EClinicalMedicine最新文献

Background: Little is known about the complex associations of socioeconomic status (SES) and healthy lifestyle with cognitive dysfunction.

Methods: Using data from the Health and Retirement Study (HRS) [2008-2020] and the English Longitudinal Study of Ageing (ELSA) [2004-2018], SES was constructed by latent class analysis using education level, total household income and wealth. Overall healthy lifestyle was derived using information on never smoking, low to moderate alcohol consumption (drinks/day: (0, 1] for women and (0, 2] for men), top tertile of physical activity, and active social contact.

Findings: A total of 12,437 and 6565 participants from the HRS and ELSA were included (40.8% and 46.0% men and mean age 69.3 years and 65.1 years, respectively). Compared with participants of high SES, those of low SES had higher risk of incident dementia (hazard ratio 3.17, 95% confidence interval 2.72-3.69 in the HRS; 1.43, 1.09-1.86 in the ELSA), and the proportions mediated by overall lifestyle were 10.4% (7.3%-14.6%) and 2.7% (0.5%-14.0%), respectively. Compared with participants of high SES and favorable lifestyle, those with low SES and unfavorable lifestyle had a higher risk of incident dementia (4.27, 3.40-5.38 in the HRS; 2.02, 1.25-3.27 in the ELSA) and accelerated rate of global cognitive decline (β = -0.058 SD/year; 95% CI: -0.073, -0.043 in the HRS; β = -0.049 SD/year; 95% CI: -0.063, -0.035 in the ELSA).

Interpretation: Unhealthy lifestyle only mediated a small proportion of the socioeconomic inequality in dementia risk in both US and UK older adults.

Funding: This work was supported by grants from the National Natural Science Foundation of China (82088102 and 82370819), the National Key R&D Program of China (2023YFC2506700), the Shanghai Municipal Government (22Y31900300), the Shanghai Clinical Research Center for Metabolic Diseases (19MC1910100), the Innovative Research Team of High-Level Local Universities in Shanghai, the Special Project for Clinical Research in Health Industry of Shanghai Municipal Health Commission (202340084), and Ruijin Hospital Youth Incubation Project (KY20240805). Y.X. is supported by the National Top Young Talents program.

Background: School-age children in sub-Saharan Africa suffer an underappreciated burden of malaria which threatens their health and education. To address this problem, we compared the efficacy of two school-based chemoprevention approaches: giving all students intermittent preventive treatment (IPT) or screening and treating only students with detected infections (IST).

Methods: In a three-arm, open-label, randomized, controlled trial (NCT05244954) in Malawi, 746 primary school students, aged 5-19 years, were individually randomized within each grade-level to IPT (n = 249), IST with a high-sensitivity rapid diagnostic test (hs-RDT, n = 248), or control (n = 249). At six-week intervals three times within the peak malaria transmission season (February-June 2022) treatment with dihydroartemisinin-piperaquine (DP) was administered to girls <10 years and all boys, and chloroquine to older girls. The primary outcome was Plasmodium falciparum (Pf) infection detected by PCR 6-8 weeks after the final intervention. Secondary outcomes included anaemia, clinical malaria, and scores on tests of attention, literacy, and math. Analysis was by modified intention-to-treat.

Findings: Outcomes analyses included 727 (97%) participants. At the end of the study, prevalence of Pf infection was 17% (41/243) in the IPT arm, 24% (58/244) in the IST arm, and 53% (127/240) in the control arm. Compared to controls, IPT and IST reduced the odds of Pf infection (IPT adjusted odds ratio [aOR]: 0.18 (95% CI: 0.11, 0.27); p < 0.0001; IST aOR: 0.27 (95% CI: 0.18, 0.40); p < 0.0001). However, only participants receiving IPT had a lower incidence of clinical malaria (0.19 cases per person per six months (95% CI: 0.14, 0.27) vs 0.56 (95% CI: 0.46, 0.68); incidence rate ratio: 0.38 (95% CI: 0.26, 0.55); p < 0.0001)) and prevalence of anaemia (8% [20/243] vs 15% [36/240]; aOR: 0.49 (95% CI: 0.27, 0.91); p = 0.023) compared to controls. Literacy scores were higher in both intervention arms. No between group differences in tests of attention or math or number of serious adverse events were found.

