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Association of ambient air pollution exposure with psychological distress in mid and later adulthood: A 26-year prospective cohort study
Get PDFBackground
Existing evidence on associations between exposure to air pollution and psychological distress from middle to older age is limited by consideration of short exposure periods, poor historical covariates, exposures and outcomes, and cross-sectional study designs. We aimed to examine this association over a 26-year period between ages 43 and 69.
Methods
We utilised data from the Medical Research Council National Survey of Health and Development Study (the 1946 British birth cohort). Land-use regression models estimated exposure to specific air pollutants using household addresses for 1991 (NO2), 2001 (PM10, NO2), and 2010 (NO2, NOx, PM10, PM2.5, PMcoarse, PM2.5abs). These were linked to the closest data collection wave at ages 43, 53 and 60-64, respectively. Psychological distress was assessed through the 28-item version of the General Health Questionnaire (GHQ-28), at ages 53, 60-64 and 69. Associations between each of the pollutants with psychological distress were analysed using generalised linear mixed models, adjusted for pollution exposure before age 43, assigned sex, social class, smoking status, neighbourhood deprivation, and previous mental health problems. We also examined effect modification by social class.
Results
At age 69, 2125 participants completed the GHQ-28. In fully adjusted models, higher NO2 exposure was associated with higher GHQ-28 scores across a 26-year period (β=0.023, 95%CI:0.005, 0.040 per interquartile range increase in exposure), whereas higher exposure to PM10 was associated with lower GHQ-28 scores across a 16-year period (β=-0.021, 95%CI:-0.037, -0.006). There was no evidence of associations between exposure to other pollutants at age 60-64 and GHQ-28 at age 69. We found no effect modification by social class.
Conclusions
In this cohort there was some evidence of an association between higher cumulative exposure to NO2 and higher psychological distress, but mixed associations with other exposures. Policies to reduce pollutant exposure may help improve psychological symptoms in middle to late adulthood
Perspectives on the use and availability of Chimeric Antigen Receptor T Cells (CAR-T) and Cell Therapies: A worldwide cross-sectional survey by the Worldwide Network for Blood and Marrow Transplantation (WBMT)
Get PDFChimeric antigen receptor T cell therapy (CAR-T) cells represent a new generation of autologous, allogeneic and personalised cell-based therapies that have revolutionised the treatment of B cell haematological malignancies. Despite their significant effectiveness in treating challenging relapsed and refractory diseases, access to this cutting-edge treatment remains a critical issue globally, even in high income countries. To gain insights into these challenges, the Worldwide Network for Blood & Marrow Transplantation (WBMT) initiated a survey focused on the state of CAR-T and cellular therapy availability worldwide. The survey aimed to identify the accessibility, manufacturing capabilities, apheresis, accreditation, reimbursement, presence of regulatory frameworks and legal oversight of these cell-based therapies.
The survey included questions on demographics, the respondent's centre, CAR-T availability, details about haematopoietic stem cell transplant programs, supply and indications for CAR-T, quality assurance, and information about other cell and gene therapy products beside CAR-T. Conducted online over three months in 2023, the survey garnered 181 complete responses from various geographical regions, from North America, Asia, Europe, South and Central America, Australia and New Zealand, and Africa.
Our findings suggested a promising level of awareness and interest in CAR-T therapy globally, even in lower-income regions. However, survey respondents cited cost as the primary barrier to access, alongside infrastructure and governmental support issues. The survey also highlighted the varying reimbursement strategies across regions, with costs in Europe and North America being relatively similar while Asia showed more variability. There was also variability in the regulatory and accreditation frameworks associated with delivery of these novel therapies
As CAR-T therapy continues to grow, innovative solutions such as global partnerships, in-house production, and the establishment of cellular therapy centres in developing countries are essential. Addressing the challenges of access requires a comprehensive approach that combines efforts to lower costs, enhance healthcare infrastructure, and foster international collaborations, ensuring that CAR-T therapy becomes available to all who need it
Disparities in the care and direct-acting oral anticoagulant (DOAC) management in atrial fibrillation (AF) and chronic kidney disease (CKD) in English primary care between 2018 and 2022: primary care sentinel network database study
Get PDFBackground
In England, most prescribing of direct-acting oral anticoagulants (DOACs) for patients with chronic kidney disease (CKD) and atrial fibrillation (AF) takes place in primary care. The 2024 European Society of Cardiology guidelines introduced the AF-CARE ((C) comorbidities and risk factors; (A) avoid stroke and thromboembolism by appropriate prescription of oral anticoagulants; (R) rate and rhythm control; (E) evaluation and reassessment should be individualised for every patient, with a dynamic approach) framework to address this.
