BMC Medicine最新文献

Background: Aging is a major risk factor for type 2 diabetes (T2D), but individuals of the same chronological age may vary in their biological aging rate. The associations of Phenotypic Age Acceleration (PhenoAgeAccel), a new accelerated biological aging indicator based on clinical chemistry biomarkers, with the risk of dynamic progression remain unclear. We aimed to assess these associations and examine whether these associations varied by genetic risk and lifestyle.

Methods: We conducted a prospective cohort study that included 376,083 adults free of T2D and diabetes-related events at baseline in UK Biobank. PhenoAgeAccel > 0 and ≤ 0 were defined as biologically older and younger than chronological age. The outcomes of interest were incident T2D, diabetic complications, and mortality. Hazard ratios (HRs) with 95% confidence intervals (CIs) and population attributable fractions (PAFs) for these associations were calculated using multi-state model.

Results: During a median follow-up of 13.7 years, 17,615 participants developed T2D, of whom, 4,524 subsequently developed complications, and 28,373 died. Being biologically older was associated with increased risks of transitions from baseline to T2D (HR 1.77, 95% CI 1.71-1.82; PAF 24.8 [95% CI 23.5-26.2]), from T2D to diabetic complications (1.10, 1.04-1.17; 4.4 [1.4-7.4]), from baseline to all-cause death (1.53, 1.49-1.57; 17.6 [16.6-18.6]), from T2D to all-cause death (1.14, 1.03-1.26; 7.4 [1.8-13.0]), and from diabetic complications to all-cause death (1.32, 1.15-1.51; 15.4 [7.5-23.2]) than being biologically younger. Additionally, participants with older biological age and high genetic risk had a higher risk of incident T2D (4.76,4.43-5.12;18.2 [17.5-19.0]) than those with younger biological age and low genetic risk. Compared with participants with younger biological age and healthy lifestyle, those with older biological age and unhealthy lifestyle had higher risks of transitions in the T2D trajectory, with HRs and PAFs ranging from 1.34 (1.16-1.55; 3.7 [1.8-5.6]) to 5.39 (5.01-5.79; 13.0 [12.4-13.6]).

Conclusions: PhenoAgeAccel was consistently associated with an increased risk of all transitions in T2D progression. It has the potential to be combined with genetic risk to identify early T2D incidence risk and may guide interventions throughout T2D progression while tracking their effectiveness.

Background: Tertiary lymphoid structures (TLS) correlate with tumour prognosis and immunotherapy responses in gastric cancer (GC) studies. However, understanding the complex and diverse immune microenvironment within TLS requires comprehensive analysis.

Methods: We examined the prognostic impact of TLS within the tumour core (TC) of 59 GC patients undergoing immunotherapy. Multispectral fluorescence imaging was employed to evaluate variations in immune cell infiltration across different TLS sites among 110 GC patients, by quantifying immune cell density and spatial characteristics. We also generated a single-cell transcriptomic atlas of TLS-positive (n = 4) and TLS-negative (n = 8) microenvironments and performed spatial transcriptomics (ST) analysis on two samples.

Results: TLS presence in the TC significantly correlated with improved immune-related overall survival (P = 0.049). CD8⁺LAG-3^-PD-1⁺TIM-3^-, CD4⁺PD-L1⁺, and CD4⁺FoxP3^- T cell densities were significantly higher in the TLS within TC compared to tumour and stromal regions. Immune cells within TLS exhibited closer intercellular proximity than those outside TLS. Five key density and spatial characteristics of immune cells within TLS in the TC were selected to develop the Density and Spatial Score risk model. Single-cell RNA sequencing revealed strong intercellular interactions in the presence of TLS within the microenvironment. However, TLS-absent environment facilitated tumour cell interactions with immune cells through MIF- and galectin-dependent pathways, recruiting immunosuppressive cells. ST analysis confirmed that T and B cells co-localise within TLS, enhancing immune response activation compared to cancer nests and exerting a strong anti-tumour effect.

Conclusions: TLS presence facilitates frequent cell-to-cell communication, forming an active immune microenvironment, highlighting the prognostic value of TLS.

Background: Visceral adipose tissue (VAT) is well established as a pathogenic fat depot, whereas superficial subcutaneous adipose tissue (SAT) is associated with either an improved or neutral cardiovascular state. However, it is unclear to what extent VAT area (VATcm²) and its proportion of total abdominal adipose tissue (VAT%) are distinguished in predicting cardiometabolic status and clinical outcomes during weight loss.

