The natural history of coronavirus disease 2019 (COVID-19) has yet to be fully described. Here, we use patient-level data from the Information System for Research in Primary Care (SIDIAP) to ...summarise COVID-19 outcomes in Catalonia, Spain. We included 5,586,521 individuals from the general population. Of these, 102,002 had an outpatient diagnosis of COVID-19, 16,901 were hospitalised with COVID-19, and 5273 died after either being diagnosed or hospitalised with COVID-19 between 1st March and 6th May 2020. Older age, being male, and having comorbidities were all generally associated with worse outcomes. These findings demonstrate the continued need to protect those at high risk of poor outcomes, particularly older people, from COVID-19 and provide appropriate care for those who develop symptomatic disease. While risks of hospitalisation and death were lower for younger populations, there is a need to limit their role in community transmission.
Objective
To describe the impact of the COVID‐19 pandemic on trends in incidence rates (IR) of diagnoses of eating disorders (ED) among adolescents and young adults.
Methods
Population‐based cohort ...study using primary care records of people aged 10–24 years between January, 2016 and December, 2021 in Catalonia, Spain. IRs were calculated monthly and grouped by the different stages of the COVID‐19 pandemic in Catalonia: (1) the pre‐lockdown (January, 2016–February, 2020), (2) lockdown (March–June, 2020) and, (3) post‐lockdown (July, 2020–December, 2021) periods. Incidence rate ratios (IRR) relative to the corresponding periods in 2018–2019 were calculated.
Results
A total of 1,179,009 individuals were included. The IR was 9.2 per 100,000 person‐months (95% confidence intervals CI: 8.9–9.5) during the pre‐lockdown period. It decreased during the lockdown period (6.3 per 100,000 person‐months 5.5–7.3), but substantially increased during the following period (19.4. per 100,000 person‐months 18.7–20.1). While large reductions in IRs were observed for both sexes during the lockdown period (IRR 95% CI: 0.65 0.54–0.78 in females and 0.46 0.29–0.71 in males), substantial increases during the post‐lockdown period were limited to females, and were particularly pronounced among those aged 10–14 and 15–19 years (2.50 2.23–2.80 and 2.29 2.07–2.54, respectively).
Discussion
The COVID‐19 pandemic has resulted in a substantial increase in ED diagnoses, primarily driven by higher rates among adolescent females.
Public Significance
This population‐based cohort study demonstrated a substantial increase in incidence rates of eating disorders in primary care following the end of lockdown in Catalonia, Spain, with adolescent girls seen to be most affected.
Hepatocellular carcinoma (HCC) development entails changes in liver metabolism. Current knowledge on metabolic perturbations in HCC is derived mostly from case‐control designs, with sparse ...information from prospective cohorts. Our objective was to apply comprehensive metabolite profiling to detect metabolites whose serum concentrations are associated with HCC development, using biological samples from within the prospective European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (>520 000 participants), where we identified 129 HCC cases matched 1:1 to controls. We conducted high‐resolution untargeted liquid chromatography‐mass spectrometry‐based metabolomics on serum samples collected at recruitment prior to cancer diagnosis. Multivariable conditional logistic regression was applied controlling for dietary habits, alcohol consumption, smoking, body size, hepatitis infection and liver dysfunction. Corrections for multiple comparisons were applied. Of 9206 molecular features detected, 220 discriminated HCC cases from controls. Detailed feature annotation revealed 92 metabolites associated with HCC risk, of which 14 were unambiguously identified using pure reference standards. Positive HCC‐risk associations were observed for N1‐acetylspermidine, isatin, p‐hydroxyphenyllactic acid, tyrosine, sphingosine, l,l‐cyclo(leucylprolyl), glycochenodeoxycholic acid, glycocholic acid and 7‐methylguanine. Inverse risk associations were observed for retinol, dehydroepiandrosterone sulfate, glycerophosphocholine, γ‐carboxyethyl hydroxychroman and creatine. Discernible differences for these metabolites were observed between cases and controls up to 10 years prior to diagnosis. Our observations highlight the diversity of metabolic perturbations involved in HCC development and replicate previous observations (metabolism of bile acids, amino acids and phospholipids) made in Asian and Scandinavian populations. These findings emphasize the role of metabolic pathways associated with steroid metabolism and immunity and specific dietary and environmental exposures in HCC development.
What's new?
