BMC Medicine最新文献

Background: Pulmonary function is increasingly recognized as a key factor in metabolic diseases. However, its link to gout risk remains unclear. The study aimed to investigate the relationship between pulmonary function and the risk of developing gout and the underlying biological mechanisms.

Methods: Our study included 420,002 participants with complete pulmonary function data from the UK Biobank. Logistic regression was used to evaluate gout prevalence among individuals with different pulmonary function statuses. Propensity score matching (PSM) created balanced groups, while Cox regression gauged the risk association between reduced lung capacity and gout compared with normal function. Mendelian randomization (MR) analysis was used to verify causal associations. Non-linear correlations were assessed with restricted cubic spline (RCS) analysis, and mediation analysis was used to explore the role of blood biomarkers. Mediation analyses were used to investigate the potential mediating role of biomarkers in the association.

Results: Cross-sectional analysis revealed a higher prevalence of gout in individuals with preserved ratio of impaired spirometry (PRISm) of 6.31% and chronic obstructive pulmonary disease (COPD) of 6.26% than in those with normal pulmonary function (3.45%). After adjustment for covariates, both PRISm (odds ratio [OR] 1.24, 95% confidence interval [CI] 1.17-1.31) and COPD (OR 1.14, 95% CI 1.07-1.22) were significantly associated with gout. Longitudinal analysis confirmed that impaired pulmonary function significantly increased the risk of developing gout (hazard ratio [HR] 1.32, 95% CI 1.24-1.40). MR further revealed a potential causal effect of decreased pulmonary function on an increased risk of gout. Subgroup analysis revealed significant interactions between impaired pulmonary function and several factors, including body mass index (BMI), levels of physical activity, and diabetes status, in their associations with the risk of gout. RCS analysis showed a nonlinear relationship between pulmonary function indicators and gout incidence, characterized by an inverse S-shaped curve. Mediation analysis revealed that urate levels (49.1% mediation proportion), C-reactive protein (CRP) levels (6.62%), monocyte counts (1.33%), and neutrophil counts (4.85%) significantly mediated the relationship between pulmonary function and the risk of gout.

Conclusions: Our study revealed a significant association between impaired pulmonary function and an increased risk of developing gout. The association might be partially mediated by biomarkers including urate levels, inflammatory markers, and immune cell counts.

Background: Palliative sedation involves the intentional proportional lowering of the level of consciousness in patients with life-limiting disease who are experiencing refractory suffering. The efficacy of palliative sedation needs to be monitored to ensure patient comfort. The aim of this study was to evaluate the efficacy using discomfort levels combined with sedation/agitation levels.

Methods: In this prospective observational study, adult patients with advanced malignancies were recruited from hospice units, palliative care units, and hospital wards in five European countries. Health care professionals used proxy observations of discomfort levels (Discomfort Scale-Dementia of Alzheimer Type, range 0-27) and sedation/agitation levels (Richmond Agitation-Sedation Scale modified for palliative care inpatients), range - 5 to + 4) to evaluate the efficacy of palliative sedation.

Results: In 78 participants, discomfort levels were monitored during palliative sedation. The mean discomfort score before start was 9.4 points (95% CI 8.3-10.5), which showed a significant decrease of 6.0 points (95% CI 4.8-7.1) after start of sedation for the total sedation period. In the multivariable analysis, no significant factors influencing baseline discomfort levels were identified. The discomfort and depth of sedation scores were found to be positively correlated, with an r of 0.72 (95% CI 0.61-0.82). The internal consistency of the discomfort scale was good (0.83), but the "Noisy breathing" item was less informative of the total discomfort score.

Conclusions: The efficacy of palliative sedation can be evaluated by measuring discomfort levels combined with sedation/agitation levels. The measurement of discomfort levels might provide a more specific and detailed evaluation of adequate sedation.

Trial registration: This study is registered at ClinicalTrials.gov since January 22, 2021, registration number: NCT04719702.

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is recommended for patients with KMT2A-rearranged (KMT2A-r) leukemia whereas relapse remains high. We aimed to determine whether intensified conditioning containing decitabine (Dec) could reduce relapse compared with standard myeloablative conditioning in adult patients with KMT2A-r leukemia.

Methods: We performed a multicenter retrospective study at seven institutions in China. Eligible patients were aged 14 years or older at transplantation, had a diagnosis of KMT2A-r leukemia, and underwent the first allo-HSCT. Standard myeloablative conditioning regimens (standard group) included BuCy (busulfan 3.2 mg/kg/day on days -7 to -4; cyclophosphamide 60 mg/kg/day on days -3 to -2) and TBI-Cy (total body irradiation 4.5 Gy/day on days -5 to -4; Cy 60 mg/kg/day on days -3 to -2). Intensified conditioning regimens containing Dec (intensified group) consisted of Dec-BuCy (Dec 20 mg/m²/day on days -14 to -10; the same dose of BuCy) and Dec-TBI-Cy (Dec 20 mg/m²/day on days -10 to -6; the same dose of TBI-Cy).