Objective
To describe any health disparities in CKD and AF, including anticoagulation management and correct dosing of DOACs.
Methods
Using English primary care sentinel network data from 2018 to 2022, demographics of AF and CKD including anticoagulation and appropriate DOAC dosing according to creatinine clearance and other factors were assessed. The study also examined disparities in CKD and AF in relation to socioeconomic status and ethnicity. We defined socioeconomic status by Index of Multiple Deprivation (IMD), a weighted composite index combining information from the domains of deprivation including income.
Results
Of 10 513 950 people registered with general practices in the sentinel network, 2.9% (n=304 678) were aged ≥18 years with a diagnosis of AF. The prevalence of CKD in AF was 26.0% (n=79 210) and 63.3% of people eligible for anticoagulation were prescribed a DOAC. Among the 54 897 people with AF and CKD 3 or 4, greater likelihood of DOAC prescribing was associated with higher socioeconomic status. Socioeconomic disparities in anticoagulation increased through the 5 years. No association was identified between ethnicity and likelihood of being anticoagulated.
In terms of correct dosing, there was no association with socioeconomic status. Overdosing was more frequent than underdosing. Incorrect dosing was associated with male sex (OR 0.80 (95% CI 0.74, 0.86)), dementia (OR 0.94 (0.83, 1.07)) and frailty (OR 0.42 (0.37, 0.48)).
Conclusions
People in the most deprived IMD quintile were least likely to be anticoagulated. Incorrect DOAC dosing was associated with male sex, increasing frailty and dementia. Socioeconomic and health disparities are apparent in anticoagulation prescribing and should be addressed in line with the AF-CARE framework
Migraine and functional neurological disorder (FND)—a review of comorbidity and potential overlap
Get PDFMigraine and functional neurological disorder (FND) are two of the most common conditions in neurological practice. It is assumed that the two conditions have distinct underlying mechanisms. However, it can be clinically challenging to disentangle their relative contributions to a patient's symptoms. In addition, apart from the relationship between persistent postural perceptual dizziness (PPPD) and migraine, the frequency of co-occurrence has not been characterized in detail. Contemporary conceptualizations of FND have driven a re-evaluation of its relationship to other neurological disorders, including migraine. We carried out a narrative review of the literature examining the co-occurrence of migraine and FND. We also explored their comorbidities, aetiological risk factors and mechanisms, focusing especially on areas of potential overlap.
Our review suggests increased frequency of migraine in people with functional seizures compared to epilepsy, but data from people with functional motor symptoms is mixed. Robust epidemiological studies evaluating the frequency of FND in migraine are lacking. Similar to other neurological disorders, migraine is an established trigger of FND. Female gender, adverse childhood experiences and comorbid psychiatric and functional disorders, such as irritable bowel syndrome and fibromyalgia, are more common in both conditions than in controls, but perhaps more so in FND. Mechanistic research in both conditions highlights converging frameworks of dysregulated allostatic/stress responses in the context of predictive processing models of the brain. This has implications for pharmaceutical and rehabilitation treatments.
