ObjectiveWe aimed to describe the associations of age and sex with the risk of COVID-19 in different severity stages ranging from infection to death.DesignSystematic review and meta-analysis.Data ...sourcesPubMed and Embase through 4 May 2020.Study selectionWe considered cohort and case–control studies that evaluated differences in age and sex on the risk of COVID-19 infection, disease severity, intensive care unit (ICU) admission and death.Data extraction and synthesisWe screened and included studies using standardised electronic data extraction forms and we pooled data from published studies and data acquired by contacting authors using random effects meta-analysis. We assessed the risk of bias using the Newcastle-Ottawa Scale.ResultsWe screened 11.550 titles and included 59 studies comprising 36.470 patients in the analyses. The methodological quality of the included papers was high (8.2 out of 9). Men had a higher risk for infection with COVID-19 than women (relative risk (RR) 1.08, 95% CI 1.03 to 1.12). When infected, they also had a higher risk for severe COVID-19 disease (RR 1.18, 95% CI 1.10 to 1.27), a higher need for intensive care (RR 1.38, 95% CI 1.09 to 1.74) and a higher risk of death (RR 1.50, 95% CI 1.18 to 1.91). The analyses also showed that patients aged 70 years and above have a higher infection risk (RR 1.65, 95% CI 1.50 to 1.81), a higher risk for severe COVID-19 disease (RR 2.05, 95% CI 1.27 to 3.32), a higher need for intensive care (RR 2.70, 95% CI 1.59 to 4.60) and a higher risk of death once infected (RR 3.61, 95% CI 2.70 to 4.84) compared with patients younger than 70 years.ConclusionsMeta-analyses on 59 studies comprising 36.470 patients showed that men and patients aged 70 and above have a higher risk for COVID-19 infection, severe disease, ICU admission and death.PROSPERO registration numberCRD42020180085.
Smoking is a major risk factor for bladder cancer (BC). This meta-analysis updates previous reviews on smoking characteristics and BC risk, and provides a more quantitative estimation of the ...dose-response relationship between smoking characteristics and BC risk.
In total, 89 studies comprising data from 57 145 BC cases were included and summary odds ratios (SORs) were calculated. Dose-response meta-analyses modelled relationships between smoking intensity, duration, pack-years and cessation and BC risk. Sources of heterogeneity were explored and sensitivity analyses were conducted to test the robustness of findings.
Current smokers (SOR = 3.14, 95% CI = 2.53-3.75) and former smokers(SOR = 1.83, 95% CI = 1.52-2.14) had an increased risk of BC compared with never smokers. Age at first exposure was negatively associated with BC risk. BC risk increased gradually by smoking duration and a risk plateau at smoking 15 cigarettes a day and 50 pack-years was observed. Smoking cessation is most beneficial from 20 years before diagnosis. The population-attributable risk of BC for smokers has decreased from 50% to 43% in men and from 35% to 26% in women from Europe since estimated in 2000. Results were homogeneous between sources of heterogeneity, except for lower risk estimates found in studies of Asian populations.
Active smokers are at an increased risk of BC. Dose-response meta-analyses showed a BC risk plateau for smoking intensity and indicate that even after long-term smoking cessation, an elevated risk of bladder cancer remains.
Highly sensitive and specific urine-based tests to detect either primary or recurrent bladder cancer have proved elusive to date. Our ever increasing knowledge of the genomic aberrations in bladder ...cancer should enable the development of such tests based on urinary DNA.
DNA was extracted from urine cell pellets and PCR used to amplify the regions of the TERT promoter and coding regions of FGFR3, PIK3CA, TP53, HRAS, KDM6A and RXRA which are frequently mutated in bladder cancer. The PCR products were barcoded, pooled and paired-end 2 x 250 bp sequencing performed on an Illumina MiSeq. Urinary DNA was analysed from 20 non-cancer controls, 120 primary bladder cancer patients (41 pTa, 40 pT1, 39 pT2+) and 91 bladder cancer patients post-TURBT (89 cancer-free).
