Better evaluation of the contribution of the main diseases, injuries, and risk factors for mortality and life expectancy is crucial for more efficient policy making at the national and subnational levels in Iran. The aim of this study is to assess the effect of emerging causes of mortality on health, specifically COVID-19, which can help policy makers implement preventive measures in similar situations. In this systematic analysis of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, we present estimates of cause-specific mortality at the national and subnational levels in Iran from 1990 to 2023. New to this iteration of GBD, we present a decomposition analysis of the contribution of specific causes of death to net gain or loss in life expectancy across 31 provinces of Iran. We used an array of data sources including censuses, vital registration, and surveys for national and subnational estimates. The two leading causes of death in Iran were ischaemic heart disease and stroke in both 1990 and 2019. However, in 2020 and 2021, the COVID-19 pandemic displaced the leading causes of death, ranking first with age-standardised mortality rates of 286·2 deaths (95% uncertainty interval 267·9-310·5) per 100 000 in 2020 and 250·0 deaths (233·2-272·5) per 100 000 in 2021. COVID-19 ranked second and tenth in 2022 and 2023, respectively. Life expectancy at birth for both sexes combined declined from 78·0 years (77·7-78·1) in 2019 to 74·3 years (74·0-74·4) in 2020. It steadily recovered to 78·8 years (78·5-79·2) in 2023. COVID-19 was the main cause of loss in life expectancy, by 4·19 years, between 2019 and 2020. There was a net gain of 12·4 years in life expectancy in Iran from 1990 to 2023. The net gain at the national level can be mostly attributed to reduced mortality from ischaemic heart disease (2·61 years), stroke (1·63 years), neonatal disorders (1·26 years), transport injuries (0·88 years), and neoplasms (0·64 years). The decline in mortality rates of major causes continued to 2023 despite the pandemic. An exception was Alzheimer's disease, which showed a 4·0% increase in rate between 2019 and 2023 and led to a net loss of 0·04 years in life expectancy since 1990. Diabetes led to a net loss of 0·09 years since 1990. There were variations between provinces in terms of age-standardised rates and the net change in life expectancy before and after the COVID-19 pandemic. The COVID-19 pandemic disrupted the rising trend of life expectancy in Iran, varying across provinces. Findings show that the health-care infrastructure and policies in Iran were not efficient in controlling the pandemic in 2020 and 2021, mainly due to inadequate vaccination coverage and timeliness, specifically for vulnerable subgroups. Sanctions may have aggravated the effect of COVID-19 on loss in life expectancy of Iranians. Despite the pandemic, the declining trend in age-standardised rates for top causes of mortality has continued to 2023, leading to a full recovery of life expectancy and underscoring the ultimate resilience of Iran's health system. Gates Foundation.
Breast cancer is a leading cause of mortality and morbidity among females worldwide. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, we provided an updated comprehensive assessment of the epidemiological trends, disease burden, and risk factors associated with breast cancer globally, regionally, and nationally from 1990 to 2023. Breast cancer incidence, mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) were estimated by age and sex for 204 countries and territories from 1990 to 2023. Mortality estimates were generated using GBD Cause of Death Ensemble models, leveraging data from population-based cancer registration systems, vital registration systems, and verbal autopsies. Mortality-to-incidence ratios were calculated to derive both mortality and incidence estimates. Prevalence was calculated by combining incidence and modelled survival estimates. YLLs were established by multiplying age-specific deaths with the GBD standard life expectancy at the age of death. YLDs were estimated by applying disability weights to prevalence estimates. The sum of YLLs and YLDs equalled the number of DALYs. Breast cancer burden attributable to seven risk factors was examined through the comparative risk assessment framework. The GBD forecasting framework was used to forecast breast cancer incidence and mortality from 2024 to 2050. Age-standardised rates were calculated for each metric using the GBD 2023 world standard population. In 2023, there were an estimated 2·30 million (95% uncertainty interval [UI] 2·01 to 2·61) breast cancer incident cases, 764 000 deaths (672 000 to 854 000), and 24·1 million (21·3 to 27·5) DALYs among females globally. In the World Bank low-income group, where a low age-standardised incidence rate (ASIR) was estimated (44·2 per 100 000 person-years [31·2 to 58·4]), the age-standardised mortality rate (ASMR) was the highest (24·1 per 100 000 [16·8 to 31·9]). The highest ASIR was in the high-income group (75·7 per 100 000 [67·1 to 84·0]), and the lowest ASMR was in the upper-middle-income group (11·2 per 100 000 [10·2 to 12·3]). Between 1990 and 2023, the ASIR in the low-income group increased by 147·2% (38·1 to 271·7), compared with a 1·2% (-11·5 to 17·2) change in the high-income group. The ASMR decreased in the high-income group, changing by -29·9% (-33·6 to -25·9), but increased by 99·3% (12·5 to 202·9) in the low-income group. The increase in age-standardised DALY rates followed that of ASMRs. Risk factors such as dietary risks, tobacco use, and high fasting plasma glucose contributed to 28·3% (16·6 to 38·9) of breast cancer DALYs in 2023. The risk factors with a decrease in attributable DALYs between 1990 and 2023 were high alcohol use and tobacco. By 2050, the global incident cases of breast cancer among females were forecast to reach 3·56 million (2·29 to 4·83), with 1·37 million (0·841 to 2·02) deaths. The stable incidence and declining mortality rates of female breast cancer in high-income nations reflect success in screening, diagnosis, and treatment. In contrast, the concurrent rise in incidence and mortality in other regions signals health system deficits. Without effective interventions, many countries will fall short of the WHO Global Breast Cancer Initiative's ambitious target of achieving an annual reduction of 2·5% in age-standardised mortality rates by 2040. The mounting breast cancer burden, disproportionately affecting some of the world's most vulnerable populations, will further exacerbate health inequalities across the globe without decisive immediate action. Gates Foundation, St Jude Children's Research Hospital.
