Switching from linear to macrocyclic gadolinium‐based contrast agents halts the relative T 1 ‐Weighted signal increase in deep gray matter of children with brain tumors: A retrospective study

BackgroundStudies have shown signal intensity (SI) changes in the brains of children exposed to repeated doses of a gadolinium‐based contrast agent (GBCA).HypothesisThe trajectory of changes in relative dentate nucleus (DN) and globus pallidus (GP) SI in children receiving multiple doses of GBCA will alter when switched from linear to macrocyclic agents.Study TypeRetrospective longitudinal.PopulationThirty‐five children, age range 0.5–17.0 years, undergoing brain tumor follow‐up between 2006 and 2017.Field Strength/SequenceUnenhanced T1WI, serial scans at both 1.5T and 3T.AssessmentRegions of interest were drawn on DN, GP, and SIs normalized to middle cerebellar peduncle (DN/MCP) and cerebral white matter (GP/CWM), respectively. A change in SI ratios as a function of dose (slope gradient) calculated according to the type of contrast agent received: linear only, macrocyclic only, or switchover from linear to macrocyclic. For the latter, gradients were compared before and after switchover. The effect of anticancer treatment on slope gradient was tested.Statistical TestsOne‐sample t‐test or Mann–Whitney U‐test for slope gradients differing from zero. Independent samples t‐tests to compare slope gradient groups. Paired sample t‐tests to compare slope gradients before and after switchover.ResultsA significant (P < 0.05) increase in SI ratio was observed following multiple doses of linear but not macrocyclic agents: mean percentage increase per dose in SI was 0.063% vs. –0.034% for DN/MCP, and 0.078% vs. 0.004% for GP/CWM ratios. A significant (P < 0.05) change of SI trajectory in the DN/MCP ratio was demonstrated when switching from a linear to macrocyclic agent. There was no difference in SI trajectory between patients who had anticancer therapies and those who did not, DN/MCP P = 0.740; GP/BWM P = 0.694.Data ConclusionSwitching from linear to macrocyclic gadolinium‐based contrast agents seems to halt the relative T1 signal increase in deep gray matter in children. Anticancer treatments appeared to have no impact on the trajectory of T1 SI

PROTOCOL: What is the effect of intergenerational activities on the wellbeing and mental health of older people?

This is the protocol for a Campbell systematic review. The objectives are as follows: This systematic review will examine the impact of intergenerational interventions on the mental health and wellbeing of older people and will identify areas for future research as well as key messages for service commissioners

What is the effect of intergenerational activities on the wellbeing and mental health of older people?: A systematic review

