EClinicalMedicine最新文献

Background: Hypertensive disorders of pregnancy are a leading cause of maternal and perinatal morbidity and mortality. If women at high risk for developing complications could be identified early, level of care could be triaged, limited resources could be correctly allocated and targeted interventions to prevent complications could be implemented.

Methods: We updated a systematic review and meta-analysis and added single outcomes. Women with hypertensive disorders of pregnancy were included. Exposures were tests predicting adverse maternal and/or perinatal outcomes. We searched Medline, Embase, CINAHL, and Cochrane library from January 2016-February 2024. We included studies identified from the previous review. We calculated effect measures. For similar predictive tests and outcomes, area under the receiver-operating-characteristic curve (AUROC) were pooled. This study was registered by PROSPERO: CRD42022336368.

Findings: Of the 2898 studies identified, 80 were included. Thirty were added from the previous review resulting in 110 included studies with 506,178 women. Despite more than 1500 tests being performed, most outcomes could not be pooled due to heterogeneity in populations, tests, and outcome definitions. For maternal outcomes, only studies reporting on the Pre-eclampsia Integrated Estimate of RiSk (fullPIERS) model could be pooled. For the composite outcome within 48-h the AUROC was 0.78 (95% CI 0.71-0.86, N = 8). There was significant heterogeneity (I ²  = 95.7%). For perinatal outcomes, data were pooled for pulsatility index in the umbilical artery and soluble FMS-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio. Biomarkers like the sFlt-1/PlGF ratio showed promising predictive performance for some outcomes but were not externally validated.

Interpretation: Despite including over 100 studies with more than 1500 predictors, we were unable to pool any single maternal outcomes and only a few individual perinatal outcomes. The fullPIERS model was externally validated, showing moderate accuracy which varied across studies and should be validated in each new population. Angiogenic biomarkers showed promise but need validation. Future studies should use standardized outcome measures and validate promising tests.

Funding: VB is supported by the Swedish Research Council, Grant number 2020-01481. University of Gothenburg.

The co-occurrence of autism and gender diversity has been increasingly studied in the past decade. It is estimated that ∼11% of transgender and gender-diverse (TGD) individuals are diagnosed with autism. However, there is insufficient knowledge about appropriate gender-related clinical care for autistic TGD individuals. We performed a scoping review of current clinical guidance for the care of TGD individuals to identify what was said about autism. Clinical guidance documents were searched in PubMed, Web of Science, Google Scholar, Embase, Guidelines International Network, and TRIP medical database, as well as reference mining and expert recommendation. Evidence was synthesised by narrative synthesis, recommendation mapping, and reference frequency analysis. Out of the identified 31 clinical guidance documents, only eleven specifically mentioned the intersection between autism and TGD. Key concepts among the available recommendations included advocating for a multidisciplinary approach; emphasising the intersectionality of autism and gender-diverse experiences during assessments; and-importantly-recognising that autism, in itself, does not serve as an exclusion criterion for receiving gender-related care. However, detailed and practical clinical guidance is lacking due to a gap in evidence. Empirical research into the care experiences and outcomes of autistic TGD individuals using a developmental, lifespan, and strengths-based approach is needed to generate evidence-informed and tailored guidance.

Funding: This study was funded through a Canadian Institutes of Health Research Sex and Gender Science Chair program (GSB 171373) awarded to M-CL.

This literature review discusses current health disparities in cancer care in the United Kingdom, spanning access to services, diagnosis, and outcomes. These inequities stem from a complex interplay of factors such as health literacy, ethnicity, socioeconomic status, age, gender, geography, and lifestyle choices. Health literacy plays a crucial role in timely healthcare seeking and diagnosis, while cultural beliefs significantly shape perceptions and behaviours. Socioeconomic barriers often result in delayed diagnosis and inferior outcomes due to limited access to preventive measures and high-quality treatment. Barriers to timely diagnosis include non-specific symptoms, variations in diagnostic intervals influenced by age and gender, and non-attendance at secondary care appointments. Addressing these challenges necessitates initiatives aimed at improving health literacy, implementing culturally sensitive screening approaches, and enhancing accessibility to both primary and secondary care services.