Chronic hepatitis B (CHB) and hepatitis D (CHD) remain global health challenges, where sustained care engagement, treatment adherence and regular monitoring are essential but often limited by stigma and healthcare access. Digital health tools offer new opportunities to bridge these gaps. This study aimed to adapt the NORA mobile health app for CHB and CHD patients and evaluate its real-world utility in improving knowledge, adherence, communication and quality of life. We conducted a prospective, comparative study (February 2022-April 2024) including adult CHB (HBsAg-positive, HBeAg-negative) or CHD (anti-HDV or HDV-RNA-positive) patients with mobile access and Spanish proficiency. The app offered educational content, medication reminders, quality-of-life questionnaires (CLDQ, FACIT-F, EQ-5D-5L), a chat function and a knowledge test. Sociodemographic, clinical and usage data were analysed. Of 406 patients evaluated (356 CHB, 50 CHD), 277 CHB and 41 CHD patients were eligible. Participation was high (CHB: 88.4%; CHD: 90.2%), with active use in 48.1% and 70.3%, respectively. App users were more often male and Caucasian, and CHD users more frequently had detectable HDV-RNA. Patients with inactive HBV infection were less likely to use the app over the medium term (OR = 0.462, p = 0.003), and those who did use the app missed fewer clinic visits than nonusers (8.4% vs. 18.1%; OR = 0.41, p = 0.016). Among users, 85 were on antiviral therapy, 67% used the medication reminder, and chat use was higher in CHD and in treated patients (p = 0.004). High adherence (68% CHB, 84% CHD) and knowledge gains were observed, particularly in CHB with higher education. CHD patients showed worse baseline quality of life and greater declines over time. This first real-world study of a tailored mobile health (mHealth) app for CHB and CHD showed improved patient knowledge, adherence, communication and quality-of-life monitoring, with greater engagement in patients with advanced disease.
Alcohol-related liver disease (ALD) is a global health concern, and harmful alcohol use negatively affects clinical outcomes and health-related quality of life (HRQOL). Previous studies have demonstrated impaired HRQOL in chronic liver disease, including ALD; however, evidence remains limited regarding whether hepatologist-delivered abstinence support in outpatient practice can improve HRQOL. Digital interventions such as smartphone journaling apps may support behavior change, but their effectiveness in hepatology-led care settings has not been well established. This study aimed to prospectively evaluate changes in HRQOL over time among patients with ALD receiving routine hepatologist-led abstinence support supplemented by a smartphone-based journaling app. This was a prospective single-arm observational study. Eligibility criteria included a diagnosis of ALD, outpatient follow-up in hepatology, advice to abstain from alcohol, and written informed consent; patients were excluded if they reported abstinence for >1 year, had no intention to reduce or abstain from alcohol, or declined medical follow-up. In total, 21 outpatients with ALD (mean age 51, SD 3 years; men: n=12, 57.1%) were enrolled from a gastroenterology and hepatology outpatient clinic between August 2021 and July 2023 (convenience sampling). Participants attended scheduled visits at 4, 8, 12, and 24 weeks and received brief abstinence counseling by hepatologists while using a journaling app. HRQOL was assessed using the Japanese version of the 36-Item Short Form Health Survey version 2 at entry, week 8, and week 24. Changes in subscale and summary scores were analyzed using paired t tests (2-sided α=.05) with 95% CIs; when normality assumptions were not met, Wilcoxon signed-rank tests were applied. From entry to week 8, significant improvements were observed in physical functioning (mean difference [MD] +4.70, 95% CI 1.62-7.78; P=.005), role physical (MD +7.87, 95% CI 1.05-14.70; P=.02), general health (MD +5.82, 95% CI 1.74-9.88; P=.007), and role emotional (MD +7.85, 95% CI 0.29-15.41; P=.04). The Physical Component Summary score also improved (MD +4.78, 95% CI 1.22-8.34; P=.01). These findings were consistent in sensitivity analysis using the Wilcoxon signed-rank test. No significant changes were observed in mental or social HRQOL domains. In subgroup analyses, patients who maintained abstinence during the first 8 weeks (7/21, 33.3%) showed continued improvement in physical HRQOL up to 24 weeks, whereas those who continued drinking (11/21, 52.4%) did not exhibit meaningful change. In this exploratory observational study, hepatologist-led abstinence support supplemented by a smartphone-based journaling app was associated with improvements in physical HRQOL. Unlike previous studies that have focused on addiction specialist-led interventions, this study evaluated abstinence support delivered by hepatologists in routine outpatient practice, providing a real-world assessment of a digitally supported approach. These findings suggest that hepatologist-led, digitally supported care may be a feasible strategy in clinical settings with limited access to specialized addiction services.