Methods: We integrated magnetic resonance imaging (MRI) measurements of VAT, deep-SAT, and superficial-SAT from two 18-month lifestyle weight loss clinical trials, CENTRAL and DIRECT PLUS (n = 572).

Results: At baseline, the mean VATcm² was 144.8cm² and VAT% = 28.2%; over 18 months, participants lost 28cm² VATcm² (- 22.5%), and 1.3 VAT% units. Baseline VATcm² and VAT% were similarly associated with metabolic syndrome, hypertension, and diabetes status, while VAT% better classified hypertriglyceridemia. Conversely, higher VATcm² was associated with elevated high-sensitivity C-reactive protein (hsCRP), while VAT% was not. After 18 months of lifestyle intervention, both VATcm² and VAT% loss were significantly associated with decreased triglycerides, HbA1c, ferritin, and liver enzymes, and increased HDL-c levels beyond weight loss (FDR < 0.05). Only VATcm² loss was correlated with decreased HOMA-IR, chemerin, and leptin levels.

Conclusions: MRI follow-up of 572 participants over 18 months of weight loss intervention suggests that although increased VATcm² and VAT% exhibit similar clinical manifestations, it might be preferable to examine VAT% when exploring lipid status, while VATcm² may better reflect inflammatory and glycemic states.

Trial registration: CENTRAL (Clinical-trials-identifier: NCT01530724); DIRECT PLUS (Clinical-trials-identifier: NCT03020186).

Background: Needle procedures, such as vaccinations, blood draws, and intravenous cannulation, are the most frequent source of childhood pain, causing fear and reducing the uptake of medical procedures. Every child has the right to expect pain relief, and we have evidence-based tools to reduce needle procedure-related pain. Therefore, the lack of analgesic provision for needle pain is not justified. We argue that better informed and motivated healthcare professionals and families can advocate for appropriate pain relief in every child, every time.

Observations: Engaging communication campaigns are needed to educate our healthcare professionals. Evidence-based modalities such as topical anaesthesia, sucrose or breastfeeding, comfort positioning, and age-appropriate distractions should be available for every child during needle procedures. However, high-quality information is not enough to change behaviour-healthcare professionals need to be motivated, encouraged, and inspired. Parents and carers should be empowered to advocate for their children and be aware that their child has the right to receive pain relief during these procedures. CONCLUSIONS AND RELEVANCE: This is a call to action-we need collaboration between academics, healthcare professionals, industry and charities, to expedite behavioural change and parental advocacy through high-quality communication strategies. Effective pain management in infants and children can play a crucial role in promoting the uptake of vaccinations and medical procedures and can influence future attitudes to pain.

Background: Patients with advanced chronic kidney disease requiring initiation of kidney replacement therapy (KRT) are frequently asked to enact complex management plans. Treatment burden has been defined as the effect of healthcare workload and the capacity a person has to manage this workload has on wellbeing. The aim of this review is to examine the experience of healthcare workload and the factors that affect capacity to meet that workload for people transitioning onto KRT for the first time, using a framework synthesis of published literature informed by normalisation process theory (NPT) and theory of patient capacity (TPC).

Methods: Medline, Scopus and CINAHL were systematically searched with manual citation and reference searching. Studies were included if meeting the criteria of adults aged 18 or over transitioning for the first time onto any modality of KRT (haemodialysis, peritoneal dialysis or kidney transplantation), using qualitative methodologies to describe any aspect of experiences of healthcare workload or any factors that affect capacity to manage workload were included. Abstracts and full papers were independently screened by two reviewers and data extraction and quality appraisal were also independently conducted by two reviewers. Qualitative data were analysed using framework synthesis informed by NPT and TPC.

Results: A total of 24,380 studies were screened, 406 full texts were reviewed and 18 studies were included. There were four broad categories of workload described: making sense of KRT, working out what to do and how to do it, meeting the challenges of KRT, and reflecting on work done. Patient capacity influenced the experience of all types of workload and the treatment burden generated by the work.

Conclusions: Transitioning onto KRT is a period of very high healthcare workload and potentially high treatment burden. The relationship between healthcare workload and capacity to handle workload is complex, multifactorial and changes over time. By better understanding workload, capacity and burden during transition, we can develop better ways of measuring these important aspects of care and develop interventions to reduce treatment burden in those transitioning onto KRT.

Background: To address the public health concern of cervical cancer (CC), 194 countries committed to eliminate it at the initiative of the World Health Organization (WHO). We summarised quantitative results concerning CC elimination across these countries, including the progress in implementing three prevention levels (human papillomavirus [HPV] vaccination, CC screening, and treatment for patients with CC) and achievement of interim Global Strategy for Cervical Cancer Elimination targets.