Results: Between April 2009 and December 2019, 218 patients were included in this study, of whom 105 were in the intensified group and 113 were in the standard group. The 3-year cumulative incidence of relapse was 17.6% and 34.5%, overall survival was 71.3% and 61.0%, disease-free survival was 70.1% and 56.0%, and non-relapse mortality was 12.3% and 9.5% in the intensified and standard groups, respectively (P = 0.001; P = 0.034; P = 0.005; P = 0.629). Subgroup analysis showed that the relapse rate of intensified conditioning was lower than that of standard conditioning in multiple subgroups, including different leukemia types, disease status at transplantation, high-risk cytogenetics and Bu-based regimens. There was no difference in regimen-related toxicity, engraftment, or graft-versus-host disease between the intensified and standard groups.

Conclusions: These results suggest that intensified conditioning containing Dec might be a better strategy than standard myeloablative conditioning for adult patients with KMT2A-r leukemia undergoing allo-HSCT.

Background: Unhealthy visual food cues in outdoor public spaces are external drivers of unhealthy diets. Food cues are visible situations associated with food-related memories. This study aimed to gain insight into the (un)healthy food cues residents notice in outdoor public spaces in Dutch municipalities. It also aimed to explore residents' perceptions of food cues' influence on eating behaviour to gain insight into the acceptability of food cues and support for governmental food cue regulation.

Methods: An exploratory study was conducted among 101 adults who photographed outdoor visual food cues in their municipality and answered survey questions about the food cues using a bespoke app ('myfoodenvironment'). Participant and food cue characteristics were analysed. Associations between those characteristics, perceived influence on eating behaviour, acceptability of food cues and support for regulation were analysed.

Results: Participants took 461 photographs of food cues. Most food cues visualised food (73.8%), 54.4% of which showed only unhealthy food. Food cues photographed by participants with a high level of education and those located near a food service outlet were more often perceived as stimulating others to eat compared to those photographed by participants with a middle education level and located near a food store or along the road (Fisher's exact test: p < 0.001 and p = 0.001, respectively). For most photographs, participants found the presence of food cues acceptable and were opposed to governmental cue regulation. However, when food cues visualised healthy food, they were more likely to be found acceptable than when visualising unhealthy food (χ² (4; N = 333) = 16.955; p = 0.002). Besides, when food cues visualised unhealthy food, participants were less likely to oppose governmental regulation of those types of cues, than when visualising healthy food (Fisher's exact test: p = 0.002).

Conclusions: Unhealthy food cues in outdoor public spaces were predominantly photographed by the participants. Yet, for most photographs, participants found the food cues acceptable and opposed governmental food cue regulation, although acceptance was higher for healthy food cues and opposition was lower for unhealthy food cues. These findings can serve as input for policymakers to develop governmental food cue regulations that may gain public support.

Background: Risk prediction models can identify individuals at high risk of chronic liver disease (CLD), but there is limited evidence on the performance of various models in diverse populations. We aimed to systematically review CLD prediction models, meta-analyze their performance, and externally validate them in 0.5 million Chinese adults in the China Kadoorie Biobank (CKB).

Methods: Models were identified through a systematic review and categorized by the target population and outcomes (hepatocellular carcinoma [HCC] and CLD). The performance of models to predict 10-year risk of CLD was assessed by discrimination (C-index) and calibration (observed vs predicted probabilies).

Results: The systematic review identified 57 articles and 114 models (28.4% undergone external validation), including 13 eligible for validation in CKB. Models with high discrimination (C-index ≥ 0.70) in CKB were as follows: (1) general population: Li-2018 and Wen 1-2012 for HCC, CLivD score (non-lab and lab) and dAAR for CLD; (2) hepatitis B virus (HBV) infected individuals: Cao-2021 for HCC and CAP-B for CLD. In CKB, all models tended to overestimate the risk (O:E ratio 0.55-0.94). In meta-analysis, we further identified models with high discrimination: (1) general population (C-index ≥ 0.70): Sinn-2020, Wen 2-2012, and Wen 3-2012 for HCC, and FIB-4 and Forns for CLD; (2) HBV infected individuals (C-index ≥ 0.80): RWS-HCC and REACH-B IIa for HCC and GAG-HCC for HCC and CLD.

Conclusions: Several models showed good discrimination and calibration in external validation, indicating their potential feasibility for risk stratification in population-based screening programs for CLD in Chinese adults.