Non-induced sputum galactomannan (GM) testing is increasingly used in routine evaluation of suspected invasive pulmonary aspergillosis (IPA), yet its real-world performance and the clinical implications of negative results remain incompletely characterised. We aimed to evaluate its diagnostic performance relative to bronchoscopic mycological findings and to describe the short-term evolution of GM results in routine practice. We retrospectively analysed adult patients who underwent non-induced sputum GM testing between 2017 and 2025. Diagnostic performance was assessed in patients with paired sputum and bronchoscopic samples obtained within 7 days using a bronchoscopy-based composite mycological reference standard (defined as bronchoscopic GM index ≥ 0.5, positive Aspergillus culture, or histopathological evidence of invasion). Longitudinal GM evolution was described in patients with initially negative sputum GM results. Among 1002 patients, 73 had paired samples. Sputum GM demonstrated a sensitivity of 73.7% (95% CI 53.9-93.5%), specificity of 72.2% (95% CI 60.3-84.2%), positive predictive value of 48.3% (95% CI 30.1-66.5%), and negative predictive value of 88.6% (95% CI 79.3-98.0%) for composite bronchoscopic mycological positivity. Higher sputum GM indices were associated with increasing rates of composite bronchoscopic mycological positivity (P for trend = 0.003). Among patients with initially negative sputum GM who underwent repeat testing, early follow-up (days 8-30) showed GM signal evolution in 15.1% of retested patients, whereas subsequent serum or bronchoscopic GM positivity remained uncommon (3.8%); both proportions increased with longer observation. In routine clinical practice, non-induced sputum GM testing demonstrates moderate diagnostic performance relative to bronchoscopic mycological findings. Negative results were associated with low short-term rates of subsequent bronchoscopic or serum GM positivity. These findings may inform short-term clinical reassessment, particularly in settings where bronchoscopy is not readily available.
Artificial intelligence (AI) is reshaping modern medicine, and gastroenterology and hepatology are among the specialties where its impact is becoming increasingly evident. AI has demonstrated the ability to process and analyze large amounts of clinical, radiological, endoscopic, and multi-omics data, offering unprecedented opportunities to enhance diagnostic accuracy, optimize therapeutic decision-making, and reduce variability in clinical practice. In endoscopy, computer-aided detection and diagnosis systems have shown consistent improvements in adenoma detection rates and real-time polyp characterization, while in hepatology, machine learning models outperform traditional scores for non-invasive assessment of liver fibrosis. Furthermore, multimodal approaches integrating genomics, microbiome, and imaging data are paving the way for precision medicine in inflammatory bowel disease and other complex digestive conditions. Despite these promising advances, significant barriers remain. The quality and heterogeneity of training data, the lack of rigorous external validation, and the opaque "black box" nature of many algorithms limit their clinical reliability. Ethical challenges, including accountability in case of diagnostic errors, protection of patient privacy, cost, and equitable access, also need to be addressed. This narrative review summarizes the current applications of AI in gastroenterology and hepatology, critically examines methodological and ethical challenges, and outlines future perspectives. Responsible, transparent, and equitable implementation will be essential for AI to transition from an emerging promise to a consolidated tool that improves outcomes and advances personalized digestive care.
Early detection of hepatocellular carcinoma (HCC) in patients with compensated cirrhosis (CC) is critical for improving prognosis. The GAAD algorithm (gender [biological sex], age, alpha-fetoprotein [AFP], protein induced by vitamin K absence-II [PIVKA-II]) demonstrated good performance for the detection of early-stage HCC. This study aimed to assess the cost-effectiveness of the GAAD algorithm for HCC surveillance in patients with CC in Italy, from the Italian Health Service perspective. A probabilistic micro-simulation Markov model was adapted to the Italian context to estimate lifetime clinical outcomes and costs of CC patients undergoing bi-annual surveillance with ultrasound (US), US+AFP, GAAD, and US+GAAD. Clinical inputs and utility values were derived from Italian real-world data and published literature. Direct healthcare costs were collected from Italian sources. Costs and outcomes were discounted at an annual 3% rate. Sensitivity analyses were conducted to evaluate the uncertainties in input parameters. In a simulated cohort of 100,000 CC patients, QALYs and costs per patient were 6.53 and €35,524 for US, 6.56 and €35,825 for US+AFP, 6.57 and €35,423 for GAAD, and 6.58 and €35,939 for US+GAAD. Compared to US and US+AFP, GAAD was dominant, while US+GAAD was cost-effective (ICUR of €9,482 and €10,951 per QALY gained, respectively). At a willingness-to-pay threshold of €30,000, GAAD was the most cost-effective strategy. Sensitivity analyses confirmed the robustness of results. Assumptions were required to estimate the diagnostic performance of US+GAAD, given the absence of prospective validation data. Some clinical parameters were derived from non-Italian sources, which may limit generalizability. GAAD, alone or combined with US, is a cost-effective strategy for HCC surveillance in CC patients in Italy, improving the detection of early-stage disease. Better performance data for US+GAAD is needed to confirm results.