Background: Cardiovascular disease (CVD) is increasing in prevalence and affects up to 4% of pregnancies in otherwise healthy persons. The specific factors that drive the development of CVD in pregnant people are poorly characterised. This study aimed to determine whether the mode of delivery in singletons affects the risk of cardiovascular morbidity and mortality within one year in patients without prior CVD.

Methods: We designed a retrospective cohort study utilising the Nationwide Readmissions Database (NRD) to identify singleton delivery hospitalisations in the United States from Jan 1, 2010 to Nov 30, 2018. International Classification of Disease (ICD) versions 9 and 10 codes were used to identify patients with readmission for CVD within the calendar year of index delivery. Patients aged 15-54 who underwent a singleton vaginal or caesarean delivery were included. Patients with pre-existing CVD hospitalisations before or during delivery, ectopic pregnancies, or abortive outcomes were excluded. Participant data was retrieved from the NRD database. The primary outcome was hospital readmission, defined by ICD 9 and 10 codes for fatal or non-fatal CVD in the same calendar year as delivery. Cox proportional hazard regression models were used to adjust for confounders. These included maternal age, hospital bed size, hospital type, hospital teaching status, income quartile, insurance, and year of delivery. Additional sub-analyses were performed adjusting for hypertensive disorders of pregnancy and diabetes mellitus.

Findings: Of the 14,179,299 singleton deliveries, 32% (n = 4,553,492) underwent a caesarean. CVD readmissions occurred in 255.2 per 100,000 (n = 11,710) caesarean deliveries compared with 133.9 per 100,000 (n = 12,507) vaginal deliveries (rate difference [RD], 121.4, 95% confidence interval [CI], 114.8-127.9; hazard ratio [HR] adjusted for all confounders including hypertensive disorders of pregnancy and diabetes mellitus was 1.42, 95% CI 1.35-1.50). This association was highest in the first 0-29 days following delivery (HR 1.68, 95% CI 1.59-1.78). The risk of readmission for CVD persisted for one year.

Interpretation: These findings suggest that caesarean delivery of singletons is associated with a higher risk of cardiovascular morbidity in patients without pre-existing CVD. This risk was highest in the first month but remained elevated for one year after delivery. These findings add to the accumulating evidence that undergoing caesarean delivery may have long-standing health implications and support the extension of the post-partum surveillance period. Limitations of this study include the lack of adjustment for body mass index, race, and parity. We were also unable to determine the reason for the caesarean delivery.

Funding: None.

Neurodivergent (ND) individuals exhibit variations in communication, behaviors, and cognition, which present both opportunities and challenges in healthcare settings. Anesthesiologists can offer personalized and compassionate care to ND patients throughout the surgical process. Yet, often, there is limited knowledge of the specific actions that anesthesiologists can take to build a healthcare environment that fully recognizes and meets the unique needs of ND patients. This document highlights the importance of integrating tailored communication and supportive strategies throughout the distinct stages of perioperative and intraoperative care.

Background: Prospective data is limited on the efficacy and safety of consolidative stereotactic radiotherapy (SRT) in metastatic epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients harboring oligo-residual disease (ORD) after first-line third-generation EGFR-tyrosine kinase inhibitors (TKIs).

Methods: In this single-arm, phase II trial, 61 patients from two academic centers were enrolled from March 2021 to March 2023. All these patients had metastatic EGFR-mutant NSCLC and harbored ORD after first-line third-generation EGFR-TKIs. Consolidative SRT was performed and EGFR-TKIs were not held during SRT. The primary endpoint was progression-free survival (PFS) and the secondary endpoints included overall survival and treatment-related adverse events (TRAEs). A prespecified propensity score matched (PSM) comparison was conducted with a contemporary cohort of patients who developed ORD but received EGFR-TKIs alone. This trial was registered with ClinicalTrails.gov, NCT04764214.