Despite the small quantities of DNA extracted from some urine cell pellets, 96% of the samples yielded mean read depths >500. Analysing only previously reported point mutations, TERT mutations were found in 55% of patients with bladder cancer (independent of stage), FGFR3 mutations in 30% of patients with bladder cancer, PIK3CA in 14% and TP53 mutations in 12% of patients with bladder cancer. Overall, these previously reported bladder cancer mutations were detected in 86 out of 122 bladder cancer patients (70% sensitivity) and in only 3 out of 109 patients with no detectable bladder cancer (97% specificity).
This simple, cost-effective approach could be used for the non-invasive surveillance of patients with non-muscle-invasive bladder cancers harbouring these mutations. The method has a low DNA input requirement and can detect low levels of mutant DNA in a large excess of normal DNA. These genes represent a minimal biomarker panel to which extra markers could be added to develop a highly sensitive diagnostic test for bladder cancer.
•Residents infected with COVID-19 between December 2021 and March 2023 in Luxembourg were enrolled in a nationwide retrospective cohort study.•Complete primary vaccination conferred 49.5% protection ...against death, one booster 69.0%, and two boosters 76.2%•Complete primary vaccination conferred 38.8% protection against hospitalization, one booster 62.1%, and two boosters 71.6%•The vaccination against COVID-19 lowered mortality by 55.8% and hospital admissions by 49.1%.
Luxembourg experienced major consecutive SARS-CoV-2 infection waves due to Omicron variants during 2022 while having achieved a high vaccination coverage in 2021. We investigated the risk factors associated to severe outcomes (i.e., hospitalisation, deaths) and estimated vaccine effectiveness (VE) as well as the role of immunity conferred by prior infections against severe outcomes in adults.
We linked reported SARS-CoV-2 cases among residents aged ≥ 20 years with vaccination data and SARS-CoV-2 related hospitalisations and deaths. Cases were followed-up until day 14 for COVID-19 related hospital admission and up to day 28 for mortality after a positive test. We analysed the association between the vaccination status and severe forms using proportional Cox regression, adjusting for previous infection, age, sex and nursing homes residency. VE was measured as 1-adjusted hazard ratio of vaccinated vs unvaccinated individuals. The population preventable fraction was computed using the adjusted hazard ratio and the proportion of cases within the vaccination category.
Between December 2021, and March 2023, we recorded 187143 SARS-CoV-2 cases, 1728 (0.93%) hospitalizations and 611 (0.33%) deaths. The risk of severe outcomes increased with age, was higher among men and nursing home residents. Compared to unvaccinated adults, VE against hospitalization was 38.8% (95%CI: 28.1%-47.8%) for a complete primary cycle of vaccination, 62.1% (95%CI: 57.0%-66.7%) for one booster, and 71.6% (95%CI: 66.7%-76.2%) for two booster doses. VE against death was respectively 49.5% (95%CI: 30.8%-63.3%), 69.0% (95%CI: 61.2%-75.3%) and 76.2% (95%CI: 68.4%-82.2%). Previous infection was not associated with lower risk of hospitalisation or mortality. The vaccination lowered mortality by 55.8 % (95%CI: 46.3%-62.8%) and reduced hospital admissions by 49.1% (95%CI: 43.4%-54.4%).
Complete vaccination and booster but not previous infection were protective against hospitalization and death. The vaccination program in Luxembourg led to substantial reductions in SARS-CoV-2-related mortality and hospitalizations at the population level.