Chronic hepatitis delta (CHD) is the most severe form of viral hepatitis and is associated with accelerated progression to cirrhosis and liver failure. Bulevirtide has shown promising results in trials, but real-world data on its effectiveness, safety and impact on patient-reported outcomes (PROs) remain limited. To evaluate the effectiveness, safety, and PROs (quality-of life-QoL; adherence) of bulevirtide therapy in CHD patients undergoing a dedicated pharmacist-led patient-education program (PEP). A prospective observational study enrolled 31 consecutive CHD patients receiving bulevirtide 2 mg daily at a tertiary referral centre. Virological, biochemical and combined responses were assessed at weeks 24, 48 and 60. QoL (through EQ-5D-5L questionnaire), adherence (proportion of days covered), and adverse events were monitored during follow-up. Bulevirtide significantly reduced HDV-RNA by week 24 (p < 0.01), with further reductions at week 48 (p = 0.05) and 60 (p < 0.01). Liver tests improved significantly from baseline to week 24 (p < 0.01) and remained stable. Combined response was achieved in 43.7% of patients by week 60. QoL improved significantly (p = 0.03), and adherence was excellent (≥ 90%). Adverse events were mostly mild and transient. In real-world clinical practice, bulevirtide achieved sustained virological and biochemical improvements with favourable safety and quality-of-life outcomes, confirming its effectiveness in routine management of CHD. While the 60-week data (n = 16) are exploratory due to the sample size, these findings confirm its effectiveness and safety in routine management of CHD.
Objective: To assess the disease burden of non-alcoholic fatty liver disease (NAFLD)-related cirrhosis in China from 1990 to 2021. Methods: Data were obtained from the Global Burden of Disease (GBD) 2021 study. The age-standardized rate was calculated using the direct standardization method with the GBD world standard population as the reference. The Joinpoint model was used to calculate the change of NAFLD-related cirrhosis in China, and the age-period-cohort analysis was used to estimate the independent effects of age, period, and cohort. Results: In 2021, the age-standardized incidence rate (ASIR) of NAFLD-related cirrhosis in China was 621/100 000, with the age-standardized prevalence rate (ASPR) of 15 606/100 000 and the age-standardized mortality rate (ASMR) of 0.31/100 000. The average annual percentage change (AAPC) of ASIR of the whole population from 1990 to 2021 was 0.74% (95%CI: 0.69%, 0.78%). There was a decreasing trend in the ASMR of the whole population with an AAPC of -1.73% (95%CI:-2.06%, -1.40%). The age effect showed a fluctuating downward trend in the overall incidence rate with age. The overall mortality rate showed an increasing trend. The period effect showed that the period rate ratios (RR) first decreased and then increased, with the highest incidence risk in 2017-2021. The period RR of incidence rate was 1.16 (95%CI: 1.11, 1.21). The trend of RR change in mortality rate showed a decreasing tendency, with the highest mortality risk in 1992-1996. The RR of mortality risk was 1.50 (95%CI: 1.43, 1.58). The cohort effect showed a significant increase in incidence risk and a decreasing trend in mortality risk from 1977 to 2002. Conclusion: The overall disease burden of NAFLD-related cirrhosis in China has shown a continuous upward trend from 1990 to 2021, and there are significant gender and age differences. 目的： 探究1990—2021年中国非酒精性脂肪性肝病（NAFLD）相关肝硬化的疾病负担。 方法： 利用2021年全球疾病负担研究（GBD 2021）中的中国NAFLD相关肝硬化负担数据，年龄标准化率采用直接标准化法并以GBD世界标准人口为参照进行计算，采用连接点模型分析趋势变化，采用年龄-时期-队列模型分析来估计年龄、时期和队列的独立影响。 结果： 2021年，中国NAFLD相关肝硬化的年龄标准化发病率为621/10万，年龄标准化患病率为15 606/10万，年龄标准化死亡率为0.31/10万。1990—2021年全人群年龄标准化发病率（ASIR）平均年度变化百分比（AAPC）为0.74%（95%CI：0.69%，0.78%）。全人群年龄标准化死亡率（ASMR）呈下降趋势，AAPC为-1.73%（95%CI：-2.06%，-1.40%）。年龄效应显示，随年龄增长发病率总体呈波动式下降的趋势。死亡率总体呈升高趋势。时期效应显示时期率比值（RR）呈先减低后升高趋势，2017—2021年发病风险最高，发病率的时期RR为1.16（95%CI：1.11，1.21）；死亡率的时期变化RR值变化趋势呈降低趋势，1992—1996年死亡风险最高，死亡率的风险RR值为1.50（95%CI：1.43，1.58）。队列效应显示，1977—2002年发病风险明显升高，死亡风险呈降低趋势。 结论： 1990—2021年中国NAFLD相关肝硬化的疾病负担总体呈持续上升趋势，且存在性别和年龄差异。.