Interpretation: Results support implementation of IST with hs-RDTs or IPT for reduction in the prevalence of infection. Based on reductions in clinical malaria, IPT may provide additional benefits warranting further consideration by school-based malaria chemoprevention programs.

Funding: Doris Duke Charitable Foundation Clinical Scientist Development Award 2021191, U.S. NIH K24AI114996 & K23AI135076.

Background: We aimed to compare the risk of incident depression, anxiety, non-fatal self-harm and completed suicide in survivors from a wide range of cancers versus cancer-free individuals.

Methods: We used electronic health records from the United Kingdom Clinical Practice Research Datalink linked to cancer registry data, hospital admissions data and death records between 1998 and 2021. Adult survivors of the 20 most common cancers were matched (age, sex, general practice) 1:10 to cancer-free individuals. Cox regression models, adjusted for shared risk factors, were used to estimate associations between cancer survivorship and mental health outcomes.

Findings: 853,177 adults with cancer diagnosed in 1998-2018 were matched to 8,106,643 cancer-free individuals. Survivors of all 20 cancer types under study had a higher risk of experiencing a new episode of anxiety and depression during follow-up compared with cancer-free individuals; there was also evidence of raised risks of non-fatal self-harm in 17/20 cancers and completed suicide in 8/20 cancers. Effect sizes were greatest in cancers with poorer 5-year survival: hazard ratios (HRs) for anxiety and depression of 1.1-1.2 were seen for malignant melanoma survivors, while HRs for both outcomes were >2.5 for lung and oesophageal cancer survivors. HRs were highest in the first year from cancer diagnosis, reducing over time since diagnosis. However, 5-year cancer survivors still experienced elevated risks of a subsequent new episode of anxiety or depression, in 18/20 cancers.

Interpretation: Survivors of the 20 most common cancers were at increased risk of experiencing depression and anxiety, and these increased risks persisted in medium-to long-term cancer survivors. Substantially raised risks of non-fatal self-harm and completed suicide were also seen for several types of cancer. The risks of all mental health outcomes were generally higher in survivors of cancers with poorer prognosis. Our findings suggest a need for improved psychological support for all patients with cancer.

Funding: Wellcome Trust.

Background: Timely and economic provision of revascularisation procedures is a major healthcare need. We aimed to examine the safety and efficacy of daycase-based lower extremity endovascular revascularisation procedures in patients with peripheral artery disease.

Methods: In this systematic review and meta-analysis, we searched MEDLINE and Embase for studies from Jan 01, 2000 through Apr 01, 2024 reporting complications of lower limb endovascular revascularisation procedures with same-day discharge. Eligibility-criteria, complications, and patient characteristics were extracted, methodological quality assessed (adapted Newcastle-Ottawa Scale), and meta-analyses of complications and technical success performed to provide pooled estimates. This study is registered with PROSPERO, CRD42022316466.

Findings: Thirty observational studies (17 retrospective, 13 prospective) and 1 RCT reported 2427 minor and 653 major complications after 99,600 daycase procedures (93,344 patients). Eighteen studies reported daycase eligibility-criteria including 'responsible adult companion' (78%), 'proximity to hospital', and 'telephone availability' and excluding unstable and severe co-morbidities, offset coagulation, and severe chronic kidney disease. Pooled incidences of minor (4.7% [95% CI 3.8-5.6%], I ² = 96%) and major (0.64% [95% CI 0.48-0.79%], I ²  = 46%) complications were low and technical success high (93% [95% CI 91-96%], I ² = 97%). Most complications were related to the puncture site. Pooled conversion-to-hospitalisation rates and re-admission after discharge were 1.6% (95% CI 1.1-2.2%, I ² = 82%) and 0.11% (95% CI 0.095-0.23%, I ² = 97%), respectively. Meta-regression identified that minor complications decreased since 2000. Male sex and coronary artery disease were associated with more frequent, and higher age and closure device use with less minor complications. Diabetes mellitus and chronic kidney disease were associated with less major complications. Six studies reported complication rates both in daycases and inpatients and there was no significant difference (-0.8% [95% CI -1.9 to 0.3%]).