Background: Retinoblastoma (RB), an aggressive intraocular malignancy, significantly adds to the global disease burden in early childhood. This study offers insights into the global burden of retinoblastoma (RB) in children aged 0-9 years, examining incidence, mortality, and DALYs from 1990 to 2021, across age, sex, location, and SDI levels. It aims to inform health policy, resource allocation, and RB combat strategies.

Methods: Data were retrieved from newly released Global Burden of Disease (GBD) study. The measures were estimated both as numerical counts and age-standardised rates per 100,000 population. Joinpoint regression analysis was used to rigorously examine temporal trends, estimating the average annual percentage change (AAPC). Spearman's correlation test was used to examine the relationship between SDI and the burden of RB by location and year.

Results: Globally, the age-standardised incidence rate (ASIR), age-standardised mortality rate (ASMR), and age-standardised DALYs rate (ASDR) for RB among young children in 2021 were 0.09 [95% uncertainty interval (UI): 0.05 to 0.13], 0.04 (95%UI: 0.03 to 0.06), and 3.65 (95%UI: 2.21 to 4.96), respectively. Despite an overall increasing trend in incidence [AAPC: 0.62; 95% confidence interval (CI): 0.42 to 0.82], the RB incidence rate demonstrated a significant decline from 2019 to 2021, while mortality and DALYs rate for RB showed overall downward trends. Trends in ASIR varied across regions, with the highest increase in East Asia. Among all GBD regions, only Southern Sub-Saharan Africa exhibited rising trends in mortality and DALYs rate. Gender comparisons showed negligible differences in ASIR, ASMR and ASDR in 2021. Moreover, the highest disease burden was noted in early neonatal (0-6 days), and in children aged 2-4 years at both global and regional levels. Analysis by SDI indicated that RB incidence rates increased with higher SDI levels. In addition, a significantly negative correlation was found between SDI level and both ASMR and ASDR of RB among children aged 0-9 years.

Conclusions: From 1990 to 2021, RB-related incidence, mortality, and DALYs varied by age and location. Evaluating spatiotemporal trends underscores the impact of health policies and substantial public health interventions on RB control.

Background: Previous studies have identified sarcopenia as a significant risk factor for cardiovascular disease (CVD). However, these studies primarily focused on sarcopenia status at baseline, without considering changes in sarcopenia status during follow-up. The aim of this study is to investigate the association between changes in sarcopenia status and the incidence of new-onset cardiovascular disease.

Methods: This study utilized prospective cohort data from the China Health and Retirement Longitudinal Study (CHARLS). Sarcopenia status was assessed using the 2019 Asian Working Group for Sarcopenia (AWGS) algorithm and categorized as non-sarcopenia, possible sarcopenia, or sarcopenia. Changes in sarcopenia status were evaluated based on assessments at baseline and at the second follow-up survey 2 years later. CVD was identified through self-reported physician diagnoses of heart disease, including angina, myocardial infarction, congestive heart failure, and other heart problems, or stroke. Cox proportional hazards models were employed to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for potential confounding factors.

Results: Based on the inclusion and exclusion criteria, a total of 7499 CHARLS participants were included in the analysis, with 50.8% being female and an average age of 58.5 years. Compared to participants with stable non-sarcopenia status, those who progressed from non-sarcopenia to possible sarcopenia or sarcopenia exhibited a significantly increased risk of new-onset CVD (HR 1.30, 95% CI 1.06-1.59). Conversely, participants who recovered from sarcopenia to non-sarcopenia or possible sarcopenia had a significantly reduced risk of new-onset CVD compared to those with stable sarcopenia status (HR 0.61, 95% CI 0.37-0.99). Among participants with baseline possible sarcopenia, those who recovered to non-sarcopenia had a significantly lower risk of new-onset CVD compared to those with stable possible sarcopenia status (HR 0.67, 95% CI 0.52-0.86).

Conclusions: Changes in sarcopenia status are associated with varying risks of new-onset CVD. Progression in sarcopenia status increases the risk, while recovery from sarcopenia reduces the risk of developing cardiovascular disease.

Background: Helicobacter pylori infection causes gastritis, peptic ulcers, and gastric cancer. The infection is typically acquired in childhood and persists throughout life. The major impediment to successful therapy is antibiotic resistance. This systematic review and meta-analysis aimed to comprehensively assess the global prevalence of antibiotic resistance in pediatric H. pylori infection.

Methods: We performed a systematic search of publication databases that assessed H. pylori resistance rates to clarithromycin, metronidazole, levofloxacin, amoxicillin, and tetracycline in children. The WHO region classification was used to group pooled primary and secondary resistance estimates along with 95% confidence interval (CI). H. pylori antibiotic resistance rates were retrieved and combined with odds ratios (95% CI) to investigate the global prevalence and temporal trends. Subgroup analysis of the prevalence of antibiotic resistance was conducted by country, age groups, and susceptibility testing methods.