Changes in liver function precede the development of hepatocellular carcinoma (HCC). Many of these changes can be detected in the blood, as can biomarkers related to lifestyle or environmental exposures that may affect HCC risk. In this study, based on a large, prospective observational cohort, the authors used high resolution mass spectrometry‐based metabolomics to identify alterations in circulating levels of 92 metabolites associated with HCC risk, 14 of which could be annotated with high confidence and some of which were observed up to 10 years prior to diagnosis. These results offer insight into early metabolic perturbations and mechanisms leading to this deadly cancer.
Background
Thrombosis with thrombocytopenia syndrome (TTS) has been reported among individuals vaccinated with adenovirus‐vectored COVID‐19 vaccines. In this study, we describe the background ...incidence of non‐vaccine induced TTS in six European countries.
Methods
Electronic medical records from France, the Netherlands, Italy, Germany, Spain, and the United Kingdom informed the study. Incidence rates of cerebral venous sinus thrombosis (CVST), splanchnic vein thrombosis (SVT), deep vein thrombosis (DVT), pulmonary embolism (PE), and myocardial infarction or ischemic stroke, all with concurrent thrombocytopenia, were estimated among the general population of persons in a database between 2017 and 2019. A range of additional potential adverse events of special interest for COVID‐19 vaccinations were also studied in a similar manner.
Findings
A total of 38 611 617 individuals were included. Background rates ranged from 1.0 (95% CI: 0.7–1.4) to 8.5 (7.4–9.9) per 100 000 person‐years for DVT with thrombocytopenia, from 0.5 (0.3–0.6) to 20.8 (18.9–22.8) for PE with thrombocytopenia, from 0.1 (0.0–0.1) to 2.5 (2.2–2.7) for SVT with thrombocytopenia, and from 1.0 (0.8–1.2) to 43.4 (40.7–46.3) for myocardial infarction or ischemic stroke with thrombocytopenia. CVST with thrombocytopenia was only identified in one database, with incidence rate of 0.1 (0.1–0.2) per 100 000 person‐years. The incidence of non‐vaccine induced TTS increased with age, and was typically greater among those with more comorbidities and greater medication use than the general population. It was also more often seen in men than women. A large proportion of those affected were seen to have been taking antithrombotic and anticoagulant therapies prior to their event.
Interpretation
Although rates vary across databases, non‐vaccine induced TTS has consistently been seen to be a very rare event among the general population. While still remaining very rare, rates were typically higher among older individuals, and those affected were also seen to generally be male and have more comorbidities and greater medication use than the general population.
The relationship between cancer and coronavirus disease 2019 (COVID‐19) infection and severity remains poorly understood. We conducted a population‐based cohort study between 1 March and 6 May 2020 ...describing the associations between cancer and risk of COVID‐19 diagnosis, hospitalisation and COVID‐19‐related death. Data were obtained from the Information System for Research in Primary Care (SIDIAP) database, including primary care electronic health records from ~80% of the population in Catalonia, Spain. Cancer was defined as any primary invasive malignancy excluding non‐melanoma skin cancer. We estimated adjusted hazard ratios (aHRs) for the risk of COVID‐19 (outpatient) clinical diagnosis, hospitalisation (with or without a prior COVID‐19 diagnosis) and COVID‐19‐related death using Cox proportional hazard regressions. Models were estimated for the overall cancer population and by years since cancer diagnosis (<1 year, 1‐5 years and ≥5 years), sex, age and cancer type; and adjusted for age, sex, smoking status, deprivation and comorbidities. We included 4 618 377 adults, of which 260 667 (5.6%) had a history of cancer. A total of 98 951 individuals (5.5% with cancer) were diagnosed, and 6355 (16.4% with cancer) were directly hospitalised with COVID‐19. Of those diagnosed, 6851 were subsequently hospitalised (10.7% with cancer), and 3227 died without being hospitalised (18.5% with cancer). Among those hospitalised, 1963 (22.5% with cancer) died. Cancer was associated with an increased risk of COVID‐19 diagnosis (aHR: 1.08; 95% confidence interval 1.05‐1.11), direct COVID‐19 hospitalisation (1.33 1.24‐1.43) and death following hospitalisation (1.12 1.01‐1.25). These associations were stronger for patients recently diagnosed with cancer, aged <70 years, and with haematological cancers. These patients should be prioritised in COVID‐19 vaccination campaigns and continued non‐pharmaceutical interventions.
What's new?
