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Doxycycline Use in Adolescent Psychiatric Patients and Risk of Schizophrenia:An Emulated Target Trial
No full textOBJECTIVE: As many as half of individuals who develop psychosis had attended child and adolescent psychiatric services at some stage in childhood, highlighting substantial opportunities for prevention within these services if an effective preventive intervention were identified. The authors hypothesized that adolescent psychiatric patients exposed to doxycycline, an antibiotic with putative neuroprotective properties, would have a lower risk of developing schizophrenia.METHODS: This was an emulated target trial using nationwide Finnish health register data on all individuals born between 1987 and 1997 who attended adolescent psychiatric services between ages 13 and 18 and had used any antibiotics. Individuals were followed from first dispensed antibiotic prescription up to age 30. The main outcome was recorded schizophrenia diagnosis. The g-formula was used to estimate schizophrenia risk across doxycycline exposure levels (cumulative dose doxycycline use: no doxycycline use; low use, <1,499 mg; medium use, 1,500-2,999 mg; high use, ≥3,000 mg) during different follow-up periods.RESULTS: A total of 56,395 individuals had attended adolescent psychiatric services and had used antibiotics; of these, 16,189 (28.7%) had used doxycycline. The risk of schizophrenia after 10 years of follow-up was 2.1% (95% CI=1.9, 2.3) for individuals who had used non-doxycycline antibiotics. In comparison, the risk of schizophrenia at 10 years was significantly lower in adolescent psychiatric patients treated with doxycycline (low cumulative dose: 1.4%, risk ratio=0.70, 95% CI=0.48, 0.85; medium cumulative dose: 1.4%, risk ratio=0.65, 95% CI=0.25, 1.04; high cumulative dose: 1.5%, risk ratio=0.70, 95% CI=0.43, 0.97).CONCLUSIONS: These findings raise the tentative but exciting possibility that doxycycline treatment may reduce schizophrenia risk in adolescent psychiatric patients.</p
The personal roles dimension of the theory of work and personal role reconciliation:A constructivist grounded theory study
No full textBackground: Although the theory of work and personal role reconciliation has been recently published, the personal roles dimension has not yet been explored in depth. This article aims to describe its theorization.Methods: Constructivist grounded theory was employed to conceptualize the phenomenon of interest from the perspectives of nurses, their families, and administrative staff. Data were derived from 202 h of non-participant observation in two high-complexity hospitals in Chile (one public and one private), 57 institutional documents, and 51 in-depth interviews. Data analysis followed the constant comparative method and multilevel coding. To ensure methodological rigor, the study adhered to the 13 criteria for constructivist grounded theory research proposed by Charmaz and Thornberg and was approved by a Scientific Ethics Committee.Results: Personal roles are defined as the set of behaviors associated with the personal context of intensive care unit nurses, which are shaped by eight sources of interaction: (1) Family dimension; (2) Extended family; (3) Community groups; (4) Recreation spaces; (5) Religious institutions; (6) Health care institutions; (7) Educational institutions; and (8) Other public services.Conclusion: The study presents the theorization process of the personal dimension involved in the reconciliation of work and personal roles among nurses in Intensive Care Units. Personal roles are essential to understanding this reconciliation process. The findings provide evidence of the existence of eight sources of interaction, which are influenced by the cultural context
Small Interfering RNA Therapy Targeting the Long Noncoding RNA SMILR for Therapeutic Intervention in Coronary Artery Bypass Graft Failure
Get PDFCoronary artery bypass graft (CABG) surgery remains the gold standard of care to prevent myocardial ischemia in patients with advanced atherosclerosis; however, poor long-term graft patency remains a considerable and long-standing problem. Excessive vascular smooth muscle cell (SMC) proliferation in the grafted tissue is recognized as central to late CABG failure. We previously identified SMILR, a human-specific SMC-enriched long noncoding RNA that drives SMC proliferation, suggesting that targeting SMILR expression could be a novel way to prevent neointima formation, and thus CABG failure. Here, we sought to identify a lead siRNA for clinical development. We describe the design and synthesis of a library of 76 chemically enhanced SMILR-targeting siRNA. From this library, we identify a lead siRNA, BHF7, which demonstrates potent and reproducible silencing of SMILR expression, and which robustly blocks vascular smooth muscle cell proliferation, both in vitro and in the ex vivo human saphenous vein model. We further demonstrate using RNA-sequencing that BHF7 down-regulates the expression of genes associated with proliferation and does not induce the expression of interferon or apoptosis genes, suggesting it has a favorable safety profile, both on- and off-target. Finally, we performed TUNEL staining on BHF7-treated tissues and measured the levels of cleaved caspase-3 by enzyme-linked immunosorbent assay after BHF7 treatment. This demonstrated that BHF7 does not induce a cytotoxic response either in vitro or ex vivo. Collectively, these data represent a preclinical package into the function and specificity of BHF7 which warrants further investigation into the possibility of utilizing BHF7 as a novel, ex vivo RNA therapeutic for the prevention of CABG failure in humans
