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Putamen iron quantification in diseases with neurodegeneration: a meta-analysis of the quantitative susceptibility mapping technique
No full textQuantitative susceptibility mapping (QSM) is an MRI technique that accurately measures iron concentration in brain tissues. This meta-analysis synthesized evidence from 30 studies that used QSM to quantify the iron levels in the putamen. The PRISMA statement was adhered to when conducting the systematic reviews and meta-analyses. We conducted a meta-analysis using a random-effects model, as well as subgroup analyses (disease type, geographic region, field strength, coil, disease type, age, and sex) and sensitivity analysis. A total of 1247 patients and 1035 controls were included in the study. Pooled results showed a standardized mean difference (SMD) of 0.41 (95% CI 0.19 to 0.64), with the strongest effect seen in Alzheimer's disease (AD) at 1.01 (95% CI 0.50 to 1.52). Relapsing-remitting multiple sclerosis (RRMS) also showed increased putaminal iron at 0.37 (95% CI 0.177 to 0.58). No significant differences were observed in Parkinson's disease (PD). No significant differences were found between subgroups based on geographic region, field strength, coil, disease type, age, and sex. The studies revealed significant heterogeneity, with field strength as the primary source, while other factors, such as disease type, location, age, sex, and coil type, may have contributed. The sensitivity analysis showed that these factors did not have a significant influence on the overall results. In summary, this meta-analysis supports abnormalities in putaminal iron content across different diseases with neurodegeneration, especially AD and RRMS, as measured by QSM. This highlights the potential of QSM as an imaging biomarker to better understand disease mechanisms involving disturbances in brain iron homeostasis.https://link.springer.com/article/10.1007/s11682-024-00895-
Prone positioning and right ventricular protection during extracorporeal membrane oxygenation for severe acute respiratory distress syndrome
No full texthttps://journals.lww.com/asaiojournal/fulltext/9900/prone_positioning_and_right_ventricular_protection.516.asp
Quantifying the effect of vaccination on transmission in modelling studies
No full texthttps://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00248-7/fulltex
Caplacizumab in paediatric immune thrombotic thrombocytopenic purpura (iTTP): the UK TTP Registry experience
No full textPaediatric thrombotic thrombocytopenic purpura (TTP) is an ultra-rare disease. Immune TTP (iTTP) is driven by anti-ADAMTS13 autoantibodies causing an imbalanced VWF:ADAMTS13 axis, and rarer still in children, but potentially life-threatening. Caplacizumab is licensed for iTTP treatment in adults and adolescents aged 12 years and older who weigh 40kg plus. There is a need to clarify whether caplacizumab can be used in younger children. We retrospectively describe caplacizumab use in 16 patients under 18 years of age from the UK TTP Registry, including 4 children aged less than 12 years. For patients weighing less than 40kg (n=3), caplacizumab was dosed at 5mg od. The youngest patient was 33 months old at diagnosis. Plasma exchange (PEX) was used in 15 patients, with a median of 5 exchanges required before platelet count normalisation (range 2-9). One patient was managed without plasma exchange. All patients achieved normalisation of platelet count (median 5.5 days, range 3-28) and ADAMTS13 activity (median 35 days, range 8 to 149), with a median hospital admission of 11 days (range 5 to 26). There were no refractory patients. One patient relapsed at 9 months post presentation. Bleeding requiring VWF supplementation and reduction of caplacizumab use occurred in one patient with severe epistaxis, with no significant intracranial or gastrointestinal bleeding. We demonstrate the efficacy and safety of caplacizumab in the paediatric population, synonymous with the adult trial data: primarily, reduction of PEX compared with the pre-caplacizumab era. This has implications for intensification and duration of admission, particularly relevant in paediatric care.https://ashpublications.org/bloodadvances/article/doi/10.1182/bloodadvances.2024013488/516851/Caplacizumab-in-paediatric-immune-thromboti
Tardive dyskinesia with antipsychotic medication in children and adolescents: A systematic literature review
No full textBACKGROUND: Tardive dyskinesia (TD) is a persisting, and potentially irreversible, movement disorder associated with treatment with dopamine receptor antagonists. Few data are available on the risk of TD in children and adolescents treated with antipsychotic medication. OBJECTIVE: To review the literature on incidence, risk factors, and treatment options for antipsychotic-associated TD in children and adolescents (aged < 18 years). METHODS: Relevant articles were identified through a systematic search of Embase and Medline performed in January 2024. Methodological quality was assessed using the Newcastle-Ottawa Scale and Joanna Briggs Institute Critical Appraisal tools. RESULTS: Thirteen studies were identified. The reported TD point prevalence was 5-20%, with higher rates in studies involving typical antipsychotics. Lower estimates (around 1%) emerged from analyses of clinical database data suggesting underdiagnosis in clinical practice. Risk factors included treatment with typical antipsychotics, higher doses, longer duration of exposure, older