The World Federation for Ultrasound in Medicine and Biology (WFUMB) guidance update 2024 proposed a 'rule-of-4' using ARFI liver stiffness measurement (LSM) to stratify the risk of decompensation events. This rule identifies advanced chronic liver disease (ACLD) at a threshold of ≥ 13 kPa and indicates a high probability of clinically significant portal hypertension (CSPH) above 21 kPa. We prospectively enrolled 187 patients undergoing same-day SSI-2D-LSM (Aixplorer SuperSonic Imagine) and hepatic venous pressure gradient (HVPG) measurement. Patients were stratified into three LSM groups < 13 kPa, 13-21 kPa and > 21 kPa and followed for decompensation events for 1 year (Y1). The cohort comprised 31 (16.6%) patients with LSM < 13 kPa (non-ACLD); 33 (17.6%) LSM 13-21 kPa (ACLD) and 123 (65.8%) LSM > 21 kPa (high CSPH probability). The corresponding median HVPG values were 5 [IQR: 3-7] vs. 10 [7-14] vs. 17 [13-21] mmHg, respectively, and the corresponding CSPH prevalence was 6.5%, 54.5% and 91.9%. In ROC analysis to predict CSPH, SSI-2D-LSM demonstrated high accuracy (AUC: 0.83). Validating the new WFUMB extension of the 'rule-of-4', the recommended > 21 kPa threshold identified CSPH with a specificity of 80.0% and a PPV of 83.1%. In competing risk analysis, the Y1-decompensation rate was 0%, 10% and 24.7% of patients in the < 13 kPa, 13-21 kPa and > 21 kPa groups, respectively. For prediction of Y1-decompensation risk in the compensated ACLD (cACLD) subgroup, HVPG demonstrated the highest predictive accuracy (AUC: 0.92), while SSI-2D-LSM (AUC: 0.75) performed similarly to vibration-controlled transient elastography (VCTE: AUC: 0.77; AUC-comparison: p = 0.837). The WFUMB 'rule-of-4' for ARFI-LSM allows for accurate and point-of-care non-invasive risk stratification of patients with liver disease. Specifically, the short-term risk of decompensation starts at SSI-2D-LSM ≥ 13 kPa and becomes considerable at SSI-2D-LSM > 21 kPa (indicating high CSPH probability). These findings support the broader implementation of ARFI-LSM for risk assessment in clinical routine.
Multimodal prehabilitation may improve surgical outcomes in selected populations, but its real-world effectiveness remains unclear. The aim of this study was to evaluate the effect of hospital-wide implementation of multimodal prehabilitation on postoperative complications and length of hospital stay in a diverse surgical population. This single-centre, non-randomized stepped-wedge study (F4S PREHAB) was conducted at Radboudumc, Nijmegen, The Netherlands from March 2019 to April 2024. Patients who underwent elective surgery across 20 clinical pathways received either standard preoperative care or multimodal prehabilitation comprising supervised exercise, nutritional support, psychological counselling, and smoking and alcohol cessation support. The primary outcome was the incidence and severity of postoperative complications within 30 days, with assessment of Clavien-Dindo (CD) grade ≥II complications and the dichotomized Comprehensive Complication Index (CCI). The secondary outcome was the length of hospital stay. Analyses used generalized linear models adjusted for time of inclusion and clinical pathway, as well as other confounders in some models. Subgroup analyses focused on patients who underwent high-risk gastrointestinal (GI) oncological surgery. During the study interval, 4131 patients received usual care (2660 patients) or prehabilitation (1471 patients). A total of 367 patients (24.9%) attended at least nine exercise sessions, indicating partial adherence. No significant differences between groups were found with regard to postoperative CD grade ≥II complications (adjusted risk ratio 1.02 (95% c.i. 0.90 to 1.16)) and CCI >22.6 (adjusted risk ratio 1.03 (95% c.i. 0.86 to 1.23)) or length of hospital stay (adjusted incidence rate ratio 1.04 (95% c.i. 0.92 to 1.18)). In the high-risk GI oncological surgery subgroup (1230 patients), the relative reduction in CD grade ≥II complication risk was 9%, but this was not statistically significant (adjusted risk ratio 0.91 (95% c.i. 0.75 to 1.10)). Hospital-wide implementation of multimodal prehabilitation did not reduce postoperative complications or length of hospital stay. A greater effect in high-risk patients suggests a targeted approach may be more effective. Future research should identify such patients and evaluate effectiveness of prehabilitation in this population.
