EClinicalMedicine最新文献

Background: Lower socioeconomic position (SEP) is a risk factor for poor-quality end-of-life cancer care, but mechanisms of this disparity are not fully understood. We investigated whether receipt of specialised palliative care (SPC) mediates the effect of SEP on end-of-life cancer care quality outcomes.

Methods: This cohort study included all adults who died with cancer from 2015 to 2021, in Ontario, Canada. We performed a mediation analysis using material deprivation as a measure of SEP, classified into quintiles from least (Q1) to most deprived (Q5). End-of-life outcomes included receipt of systemic anticancer treatment (SACT) and high health services use (≥2 emergency department visits, ≥2 hospitalisations, ≥1 intensive care unit admission) in the last 30 days of life, and home death. Generalised linear models estimated the adjusted odds ratio (aOR) for each outcome, and direct effect of SEP, and the indirect effect via SPC, across each quintile (Q1 = reference).

Findings: Among 173,915 patients, SPC mediated the effects of SEP on end-of-life outcomes. Compared to Q1, patients in Q2-Q5 were progressively less likely to receive SACT at end-of-life (aOR [95% CI], Q3: 0.89 [0.84-0.93]; Q5: 0.77 [0.74-0.81]), or to die at home (Q3: 0.90 [0.87-0.93]; Q5: 0.78 [0.76-0.81]); lack of SPC partially mediated these effects, blunting the effect on SACT and augmenting the effect on home deaths. Compared to Q1, patients in Q2 to 5 were more likely to experience high health services use (Q3: 1.06 [1.02-1.10]; Q5: 1.12 [1.08-1.16]); lack of SPC fully mediated this effect, driven by increasing likelihood of multiple emergency department visits in more deprived quintiles.

Interpretation: Receipt of SPC mediated the effects of SEP on end-of-life quality outcomes. Equitable access to SPC for all patients with cancer may mitigate these disparities.

Funding: This study was supported by an Operating Grant from the Canadian Institutes of Health Research (Dr. Zimmermann), the Harold and Shirley Lederman Chair in Palliative Care and Psychosocial Oncology (Grant number MM1-174912; Dr. Zimmermann), a Doctoral Research Award: Canada Graduate Scholarship (Grant number FBD-181354; Dr. Iqbal) from the Canadian Institutes of Health Research (CIHR), and a Peterborough KM Hunter Charitable Foundation Graduate Award in Cancer Research (Dr. Iqbal).

Background: Incentive-based intervention has been widely implemented for HIV prevention and care, necessitating an urgent evidence-based synthesis of the extensive new evidence.

Methods: We conducted a global systematic review and meta-analysis (PROSPERO: CRD42022368634) of randomised controlled trials (RCTs) identified through MEDLINE, Web of Science, and Google Scholar, Embase, Scopus, and region-specific databases (inception to Sep 10, 2024). Two reviewers independently selected studies using the Covidence online tool. Eligible studies with money-type, non-money type, and lottery type of incentives reporting outcomes along HIV prevention and care continuum were included. Cochrane Risk-of -Bias Tool (ROB) and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach were used to assess risk of bias and evidence grading. We pooled risk ratio (RR) using random-effects model versus standard care.

Findings: We included 62 RCTs with 118,432 participants from 16 countries, over half of which were published in the recent five years. Compared to standard care, incentive-based intervention was associated with improvements from a 1.8 times increase in HIV testing uptakes (15 studies, 82,327 participants, RR 1.83 [95% CI: 1.31-2.54], I² = 99%) to a 1.25 times increase in viral suppression (14 studies, 14,341 participants, RR 1.25 [1.14-1.38], I² = 75%). When limited to monetary-type incentives, it is associated with 2.13 times of HIV testing uptakes (nine studies, 17,320 participants, [95% CI: 1.36-3.33], I² = 98%). When limited to studies with 2-3 months implementation, it is associated with 2.82 times of HIV testing uptakes (four studies, 25,167 participants, [95% CI: 1.10-7.21], I² = 98%) The effect of incentives varied across countries with different income levels, but consistent across different sexes. There were negative effects found in studies with outcomes of reducing HIV incidence, STI prevalence, and mortality.