age, female gender, higher baseline Abnormal Involuntary Movements Scale (AIMS) scores, intellectual impairment, and perinatal complications. CONCLUSION: Although relatively few cases have been reported in children and adolescents, TD remains a risk in this population. Individuals receiving antipsychotics should be monitored carefully for the emergence of abnormal movements. Other than dose reduction, discontinuation, or switch to a lower-risk antipsychotic, few interventions have demonstrated efficacy. The strongest evidence for pharmacological treatment is for VMAT-2 inhibitors (valbenazine and deutetrabenazine), but these drugs are not licensed for use in children. To reduce risk, antipsychotics should be prescribed only if necessary, at the minimum effective dose and for the minimum necessary duration.https://link.springer.com/article/10.1007/s40264-024-01446-
A pragmatic randomised controlled trial of the effectiveness and cost-effectiveness of Well Parent Japan in routine care in Japan: The training and nurturing support for mothers (TRANSFORM) study
Get PDF2024 The Author(s). Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and
Adolescent Mental Health.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and
distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.BACKGROUND: Well Parent Japan (WPJ) is a new hybrid group parent training programme combining sessions to improve mothers' psychological well-being with a culturally adapted version of the New Forest Parenting Programme (NFPP). This study investigates the effectiveness and cost-effectiveness of WPJ against treatment as usual (TAU) within Japanese child mental health services. METHODS: TRANSFORM was a pragmatic multi-site randomised controlled trial (RCT) with two parallel arms. Altogether 124 mothers of 6-12-year-old children with DSM-5 ADHD were randomised to WPJ (n = 65) or TAU (n = 59). Participants were assessed at baseline, post-treatment and three-month follow-up. The primary outcome was parent-domain stress following intervention. Secondary outcomes included maternal reports of child-domain stress, parenting practices, parenting efficacy, mood, family strain, child behaviour and impairment. Objective measures of the parent-child relationship were collected at baseline and post-treatment. Data analysis was intention to treat (ITT) with treatment effects quantified through analysis of covariance (ANCOVA) via multilevel modelling. An incremental cost-effectiveness ratio (ICER) assessed WPJ's cost-effectiveness. RESULTS: WPJ was superior to TAU in reducing parent-domain stress post-treatment (adjusted mean difference = 5.05, 95% CI 0.33 to 9.81, p = .036) and at follow-up (adjusted mean difference 4.82, 95% CI 0.09 to 9.55, p = .046). Significant WPJ intervention effects were also observed for parenting practices, parenting efficacy and family strain. WPJ and TAU were not significantly different post-intervention or at follow-up for the other secondary outcomes. The incremental cost of WPJ was 34,202 JPY (315.81 USD). The probability that WPJ is cost-effective is 74% at 10,000 JPY (USD 108.30) per one-point improvement in parenting stress, 92% at 20,000 JPY (216.60 USD). The programme was delivered with high fidelity and excellent retention. CONCLUSIONS: WPJ can be delivered in routine clinical care at modest cost with positive effects on self-reported well-being of the mothers, parenting practices and family coping. WPJ is a promising addition to psychosocial interventions for ADHD in Japan.https://acamh.onlinelibrary.wiley.com/doi/full/10.1111/jcpp.1400
Variation in systemic antibiotic treatment for diabetic foot osteomyelitis in England and Wales: a multi-centre case review
Get PDFCopyright: © 2024 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).Background: Diabetic foot osteomyelitis (DFO) is a major complication and can lead to significant morbidity and mortality. Systemic antibiotic therapy is often initiated first line to achieve quiescence of infection. To perform a multi-centre case review of systemic antibiotic intervention to treat adults with DFO in England and Wales and compare with national guidelines ‘Diabetic foot problems: prevention and management’. Methods: Eight centres from England and Wales retrospectively collated data from a minimum of five adults (aged ≥ 18 years) from electronic case records. All patients were treated with systemic antibiotics following a new diagnosis of DFO (1 June 2021–31 December 2021). Results: 40 patients (35 males and 5 females) were included; the mean age was 62.3 years (standard deviation (SD) 13.0). Patients commenced systemic oral 14 (35%) or intravenous 26 (65%) antibiotic therapy following a new diagnosis of DFO. Twenty-seven (67.5%) patients were medically or surgically managed in the 12-week period with clinical quiescence of infection. Twenty-one patients (52.5%) had no recurrence of DFO infection within 12 weeks; seventeen (42.5%) of these patients had clinical quiescence of infection with systemic antibiotics alone without surgical intervention and nine (22.5%) of these cases had no recurrence of DFO. There were no cases of major amputation or death. All centres showed significant in-centre variability in systemic antibiotic management; variability was reported in the clinical and quantity indicators specifically to antibiotic selection, single versus dual therapy, mode of delivery and duration of treatment. Conclusions: This case review identifies there is existing variation when treating adults with systemic antibiotics for DFO. Further national guidance is required to standardise service delivery and care to improve patient outcomes.https://www.mdpi.com/2077-0383/13/11/308