The relationship between migraine and FND is poorly studied. An overview of their overlap offers a model of non-dualistic thinking within a clinical neuroscience framework for future studies
Glucagon-Like Peptide (GLP-1) Receptor Agonists in Inflammatory Bowel Disease: Mechanisms, Clinical Implications, and Therapeutic Potential
No full textGlucagon-like peptide-1 receptor agonists are increasingly recognised for their potential dual benefit in inflammatory bowel disease, offering metabolic advantages alongside emerging anti-inflammatory, immunomodulatory, and gut barrier-enhancing effects. Pre-clinical data demonstrate attenuation of inflammation, preservation of epithelial integrity, and modulation of the microbiome in colitis models. Early retrospective studies in patients with inflammatory bowel disease suggest improved clinical outcomes, such as reduced hospitalisation and surgery rates, particularly in those with obesity. Glucagon-like peptide-1 receptor agonists are already widely used for obesity and diabetes, including increasing self-administration by patients outside medical supervision. Their impact on drug absorption, safety in gastrointestinal disease, and interactions with existing inflammatory bowel disease therapies require further exploration. This review synthesises the mechanistic rationale, pre-clinical evidence, and clinical data to date, highlighting the potential utility and safety considerations of glucagon-like peptide-1 receptor agonists in inflammatory bowel disease and emphasises the need for robust prospective trials to ascertain their safety and efficacy in this patient population
Interdisciplinary recommendations for recurrent hyperkalaemia: insights from the GUARDIAN-HK European Steering Committee
Get PDFRecurrent hyperkalaemia (HK) is associated with increased morbidity and mortality, and is common among patients with cardiorenal disease. Many of these patients require renin–angiotensin–aldosterone system inhibitor (RAASi) therapies that further enhance the risk of HK. Every acute HK episode constitutes an opportunity to treat and prevent recurrent HK. This report aims to support multidisciplinary team efforts in managing patients who may be affected by recurrent HK. A panel of nine European experts in the management of HK (four nephrologists, four cardiologists, one internist) reviewed existing guidance and evidence on the diagnosis and management of HK at a face-to-face (26th September 2023) and two virtual meetings (24th January and 14th March 2024). The panel developed 10 consensus recommendations and a management algorithm across three domains: duty of care, identifying patients at risk of HK recurrence and managing the risk of HK recurrence. Early identification and management of those at risk of recurrent HK will improve clinical outcomes but requires an interdisciplinary, co-ordinated approach. Disease-modifying therapies such as RAASi should no longer be considered reversible causes of HK, and efforts should be taken to up-titrate these to guideline-directed target doses even in the setting of an acute HK event. Every acute HK episode constitutes an opportunity to treat and prevent recurrent HK, contributing to long-term clinical benefits. The recommendations, intentionally broad in scope, complement existing management guidelines and plans, fostering a collective responsibility among healthcare professionals managing patients with HK
Impact of hypertensive disorders on disease progression in pregnancies affected by early‐onset fetal growth restriction
Get PDFIntroduction
Fetal growth restriction is a leading cause of perinatal morbidity, often linked to placental insufficiency. Hypertensive disorders frequently coexist with fetal growth restriction and may alter its clinical course. The objective of this study is to examine how hypertensive disorders influence the onset, progression, and timing of birth in pregnancies affected by fetal growth restriction. Secondary outcomes were indications for delivery and neonatal outcomes.
Material and Methods
A retrospective cohort study of pregnancies diagnosed with fetal growth restriction prior to 36 weeks' gestation and monitored under the TRUFFLE protocol between January 2013 and July 2024 at a tertiary fetal medicine unit in the UK. Pregnancies were stratified by maternal blood pressure status: normotensive, hypertensive disorder of pregnancy, or preexisting chronic hypertension. Clinical characteristics, antenatal surveillance findings, delivery indications, and neonatal outcomes were compared between groups.
Results
One hundred and ninety‐six singleton pregnancies met the inclusion criteria. 68% of the cohort were affected by chronic hypertension or new‐onset hypertensive disorders of pregnancy. Hypertensive pregnancies had significantly shorter intervals from fetal growth restriction diagnosis to delivery (9 days (IQR 5–19) for chronic hypertension, 12 days (IQR 3–24) for hypertensive disorders of pregnancy, 23 days (IQR 8–35) in normotensive pregnancies (p = 0.001)) and earlier gestational age at delivery (29 + 5 weeks (IQR 27 + 3–32 + 3) for chronic hypertension and 30 + 5 weeks (IQR 28 + 4–32 + 6) for hypertensive disorders of pregnancy — versus 32 + 0 weeks (IQR 29 + 1–33 + 6) in normotensive cases; p = 0.023). A higher proportion of hypertensive pregnancies were delivered for maternal indications (37.5% hypertensive disorders of pregnancy, 39.5% chronic hypertension) compared to 14.5% in normotensive pregnancies (p = 0.004), while normotensive pregnancies were more frequently delivered due to abnormal umbilical artery Dopplers (29.0% vs. 14.6% hypertensive disorders of pregnancy, 13.2% chronic hypertension; p = 0.041). Neonates of mothers with chronic hypertension had higher birthweight centiles (p = 0.004), but neonatal outcomes were comparable across all groups.