Findings: All patients received consolidative SRT. With a median follow-up of 21.1 months, the median PFS was 29.9 (80% CI 22.4-32.4) months and the lower boundary exceeded the predefined threshold, meeting the primary endpoint. TRAEs occurred in 43 (70%) patients, with pneumonitis (27.9%) and esophagitis (26.2%) being the most common toxicities. Four patients (6.6%) reported grade ≥3 TRAEs, each for pneumonitis, esophagitis, leukopenia, and cranial radiation necrosis. PSM analysis showed significantly prolonged PFS in EGFR-TKI + SRT group compared to EGFR-TKI group (HR 0.46, 80% CI 0.20-0.61; p = 0.002).

Interpretation: Consolidative SRT is associated with an encouraging PFS in first-line third-generation EGFR-TKI-treated metastatic NSCLC patients harboring ORD, with generally acceptable toxicities. Further confirmatory studies are warranted.

Funding: Hui Lan Public Welfare and the Chinese Society of Clinical Oncology Foundation.

Background: The WHO projects a global shortage of 4.3 million physicians by 2030, with the largest deficits in developing and conflict-affected regions. Our aim is to train competent physicians rapidly and affordably through remote education programs.

Methods: We developed an online medical training curriculum with four levels, focusing on different aspects of human body systems using a competency-based, student-centered approach. This study evaluates the first three levels; level four (internship) is outside this scope. The 105 medical students from eight Afghan universities were randomly assigned to nine groups. The curriculum includes Entrustable Professional Activities (EPA) for the cardiovascular system: level 1 covers basic medical sciences, level 2 pathology and basic clinical skills, and level 3 full clinical competencies. EPAs were delivered asynchronously online via Lecturio, CyberPatient, and Zoom. The 30-day intervention included 4 h of weekly online classes for formative assessment, collaborative learning, and evaluation, supervised by medical faculty members. Virtual pre- and post-intervention evaluations used multiple-choice questions and objective structured clinical examination (OSCE). We also conducted a satisfaction survey and open interview forum. Data triangulation from observations, surveys, and interviews validated curriculum effectiveness. The benchmarking method assessed cost-effectiveness.

Findings: Pre- and post-intervention analysis showed a significant increase in clinical competencies and knowledge acquisition (P < 0.0001). The CyberPatient intervention improved clinical competency quality (P < 0.0001) and shortened decision-making time (P < 0.001). Cost analysis revealed that a virtual medical university would be 95% more cost-effective than traditional medical education.

Interpretation: Integrating virtual technology with modern curriculum concepts in pre-internship years can effectively address healthcare training gaps and enhance education quality for healthcare workers at a low cost.

Funding: Provided by CanHealth International. A UBC spin-off not-for-profit organization.

Background: Retinoblastoma is considered a lethal but curable malignancy often presenting in childhood. We investigated its global, regional, and national burden among infants and young children from 1990 to 2021.

Methods: We obtained data on retinoblastoma incidence, prevalence, mortality, and disability-adjusted life years (DALYs) from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021. Trends were analysed using joinpoint regression to calculate annual percentage changes. Spearman's rank correlation and locally estimated scatterplot smoothing regression were used to assess the relationship between retinoblastoma burden and sociodemographic index.

Findings: In 2021, the global incidence, prevalence, mortality, and DALYs of retinoblastoma were 0.82 (95% uncertainty interval [UI], 0.48-1.10), 7.46 (95% UI, 4.42-10.08), 0.37 (95% UI, 0.22-0.51), and 32.81 (95% UI, 19.9-45.21), respectively. From 1990 to 2021, the global incidence and prevalence rates of retinoblastoma increased, with average annual percentage changes (AAPCs) of 0.67 (95% confidence interval [CI], 0.49-0.85] and 0.68 (95% CI, 0.50-0.86), respectively. Conversely, those of related mortality and DALYs decreased, with AAPCs of -0.64 (95% CI, -0.79 to -0.49) and -0.63 (95% CI, -0.78 to -0.48), respectively. Children aged 2-4 years and those in low-income regions exhibited the highest burden. Negative correlations were found between sociodemographic index and retinoblastoma burden.

Interpretation: Advancements in retinoblastoma detection and treatment have increased its reported incidence and prevalence while reducing its mortality and DALYs. Nonetheless, substantial socioeconomic and geographic disparities persist. In low-income countries, the incidence has decreased, possibly reflecting challenges such as limited healthcare access and underreporting, necessitating targeted interventions and improved healthcare access.