Interpretation: Incentive-based interventions are associated with improved outcomes across the HIV prevention and care continuum, with inconsistency between incentive types, implementation duration, income-levels of countries. The results of its implementation, including outcomes and sustainability, are required to maximize its effectiveness in practice.

Funding: National Natural Science Foundation of China and Guangdong Province (Grant No. 82304201 and 2024A1515012123).

Background: Previous trials have indicated the potential of arbaclofen for improving social difficulties among autistic children and adolescents with fluent speech. AIMS-2-TRIALS-Clinical Trial 1 (AIMS-2-CT1) examined whether arbaclofen is superior to placebo in improving social function and other secondary outcomes, along with safety and tolerability profiles.

Methods: AIMS-2-CT1 is a multi-site, placebo-controlled double-blind, parallel group Phase II randomized clinical trial. Recruitment was conducted in 7 sites in Spain, United Kingdom and France between September 2019 and September 2022. Eligible participants were randomized 1:1, stratified by age and site, for a 16-week treatment period. Age of participants ranged from 5 to 17 years of age. Primary outcome: Socialization domain of the Vineland Adaptive Behavior Scales change. Secondary outcome measures: CGI-S (Clinical Global Impression-Severity), CGI-I (Clinical Global Impression-Improvement), Social Responsiveness Scale (SRS-2), Autism Impact Measure (AIM), behavioral measurements (CBCL, ABC-C) and Quality of Life (PedsQL). Safety and tolerability were assessed via several instruments. Clinical trial registration: EudraCT number: 2018-000942-21 and ClinicalTrials.gov registry number: NCT03682978. Last protocol v.9.1, dated June 18th, 2022.

Findings: 122 participants (out of 123 randomized) comprised the Intention-to-treat sample (59/63 arbaclofen/placebo); 85%/95% of participants on arbaclofen/placebo completed the study.Improvements in the primary endpoint and pre-specified key secondary outcomes did not achieve statistical significance [effect size 1.30 (95% CI: -2.6, 5.1)]. Results on all secondary endpoints favored arbaclofen, with significant improvements on many secondary outcomes including the SRS, the AIM Total scores, some subscales of the ABC, and QoL measures. One Serious Adverse Event (psychotic symptoms) was reported on placebo. Sleep-related problems were more frequent on arbaclofen (N = 34, 57.6% in participants on arbaclofen and N = 22, 34.9% in participants on placebo).

Interpretation: Although we found no significant effect on the primary outcome, improvements were apparent on several secondary measures of autistic related behaviors as well as quality of life. Arbaclofen shows promise in addressing some autistic difficulties and in improving quality of life, but larger scale trials are needed to further advance our understanding of its potential and to inform future drug development in autism.

Funding: Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777394.

[This corrects the article DOI: 10.1016/j.eclinm.2025.103682.].

Background: Limited knowledge exists on the impact of prenatal exposure to maternal cancer (treatment) on child motor development. We aimed to assess motor outcomes in toddlers and explore potential associations with perinatal and treatment-related factors.

Methods: This national cohort study reports a cross-sectional analysis of children prenatally exposed to maternal cancer who completed the planned 18-month motor assessment at the national Cancer in Pregnancy offspring outpatient clinic (2018-2024), Princess Máxima Center for Pediatric Oncology. Motor development was assessed using the Bayley Scales of Infant and Toddler Development (BSID-III-NL), with outcomes expressed as Z-scores compared with Dutch norms (delay defined as Z < -1). Multivariable linear regression examined associations between predefined prenatal exposures (gestational age at birth, birthweight, timing of maternal treatment, chemotherapy, systemic therapy) and postnatal family burden with motor outcomes. This study is registered with ClinicalTrials.gov, NCT00330447.

Findings: Of 102 eligible children, 96 (94.2%) were included (mean age 19.8 months; mean gestational age 36.8 weeks). Mean Z-scores were -0.38 (95% CI: -0.56, -0.20) for gross motor and 0.09 (95% CI: -0.08, 0.25) for fine motor development. Delayed gross motor development was observed in 32 children (33%), and delayed fine motor development in 16 children (17%). Regression analyses showed no significant associations between gross motor development and the studied prenatal or postnatal factors. Fine motor scores were lower in children with lower gestational age at birth (β = 0.085; 95% CI: 0.011, 0.159) and higher postnatal family burden (β = -0.736; 95% CI: -1.211, -0.261).

