BMJ medicine最新文献

Abstract:

Objective: To estimate the benefits, burden, and harms of implementing computer aided detection (CADe) of polyps in colonoscopy of population based screening programmes for colorectal cancer.

Design: Microsimulation modelling study.

Setting: Cost effectiveness working package in the OperA (optimising colorectal cancer prevention through personalised treatment with artificial intelligence) project. A parallel guideline committee panel (BMJ Rapid recommendation) was consulted in defining the screening interventions and selection of outcome measures.

Population: Four cohorts of 100 000 European individuals aged 60-69 years.

Intervention: The intervention was one screening of colonoscopy and a screening of colonoscopy after faecal immunochemical test every other year with CADe. The comparison group had the same screening every other year without CADe.

Main outcome measures: Benefits (colorectal cancer incidence and death), burden (surveillance colonoscopies), and harms (colonoscopy related adverse events) over 10 years were measured. The certainty in each outcome was assessed by use of the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach.

Results: For 100 000 individuals participating in colonoscopy screening, 824 (0.82%) were diagnosed with colorectal cancer within 10 years without CADe versus 713 (0.71%) with CADe (risk difference -0.11% (95% CI -0.43% to 0.21%)). For faecal immunochemical test screening colonoscopy, the risk was 5.82% (n=5820) without CADe versus 5.77% (n=5770) with CADe (difference -0.05% (-0.33% to 0.15%)). The risk of surveillance colonoscopy increased from 26.45% (n=26 453) to 32.82% (n=32 819) (difference 6.37% (5.8% to 6.9%)) for colonoscopy screening and from 52.26% (n=52 263) to 53.08% (n=53 082) (difference 0.82% (0.38% to 1.26%)) for faecal immunochemical test screening colonoscopy. No significant differences were noted in adverse events related to the colonoscopy between CADe and no CADe. The model estimates were sensitive to the assumed effects of screening on colorectal cancer risk and of CADe on adenoma detection rates. All outcomes were graded as low certainty.

Conclusion: With low certainty of evidence, adoption of CADe in population based screening provides small and uncertain clinical meaningful benefit, no incremental harms, and increased surveillance burden after screening.

Abstract:

Objective: To examine separate and joint associations between pre-existing cardiometabolic comorbidities and all cause and cause specific mortality in adults with cancer.

Design: Multinational cohort study.

Setting: Seven European countries from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, 1 January 1992 to 31 December 2013.

Participants: 26 987 participants (54% women) who developed a first primary cancer. 2113 had a history of type 2 diabetes, 1529 had a history of cardiovascular disease, and 531 had a history of both, at the time of diagnosis of cancer.

Main outcome measures: Hazard ratios (95% confidence intervals, CIs) for associations between pre-existing cardiometabolic comorbidities and all cause and cause specific mortality in adults with cancer, estimated with multivariable Cox regression models. Associations were also estimated by groups of five year relative survival of cancer (survival ≤40%, 40-80%, and ≥80%) according to Surveillance, Epidemiology, and End Results (SEER) statistics, and for the most common site specific cancers.

Results: At the time of diagnosis of cancer, 84.5% (n=22 814) of participants had no history of a cardiometabolic disease, 7.8% (n=2113) had a history of type 2 diabetes, 5.7% (n=1529) had a history of cardiovascular disease, and 2.0% (n=531) had a history of both cardiovascular disease and type 2 diabetes. 12 782 deaths (10 492 cancer deaths) occurred over a mean follow-up period of 7.2 years. After multivariable adjustments, pre-existing comorbidities were positively associated with all cause mortality, with hazard ratios 1.25 (95% CI 1.17 to 1.34), 1.30 (1.21 to 1.39), and 1.60 (1.42 to 1.80) for participants with type 2 diabetes, cardiovascular disease, or both, respectively, compared with participants with no cardiometabolic comorbidity. Corresponding hazard ratios for cancer specific mortality were 1.13 (95% CI 1.05 to 1.22), 1.13 (1.04 to 1.23), and 1.33 (1.16 to 1.53), respectively. Associations for all cause mortality were stronger among participants with cancers with a five year relative survival ≥80%. In a subsample, duration of type 2 diabetes (P_interaction=0.73) or cardiovascular disease (P_interaction=0.24), categorised as <5 years or ≥5 years, did not modify associations between these comorbidities and all cause mortality.

Conclusions: In this study, cardiovascular disease or type 2 diabetes, or a combination of both, before a diagnosis of cancer, was associated with increased mortality (all cause mortality, and cancer and cardiovascular disease specific mortality). These findings support a direct role of cardiometabolic comorbidities on the prognosis of cancer.