Conclusions
Incidence of hypertension in the context of fetal growth restriction significantly impacts timing and gestational age of delivery and birthweight centile. An integrated approach to combine maternal and fetal monitoring in these pregnancies is required to optimize birth outcomes
Subclinical Postpartum Renal Structure After Hypertensive Pregnancy Disorders
Get PDFBACKGROUND:
Hypertensive pregnancies are associated with increased risks of renal failure in pregnancy and later life. However, traditional markers of renal function normalize postpartum, making identification of those at future disease risk difficult. We studied whether the type and severity of hypertensive pregnancy associated with postpartum renal structure.
METHODS:
One hundred twenty-five women from interventional trials (61 preeclamptic, 33 gestational hypertension, and 31 normotensive pregnancy), aged ≥18 years, were imaged using magnetic resonance imaging 6 to 12 months postpartum. Anthropometric, demographic, blood pressure, and blood sample data were collected during pregnancy and postpartum. Kidney volume indexed to body surface area and corticomedullary differentiation were compared between groups using a 1-way ANCOVA, whereas associations with other outcomes were assessed using correlation tests.
RESULTS:
Postpartum total kidney volume indexed to body surface area was smaller in women who had preeclampsia compared with those who had gestational hypertension or a normotensive pregnancy (P=0.049). Total kidney volume postpartum correlated with estimated glomerular filtration rate at delivery (P<0.001). However, smaller volumes were not explained by reduced corticomedullary differentiation, which only differed in women with gestational hypertension compared with preeclamptic (P=0.02) and normotensive women (P=0.007). There were no associations between renal measures and blood pressure during or after pregnancy.
CONCLUSIONS:
At 6 to 12 months postpartum, preeclamptic women have smaller kidney volumes than women with gestational hypertension or normotensive pregnancies. These smaller volumes relate to lower renal function at delivery but not corticomedullary differentiation, which only differed in women with gestational hypertension.
REGISTRATION:
URL: https://www.clinicaltrials.gov; Unique identifiers: NCT04273854 and NCT05434195
Kinetics of early peanut allergy development and resolution in the EAT, LEAP, and PAS cohorts
Get PDFBACKGROUND: Little is known about the development and resolution of early peanut allergy (PA). OBJECTIVE: We examined the natural history and biomarkers of PA longitudinally in 3 cohorts. METHODS: PA development was examined in the Enquiring About Tolerance (EAT), Learning Early About Peanut (LEAP), and Peanut Allergy Sensitization (PAS) cohorts. Early PA was defined by skin prick test result of >4 mm by 12 months or oral food challenge at study entry. PA was confirmed by oral food challenge at study end point (36 months for EAT, 60 months for LEAP/PAS). Four groups were defined: early PA development with persistence (EP); early PA development with resolution (ER); late PA development (LA); and never peanut allergic. Clinical characteristics and biomarkers were compared between the groups. RESULTS: A total of 56.3% of peanut-allergic children developed PA by 12 months; 32.1% had early PA resolution by study end point. The rate of early PA resolution was 54.2% in EAT, 41.4% in LEAP, and 18.6% in PAS cohorts. Median skin prick test wheals for EP, ER, and LA were 6, 2, and 0 mm at baseline, and 10, 0, 9 mm at study end point. Median peanut-specific IgE (sIgE) levels for EP, ER, and LA were 5.9, 0.4, and 0.3 kUA/L (P 0.1 kUA/L) compared to EP. ER showed component expansion from baseline to 12 months but component retraction by study end point. Absence of eczema and egg allergy, low peanut-sIgE, or skin prick test result were predictive of PA resolution. CONCLUSION: A significant proportion of PA resolves in early childhood. Different phenotypes of PA display different biomarkers trajectories
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