BACKGROUND: Opportunities for social connection between generations have diminished over the last few decades around the world as a result of changes in the way that we live and work. The COVID-19 pandemic has exacerbated loneliness for many with young and old being kept apart for safety. The Public Health England prevention concordat for better mental health (Office for Health Improvement and Disparities) aims to bring a prevention-focused approach to improving public mental health. The concordat promotes evidence-based planning and commissioning to increase the impact on reducing health inequalities using sustainable and cost-effective interventions that impact on the wider determinants of mental health and wellbeing for children and young people and older people. Intergenerational activities could provide an opportunity to support both populations. In 2023, we produced an evidence and gap map to illustrate the amount and variety of research on intergenerational interventions and the gaps in research that still exist in this area. The review conducted here is based on the evidence in that map. OBJECTIVES: This systematic review examines the impact of intergenerational interventions on the wellbeing and mental health of older people and identifies areas for future research as well as key messages for service commissioners. SEARCH METHODS: We searched an evidence and gap map published in 2022 (comprehensive searches conducted July 2021 and updated June 2023) to identify randomised controlled trials of intergenerational interventions that report mental health and wellbeing outcomes for older people. SELECTION CRITERIA: Randomised controlled trials of intergenerational interventions that involved unrelated younger and older people with at least one skipped generation between them and reported mental health or wellbeing outcomes for older people were included in this review. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by The Campbell Collaboration. We conducted data extraction and Cochrane risk of bias assessments in EPPI reviewer. Where data allowed meta-analyses were conducted in STATA. MAIN RESULTS: This review includes 14 trials from six different countries. The trials had some important methodological weaknesses. Interventions were mainly delivered in-person and often in groups. They included visiting programmes, school volunteering programmes, music-based interventions and task-oriented interventions such as activities set in a multigenerational park, reminiscing activities, aggression management programmes, learning a language, making local environmental changes and in-school project work. Intergenerational interventions showed a small positive trend towards improving self-esteem (effect size [ES]: 0.33, 95% confidence interval [CI]: -0.35, 1.01) and depression (ES: 0.19, 95% CI: -0.23, 0.60) for older people participating. However, due to the small study sizes and low number of studies available, we cannot be confident about any effects. The results for other mental health and wellbeing outcomes are reported but due to little overlap in similar assessments across the studies, we could not combine them to assess the strength of evidence. There were no data about social isolation, spiritual health or sense of community. There are no long-term studies and no data on equity. We still know very little about what works and how or why. Whilst some interventions do use theories and logic to inform their development others do not. More exploration of this is needed. AUTHORS’ CONCLUSIONS: Commissioners and intervention developers should ensure interventions provide sufficient theoretical evidence for the logic behind the proposed intervention and should improve their consideration of equity within the interventions Research on intergenerational interventions need more consistent and agreed measures for reporting outcomes including community outcomes (core outcome sets). More understanding is needed on how best to measure 'community' outcomes. Research on intergenerational interventions should measure outcomes for BOTH the older and younger population engaged in the intervention-these may or may not be the same outcomes reflected in both populations. Further research is needed on the long-term impact of interventions on outcomes (whether participants need to keep being involved in an 'intervention' to continue to benefit) and sustainability of interventions beyond the initial funding of the research project. Supporting this our stakeholders highlighted that interventions that are initiated for research and then end (usually within a year) are not helpful

Global Kidney Exchange: Analysis and Background Papers from the Perspective of the Right to Health

Global Kidney Exchange (GKE) is a program aimed at facilitating trans-national kidney donation. Although its proponents aim at reducing the unmet demand of kidneys in the United States through the trans-nationalization of kidney exchange programs, the World Health Organization (WHO) and The Transplantation Society (TTS) have expressed concerns about its potential effect on black markets of organs and transnational organ trafficking, as well as on low- or middle-income countries health systems. For GKE to be implemented, it would need to be permitted to operate in at least some low- or middle-income countries. What are the right to health implications of GKE’s implementation? With the aim of answering this question, the eighteen University of Denver students in the First Year Seminar course I taught in autumn 2017 with the title “The Right to Health in Theory and Practice”, identified and researched the different aspects that would affect this issue, and produced the analysis we present in this report. Based on our analysis, the potential right to health implications of GKE are: First, the program may improve timely access to organ donation primarily to patients with health insurance in the United States. Second, a large-scale implementation of the program may have a positive impact on health costs savings, which potentially could benefit the United States health system. Third, on a global health level, the program relies on existing health inequalities among countries in terms of funding, human resources, and health system strengthening, and it is likely to exacerbate those inequalities. Fourth, the program has the potential of negatively affecting the efforts that low- and middle-income countries are already doing to address end-stage renal failure, including the improvement of their own organ donation systems. Finally, given what we have learned about the current situation of organ trafficking, it is easy to think that GKE would unintentionally end up being linked to chains of organ trade. The only way how a program like GKE could have a positive impact from a right to health perspective is if it establishes local partnerships that have the effect of decreasing health inequalities. Additionally, we identified some issues of concern that are beyond the level of influence of local authorities: the unmet demand of kidneys in high-income countries is a reality that incentivizes organ trade and transplant tourism, and this is a problem in need of solutions; transnational organ trafficking as well as human trafficking with the purpose of organ donation are problems that need more visibility; for a global exchange of organs to be implemented, it would need to rely on supranational or transnational regulation and oversight; and the global epidemic of chronic kidney disease needs to be addressed through a public health perspective that emphasizes prevention

