BMC Medicine最新文献

Background: Nirsevimab, a long-acting monoclonal antibody, and RSVpreF, a maternal vaccine, are newly approved respiratory syncytial virus (RSV) prophylactics for infants in Canada. Both have the potential to expand prevention efforts, but there is limited evidence regarding their cost-effectiveness and how it varies across the country, despite disparate hospitalisation rates and resource use among different populations.

Methods: We developed a decision tree model to follow twelve monthly birth cohorts through their first year of life, incorporating risk differentiation based on Canadian region, prematurity, and comorbidities. The model tracked medically attended infections, including hospitalisations, intensive care unit admissions, and outpatient visits, comparing costs (in 2024 Canadian dollars) and effectiveness (in quality-adjusted life years (QALYs)) of nine different immunisation strategies compared to no intervention. The analysis was conducted from both healthcare and societal perspectives. We conducted threshold price analyses, varying the price-per-dose of each product to determine the threshold prices at which expanded coverage becomes cost-effective.

Results: At base case prices, the optimal strategy varies by region, but in all cases, the optimal strategy is both cost-saving and more effective than no intervention. In southern Canada, it is optimal to immunise only palivizumab-eligible infants (those born very prematurely or with high-risk comorbidities) with nirsevimab, resulting in cost savings of $4.14 and QALY gains of 0.000022 QALY per infant compared to no intervention. In the Northwest Territories, it is best to expand protection with nirsevimab to include all preterm infants (cost savings of $28.68 and QALY gains of 0.00007 per infant). In Nunavik and Nunavut, immunising all infants under 6 months and all infants under twelve months with nirsevimab are the best strategies, respectively (cost savings of $399.61 and QALY gains of 0.000821 per infant in Nunavik, and cost savings of $1067.03 and QALY gains of 0.000884 per infant in Nunavut). Universal, country-wide immunisation with nirsevimab would require a price-per-dose of under $112 to become the most cost-effective prevention strategy.

Conclusions: The optimal strategy for preventing respiratory syncytial virus disease in Canadian infants depends on product price and regional risk level and resource use. Canadian policy should account for these factors.

Background: Early detection of cancer can help patients with more effective treatments and result in better prognosis. Unfortunately, established cancer screening technologies are limited for use, especially for multi-cancer early detection. In this study, we described a serum-based platform integrating surface-enhanced Raman spectroscopy (SERS) technology with resampling strategy, feature dimensionality enhancement, deep learning and interpretability analysis methods for sensitive and accurate pan-cancer screening.

Methods: Totally, 1655 early-stage patients with breast cancer (BC, n = 569), lung cancer (LC, n = 513), thyroid cancer (TC, n = 220), colorectal cancer (CC, n = 215), gastric cancer (GC, n = 100), esophageal cancer (EC, n = 38), and 1896 healthy controls (HC) were enrolled. The serum SERS spectra were obtained from each participant. Data dimension enhancement was conducted by heatmap transformation and continuous wavelet transform (CWT). The dimensionalization SERS spectral data were subsequently analyzed by residual neural network (ResNet) as convolutional neural network (CNN) algorithm. Class activation mapping (CAM) method was performed to elucidate the potential biological significance of spectral data classification.

Results: All participants were divided into a training set and a test set with a ratio of 7:3. The BorderlineSMOTE method was selected as the most appropriate resampling strategy and the deep neural network (DNN) model achieved desirable performance among all groups (accuracy rate: 93.15%, precision rate: 88:46%, recall rate: 85.68%, and F1-score: 86.98%), with the generated AUC values of 0.991 for HC, 0.995 for BC, 0.979 for LC, 0.996 for TC, 0.994 for CC, 0.982 for GC, and 0.941 for EC, respectively. Furthermore, the combination use of SERS spectra data and ResNet (form of heatmap) were also capable of effectively distinguishing different categories and making accurate predictions (accuracy rate: 94.75%, precision rate: 89.02, recall rate: 86.97, and F1-score: 87.88), with the AUC values of 0.996 for HC, 0.995 for BC, 0.988 for LC, 0.999 for TC, 0.993 for CC, 0.985 for GC, and 0.940 for EC, respectively. Additionally, strong wave number range of the spectral data was observed in the CAM analysis.

Conclusions: Our study has offered a highly effective serum SERS-based approach for multi-cancer early detection, which might shed new light on cancer screening in clinical practice.

Background: Processed packaged foods are readily available in Fiji; however, the extent to which ultra-processed foods (UPFs) currently contribute to energy and nutrient intake is unknown. This study aimed to assess the contribution of UPFs to total energy intake and nutrients of concern (sodium, sugar, fat) in a representative sample of adults in the central division of Fiji, identify the main food category sources of UPFs and assess variation by sociodemographic characteristics.