Interpretation: After careful evaluation of eligibility, lower limb angioplasty can be performed safely with high technical success in a daycase setting. Most complications arise from the puncture site and not the procedure itself highlighting the importance of optimal access site management. The heterogeneity between studies warrants standardised monitoring of complications and outcomes.

Funding: European Partnership on Metrology, co-financed from European Union's Horizon Europe Research and Innovation Programme and UK Research and Innovation, and Medical Research Council.

Background: Unresectable Hepatocellular Carcinoma (uHCC) poses a substantial global health challenge, demanding innovative prognostic and therapeutic planning tools for improved patient management. The predominant treatment strategies include Transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC).

Methods: Between January 2014 and November 2021, a total of 1725 uHCC patients [mean age, 52.8 ± 11.5 years; 1529 males] received preoperative CECT scans and were eligible for TACE or HAIC. Patients were assigned to one of the four cohorts according to their treatment, four transformer models (SELECTION) were trained and validated on each cohort; AUC was used to determine the prognostic performance of the trained models. Patients were stratified into high and low-risk groups based on the survival scores computed by SELECTION. The proposed AI-based treatment decision model (ATOM) utilizes survival scores to further inform final therapeutic recommendation.

Findings: In this study, the training and validation sets included 1448 patients, with an additional 277 patients allocated to the external validation sets. The SELECTION model outperformed both clinical models and the ResNet approach in terms of AUC. Specifically, SELECTION-TACE and SELECTION-HAIC achieved AUCs of 0.761 (95% CI, 0.693-0.820) and 0.805 (95% CI, 0.707-0.881) respectively, in predicting ORR in their external validation cohorts. In predicting OS, SELECTION-TC and SELECTION-HC demonstrated AUCs of 0.736 (95% CI, 0.608-0.841) and 0.748 (95% CI, 0.599-0.865) respectively, in their external validation sets. SELECTION-derived survival scores effectively stratified patients into high and low-risk groups, showing significant differences in survival probabilities (P < 0.05 across all four cohorts). Additionally, the concordance between ATOM and clinician recommendations was associated with significantly higher response/survival rates in cases of agreement, particularly within the TACE, HAIC, and TC cohorts in the external validation sets (P < 0.05).

Interpretation: ATOM was proposed based on SELECTION-derived survival scores, emerges as a promising tool to inform the selection among different intra-arterial interventional therapy techniques.

Funding: This study received funding from the Beijing Municipal Natural Science Foundation, China (Z190024); the Key Program of the National Natural Science Foundation of China, China (81930119); The Science and Technology Planning Program of Beijing Municipal Science & Technology Commission and Administrative Commission of Zhongguancun Science Park, China (Z231100004823012); Tsinghua University Initiative Scientific Research Program of Precision Medicine, China (10001020108); and Institute for Intelligent Healthcare, Tsinghua University, China (041531001).

Background: Suboptimal diet quality is a key risk factor for premature death. Assuming relatively stable energy intake among individuals, changes in nutrient intakes occur by exchanging different nutrients. Therefore we aimed to examine the association of isocaloric substitution of dietary (macro)nutrients with all-cause mortality using network meta-analysis (NMA).

Methods: For this systematic review and NMA of prospective observational studies MEDLINE, Embase, and Scopus were searched from inception to February 13th, 2024. Eligible studies reported substitution analyses for quantity and/or quality of macronutrients, including carbohydrates, proteins, and fatty acids on all-cause mortality. Random-effects NMA were used in order to evaluate the pooled hazard ratios (HR) and 95% confidence intervals (CI) of substituting each included nutrient with another. We assessed risk of bias with the ROBINS-E tool, and the certainty of evidence (CoE) using the Grading of Recommendations Assessment, Development and Evaluations (GRADE) approach. This study is registered with PROSPERO (CRD42023450706).