We previously reported the 10-year effects of colonoscopy screening on colorectal cancer incidence and mortality. Here, we report the effects after 13 years of follow-up. In this multicountry, population-based randomised controlled trial, 84 583 men and women aged 55-64 years at enrolment from Norway, Poland, and Sweden were randomly allocated (1:2) to colonoscopy screening or no screening and analysed. The primary outcomes were colorectal cancer incidence and mortality after 10-15 years of follow-up in intention-to-screen analyses, with first analysis after 10 years, and repeated every other year or at longer intervals. This trial is registered with ClinicalTrials.gov, NCT00883792, and is ongoing. At 13 years of follow-up, colorectal cancer incidence was 375 colorectal cancers (1·46%) of 28 217 individuals in the screening group and 912 colorectal cancers (1·80%) of 56 366 individuals in the no-screening group. The risk ratio (RR) was 0·81 (95% CI 0·71-0·90) in intention-to-screen analyses and 0·55 (0·33-0·81) in per-protocol analyses. The risk for proximal colorectal cancer was 129 (0·51%) in the screening group versus 283 (0·56%) in the no-screening group (RR 0·91 [0·71-1·09]), and the risk for distal colorectal cancer was 224 (0·87%) in the screening group versus 563 (1·11%) in the no-screening group (RR 0·79 [0·65-0·89]; interaction p<0·0001). In men, the colorectal cancer risk was 214 (1·69%) of 14 154 in the screening group and 541 (2·19%) of 28 247 in the no-screening group (RR 0·77 [0·64 to -0·88]); in women, the risk was 161 (1·24%) of 14 063 in the screening group versus 371 (1·43%) of 28 119 in the no-screening group (RR 0·87 [0·70 to 1·02]; interaction p<0·0001). Colorectal cancer mortality was 106 (0·41%) of 28 217 in the screening group and 236 (0·47%) of 56 366 in the no-screening group (intention-to-screen RR 0·88 [0·68-1·08], per-protocol RR 0·70 [0·26-1·25]). The observed colorectal cancer mortality in the non-screening group (0·47%) was substantially lower than expected at the time of designing the trial (0·82%). One colonoscopy significantly reduced colorectal cancer incidence but not mortality over 13 years. Colorectal cancer mortality was lower in both study groups than when the trial was designed. The Norwegian Research Council, the Nordic Cancer Union, the Norwegian Cancer Society, and the Health Fund of South-East Norway.
Inflammatory bowel disease (IBD) encompasses chronic gastrointestinal disorders that significantly impact patients' quality of life (QoL). While clinical trials support the efficacy and safety of vedolizumab, real-world data linking its effectiveness to QoL-related patient-reported outcomes remain limited. This prospective observational study assessed the effects of 14-week vedolizumab induction therapy on QoL (i.e., fatigue, mood, and sleep disturbances), clinical response, safety, and predictors of response. A total of 257 patients with ulcerative colitis (UC; n = 205) and Crohn's disease (CD; n = 52) received 14-week vedolizumab induction therapy. Disease activity, QoL (assessed using the total Inflammatory Bowel Disease Questionnaire [IBDQ]), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-Fatigue]), mood and sleep disturbances (PROMIS Depression and Sleep Disturbance scales), and selected biomarkers were evaluated. Clinical response was assessed using the Mayo score for UC and Crohn's Disease Activity Index (CDAI) score for CD. At Week 14, clinical response was observed in 82% of UC patients and 82.7% of CD patients. Median total IBDQ scores increased by 45.0 points in UC and 31.5 points in CD (p < 0.001). Median prorated FACIT-Fatigue scores increased by 5.0 points in both groups (p < 0.001), while median prorated PROMIS Sleep Disturbance and Depression T-scores decreased (p < 0.05). Improvement in QoL was moderately correlated with clinical response (r = 0.5). In logistic regression analysis, baseline patient characteristics indicative of advanced disease were associated with a reduced likelihood of clinical and QoL response to treatment. A total of 28 adverse events were reported, including 11 serious events and four treatment-related events. Vedolizumab reduced disease activity and led to a rapid improvement in QoL during the 14-week induction therapy in patients with IBD. Clinical response was positively correlated with QoL improvement. Predictors of reduced response were consistent with features of advanced disease.
Placental schistosomiasis (PS) is underdiagnosed and may compromise maternal and neonatal health. This study estimated the prevalence of PS in a rural Gabonese population of pregnant women with confirmed S. haematobium infection using light microscopy of macerated placental tissue. This is a cross-sectional, diagnostic proof-of-concept study which applied an improved placenta maceration technique in real-world conditions to diagnose PS. Performing light microscopic assessment of a single sample of 10 mL urine, we screened pregnant women for S. haematobium infection who sought antenatal care in Lambaréné (Gabon) between January 2022 and January 2023. Women positive for S. haematobium infection were followed up until delivery. Additionally, a subsample of women with negative urine samples was recruited as a non-infected control group (1:1 ratio infected and non-infected groups) and followed up until delivery. Only participants with available macerated placental samples were considered for final analysis. Placental samples were subjected to light-microscopy-based screening for S. haematobium eggs and PS was considered present if a least one S. haematobium egg was detected. Positive light microscopic placental samples were confirmed by qPCR. Among 318 women screened for S. haematobium in urine, we found 40 (12.6%; 95% CI: 9.1-16.7%) to be positive. Together with 40 women in the non-infected control group all women were followed up until delivery. After loss-to-follow-up, 28 (70%; 28/40) women with S. haematobium infection and 20 (50%; 20/40) without infection provided placenta samples at delivery. In the group with S. haematobium infection, 14% (4/28; 95% CI: 4.0-32.7%) of women were positive for S. haematobium eggs in macerated placenta tissue. In the non-infected control group, one woman (5%; 1/20; 95% CI: 0.1-24.9%) had a positive microscopy result for PS. All five women with positive S. haematobium egg microscopy in placental tissue received a concordant qPCR result. 14% of women with S. haematobium infection also had PS. Notably, PS was also observed in 5% of women without detectable S. haematobium eggs in urine. This suggests that PS could be an underestimated phenomenon in highly endemic regions and warrants further investigations of its implications for mother-and-child health.