Methods: A random sample of 700 adults was selected from two statistical enumeration areas (one semi-urban, one rural). Participant characteristics were collected, and a three-pass 24-h diet recall was undertaken. Foods consumed were coded based on the level of processing, in alignment with the NOVA categorisation system.

Results: The contribution of UPFs to total energy, fat, sugar, and sodium intake and dietary sources of UPFs (based on the per cent daily energy contribution of UPFs from food groups) were estimated and assessed by sex, age group, ethnicity and location. A total of 534 adults participated (76% response rate, 50% female). UPFs contributed 21.5% (95% CI, 21.4% to 26.6%) of total energy intake, 22.8% (95% CI 20.5% to 25.1%) of total sodium intake, 24.0% (95% CI, 21.4% to 26.6%) of sugar intake and 18.6% (95% CI 16.5% to 20.7%) of total fat intake. Key food group contributors to UPF intake were bread and bakery products 42.9% (38.3% to 47.6%), non-alcoholic beverages 26.8% (22.4% to 31.1%), convenience foods 8.6% (6.3% to 10.8%), and meat, poultry, and meat alternatives 6.9% (4.8% to 8.9%). The contribution of UPFs to sodium, sugar and fat intake was similar for men and women; however, differences were observed by age group, ethnicity and region (semi-urban compared to rural).

Conclusions: This study identified that UPFs appear to be a large contributor to energy, sodium, fat and sugar intake in adults in the Central division of Fiji. A reduction of UPF consumption in Fiji may lead to a reduction of harmful nutrients such as sodium, fat, and sugar, crucial to reducing the diet-related burden of disease.

Background: Non-invasive multi-cancer early detection (MCED) tests have shown promise in enhancing early cancer detection. However, their clinical utility across diverse populations remains underexplored, limiting their routine implementation. This study aims to validate the clinical utility of a multimodal non-invasive circulating tumor DNA (ctDNA)-based MCED test, SPOT-MAS (Screening for the Presence Of Tumor by DNA Methylation And Size).

Methods: We conducted a multicenter prospective study, K-DETEK (ClinicalTrials.gov identifier: NCT05227261), involving 9057 asymptomatic individuals aged 40 years or older across 75 major hospitals and one research institute in Vietnam. Participants were followed for 12 months.

Results: Of the 9024 eligible participants, 43 (0.48%) tested positive for ctDNA. Among these, 17 were confirmed with malignant lesions in various primary organs through standard-of-care (SOC) imaging and biopsy, with 9 cases matching our tissue of origin (TOO) predictions. This resulted in a positive predictive value of 39.53% (95%CI 26.37-54.42) and a TOO accuracy of 52.94% (95%CI 30.96-73.83). Among the 8981 participants (99.52%) who tested negative, 8974 were confirmed cancer-free during a 12-month period after testing, yielding a negative predictive value of 99.92% (95% CI 99.84-99.96). The test demonstrated an overall sensitivity of 70.83% (95%CI 50.83-85.09) and a specificity of 99.71% (95% CI 99.58-99.80) for detecting various cancer types, including those without SOC screening options.

Conclusions: This study presents a prospective validation of a multi-cancer early detection (MCED) test conducted in a lower middle-income country, demonstrating the potential of SPOT-MAS for early cancer detection. Our findings indicate that MCED tests could be valuable additions to national cancer screening programs, particularly in regions where such initiatives are currently limited.

Trial registration: ClinicalTrials.gov ID: NCT05227261. Date of registration: 07/02/2022.

Background: Women who experience adverse pregnancy outcomes (APOs; gestational hypertension, preeclampsia (PE), gestational diabetes (GD), preterm birth (PTB), small or large for gestational age, miscarriage, multiple miscarriages, stillbirth, and offspring with major congenital anomalies) have increased risk of developing cardiovascular disease (CVD). We aimed to compare cardiometabolic health trajectories across the life course between women with and without APOs.

Methods: We studied 187,186 women with a registered pregnancy in the UK Clinical Practice Research Datalink (CPRD) GOLD linked to Hospital Episode Statistics. Fractional polynomial multilevel models were used to compare trajectories of cardiometabolic risk factors (body mass index [BMI], blood pressure [BP], cholesterol, and glucose) between women with and without a history of APOs (individual APOs in any pregnancy and number of APOs). We explored two underlying time axes: (1) time relative to first pregnancy (from 10 years before first pregnancy to 15 years after) and (2) age. Models controlled for age at first pregnancy, residential area deprivation, non-singleton pregnancy, parity, smoking status, ethnicity, and medications use.