Findings: Thirty-nine studies with 1,737,644 participants, 395,491 deaths, 297 direct comparisons, and seven nutrient-specific networks were included. Moderate CoE was found for an association with lower mortality risk when replacing 5% of energy intake from carbohydrates with polyunsaturated fatty acids (PUFA; HR: 0.90; 95%CI: 0.84, 0.95), n-6 PUFA (0.85; 0.77, 0.94), n-3 PUFA (0.72; 0.59, 0.86), and plant monounsaturated fatty acids (MUFA; 0.90; 0.85, 0.95), and when replacing 5% of energy from saturated fatty acids (SFA) and trans-fatty acids (TFA), with PUFA, MUFA, and plant-MUFA (HR_range: 0.75 to 0.91). A lower mortality risk was additionally found when 5% of animal-MUFA was replaced with plant-MUFA, and when replacing animal protein, and SFA with plant protein (HR_range: 0.81 to 0.87, moderate CoE).

Interpretation: Our results provide practical knowledge for public health professionals and can inform upcoming dietary guidelines. The beneficial association of increasing PUFA (both n-3 and n-6) and (plant-) MUFA intake while reducing carbohydrates, SFA and TFA, along with replacing animal protein and animal-MUFA with plant-based sources of protein and fat (MUFA) on the all-cause mortality risk, underscores the importance of plant-based dietary recommendations.

Funding: None.

Background: Studies from the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2021 can guide screening and prevention strategies for tracheal, bronchus, and lung (TBL) cancer. We aim to provide global, regional, and national estimates of the TBL cancer burden and its attributable risk from 1990 to 2021, including during the coronavirus disease 2019 (COVID-19) pandemic.

Methods: Incidence, age-standardised incidence rate (ASIR), deaths, age-standardised mortality rate (ASMR), disability-adjusted life years (DALYs), age-standardised rate of DALYs (ASDR), and the burden due to risk factors associated with TBL cancer were analysed from 1990 to 2021. Trends in ASIR, ASMR, and ASDR of TBL cancer during the COVID-19 pandemic (2019-2021) were also determined. All statistical analyses were performed using Join-point software (version 4.9.1.0).

Findings: Between 1990 and 2021, the global incidence, deaths, and DALYs of TBL cancer to varying degrees. However, the ASIR (Average Annual Percent Change [AAPC], -0.3 [-0.4 to -0.2]), ASMR (AAPC, -0.5 [-0.7 to -0.4]), and ASDR (AAPC, -0.9 [-1.0 to -0.7]) all showed a decreasing trend. However, the ASIR, ASMR, and ASDR of TBL cancer in males all showed a decreasing trend from 1990 to 2021. In contrast, the ASIR and ASMR of TBL cancer in females showed an increasing trend, while the ASDR showed a relatively stable trend. During the COVID-19 pandemic, the trends for ASIR, ASMR, and ASDR remained stable across both sexes combined, females, males, five socio-demographic index (SDI) quintiles, and the 21 GBD regions. In 2021, smoking was a major risk factor for TBL cancer DALYs, but the attributable ASDR for smoking decreased from 1990 to 2021 in both sexes combined, as well as individually for males and females. Conversely, the attributable ASDR for secondhand smoke, high fasting plasma glucose and occupational exposure factors increased primarily among females. Furthermore, the attributable ASDR for ambient particulate matter pollution, household air pollution from solid fuels, and low-fruit diets increased primarily in regions with lower SDI quintiles from 1990 to 2021.

Interpretation: The burden attributable to TBL cancer has increased in some populations from 1990 to 2021, highlighting the importance of implementing targeted measures to mitigate this trend. No significant change in the burden of TBL cancer was observed during the COVID-19 pandemic; however, post-COVID-19 rates still require further observation.

Funding: This study was supported by National Key Research and Development Program of China (2023YFC3503300, 2023YFC3503305), and High Level Chinese Medical Hospital Promotion Project (HLCMHPP2023085, HLCMHPP2023001, HLCMHPP2023097).

Background: This was a multicenter, single-arm dose-ranging phase 2 study aimed to assess the efficacy and safety of LY01610, a liposomal irinotecan, at various doses for patients with relapsed small cell lung cancer (SCLC).