Rationale and design of the REMBRANDT trial: A phase 3 study to evaluate the effect of obicetrapib/ezetimibe on coronary plaque characteristics
Get PDFBackgroundObicetrapib is a potent, selective cholesteryl ester transfer protein (CETP) inhibitor that significantly lowers low-density lipoprotein cholesterol (LDL-C). Additive reductions in LDL-C occur when obicetrapib is combined with ezetimibe. The impact of obicetrapib and ezetimibe fixed-dose combination (FDC) on coronary plaque burden is unknown. Favorable changes in noncalcified coronary atherosclerotic plaque volume (NCPV) may indicate a potential beneficial effect on atherosclerotic cardiovascular disease (ASCVD) events.MethodsREMBRANDT is a placebo-controlled, double-blind, randomized trial designed to assess the efficacy of obicetrapib and ezetimibe FDC on coronary plaque burden. Individuals aged 45 years or older with ASCVD (imaging evidence of vascular disease or clinically manifested ASCVD) and an LDL-C of ≥70 mg/dL despite maximally tolerated lipid-modifying therapy are eligible to participate. Eligible participants (N = 300) will be randomized in a 1:1 ratio to obicetrapib 10 mg and ezetimibe 10 mg FDC once daily or placebo tablet once daily. The primary efficacy outcome of REMBRANDT is percent change in total NCPV from baseline to 18 months as assessed by coronary computed tomographic angiography (CCTA). Secondary endpoints include absolute change in total NCPV, percent and absolute change in NCPV in the most diseased coronary segment, percent change in LDL-C, and change in perivascular fat attenuation index from baseline to 18 months.ConclusionThe REMBRANDT trial will determine whether the favorable effects of obicetrapib and ezetimibe FDC on LDL-C translate to a reduction in coronary plaque burden as a potential mechanism for ASCVD risk reduction.Clinical trial registrationNCT06305559
A global effort toward standards for data sharing in biomedical imaging:Developing Consensus and Infrastructure for Global Data Interoperability
Get PDFThe life and death of old-age social security in late-colonial Kenya
Get PDFThe last decade of colonial rule in Kenya witnessed a widespread debate about social security for African workers. The government sought to create a stable, permanent workforce, while workers wanted secure and improved conditions. Old-age security was central to these discussions, deemed necessary for the transition from the traditional security of rural land-owning to a ‘detribalised’ existence. This paper revisits the largely forgotten 1954–5 Social Security Committee, a key moment in the history of social welfare in East Africa. Formed at the intersection of colonial labour policy, humanitarian impulses, and African trade union activism, the Committee represented a rare instance of African participation in colonial social policymaking. Its deliberations on different models of social security – pensions versus provident funds, contributory versus non-contributory models, and inclusion of women, domestic workers, and peasants – exposed competing visions of race, labour, and welfare. The Committee’s recommendation for a comprehensive pension scheme echoed principles of universal social rights and risk pooling associated with the British postwar welfare state. Fiscal caution and intra-official tensions ensured it was not implemented. Kenya was left with a limited, contributory scheme that continues to frustrate many. This lost model illuminates both the ambitions and constraints shaping postcolonial welfare trajectories.<br/
Public opinion on policy interventions for regulating four unhealthy commodity industries:A cross-sectional online survey of a representative sample of British adults 2023
Get PDFBackgroundTobacco, alcohol, unhealthy food and drink, and gambling are all unhealthy commodity industries which have profound public health consequences. The tactics of these industries intending to undermine policies and scientific evidence are often similar. To counter this, greater coherence in regulatory response is needed within, and across, policy spheres. Understanding public opinion is key in this context.ObjectivesThis study assessed public support for policies targeting unhealthy commodities and factors associated with support, including sociodemographic features, current smoking, excess alcohol consumption, obesity and daily gambling.DesignAcross-sectional design, where anonymous data was drawn from the annually commissioned Action on Smoking and Health Smokefree British survey conducted online between 22nd February and 15th March 2023.Participants12,271 British adults, invited to participate from the online YouGov panel. Weighted by sociodemographic characteristics to be representative of British adults.Outcome measuresPercentage support for policies to reduce harm from unhealthy commodities; and associations between the level of support, sociodemographic features, and exposure to unhealthy commodities.AnalysisMissing data were imputed using multiple imputations and data were weighted to match the British population. The degree of public support for policies were descriptively assessed and associations between this support, sociodemographic characteristics and the harmful consumption of unhealthy commodities, were measured using logistic regression.Main findingsRespondents