Objective: To assess the association between cumulative use of anticholinergic bladder drugs and risk of all cause dementia compared with non-use and use of the β3 agonist bladder drug, mirabegron.

Design: Danish nationwide active comparator study.

Setting: National Danish registries, 1 January 2000 to 31 December 2022.

Participants: 1 29 254 individuals with dementia were matched by age and sex to 646 270 controls without dementia, identified from a cohort of 2.26 million individuals aged 60-75 years between 2000 and 2022 with no previous dementia. Two separate nested case-control populations were studied: the general population and an active comparator population of 58 242 new users of bladder drugs (2198 developed dementia and were matched to 10 990 controls). Information on medication use was based on filled prescriptions and defined daily doses.

Main outcome measures: Conditional logistic regression provided incidence rate ratios for associations between anticholinergic bladder drugs and dementia compared with non-use and mirabegron use adjusted for educational level, cardiovascular disease, diabetes, hypertension, dyslipidaemia, and Charlson Comorbidity Index.

Results: Compared with non-use, ever use of anticholinergic bladder drugs was associated with an increased risk of dementia, with an incidence rate ratio of 1.44 (95% confidence interval (CI) 1.40 to 1.48). The incidence rate ratio increased with increasing cumulative drug use, from 1.31 (95% CI 1.27 to 1.36) for 1-90 defined daily doses to 1.68 (1.59 to 1.76) for >365 defined daily doses. Compared with non-use, all types of anticholinergic bladder drugs were associated with increased incidence rate ratios for dementia: tolterodine 1.43 (95% CI 1.38 to 1.49), solifenacin 1.37 (1.29 to 1.46), trospium 1.52 (1.37 to 1.67), and fesoterodine 1.48 (1.26 to 1.74). The increased risk of dementia with use of anticholinergic bladder drugs was not seen when compared directly with the use of the β3 agonist mirabegron (incidence rate ratio 0.82, 95% CI 0.74 to 0.92), irrespective of the type of anticholinergic drug.

Conclusions: In this study, all types of anticholinergic bladder drugs were associated with an increased risk of dementia compared with non-use, but not when applying the active comparator of the β3 agonist bladder drug mirabegron. These findings highlight the relevance of using an active comparator. Future research should evaluate the risk of cognitive impairment and dementia for both types of bladder drugs.

Abstract:

Objective: To estimate the effectiveness of vaccination with a monovalent covid-19 mRNA vaccine containing the omicron XBB.1.5 subvariant against severe covid-19 disease in Denmark, Finland, and Sweden.

Design: Target trial emulation based on registry data.

Setting: Denmark, Finland, and Sweden, 1 October 2023 to 21 April 2024.

Participants: Source population of 3 898 264 individuals eligible for vaccination with the XBB.1.5 containing covid-19 mRNA vaccine at the start of the study on 1 October 2023. Study cohort comprised 1 876 282 recipients of an XBB.1.5 containing vaccine during the study period matched with 1 876 282 non-recipients. Individuals were aged ≥65 years (mean age 75.4 years, standard deviation 7.4 years) and had received at least four doses of a previous covid-19 vaccine.

Main outcome measures: Cumulative incidences of hospital admissions and deaths related to covid-19 in a follow-up period of 24 weeks after immunisation (defined as one week after vaccination) in recipients of an XBB.1.5 containing covid-19 mRNA vaccine and matched non-recipients. Cumulative incidences were used to calculate comparative vaccine effectiveness (1-risk ratio) and risk differences.

Results: The associated comparative vaccine effectiveness was 57.9% (95% confidence interval (CI) 49.9% to 65.8%) against hospital admission for covid-19 (1085 v 2635 events) and 75.2% (70.6% to 79.9%) against deaths related to covid-19 disease (348 v 1458 events) after 24 weeks of follow-up. This result corresponded to 154.7 (95% CI 78.3 to 231.0) hospital admissions for covid-19 and 120.3 (110.5 to 130.2) deaths prevented per 100 000 individuals who were vaccinated with an XBB.1.5 containing vaccine. The associated comparative vaccine effectiveness was similar irrespective of sex, age group (65-74 v ≥75 years), number of doses of previous covid-19 vaccines, subgroup of co-administered seasonal influenza vaccines, and period of when either the omicron XBB or BA.2.86 sublineage was predominant. Although the observed reduction in risk was highest during the first weeks after vaccination, comparative vaccine effectiveness was well maintained after 24 weeks of follow-up.

Conclusions: In this study, in adults aged ≥65 years, vaccination with a monovalent XBB.1.5 containing covid-19 mRNA vaccine was associated with reduced rates of hospital admissions for covid-19 and deaths related to covid-19, during the autumn and winter of 2023-24 in Denmark, Finland, and Sweden.