Methods: This study (NCT04381910) enrolled patients with relapsed SCLC at 10 hospitals across China, who have failed with previous platinum-based treatments. LY01610 was administered at doses of 60 mg/m², 80 mg/m², and 100 mg/m². Primary endpoints were investigator-assessed objective response rate (ORR) and investigator-assessed duration of response (DoR). Secondary endpoints included investigator-assessed disease control rate (DCR), investigator-assessed progression-free survival (PFS), overall survival (OS), and safety.

Findings: From September 3, 2020 to March 3, 2022, a total of 66 patients were enrolled, with 6, 30, and 30 allocated to the 60 mg/m², 80 mg/m², and 100 mg/m² dose groups, respectively, with 68% (45/66) having a chemotherapy-free interval <90 days. In all 66 patients, the ORR was 32% (21/66, 95% confidence interval [CI], 21-44), with a median DoR of 5.2 months (95% CI, 3.0-8.3). Median PFS and OS were 4.0 (95% CI, 2.9-5.5) and 9.7 (95% CI, 7.2-12.3) months, respectively. The ORR of 60 mg/m², 80 mg/m², and 100 mg/m² dose group were 33% (2/6), 33% (10/30), and 30% (9/30), respectively. The median DoR of 60 mg/m², 80 mg/m², and 100 mg/m² dose group were 4.2 (95% CI, 2.8-not reached), 6.9 (95% CI, 2.5-9.9), and 4.0 (95% CI, 2.7-6.8) months, respectively. The incidence of ≥ grade 3 treatment-related adverse events (TRAEs) in the 60 mg/m², 80 mg/m², and 100 mg/m² dose group were 33% (2/6), 47% (14/30), and 50% (15/30), respectively. The most common ≥ grade 3 TRAEs of all 66 patients were neutropenia (27%), leukopenia (24%) and anemia (15%).

Interpretation: LY01610 exhibited promising clinical efficacy and manageable safety profiles in patients with relapsed SCLC, the 80 mg/m² dose group had the best benefit-risk ratio.

Funding: This study was supported by Luye Pharma Group Ltd.

Background: Autoimmune diseases are known to be associated with an increased risk of cancer. Whether maternal immune dysregulation can have an impact on the development of haematological malignancies in offspring remains uncertain. Therefore, we explored the association between offspring risk of haematological malignancies and maternal autoimmune disease using a real-world nationwide population-based study.

Methods: In this case-control study, we identified 2172 children with haematological malignancies between 2004 and 2019 from Taiwan's National Health Insurance program and compared them with population-based controls without haematologic malignancies, who were matched with each individual at a ratio of 1:4. The medical information of the autoimmune mothers were obtained from the Taiwan Maternal and Child Health Database. Conditional logistic regression was used to estimate the odds ratio for haematologic malignancy in offspring. Furthermore, subgroup and stratified analyses were conducted.

Findings: Among the rheumatologic diseases in our study, Crohn's disease was the most common disease both in the haematological malignancy group (1.1%) and the control group (0.9%). In multivariable analysis, the odds ratio for haematological malignancy in offspring with maternal autoimmune diseases was 1.2 (95% confidence interval [CI] 0.91-1.58). The overall risk of haematologic malignancy was not significantly higher when adjusted for specific risk factors, including neonatal age, maternal age, family income, urbanization, maternal occupation, birth weight, or maternal comorbidity, except for prematurity. When comparing different autoimmune diseases among haematological malignancies and the control group, maternal psoriatic arthritis/psoriasis had the highest adjusted overall risk for haematological malignancies (adjusted OR 2.11, CI 0.89-5), followed by ankylosing spondylitis (adjusted OR 1.45, CI 0.7-3), autoimmune thyroiditis (OR 1.26, CI 0.57-2.81), systemic lupus erythematosus (OR 1.21, CI 0.48-3.02), Crohn's disease (OR 1.19, CI 0.75-1.9), and Sjogren's syndrome (OR 1.18, CI 0.65-2.15), but no significance was reached in these analyses. Multivariable analysis of risk factors associated with haematological malignancy subtypes was done. It showed no associations between maternal autoimmune disease and childhood haematological malignancies.

Interpretation: We found no significant relationship between maternal autoimmune disease and childhood haematological malignancies. The influence of maternal immune dysregulation on the next generation with respect to haematological malignancies development may be limited.

Funding: There was no funding source for this study.