Results: Women with a history of PE, gestational hypertension, or GD had higher BMI, BP, and glucose 10 years before first pregnancy compared to women without these APOs. These differences persisted 15 years post-first pregnancy. Women with a history of GD had a steeper post-partum rise in glucose. Women who experienced multiple (3 +) miscarriage, stillbirth, and/or medically indicated PTB had higher BP and BMI before and after pregnancy, with BP trajectories converging 15 years after first pregnancy. Women who experienced multiple APOs had the most adverse measurements across all cardiometabolic risk factors, with more unfavourable mean levels with each additional APO. There was little difference in cardiometabolic trajectories between women with and without a history of 1 or 2 miscarriages or congenital anomalies.

Conclusions: Women with APOs had adverse cardiometabolic profiles before first pregnancy, persisting up to 15 years post-pregnancy. Findings highlight the potential for targeted public health interventions to promote good cardiometabolic health in young adults transitioning from contraceptive use to planning pregnancies. APOs may identify young women who could benefit from monitoring CVD risk factors and interventions to improve cardiometabolic health.

Background: Cryoablation plays a key role in the comprehensive management of lung adenocarcinoma, characterized by its ability to activate antitumor immunity. This study aimed to explore the impact of cryoablation on the local immune microenvironment, focusing on regulatory T cells (Tregs) and the TGF-β pathway.

Methods: Single-cell sequencing was employed to identify differences in immune cell populations and related pathway expression between lung adenocarcinoma tissues and adjacent noncancerous tissues. Prospective observations of changes in Tregs in the peripheral blood pre- and post-cryoablation for lung adenocarcinoma were conducted at Dongfang Hospital, Beijing University of Chinese Medicine. Bulk RNA-seq analysis of mouse tumor tissues was performed to predict the potential mechanisms underlying cryoablation-induced antitumor immunity. Finally, these predictions were validated through in vitro and in vivo experiments employing cell cryoablation and mouse subcutaneous tumor transplantation models.

Results: Single-cell RNA sequencing analysis revealed intricate interactions between Tregs subpopulations and the regulation of the immune response in lung adenocarcinoma, highlighting the involvement of the TGF-β pathway. A significant decrease in the level of Tregs was noted at 30 days post-cryoablation compared to pre-surgical and 3-day post-surgery levels. The cellular and murine cryoablation models validated the inhibitory effect of cryoablation on Tregs and its potential to stimulate antitumor immunity. Additionally, the results of bulk RNA-seq demonstrated the role of cryoablation in regulating postoperative immunity via the TGF-β pathway. Cryoablation decreased the expression levels of TGF-β1, suppressed the phosphorylation of Smad2 and Smad3, and downregulated the expression of FOXP3, thereby inhibiting the conversion of CD4 + T cell precursors into Tregs. Moreover, cryoablation enhanced the expression of interferon-gamma (IFN-γ), thereby promoting its antitumor activity.

Conclusions: This study revealed the effective modification of the lung adenocarcinoma microenvironment by cryoablation through the suppression of Tregs and activation of antitumor immunity via the TGF-β pathway. These findings hold implications for optimizing cryoablation-based therapies and guiding future clinical trials on lung adenocarcinoma treatment.

Trial registration: This trial was registered with the Chinese Clinical Trial Registry (Chictr.org.cn, ChiCTR2000038580, Sep 24, 2020).

Background: In parts of Africa, women who become widowed lose housing, bank accounts, and other property and must re-marry to avoid extreme poverty. To re-marry, some women are required to undergo widow "cleansing"-condomless sex with a man who removes "impurities" ascribed to her from her husband's death-and are "inherited" as a wife of a brother-in-law. This study explores how HIV biomedical and structural interventions could reduce HIV-related harms associated with these practices.

Methods: We adapted EMOD-HIV, an HIV agent-based network transmission model previously calibrated and validated for the Nyanza region of western Kenya. Building on the model's pre-existing configuration of marriages, mortality, and widowhood, we added widow cleansing and wife inheritance with assumptions based on literature. Modeled HIV prevalence among inherited widows was validated to match observed data. We modeled the effect of widowed women, cleansers, and inheritors receiving biomedical HIV interventions (testing, treatment for those tested positive, and 1 year of pre-exposure prophylaxis (PrEP) initiated at cleansing for those tested negative) with or without structural interventions (female empowerment). We modeled low (30%) and high (70%) intervention uptake and reported HIV outcomes including cumulative infections over 2025-2050.