Studies addressing associations between cancer and severity of coronavirus disease 2019 (COVID‐19) have focused primarily on hospitalized patients. Findings have been inconsistent, however, owing to varying cancer criteria, lack of representative samples, and other factors. Here, the natural history of COVID‐19 in cancer patients during the first wave of the pandemic in 2020 in Spain was investigated in a large, representative cohort with a heterogenous cancer population. Patients with cancer were at increased risk of severe COVID‐19. Risk was notably high among those over age 70 and those with recent cancer diagnosis, hematological cancer, or lung and bladder cancer.
Purpose
Real‐world data (RWD) offers a valuable resource for generating population‐level disease epidemiology metrics. We aimed to develop a well‐tested and user‐friendly R package to compute ...incidence rates and prevalence in data mapped to the observational medical outcomes partnership (OMOP) common data model (CDM).
Materials and Methods
We created IncidencePrevalence, an R package to support the analysis of population‐level incidence rates and point‐ and period‐prevalence in OMOP‐formatted data. On top of unit testing, we assessed the face validity of the package. To do so, we calculated incidence rates of COVID‐19 using RWD from Spain (SIDIAP) and the United Kingdom (CPRD Aurum), and replicated two previously published studies using data from the Netherlands (IPCI) and the United Kingdom (CPRD Gold). We compared the obtained results to those previously published, and measured execution times by running a benchmark analysis across databases.
Results
IncidencePrevalence achieved high agreement to previously published data in CPRD Gold and IPCI, and showed good performance across databases. For COVID‐19, incidence calculated by the package was similar to public data after the first‐wave of the pandemic.
Conclusion
For data mapped to the OMOP CDM, the IncidencePrevalence R package can support descriptive epidemiological research. It enables reliable estimation of incidence and prevalence from large real‐world data sets. It represents a simple, but extendable, analytical framework to generate estimates in a reproducible and timely manner.
The disease management of long‐term breast cancer survivors (BCS) is hampered by the scarce knowledge of multimorbidity patterns. The aim of our study was to identify multimorbidity clusters among ...long‐term BCS and assess their impact on mortality and health services use. We conducted a retrospective study using electronic health records of 6512 BCS from Spain surviving at least 5 years. Hierarchical cluster analysis was used to identify groups of similar patients based on their chronic diagnoses, which were assessed using the Clinical Classifications Software. As a result, multimorbidity clusters were obtained, clinically defined and named according to the comorbidities with higher observed/expected prevalence ratios. Multivariable Cox and negative binomial regression models were fitted to estimate overall mortality risk and probability of contacting health services according to the clusters identified. 83.7% of BCS presented multimorbidity, essential hypertension (34.5%) and obesity and other metabolic disorders (27.4%) being the most prevalent chronic diseases at the beginning of follow‐up. Five multimorbidity clusters were identified: C1‐unspecific (29.9%), C2‐metabolic and neurodegenerative (28.3%), C3‐anxiety and fractures (9.7%), C4‐musculoskeletal and cardiovascular (9.6%) and C5‐thyroid disorders (5.3%). All clusters except C5‐thyroid disorders were associated with higher mortality compared to BCS without comorbidities. The risk of mortality in C4 was increased by 64% (adjusted hazard ratio 1.64, 95% confidence interval 1.52‐2.07). Stratified analysis showed an increased risk of death among BCS with 5 to 10 years of survival in all clusters. These results help to identify subgroups of long‐term BCS with specific needs and mortality risks and to guide BCS clinical practice regarding multimorbidity.
Purpose
Hydrochlorothiazide (HCTZ) use has been linked to skin cancer in northern European countries. We assessed the association between HCTZ exposure and risk of malignant melanoma (MM) and ...keratinocyte carcinoma (KC) in a European Mediterranean population.
Methods
Two parallel nested case‐control studies were conducted in Spain using two electronic primary healthcare databases, each one providing data on both exposure and outcomes: SIDIAP and BIFAP. Cancer cases were matched to 10 controls by age and gender through risk‐set sampling. The ORs and 95% CI for MM and KC associated with previous HCTZ use were estimated using conditional logistic regression. In BIFAP, KC cases were further identified as basal cell carcinoma (BCC) or squamous cell carcinoma (SCC).
Results
In adjusted analyses, both ever and cumulative high (≥50,000 mg) use of HCTZ were associated with an increased risk of KC. The risk estimates for high use were 1.30 (1.26–1.34) in SIDIAP and 1.20 (1.12–1.30) in BIFAP, with a lower risk for BCC (1.11 1.02–1.21) than for SCC (1.71 1.45–2.02). A dose–response relationship was observed between cumulative doses of HCTZ and KC risk. Inconsistent results were found for high use of HCTZ and risk of MM: 1.25 (1.09–1.43) in SIDIAP and 0.85 (0.64–1.13) in BIFAP.