Objective An increasing number of diseases is linked to deterioration of quality of life (QoL). Part of this association can be explained by socio-economic factors, which are most commonly accounted ...for. Our aim was to explore the potential contribution of other factors related to clinical burden, social interaction and functioning. Methods A cross-sectional analysis was conducted on wave 6 of the population-based Survey of Health, Ageing and Retirement in Europe (SHARE), among participants aged 50+ (n = 67 179). The Control, Autonomy, Self-Realization and Pleasure (CASP-12v1) questionnaire measured QoL. The association between number of diseases and QoL was tested in a mixed-effects linear regression model. The base model controlled for socio-economic characteristics. Factors of interest (symptoms, polypharmacy, unmet care needs, utilisation of care, social network, personal and financial help, loneliness and activities of daily living (ADL) with instrumental activities (IADL)) were added to the base model one at a time and tested for relevance (i.e. change in the beta-coefficient of the number of conditions of 15% or more). Results Symptoms, polypharmacy, loneliness and ADL/IADL appeared relevant and were retained in the final model. The association between number of conditions and QoL in the base model was -2.44 95% CI: -2.72; -2.16, while this association was -0.76 95%CI: -0.97; -0.54 after all relevant factors were included. Conclusion Factors beyond the socio-economic circumstances play an important role in explaining the association between number of conditions and QoL. These factors should be considered to better estimate the impact of chronic diseases on QoL, and for improving patient care.
Inappropriate DNA methylation is frequently associated with human tumour development, and in specific cases, is associated with clinical outcomes. Previous reports of DNA methylation in ...low/intermediate grade non-muscle invasive bladder cancer (NMIBC) have suggested that specific patterns of DNA methylation may have a role as diagnostic or prognostic biomarkers. In view of the aggressive and clinically unpredictable nature of high-grade (HG) NMIBC, and the current shortage of the preferred treatment option (Bacillus:Calmette-Guerin), novel methylation analyses may similarly reveal biomarkers of disease outcome that could risk-stratify patients and guide clinical management at initial diagnosis.
Promoter-associated CpG island methylation was determined in primary tumour tissue of 36 initial presentation high-grade NMIBCs, 12 low/intermediate-grade NMIBCs and 3 normal bladder controls. The genes HOXA9, ISL1, NKX6-2, SPAG6, ZIC1 and ZNF154 were selected for investigation on the basis of previous reports and/or prognostic utility in low/intermediate-grade NMIBC. Methylation was determined by Pyrosequencing of sodium-bisulphite converted DNA, and then correlated with gene expression using RT-qPCR. Methylation was additionally correlated with tumour behaviour, including tumour recurrence and progression to muscle invasive bladder cancer or metastases.
The ISL1 genes' promoter-associated island was more frequently methylated in recurrent and progressive high-grade tumours than their non-recurrent counterparts (60.0% vs. 18.2%, p = 0.008). ISL1 and HOXA9 showed significantly higher mean methylation in recurrent and progressive tumours compared to non-recurrent tumours (43.3% vs. 20.9%, p = 0.016 and 34.5% vs 17.6%, p = 0.017, respectively). Concurrent ISL1/HOXA9 methylation in HG-NMIBC reliably predicted tumour recurrence and progression within one year (Positive Predictive Value 91.7%), and was associated with disease-specific mortality (DSM).
In this study we report methylation differences and similarities between clinical sub-types of high-grade NMIBC. We report the potential ability of methylation biomarkers, at initial diagnosis, to predict tumour recurrence and progression within one year of diagnosis. We found that specific biomarkers reliably predict disease outcome and therefore may help guide patient treatment despite the unpredictable clinical course and heterogeneity of high-grade NMIBC. Further investigation is required, including validation in a larger patient cohort, to confirm the clinical utility of methylation biomarkers in high-grade NMIBC.
Medical treatment options and strategies for Crohn's disease (CD) have changed over the past decades. To assess its impact, we studied the evolution of the long-term disease outcome in the Dutch ...Inflammatory Bowel Disease South Limburg (IBDSL) cohort.
In total, 1,162 CD patients were included. Three eras were distinguished: 1991-1998 (n=316), 1999-2005 (n=387), and 2006-2011 (n=459), and patients were followed until 2014. Medication exposure and the rates of hospitalization, surgery, and phenotype progression were estimated using Kaplan-Meier survival analyses and compared between eras by multivariable Cox regression models. Second, propensity score matching was used to assess the relation between medication use and the long-term outcome.