Methods: Data were obtained from the International Agency for Research on Cancer, WHO, United Nations International Children's Emergency Fund, and country responses to the WHO National Capacity Survey on Non-Communicable Diseases. This retrospective analysis examined data from 194 countries and regions, stratified by national income (high-income countries (HICs) vs low- and middle-income countries (LMICs)) and geographic location (continents such as Europe, Asia, and North America). A quantitative assessment evaluated global progress in primary, secondary, and tertiary CC prevention.

Results: By 2020, four countries had achieved Target 1 (90% of girls fully vaccinated against HPV by age 15). A total of 115 countries (51 (44.35%) HICs and 64 (55.65%) LMICs)) included HPV vaccination in their national immunisation programs. As of 2021, 133 countries (50 (37.59%) HICs and 83 (62.41%) LMICs)) implemented CC screening programs. Most of these were in Europe (41, 30.83%), Asia (32, 24.06%), and North America (20, 15.04%). Additionally, 126 countries (44 (34.92%) HICs and 82 (65.08%) LMICs)) had published national guidelines on CC management. These countries were primarily in Asia (32, 25.40%) and Europe (32, 25.40%). Furthermore, 69 countries provided palliative care under both scenarios. The 10 countries with the highest annual opioid consumption (excluding methadone) for CC, in oral morphine equivalence per capita (2017), were all HICs.

Conclusions: Major inequalities persist in CC vaccination and screening across 194 countries, and access to these services is limited in most LMICs. Focusing on vulnerable populations with lower incomes and regions with stunted economic growth may help alleviate inequity and accelerate CC elimination. We also found that tertiary prevention was achieved in most LMICs, but the indicator-reported annual opioid consumption in oral morphine equivalents indirectly illustrates the under-utilisation of cancer treatment services.

Background: This study assessed the impact of chronic hepatitis B virus (HBV) infection on ovarian reserve in women.

Methods: We analyzed data from 38,861 infertile women undergoing their first in vitro fertilization (IVF) treatment (2016-2022), including 1574 HBsAg-positive cases. A control group of 1574 HBsAg-negative women was matched by age and body mass index (BMI). Comparison of clinical characteristics, antral follicle count (AFC), follicle-stimulating hormone (FSH), luteinizing hormone (LH)/FSH ratio, anti-Müllerian hormone (AMH), gonadotropins (Gn) days, total Gn dosage, number of retrieved oocytes, number of mature metaphase II (MII) oocytes, and the proportion of patients with diminished ovarian reserve (DOR; AMH < 1.1 ng/ml) between two groups.

Results: HBsAg-positive women showed lower basal AFC and AMH, higher basal FSH, received more Gn, and had fewer retrieved and MII oocytes than HBsAg-negative women. No significant differences in ovarian reserve or stimulation outcomes were found between e antigen-positive and e antigen-negative HBV-infected groups. DOR was less prevalent in HBsAg-negative women, and logistic regression indicated a higher DOR risk with HBV infection.

Conclusions: HBsAg positivity significantly impairs ovarian reserve in women, but e antigen status does not notably affect it among HBV-infected individuals.

Background: Following non-pharmaceutical interventions (NPI) lifting in 2021, an important surge in childhood lower respiratory tract infections (LRTI) was reported in several countries, raising major concerns about the middle-term consequences of such interventions. Whether this recent upsurge overwhelms the initial benefit of NPI remains unknown.

Methods: We conducted an interrupted time-series analysis based on exhaustive national surveillance systems. All hospitalisations from January 2015 to March 2023 and all ambulatory visits for LRTI from a network of 110 paediatricians from June 2017 to March 2023 were included. The main outcome was the monthly incidence of children hospitalised for LRTI per 100,000 over time, assessed by a seasonally adjusted quasi-Poisson regression model.

Results: We included 845,047 hospitalisations. The incidence of hospitalisation for LRTI significantly decreased during the NPI period (- 61.7%, 95% CI - 98.4 to - 24.9) and rebounded following NPI lifting, exceeding the pre-NPI baseline trend (+ 12.8%, 95% CI 6.7 to 19.0). We observed similar trends for hospitalisation due to bronchiolitis, pneumonia and pneumonia with pleural effusion, along with ambulatory LRTI. Overall, despite the recent rebound, 31,777 (95% CI, 25,375 to 38,179) hospitalisations for paediatric LRTI were averted since NPI implementation up to 2023.