strongly supported measures targeting industry interactions with government, and the majority believed that public health policy should be protected from industry influence (69.8% for alcohol, 75.6% for gambling, 75.0% for tobacco and 68.2% for unhealthy food and drinks manufacturers). There was also majority support for industry levies (77.1% for tobacco, 74.2% for gambling, 61.9% for alcohol, 59.5% for unhealthy food and drink), however, taxation and advertising bans received more mixed responses. Some sociodemographic factors (age and social grade) and exposure to some unhealthy commodities (current smoking, alcohol intake >14 units per week, daily gambling) were associated with differential levels of support for public health policies. However, sex and obesity did not have meaningful associations.ConclusionThe public are generally supportive of public health policies to reduce harm from tobacco, alcohol, gambling and unhealthy food and drink
Experiences and perspectives on traditional and faith healers' involvement in the care of people with severe mental health conditions in ethiopia:a scoping review
Get PDFBACKGROUND: Traditional and faith healers (TFHs) play a prominent role in the care of people with severe mental health conditions (MHCs) in many countries. Consequently, there have been calls for closer collaboration between TFHs and mental health care practitioners. This scoping review aimed to map the literature on the experiences of, and perspectives on, traditional and faith healing for people with severe MHCs in Ethiopia.METHODS: The review was conducted in accordance with the Joanna Briggs Institute methodology for scoping reviews. Pubmed, Embase, CINAHL, Scopus, Web of Science, and PsycINFO databases were searched from the earliest available records to May 2024. Online student MSc/PhD theses and catalogued Ethiopian publications up to 2015 were also searched. Studies were included if they were in English and of any study design using primary data collection. Narrative synthesis was chosen for data synthesis.RESULTS: Of the 3,824 records identified, 31 were included. There were 17 qualitative, 12 quantitative, and two mixed methods studies, conducted in most regions in Ethiopia but with more focus on urban than rural settings. Findings were synthesised under the following themes: perceived causes of MHCs; pathways to care and help-seeking preferences; identification and intervention methods used by TFHs; experience of treatment, satisfaction with care, gaps, and barriers; and collaboration between TFHs and mental health practitioners. People with severe MHCs commonly accessed TFHs first and alongside biomedical care. A substantial range of healers was identified but they were not accessible or acceptable to all communities equally. TFH interventions were diverse and some of their practices were reported to be harmful. However, there were few in-depth studies of TFH care processes. Furthermore, there was little evidence about the experience of care from the perspective of people with severe MHCs. Efforts toward collaboration emphasised the need to develop relationships within which differences could be negotiated.CONCLUSION: Although much is known about the place of TFHs within care pathways for people with MHCs in Ethiopia, there are evidence gaps in relation to the perspectives of people with MHCs and rich contextual understanding of healing processes, both of which are needed for meaningful collaboration to occur.</p
Witness to harm-holding to account. Improving patient, family and colleague experiences of fitness to practise proceedings:A mixed-methods study
Get PDFIn the United Kingdom, over 2.5 million health and social care professionals are registered by 13 statutory professional regulators. When professional conduct falls below standard, registered professionals may face an investigation into matters such as their conduct, health or competence via fitness to practise processes. Very serious cases are heard in public by an independent adjudication panel. The public, the largest source of concerns, may be asked by the regulator to be cross-examined in a hearing where their evidence may be crucial. Witness cross-examination is known to be distressing in the criminal context, where the victim is questioned about the harm they experienced and how they faced the alleged perpetrator. In fitness to practise, retelling stories could be similarly retraumatising. Our research focuses on the public (and colleagues) who raise concerns, including that they have been harmed by a professional, and examines their experience of engaging with fitness to practise processes
Decolonizing solidarity
Get PDFThis response aims to develop an understanding of ‘solidarity’ from what I take to be some of the key contributions of D&D. I do this by surveying a selection of “declarations of solidarity” issued from the Global North in the context of Israel's genocide in Gaza. I draw particular attention to Tully's critical reframing of post-war liberal political thought as “neocolonial liberalism”; his use of Edward Said's notion of the “contrapuntal ensemble” of imperialism and resistance; his account of critical dialogue within and across “hegemonic” and “subaltern” traditions, and his emphasis on “always listening to the other side”. In doing so, I hope to highlight the merits of the fundamental premises of the “dialogue tradition of political thought” that this book recovers as a “tradition”.</p
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