Over time, the immunomodulator exposure rate increased from 30.6% in the era 1991-1998 to 70.8% in the era 2006-2011 at 5 years. Similar, biological exposure increased from 3.1% (era 1991-1998) to 41.2% (era 2006-2011). In parallel, the hospitalization rate attenuated from 65.9% to 44.2% and the surgery rate from 42.9% to 17.4% at 5 years, respectively (both P<0.01). Progression to a complicated phenotype has not changed over time (21.2% in the era 1991-1998 vs. 21.3% in the era 2006-2011, P=0.93). Immunomodulator users had a similar risk of hospitalization, surgery, or phenotype progression as propensity score-matched nonusers (P>0.05 for all analyses). Similar results were found for biological users (P>0.05 for all analyses).
Between 1991 and 2014, the hospitalization and surgery rates decreased, whereas progression to complicated disease is still common in CD. These improvements were not significantly related to the use of immunomodulators and biologicals.
There is controversy whether IL-6 (receptor) antagonists are beneficial in treating COVID-19 patients. We therefore update our systematic review to answer the following research questions: (1) Do ...patients hospitalized for COVID-19 treated with IL-6 (receptor) antagonists have lower mortality compared to standard of care? (2) Do patients hospitalized for COVID-19 treated with IL-6 (receptor) antagonists have more side effects compared to standard of care? The following databases were search up to December 1st 2020: PubMed, PMC PubMed Central, MEDLINE, WHO COVID-19 Database, Embase, Web-of-Science, COCHRANE LIBRARY, Emcare and Academic Search Premier. In order to pool the risk ratio (RR) and risk difference of individual studies we used random effects meta-analysis. The search strategy retrieved 2975 unique titles of which 71 studies (9 RCTs and 62 observational) studies comprising 29,495 patients were included. Mortality (RR 0.75) and mechanical ventilation (RR 0.78) were lower and the risk of neutropenia (RR 7.3), impaired liver function (RR 1.67) and secondary infections (RR 1.26) were higher for patients treated with IL-6 (receptor) antagonists compared to patients not treated with treated with IL-6 (receptor) antagonists. Our results showed that IL-6 (receptor) antagonists are effective in reducing mortality in COVID-19 patients, while the risk of side effects was higher. The baseline risk of mortality was an important effect modifier: IL-6 (receptor) antagonists were effective when the baseline mortality risk was high (e.g. ICU setting), while they could be harmful when the baseline mortality risk was low.
Elderly onset (EO) inflammatory bowel disease (IBD) may become a more common entity as a result of population aging and the rising IBD incidence. Its management is challenging, because of ...multimorbidity, polypharmacy, and frailty. Insight into the long-term outcome is essential for optimal patient counseling and treatment. We studied the incidence and disease outcome of elderly-onset IBD in direct comparison to adult-onset (AO) IBD.
All 2823 cases with IBD from the Dutch population-based IBD South Limburg cohort, diagnosed between 1991 and 2011, were included. Long-term outcome (hospitalization, surgery, and disease phenotype) was compared between AO (<60 years at diagnosis) and EO (≥60 years at diagnosis) disease, for Crohn's disease (CD) and ulcerative colitis (UC) separately.
In total, 1162 patients with CD (136 EO/1026 AO) and 1661 patients with UC (373 EO/1288 AO) were included. The EO IBD incidence increased from 11.71 per 100,000 persons in 1991 to 23.66 per 100,000 persons in 2010, P < 0.01. Immunomodulators were less often used in EO CD (61.8% versus 77.1%, P = 0.03) and EO UC (22.8% versus 35.4%, P < 0.01), even as biologicals (25.1% versus 55.1%, P = 0.03 and 7.8% versus 18.0%, P < 0.01, respectively). No differences were observed in surgery risk (CD: hazard ratio HR 1.19; 95% confidence interval CI, 0.85-1.67 and UC: HR, 0.88; 95% CI, 0.53-1.46), or in CD phenotype progression (HR, 0.81; 95% CI, 0.52-1.25), but more patients with EO UC required hospitalization (HR, 1.29; 95% CI, 1.01-1.63).
EO IBD is rising, warranting physicians' alertness for IBD in elderly patients. The long-term outcome was not different from AO disease, despite a less frequent use of immunomodulators and biologicals.
PDF