Results: Among 1417 records obtained initially, 152 studies were selected for eligibility assessment after applying exclusion criteria in multiple steps. Ultimately, 63 studies involving 15,953 individuals were included comprising data from 28 countries in 5 WHO regions. The primary resistance rates were metronidazole 35.3% (5482/15,529, 95% CI: 28.7-42.6), clarithromycin 32.6% (5071/15,555, 95% CI: 27.7-37.9), tetracycline 2.1% (148/7033, 95% CI: 1.3-3.6), levofloxacin 13.2% (1091/8271, 95% CI: 9.3-18.4), and amoxicillin 4.8% (495/10305, 95% CI: 2.5-8.8). Raising antibiotic resistance was detected in most WHO regions.

Conclusions: The escalating trend of H. pylori antibiotic resistance in children warrants urgent attention globally. National and regional surveillance networks are required for antibiotic stewardship in children infected with H. pylori.

Background: Direct oral anticoagulants (DOACs) have been reported to be associated with a higher risk of mortality compared with an older alternative, warfarin using primary care data in the United Kingdom (UK). However, other studies observed contradictory findings. We therefore aimed to investigate the association between mortality and warfarin, compared with DOACs.

Methods: We conducted cohort studies using UK Clinical Practice Research Datalink (CPRD) Aurum and Hong Kong Clinical Data Analysis and Reporting System (CDARS) to identify the association between warfarin and hazard of mortality, compared to DOACs. Individuals with non-valvular atrial fibrillation aged ≥ 18 years who had first anticoagulant therapy (warfarin or DOAC) during 1/1/2011-31/12/2019 were included.

Results: Compared with DOAC use, a lower hazard of all-cause mortality was found in warfarin users (hazard ratio (HR) = 0.81, 95% confidence interval (CI) = 0.77-0.86) in CPRD; while a higher hazard was observed in warfarin users (HR = 1.31, 95% CI = 1.24-1.39) in CDARS, versus DOAC users. In our exploratory analysis, consistent results were seen in both databases when stratified warfarin users by time in therapeutic range (TTR) using post-baseline measurements: a lower hazard of all-cause mortality in warfarin users with TTR ≥ 65% (CPRD: HR = 0.68, 95% CI = 0.65-0.72; CDARS: HR = 0.86, 95% CI = 0.77-0.96) and increased hazard in warfarin users with TTR < 65% (CPRD: HR = 1.14, 95% CI = 1.05-1.23; CDARS: HR = 1.59, 95% CI = 1.50-1.69), versus DOAC users.

Conclusions: The differences in hazard of all-cause mortality associated with warfarin compared with DOAC, in part may depend on anticoagulation control in warfarin users. Notably, this study is unable to establish a causal relationship between warfarin and mortality stratified by TTR, versus DOACs, requiring future studies for further investigation.

Background: Despite an urgent need for multi-domain lifestyle interventions to reduce dementia risk, there is a lack of interventions which are informed by theory- and evidence-based behaviour change strategies, and no interventions in this domain have investigated the feasibility or effectiveness of behaviour change maintenance. We tested the feasibility, acceptability and cognitive effects of a personalised theory-based 24-week intervention to improve Mediterranean diet (MD) adherence alone, or in combination with physical activity (PA), in older-adults at risk of dementia, defined using a cardiovascular risk score.

Methods: Participants (n = 104, 74% female, 57-76 years) were randomised to three parallel intervention arms: (1) control, (2) MD, or (3) MD + PA for 24 weeks and invited to an optional 24-week follow-up period with no active intervention. Behaviour change was supported using personalised targets, a web-based intervention, group sessions and food provision. The primary outcome was behaviour change (MD adherence and PA levels), and the secondary outcomes included feasibility and acceptability, cognitive function, cardiometabolic health (BMI and 24-h ambulatory blood pressure) and process measures.

Results: The intervention was feasible and acceptable with the intended number of participants completing the study. Participant engagement with group sessions and food provision components was high. There was improved MD adherence in the two MD groups compared with control at 24 weeks (3.7 points on a 14-point scale (95% CI 2.9, 4.5) and 48 weeks (2.7 points (95% CI 1.6, 3.7)). The intervention did not significantly change objectively measured PA. Improvements in general cognition (0.22 (95% CI 0.05, 0.35), memory (0.31 (95% CI 0.10, 0.51) and select cardiovascular outcomes captured as underpinning physiological mechanisms were observed in the MD groups at 24 weeks.

Conclusions: The intervention was successful in initiating and maintaining dietary behaviour change for up to 12 months which resulted in cognitive benefits. It provides a framework for future complex behaviour change interventions with a range of health and well-being endpoints.

Trial registration: ClinicalTrials.gov NCT03673722.