An exploratory randomised controlled trial of a premises-level intervention to reduce alcohol-related harm including violence in the United Kingdom

&lt;b&gt;Background&lt;/b&gt;&lt;p&gt;&lt;/p&gt; To assess the feasibility of a randomised controlled trial of a licensed premises intervention to reduce severe intoxication and disorder; to establish effect sizes and identify appropriate approaches to the development and maintenance of a rigorous research design and intervention implementation.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt;&lt;p&gt;&lt;/p&gt; An exploratory two-armed parallel randomised controlled trial with a nested process evaluation. An audit of risk factors and a tailored action plan for high risk premises, with three month follow up audit and feedback. Thirty-two premises that had experienced at least one assault in the year prior to the intervention were recruited, match paired and randomly allocated to control or intervention group. Police violence data and data from a street survey of study premises’ customers, including measures of breath alcohol concentration and surveyor rated customer intoxication, were used to assess effect sizes for a future definitive trial. A nested process evaluation explored implementation barriers and the fidelity of the intervention with key stakeholders and senior staff in intervention premises using semi-structured interviews.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt;&lt;p&gt;&lt;/p&gt; The process evaluation indicated implementation barriers and low fidelity, with a reluctance to implement the intervention and to submit to a formal risk audit. Power calculations suggest the intervention effect on violence and subjective intoxication would be raised to significance with a study size of 517 premises.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt;&lt;p&gt;&lt;/p&gt; It is methodologically feasible to conduct randomised controlled trials where licensed premises are the unit of allocation. However, lack of enthusiasm in senior premises staff indicates the need for intervention enforcement, rather than voluntary agreements, and on-going strategies to promote sustainability

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Facial Identity Recognition in the Broader Autism Phenotype

Peer reviewedPublisher PD

Measuring Anxiety in Youth with Learning Disabilities: Reliability and Validity of the Multidimensional Anxiety Scale for Children (MASC)

Youth with learning disabilities (LD) are at an increased risk for anxiety disorders and valid measures of anxiety are necessary for assessing this population. We investigated the psychometric properties of the Multidimensional Anxiety Scale for Children (MASC; March in Multidimensional anxiety scale for children. Multi-Health Systems, North Tonawanda, 1998) in 41 adolescents (ages 11– 17 years) with LD. Youth and parents completed the MASC and were administered the semi-structured Anxiety Disorders Interview Schedule: Child and Parent Versions (ADIS: C/P; Silverman and Albano in The Anxiety Disorders Interview Schedule for DSM-IV-Child and Parent Versions. Psychological Corporation, San Antonio, 1996). Results found that child and parent reports of Social Anxiety on the MASC closely corresponded with ADIS-generated social phobia diagnoses, and parent total scores discriminated well among youth with and without any anxiety disorder. A multi-method multi-trait matrix provided evidence of the construct validity of the MASC total score for both parent and child reports. Our findings provide empirical evidence that parent and child versions of the MASC are useful for assessing anxiety in youth with LD

Ridinilazole: A novel therapy for Clostridium difficile infection

Clostridium difficile infection (CDI) is the leading cause of infectious healthcare-associated diarrhoea. Recurrent CDI increases disease morbidity and mortality, posing a high burden to patients and a growing economic burden to the healthcare system. Thus, there exists a significant unmet and increasing medical need for new therapies for CDI. This review aims to provide a concise summary of CDI in general and a specific update on ridinilazole (formerly SMT19969), a novel antibacterial currently under development for the treatment of CDI. Owing to its highly targeted spectrum of activity and ability to spare the normal gut microbiota, ridinilazole provides significant advantages over metronidazole and vancomycin, the mainstay antibiotics for CDI. Ridinilazole is bactericidal against . C. difficile and exhibits a prolonged post-antibiotic effect. Furthermore, treatment with ridinilazole results in decreased toxin production. A phase 1 trial demonstrated that oral ridinilazole is well tolerated and specifically targets clostridia whilst sparing other faecal bacteria. Phase 2 and 3 trials will hopefully further our understanding of the clinical utility of ridinilazole for the treatment of CDI