The increasing prevalence of inflammatory bowel disease (IBD) and constrained clinical resources necessitate a shift from fixed-interval outpatient visits towards patient-initiated, needs-based follow-up. Real-world evidence on whether such transitions maintain disease control and achieve patient acceptance remains limited. In 2024, Aalborg University Hospital (Denmark) transitioned all patients with IBD not receiving biological therapy to a digitally supported, patient-initiated monitoring model. We aimed to evaluate the quality of care and patient satisfaction after the transition. This pre-post quality improvement study included 966 patients with IBD (Crohn's disease (CD): n = 279; ulcerative colitis (UC): n = 687). Clinical data, disease activity scores, faecal calprotectin levels, and health-related quality of life were obtained from the GASTROBIO web-based regional database for two years before and up to two years after the transition. Patient satisfaction was assessed via a questionnaire adapted from the validated Danish "LUP survey". Entries of patient reported outcomes (PROs) and faecal calprotectin sampling increased following transition. The proportion of patients in faecal calprotectin-defined remission increased in both CD (63 % to 76 %; p = 0.01) and UC (62 % to 70 %; p = 0.04), while disease activity scores remained stable. Health-related quality of life improved in both CD (p = 0.02) and UC (p < 0.01). Of 966 eligible patients, 371 (38 %) completed the satisfaction survey; the majority preferred the new model over standard of care (CD: 77 %; UC: 84 %) and rated satisfaction as high or very high (CD: 66 %; UC: 71 %). Higher satisfaction correlated with better health-related quality of life in both groups (CD: Spearman's ρ =  - 0.22, p = 0.05; UC: ρ =  - 0.18, p = 0.01). A patient-initiated, digitally supported remote monitoring model maintained disease control, improved health-related quality of life, and achieved high patient satisfaction in a large real-world IBD cohort. These findings support the feasibility and scalability of needs-based IBD follow-up underpinned by an integrated digital infrastructure.
Several colorectal cancer (CRC) screening modalities are guideline-recommended in the United States but differ in screening interval and real-world adherence. Accordingly, single-round test performance may not reflect cumulative effectiveness over time. This study compared the 10-year longitudinal outcomes of two CRC screening strategies-triennial next-generation multitarget stool DNA testing (ng mt-sDNA) and decennial screening colonoscopy. The validated, microsimulation-based Colorectal Cancer and Adenoma Incidence and Mortality (CRC-AIM) model was used to estimate 10-year cumulative outcomes for two guideline-recommended screening strategies: triennial ng mt-sDNA and decennial colonoscopy. Model inputs included test performance and real-world adherence. Outcomes included CRC and precancerous lesions detected, CRC mortality reductions, and life-years gained (LYG). Sensitivity analyses examined the effects of varying screening adherence and follow-up colonoscopy adherence. Over 10 years per 1,000 individuals offered screening, ng mt-sDNA detected 13% more precancerous lesions and 11% more CRC cases than colonoscopy, with a greater proportion of CRCs identified through screening rather than symptomatic detection. ng mt-sDNA achieved greater CRC mortality reduction (33% vs 20%) and 62% more life-years gained, with consistent findings across sensitivity analyses. With real-world adherence, screening with triennial ng mt-sDNA demonstrates superior cumulative effectiveness compared with decennial colonoscopy, driven by higher adherence and favorable longitudinal performance. These findings support expanded use of noninvasive stool-based screening to reduce CRC mortality and alleviate colonoscopy capacity constraints. Broader adoption of ng mt-sDNA may enhance population-level CRC prevention by increasing participation and improving early detection. CRC screening tests are recommended at different intervals and completed at different adherence rates in clinical practice. Using a validated simulation model, we compared 10‑year real-world outcomes of repeated triennial ng mt-sDNA testing to one colonoscopy. Our findings indicate that repeated ng mt-sDNA provides greater cumulative screening effectiveness than colonoscopy over 10 years.