Results: Modeled HIV prevalence among inherited widowed women was 59.8% (95% CI: 59.5-60.2%), comparable to observed prevalence of 64.1% (95% CI: 63.2-65.4%). Among all widowed women, biomedical interventions averted 2.0% (95% CI: 1.3-2.6%) of HIV infections with low uptake and 2.6% (95% CI: 2.0-3.2%) with high uptake. Combined biomedical and structural interventions averted 7.8% (95% CI: 7.2-8.4%) of HIV infections with low uptake and 16.1% (95% CI: 15.5-16.6%) with high uptake. Impacts were smaller for men, e.g., high-uptake structural and biomedical interventions averted 1.8% (95% CI: 1.5-2.2%) of infections among cleansers and 2.7% (95% CI: 2.4-3.0%) among inheritors.

Conclusions: Widowed women are a vulnerable population with extremely high HIV prevalence. Combined biomedical and structural interventions focused on the practice of widow cleansing and wife inheritance have the potential to avert up to one-quarter of HIV infections among widowed women, and a smaller proportion among men participating in these practices.

Background: Early identification and management of sight-threatening ocular complications of diabetes using imaging or molecular biomarkers could help prevent vision loss. However, access to specialized infrastructure and expertise is limited, especially in remote areas of the world. Tear-fluid may offer an easier, non-invasive, and localized screenshot of ocular disease. To the best of our knowledge, there is no systematic review and meta-analysis on tear-fluid-based biomarkers for ocular complications in diabetes.

Methods: Articles were extracted from PubMed, Embase, Medline, and Web of Science using the MeSH and Emtree terms. The keywords include (diabetes), (diabetic retinopathy), (diabetes mellitus, type 1), (diabetes mellitus, type 2), (insulin-dependent diabetes), (insulin resistant diabetes), (tears), (lacrimal fluid), (biological marker), and (biomarker, marker). Concentrations of tear-fluid biomarkers in individuals with diabetes, diabetic ocular complications, and healthy controls were extracted and standardized mean differences (SMDs) and 95% CIs were calculated. Heterogeneity was assessed using subgroup and leave-one-out sensitivity analyses. Publication and risk of bias were performed using the Egger's test and Cochrane guidelines. The quality of evidence was evaluated using the Newcastle-Ottawa scale.

Results: Nine hundred eleven papers were identified, 19 of which met the study criteria and were included in the meta-analysis. Participants (n = 1413) belonged to three groups: healthy controls (Controls), diabetes without any complications (Diabetes), and diabetes with ocular complications (Complications). Actual concentrations were reported for TNF-α, VEGF, IL-1RA, IL-1β, IL-6, IL-8, lactoferrin, lysozyme, and MCP-1 in at least three different studies. Meta-analyses demonstrated that TNF-α concentration was significantly higher in the tear-fluid of Complications group when compared to Controls (SMD = - 1.08, 95% CIs = - 1.78, - 0.38, p = 0.003) or when compared to Diabetes (SMD = - 0.78, 95% CIs = - 1.48, - 0.09, p = 0.03). However, it was not different when Controls were compared to Diabetes (SMD = - 1.00, 95% CIs = - 2.27, 0.28, p = 0.13). VEGF demonstrated a similar trend indicating specificity of tear-fluid TNF-α and VEGF for diabetic ocular complications.

Conclusions: Across all biomolecules meta-analyzed in this study, TNF-α and VEGF were identified as the most important biomarkers that could potentially offer a non-invasive tear-fluid-based assessment of progression to ocular complications in diabetes, especially in rural and remote areas where diabetes-related expertise and infrastructure are limited.

Trial registration: PROSPERO (CRD42023441867) https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=441867 .

Background: To explore whether healthy lifestyle factors (HLFs) predict a lower risk of major macrovascular and microvascular events and death in people with type 2 diabetes (T2D) with a high risk of vascular complications.

Methods: Post hoc analyses of 11,133 participants with T2D in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial who were assigned a score ranging from 0 to 4 based on the number of baseline HLFs: never smoked, moderate-to-vigorous physical activity, ideal waist/hip ratio, and low-to-moderate alcohol consumption. Multivariable Cox models were used to determine associations of 0, 1, 2, and ≥ 3 HLFs with vascular events and all-cause mortality.

Results: Compared to participants with no HLFs, hazard ratios for participants with 3 or 4 HLFs were 0.68 (95% confidence interval [CI] 0.57-0.81) for the composite of major macrovascular or microvascular events, 0.58 (0.46-0.75) for major macrovascular events, 0.78 (0.61-0.99) for microvascular events, and 0.48 (0.37-0.63) for all-cause mortality during a median follow-up of 5 years. Each increment in HLF score was significantly associated with lower rates of these outcomes. There was no heterogeneity in the effect on any outcome by HLF across randomized intensive blood glucose control and blood pressure lowering treatments.

Conclusions: HLFs are associated with lower risks of major macrovascular and microvascular events and lower rates of death in high-risk adults with T2D.