Efficacy and cost-effectiveness of a digital guided self-management intervention to support transition from intensive care to community care in anorexia nervosa (TRIANGLE): pragmatic multicentre randomised controlled trial and economic evaluation
No full textBACKGROUND: There is uncertainty regarding how best to support patients with anorexia nervosa following inpatient or day care treatment. This study evaluated the impact of augmenting intensive treatment with a digital, guided, self-management intervention (ECHOMANTRA) for patients with anorexia nervosa and their carers. METHODS: In this pragmatic multicentre randomised controlled trial and economic evaluation, patients with a diagnosis of anorexia nervosa or atypical anorexia nervosa, aged 16+ and attending one of the 31 inpatient or day-patient services in the UK were randomised with one of their carers to receive ECHOMANTRA plus treatment as usual (TAU), or TAU alone. ECHOMANTRA was hosted on a digital platform and included a workbook, recovery-oriented video-clips and online facilitated groups (patients only, carers only, joint patient-carer). Participants were randomised on a 1:1 ratio using a minimisation algorithm to stratify by site (N = 31) and severity (defined by BMI <15 and ≥ 15 kg/m(2) at baseline). The primary outcome was patient depression, anxiety, and stress at 12 months. Primary and secondary outcomes were compared between trial arms on an intention-to-treat basis (ITT). This trial is registered with the ISRSTN registry, ISRCTN14644379. FINDINGS: Between July 01, 2017 and July 20, 2020, 371 patient-carer dyads were enrolled and randomly assigned to ECHOMANTRA + TAU (N = 185) or TAU alone (N = 186). There were no significant differences between trial arms with regards to the primary outcome (completed by N = 143 patients in the TAU group, Mean = 61.7, SD = 29.4 and N = 109 patients in the ECHOMANTRA + TAU group, Mean = 58.3, SD = 26.9; estimated mean difference 0.48 points; 95% CI -5.36 to 6.33; p = 0.87). Differences on secondary outcomes were small and non-significant (standardised effect size estimates ≤0.25). Five patients died (2 from suicide and 3 from physical complications) over the course of the trial, and this was unrelated to their participation in the study. INTERPRETATION: ECHOMANTRA added to TAU was not superior to TAU alone in reducing patient depression, anxiety, and stress symptoms. This may be explained by limited engagement with the intervention materials and changes in usual care practices since the beginning of the trial. FUNDING: National Institute for Health Research (NIHR), under its Health Technology Assessment Programme (HTA) Programme (Grant Reference Number 14/68/09). NIHR Maudsley Biomedical Research Centre (BRC), South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, Psychology and Neuroscience, and King's College London. NIHR Applied Research Collaboration South London (NIHR ARC South London) at King's College Hospital NHS Foundation Trust.https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00224-4/fulltext#articleInformatio
Age-related changes in Vancomycin protein binding: is it time to take it seriously?
No full textBackground: Vancomycin (VAN) protein binding in plasma is influenced by illness and age; hence, doses titrated according to total concentrations are fraught. In this study, model-estimated free VAN concentrations (EFVC) were compared with assumed free VAN concentrations (AFVC) in neonates, children, and adults in the intensive care unit and those on dialysis. Methods: Patient cohorts were identified from the hospital database. Demographics, clinical characteristics, total VAN concentrations, and laboratory variables were obtained from electronic health records. EFVC was derived from 6 models identified in the literature. For all models, total VAN concentration was the most important predictor; other predictors included albumin, total protein, and dialysis status. The AFVC was calculated as 50% of the total concentration (ie, assumption of 50% bound). Results: Differences between EFVC and AFVC in adults were insignificant; however, differences in pediatric intensive care unit patients, according to 2 different models, were significant: mean ± SD = 4.1 ± 1.58 mg/L and 4.7 ± 2.46 mg/L ( P < 0.001); the percentages within the free VAN trough range = 30.4% versus 55.1% and 30% versus 55.1%; and the supratherapeutic percentages = 65.2% versus 31.9% and 66.7% versus 31.9%, respectively. In neonates, the difference between EFVC and AFVC was mean ± SD = 6.9 ± 1.95 mg/L ( P < 0.001); the percentages within the free VAN trough range for continuous and intermediate dosing were 0% versus 81.3% and 14.3% versus 71.4%, and the supratherapeutic percentages were 100% versus 6.25% and 71.4% versus 0%, respectively. Conclusions: The fraction of free unbound VAN is higher in sick children and neonates than in adults. Therefore, total VAN concentrations do not correlate with the pharmacologically active free VAN concentrations in the same manner as in adults. Adjusting VAN doses in neonates and children to target the same total VAN concentration as the recommended therapeutic range for adults may result in toxicfree concentrations.https://journals.lww.com/drug-monitoring/abstract/2024/08000/age_related_changes_in_vancomycin_protein_binding_.16.asp