Interpretation: At 19 months, one in three children exposed to maternal cancer during pregnancy demonstrated delayed gross motor development. Mean gross motor scores were significantly lower compared with the BSID-III-NL normative population, whereas fine motor development did not differ from reference values. Neither gross nor fine motor development was associated with prenatal exposure to chemotherapy or systemic therapy. Fine motor outcomes were associated with gestational age and postnatal family burden. These findings highlight the need for structured motor surveillance in this population.

Funding: KWF Kankerbestrijding (KWF) grant number 13192.

Background: One major challenge in the implementation of household contact investigation (HCI) for tuberculosis (TB) in high burden settings is finding contact persons in the home for screening. Conducting HCI during evenings, weekends, or holidays, particularly in settings with high levels of poverty, may improve effectiveness and implementation.

Methods: We conducted a pragmatic, individually randomized controlled trial of HCI for TB at two sites in South Africa, comparing the effectiveness of two novel strategies for timing (during evenings and weekends in an urban area and during three annual holiday periods in a rural area) to weekday working hours. The primary outcome was the number of secondary cases identified and started on TB treatment per index participant, comparing novel versus standard timing at each site. Clinicaltrials.gov registration: NCT04520113.

Findings: From September 2020 to August 2023, we randomized 1335 index participants with TB in Limpopo to receive standard HCI and 666 to receive holiday = based HCI, and 1616 to receive standard HCI and 805 to receive evening/weekend HCI in Soshanguve. In Limpopo, standard HCI and holidy-based HCI and resulted in 0.6 and 0.7 secondary TB diagnoses started on treatment per 100 index participants, respectively (difference: 0.1 [95% CI: -0.7, 0.8, p = 0.84]). In Soshanguve, evening/weekend-based HCI and standard HCI generated 0.4 and 0.6 diagnoses started on TB treatment per 100 index participants, respectively (difference 0.3 [95% CI: -0.8, 0.4, p = 0.54]).

Interpretation: HCI conducted either during evenings/weekends or during holiday did not increase effectiveness compared to HCI conducted during weekday working hours.

Funding: Funding was provided by the United States National Institute of Allergy and Infectious Diseases (Grant # 5R01AI147681).

Background: Individuals with type 2 diabetes mellitus are treated with a growing variety of medications targeting multiple metabolic pathways. In recent years, incretins such as the GLP-1 receptor agonists have proven effective in the control of hyperglycemia but also in weight loss, where they are now separately approved as a treatment for obesity. Given the importance of obesity and metabolic syndrome as risk factors for malignancy, the impact of GLP-1 receptor agonists on cancer risk is of increasing interest. Here, we performed an analysis of the impact of GLP-1 receptor agonists and SGLT2 inhibitors on cancer risk and mortality.

Methods: We performed a multicenter retrospective cohort study using the TriNetX database of electronic health records between 2019 and 2024, including patients with a diagnosis of type 2 diabetes mellitus. Individuals prescribed GLP-1 receptor agonists, SGLT2 inhibitors, or neither were compared for the incidence of four obesity-related hematologic malignancies using a Cox proportional hazards model. Similar analysis was applied to mortality associated with these medication classes in individuals with type 2 diabetes mellitus and the hematologic malignancies under study.

Findings: GLP-1 receptor agonist use is associated with a significantly decreased risk of multiple myeloma (HR 0.64, p = 0.01), but not chronic myeloid leukemia (HR 1.06, p = 0.857), acute myeloid leukemia (HR 0.81, p = 0.354), or myelodysplastic syndrome (HR 0.98, p = 0.996). This effect was preserved in subgroups with BMI >30 and HbA1c >8%. Further, we find that in patients with multiple myeloma and acute myeloid leukemia, SGLT2 inhibitor use is associated with a significantly increased risk of mortality, independent of heart or kidney failure (MM HR 2.27, p < 0.001, AML HR 2.00, p = 0.006).

Interpretation: Our results strengthen the association between metabolic disease and multiple myeloma yet call for prospective investigation into the use of SGTL2 inhibitors in patients with specific hematologic neoplasms.

Funding: National Institutes of Health.