Conclusions: Three years after their implementation, despite an increase in LRTI incidence, the middle-term impact of NPI remains highly beneficial in preventing overall paediatric LRTI. The implementation of some societally acceptable NPI, particularly during epidemics, may be considered in the future to further reduce the burden of paediatric LRTI.

Background: Adolescent diabetes is one of the major public health problems worldwide. This study aims to estimate the burden of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) in adolescents from 1990 to 2021, and to predict diabetes prevalence through 2030.

Methods: We extracted epidemiologic data from the Global Burden of Disease (GBD) on T1DM and T2DM among adolescents aged 10-24 years in 204 countries and territories worldwide. This study calculated the age-standardized prevalence rate (ASPR) and age-standardized DALY rate (ASDR) in adolescents based on the world standard population for cross-country comparisons. Average annual percentage changes (AAPC) in age-standardized rate were calculated by linkage point regression. Correlation analyses were used to identify the relationship between age-standardized rate and sociodemographic index (SDI). The Bayesian age-period-cohort (BAPC) model was used to predict changes in the diabetes prevalence among adolescents from 2022 to 2030.

Results: In 2021, 3.4 million adolescents were living with T1DM, with an ASPR of 180.96 (95% CI 180.77-181.15), and 14.6 million were living with T2DM, with ASPR of 1190.73 (1190.13-1191.34). As national and territory SDI levels rise, the prevalence rate of T1DM increases (r = 0.44, p < 0.01), and the prevalence rate of T2DM decreases (r = - 0.18, p < 0.01). Compared with males, females had a greater age-standardized prevalence of T1DM (185.49 [185.21-185.76] vs. 176.66 [176.39-176.92]), whereas males had a greater ASPR of T2DM than females did (1241.45 [1240.58-1242.31] vs. 1138.24 [1137.40-1139.09]). This study found a negative correlation between the SDI and the ASDR for both T1DM (r = - 0.51, p < 0.01) and T2DM (r = - 0.62, p < 0.01) in adolescents. For T2DM patients, 32.84% of DALYs were attributed to high BMI, which increased by 40.78% during the study period. By 2030, 3.7 million people are projected to have T1DM, and 14.6 million are projected to have T2DM.

Conclusions: Among adolescents, the burden of T1DM and T2DM is increasing and varies by region, sex, and SDI. Therefore, targeted interventions based on regional features are needed to prevent and control adolescent diabetes. Moreover, more efforts are needed to control climate change and obesity to reduce the adolescent diabetes burden.

Background: We synthesised the current evidence in coverage and quality of delivery care, change in neonatal mortality (NMR), and causes of neonatal death in the private sector deliveries in the Indian state of Bihar from 2011 to 2021.

Methods: Women aged 15-49 years with livebirths were interviewed in three household surveys involving state-representative samples in 2011, 2016 and 2020-2021 designed to document the coverage of maternal and newborn health services and change in NMR over time. Verbal autopsy interviews were used to assign the cause of neonatal death. The coverage of private sector facilities for livebirths in each survey and the percent change over time by 38 districts in the state and select socio-demographic characteristics, along with trends in NMR and causes of neonatal death across years are reported.

Results: Private sector delivery coverage was 17.3% (95% CI = 16.6-17.9), 16.7% (95% CI = 16.2-17.2) and 26.1 (95% CI = 25.6-26.6) in 2011, 2016 and 2020-2021, respectively. A significant increase of 56.3% (95% CI = 49.3 to 63.3) in this coverage was documented between 2016 and 2020-2021 with the highest increase in the lowest wealth index quartile in urban areas. The district-wise coverage of private sector delivery ranged from 4.6% to 34.9%, 5.5% to 40.7%, and 5.9% to 62.0% in 2011, 2016 and 2020-2021, respectively. NMR was estimated at 41.3 (95% CI = 31.4-51.2), 36.6 (95% CI = 29.4-43.8), 38.6 (95% CI = 34.4-43.3) per 1000 livebirths in 2011, 2016 and 2020-2021, with no significant change over the years. Birth asphyxia was the leading cause of death in 2016 (37.8%) and 2020-2021 (33.9%) followed by preterm delivery and neonatal pneumonia; a statistically significant reduction was seen in meningitis/sepsis between 2016 and 2020-2021 (77.8%; 95% CI = - 145.4 to - 10.1).

Conclusions: This analysis contributes to a nuanced understanding of the changes in the private sector delivery in a given population over time to facilitate appropriate actions and interventions to improve newborn survival and maternal services.