Pediatric functional constipation is a highly prevalent disorder associated with significant morbidity and impaired quality of life. Despite widespread use of osmotic and stimulant laxatives, a substantial proportion of children remain symptomatic, highlighting an unmet need for novel therapies. This review provides an overview of the mechanism of action, pharmacokinetics, safety, and clinical efficacy of linaclotide for the treatment of functional constipation in children. Evidence from phase 2 dose-finding studies, a pivotal phase 3 randomized controlled trial, and real-world data is summarized. Prior pediatric experience with other prosecretory and prokinetic agents is discussed to contextualize the current therapeutic landscape. A focused literature review was conducted using PubMed/MEDLINE and regulatory sources (U.S. Food and Drug Administration [FDA]), prioritizing pediatric clinical trials and observational studies evaluating linaclotide in functional constipation. Linaclotide may represent a mechanism-based therapeutic option for pediatric patients with functional constipation who remain symptomatic despite optimized conventional therapy. By targeting guanylate cyclase-C-mediated epithelial secretion, linaclotide is associated with improvements in bowel habits and a predominantly gastrointestinal safety profile. However, the pediatric evidence base remains relatively limited, and further studies are needed to define long-term outcomes, predictors of response, and its role within treatment algorithms.
Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer-related death globally. Most CRCs arise from colorectal adenomas (CRAs), particularly advanced adenomas, which are recognized as critical precancerous lesions. Early detection and intervention at the adenoma stage are essential for alleviating the global disease burden of CRC. However, conventional screening methods such as colonoscopy are invasive and have poor compliance, underscoring the urgent need for efficient, noninvasive diagnostic alternatives. Blood-based biomarkers have gained substantial attention because of their accessibility, reproducibility, and potential for early detection. Advances in multiomics technologies including proteomics, metabolomics, transcriptomics, and epigenomics have led to the identification of numerous plasma- and serum-derived biomarkers. These include noncoding RNAs (e.g., microRNAs, circular RNAs, PIWI-interacting RNAs), DNA methylation signatures, disease-specific proteins, and metabolic profiles. Moreover, emerging platforms such as liquid biopsy, extracellular vesicle profiling, and machine learning further expand the landscape of early CRA detection. The integration of multiomics data holds promise for substantially increasing the sensitivity and specificity of early adenoma detection, offering a transformative framework for precise CRC screening and risk stratification.
Cyclical Vomiting Syndrome (CVS) poses a significant financial burden on the healthcare system due to frequent emergency department (ED) visits and hospitalizations. Data on the impact of cannabis use in CVS is conflicting. This study evaluates the impact of cannabis use on outcomes in individuals with CVS using real-world data. A retrospective cohort study was conducted using the TriNetX research network to identify adults (≥ 18 years) with CVS. Patients were categorized into two groups: CVS with cannabis use and CVS without cannabis use (controls). Using propensity score matching on demographics, body mass index, comorbidities and treatments (e.g., abortive and prophylactic therapy) cohorts were matched 1:1. Outcomes included all-cause ED visits and hospitalizations. A total of 18,588 individuals with CVS and cannabis use were matched with 18,588 individuals with CVS who did not use cannabis (controls). Cannabis users were younger (mean age [SD]: 31.9 [12.5] vs. 39.0 [19.9] years) and had higher rates of mood/anxiety disorders, gastroparesis, and substance use. They were more likely to receive abortive therapy and less likely to receive prophylactic therapy. CVS patients who used cannabis had increased rates of ED visits (hazard ratio (HR) = 1.35, 95% confidence interval (CI): 1.31-1.39) and hospitalizations (HR = 1.11, 95% CI: 1.06-1.16) in comparison to those that did not. This study is the first using real-world evidence to demonstrate increased risks of ED visits and hospitalizations among individuals with CVS who use cannabis. Cannabis use in this population should be approached with caution due to the increased risk of adverse outcomes and associated financial burden.
Objective.This scoping review maps the landscape of quantitative ultrasound (QUS) techniques for hepatic fat assessment, emphasizing their physical principles, signal-processing strategies, technological implementations, reference standards, and sources of variability, and highlights their potential to advance noninvasive liver imaging in metabolic dysfunction-associated steatotic liver disease (MASLD).Methods.Following JBI methodology and reporting in accordance with the PRISMA-ScR checklist, a comprehensive search was conducted in PubMed, MEDLINE, ScienceDirect, and Scopus for studies published from January 2010 to October 2025. Human studies evaluating QUS-based methods for hepatic fat quantification in the context of MASLD were included. Screening and data extraction were performed using standardized procedures, with iterative refinement of the data-charting framework.Results.Out of 1 265 identified records, 150 studies were included. The body of literature has evolved from initial proof-of-concept and signal-processing investigations to more recent research emphasizing clinical relevance, reproducibility, and real-world use. Publication activity rose significantly after around 2018, coinciding with the commercial release of QUS technologies. The most common methods were based on attenuation coefficients, followed by approaches using backscattering coefficients, speed-of-sound estimation, envelope statistics, and combined multiparametric techniques. Recently, MRI- proton density fat fraction has become the preferred reference standard in validation studies, whereas liver biopsy and the controlled attenuation parameter have been used less often as primary comparison methods.Conclusions.Hepatic QUS is a diverse and rapidly evolving field encompassing multiple methodological categories grounded in distinct physical principles. Although QUS offers a physically grounded and clinically promising framework for noninvasive hepatic fat assessment, substantial heterogeneity in acquisition protocols, implementation, and reporting limits comparability across platforms. Greater standardization, improved inter-manufacturer reproducibility, and further development of robust multiparametric approaches are essential to enhance its clinical utility in the management of MASLD.