxyhaemoglobin (COHb) levels were very high (13.8% ±5.8%). Some 97.1% of the individuals required oxygen therapy, and 39.4% required hyperbaric chamber treatment. Some 29.5% of the cases had no symptoms but showed COHb levels similar to those that did have symptoms (13.6% vs. 15.3%, nonsignificant difference). The asymptomatic cases had a shorter exposure time (38.3min vs. 53.3min; P<.036). CONCLUSIONS: Almost a third of the exposed individuals were asymptomatic, even with COHb levels similar to those of the symptomatic patients, and the majority of these asymptomatic patients even required oxygen treatment in a hyperbaric chamber.

Risk factors for exacerbation in chronic obstructive pulmonary disease: a prospective study.

BACKGROUND: Although acute exacerbations are key events in the progression of chronic obstructive pulmonary disease (COPD), their frequency and the factors associated with acute exacerbation are not fully known. OBJECTIVE: To determine the incidence and risk factors of very frequent exacerbations in COPD (⩾3 per year). PATIENTS AND METHODS: In a cohort study to analyse acute exacerbation and associated factors in 512 primary care patients during a 2-year follow-up, variables of interest were collected for each patient. Acute exacerbation was defined as an event that required antibiotics and/or systemic steroids (moderate) or hospital admission (severe). Odds ratios (OR) were used to determine factors associated with exacerbation. RESULTS: Incidence of exacerbation was 61.7% in the first year of follow-up and 63.9% in the second year. During the first year, the factors associated with very frequent exacerbation were previous hospital admission (OR 1.69), dyspnoea (moderate [OR 2.86] and severe-very severe [OR 5.83]) and the Charlson Index (OR 1.19); during the second year, associated factors were female sex (OR 4.17), history of previous hospital admissions (OR 2.90), smoking (smoker/ex-smoker) (OR 2.00) and forced vital capacity (OR 0.98). CONCLUSIONS: Incidence of exacerbation is high in COPD patients. Previous admission for exacerbation is a strong predictor and can identify patients at risk.