Funding: National Key R&D Project of China (2020YFA0112701), Natural Science Foundation of Guangdong Province (2024A1515013058), and Science and Technology Program of Guangzhou, China (202206080005).

Background: Obesity drives metabolic disease development. Preventing weight gain during early adulthood could mitigate later-life chronic disease risk. Increased dietary fibre intake, leading to enhanced colonic microbial fermentation and short-chain fatty acid (SCFA) production, is associated with lower body weight. Despite national food policy recommendations to consume 30 g of dietary fibre daily, only 9% of adults achieve this target. Inulin-propionate ester (IPE) selectively increases the production of the SCFA propionate in the colon. In previous studies, IPE has prevented weight gain in middle-aged adults over 6 months, compared with the inulin control. IPE is a novel food ingredient that can be added to various commonly consumed foods with a potential health benefit. This 12-month study aimed to determine whether using IPE to increase colonic propionate prevents further weight gain in overweight younger adults.

Methods: This multi-centre randomised-controlled, double-blind trial was conducted in London and Glasgow, UK. Recruited participants were individuals at risk of weight gain, aged between 20 and 40 years and had an overweight body mass index. Sealed Envelope Software was used to randomise participants to consume 10 g of IPE or inulin (control), once per day for 12 months. The primary outcome was the weight gained from baseline to 12 months, analysed by an 'Intention to Treat' strategy. The safety profile and tolerability of IPE were monitored through adverse events and compliance. This study is registered with the International Standard Randomised Controlled Trials (ISRCT) Database (ISRCT number: 16299902).

Findings: Participants (n = 135 per study arm) were recruited from July 2019 to October 2021. At 12 months, there was no significant difference in baseline-adjusted mean weight gain for IPE compared with control (1.02 kg, 95% CI: -0.37 to 2.41; p = 0.15; n = 226). Neither the IPE (+1.22 kg) nor the control arm (+0.07 kg) unadjusted mean gains in body weight reached the expected 2 kg threshold. In the IPE arm, fat-free mass was greater by 1.07 kg (95% CI: 0.21-1.93), and blood glucose elevated by 0.11 mmol/L (95% CI: 0.01-0.21). Compliance, determined by intake of ≥50% sachets, was reached by 63% of IPE participants. There were no unexpected adverse events or safety concerns.

Interpretation: Our study indicates that at 12 months, IPE did not differentially affect weight gain, compared with the inulin control, in adults between 20 and 40 years of age, at risk of obesity.

Funding: NIHR EME Programme (15/185/16).

Background: Obesity represents a major global health challenge with important clinical implications. Despite its recognized importance, the global disease burden attributable to high body mass index (BMI) remains less well understood.

Methods: We systematically analyzed global deaths and disability-adjusted life years (DALYs) attributable to high BMI using the methodology and analytical approaches of the Global Burden of Disease Study (GBD) 2021. High BMI was defined as a BMI over 25 kg/m² for individuals aged ≥20 years. The Socio-Demographic Index (SDI) was used as a composite measure to assess the level of socio-economic development across different regions. Subgroup analyses considered age, sex, year, geographical location, and SDI.

Findings: From 1990 to 2021, the global deaths and DALYs attributable to high BMI increased more than 2.5-fold for females and males. However, the age-standardized death rates remained stable for females and increased by 15.0% for males. Similarly, the age-standardized DALY rates increased by 21.7% for females and 31.2% for males. In 2021, the six leading causes of high BMI-attributable DALYs were diabetes mellitus, ischemic heart disease, hypertensive heart disease, chronic kidney disease, low back pain and stroke. From 1990 to 2021, low-middle SDI countries exhibited the highest annual percentage changes in age-standardized DALY rates, whereas high SDI countries showed the lowest.

Interpretation: The worldwide health burden attributable to high BMI has grown significantly between 1990 and 2021. The increasing global rates of high BMI and the associated disease burden highlight the urgent need for regular surveillance and monitoring of BMI.

Funding: National Natural Science Foundation of China and National Key R&D Program of China.