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 investigate the association between the use of antibiotics in early life and the development of immune mediated diseases in children and adolescents.

Design: Nationwide registry study.

Setting: National Danish registries: Danish Civil Registration System identified children born in Denmark; information on the use of antibiotics from the Danish National Prescription Registry; disease outcomes from the Danish National Prescription Registry and the Danish National Patient Registry; and relevant covariates from the Danish Medical Birth Register and the Employment Classification Module. Study period from 1 January 1998 to 31 December 2016.

Participants: Of 648 507 children born in Denmark in 1998-2006, 518 483 resided in Denmark during their first year of life, had no disease outcomes before the age of one year, and formed the final study population. The sibling population was 272 753 (126 632 sibships).

Main outcome measures: Risk of developing immune mediated diseases (asthma, allergy, eczema, coeliac disease, juvenile arthritis, and type 1 diabetes) and overweight in the total population and in a sibling matched cohort (to mitigate the influence of familial factors and unmeasured confounding), by survival analysis with Cox regression.

Results: Children were followed up for a mean of 13.2 years (standard deviation 3.12). Among the total study population, 40.3% (n=209 013) of children were prescribed systemic antibiotics before the age of one year. Use of antibiotics was associated with an increased risk of several immune mediated diseases (adjusted hazard ratios 1.20-1.53). A dose-response relation was found. When analysing sibling pairs, only asthma and eczema outcomes (adjusted hazard ratios 1.07-1.35) were associated with the use of antibiotics. No specific trends about the timing of use or type of antibiotic were found.

Conclusions: In this study, use of antibiotics in early life was linked with immune mediated diseases in childhood and adolescence, but familial and unmeasured factors within the family might provide partial explanations. The study emphasises the need to better understand the interactions between antibiotics, familial susceptibility, and immune mediated pathogenesis to identify potential preventive strategies.

Objective: To investigate the prescribing trends of indapamide, a thiazide-like diuretic, and the long term comparative effectiveness of modified release versus immediate release indapamide.

Design: Cohort study.

Setting: IQVIA Medical Research Data UK database, incorporating data from The Health Improvement Network database, 1 January 2005 to 31 December 2020.

Participants: Of 1 904 289 patients with hypertension, 86 388 started indapamide treatment during the study period. 30 021 patients received modified release and 56 367 immediate release indapamide.

Main outcome measures: Monthly prescribing trends of modified release and immediate release indapamide are described. A pragmatic trial was emulated to compare the five year risks of composite cardiovascular events (myocardial infarction and stroke) and death between modified release and immediate release indapamide. Intention-to-treat and per protocol effects of treatment were estimated with pooled logistic regression models. Confounding and selection bias were accounted for by multivariable adjustments and inverse probability weights.

Results: 1 38 414 patients who used indapamide were identified among 1 904 289 patients with hypertension. A greater increase was seen in the proportion of users of immediate release indapamide (from 0.43% in 2005 to 2.31% in 2020) than in users of modified release indapamide (from 0.71% to 0.79%). 86 388 patients (30 021 and 56 367 who started modified release and immediate release indapamide, respectively) were eligible for the trial emulation. In the intention-to-treat analysis, no difference was found in the risk of cardiovascular events (hazard ratio 0.99, 95% confidence interval (CI) 0.90 to 1.08) or death (hazard ratio 0.97, 0.92 to 1.02) between modified release and immediate release indapamide. In the per protocol analysis, a lower risk of cardiovascular events was found with modified release indapamide than with immediate release indapamide (risk difference -0.39%, 95% CI -0.71% to -0.06%; hazard ratio 0.81, 95% CI 0.68 to 0.98), which was mainly driven by myocardial infarction (risk difference -0.36%, 95% CI -0.64% to -0.08%; hazard ratio 0.80, 95% CI 0.64 to 1.01). Similar risks of death (hazard ratio 1.03, 95% CI 0.90 to 1.17) were found for the two formulations.

Conclusions: In patients treated with indapamide for hypertension, starting treatment with modified release or immediate release indapamide had similar risks for cardiovascular events or all cause mortality. In an exploratory secondary analysis, sustained treatment with modified release preparations was associated with a lower the risk of cardiovascular events but not all cause mortality compared with immediate release preparations. These findings need to be confirmed in prospective studies.

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.