Conclusions
In this European Mediterranean population, a high cumulative use of HCTZ was related to an increased risk of KC with a clear dose–response pattern.
Perturbations in levels of amino acids (AA) and their derivatives are observed in hepatocellular carcinoma (HCC). Yet, it is unclear whether these alterations precede or are a consequence of the ...disease, nor whether they pertain to anatomically related cancers of the intrahepatic bile duct (IHBC), and gallbladder and extrahepatic biliary tract (GBTC). Circulating standard AA, biogenic amines and hexoses were measured (Biocrates AbsoluteIDQ‐p180Kit) in a case‐control study nested within a large prospective cohort (147 HCC, 43 IHBC and 134 GBTC cases). Liver function and hepatitis status biomarkers were determined separately. Multivariable conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (OR; 95%CI) for log‐transformed standardised (mean = 0, SD = 1) serum metabolite levels and relevant ratios in relation to HCC, IHBC or GBTC risk. Fourteen metabolites were significantly associated with HCC risk, of which seven metabolites and four ratios were the strongest predictors in continuous models. Leucine, lysine, glutamine and the ratio of branched chain to aromatic AA (Fischer's ratio) were inversely, while phenylalanine, tyrosine and their ratio, glutamate, glutamate/glutamine ratio, kynurenine and its ratio to tryptophan were positively associated with HCC risk. Confounding by hepatitis status and liver enzyme levels was observed. For the other cancers no significant associations were observed. In conclusion, imbalances of specific AA and biogenic amines may be involved in HCC development.
What's new?
Perturbations in levels of circulating amino acid metabolites are observed in hepatocellular carcinoma (HCC). Yet it is unclear whether these imbalances are apparent from earlier stages of the disease. In this study nested within a prospective cohort, and based on pre‐diagnostically collected blood samples, here the authors show strong HCC risk associations for circulating levels of some aromatic, branched‐chain and glucogenic amino acids and biogenic amines. This observation of impaired metabolism in early HCC development may be applied towards further research into the aetiology of, and pathways leading to, this disease.
Suboptimal intakes of the micronutrient selenium (Se) are found in many parts of Europe. Low Se status may contribute to colorectal cancer (CRC) development. We assessed Se status by measuring serum ...levels of Se and Selenoprotein P (SePP) and examined the association with CRC risk in a nested case–control design (966 CRC cases; 966 matched controls) within the European Prospective Investigation into Cancer and Nutrition. Se was measured by total reflection X‐ray fluorescence and SePP by immunoluminometric sandwich assay. Multivariable incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. Respective mean Se and SePP levels were 84.0 μg/L and 4.3 mg/L in cases and 85.6 μg/L and 4.4 mg/L in controls. Higher Se concentrations were associated with a non‐significant lower CRC risk (IRR = 0.92, 95% CI: 0.82–1.03 per 25 μg/L increase). However, sub‐group analyses by sex showed a statistically significant association for women (ptrend = 0.032; per 25 μg/L Se increase, IRR = 0.83, 95% CI: 0.70–0.97) but not for men. Higher SePP concentrations were inversely associated with CRC risk (ptrend = 0.009; per 0.806 mg/L increase, IRR = 0.89, 95% CI: 0.82–0.98) with the association more apparent in women (ptrend = 0.004; IRR = 0.82, 95% CI: 0.72–0.94 per 0.806 mg/L increase) than men (ptrend = 0.485; IRR = 0.98, 95% CI: 0.86–1.12 per 0.806 mg/L increase). The findings indicate that Se status is suboptimal in many Europeans and suggest an inverse association between CRC risk and higher serum Se status, which is more evident in women.
What's new?
Selenium is an essential micronutrient with anti‐carcinogenic properties, but its association with the development of colorectal cancer is controversial. In the present study, the authors find that the selenium status in many Western Europeans is suboptimal. Higher selenium levels were inversely associated with the risk to develop colorectal carcinoma, a finding more evident in women than in men. The authors argue that in populations where the selenium status is sub‐optimal (e.g. Western Europe) increasing selenium intake may reduce colorectal carcinoma risk, while contrasting results may be obtained in regions with higher selenium intake.
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