A pilot randomised controlled trial of metacognitive therapy for prolonged grief

Objectives: Prolonged grief disorder is associated with significant distress and impairment and thus efforts to improve treatments are essential. The present pilot study tested the efficacy and feasibility of group Metacognitive Grief Therapy (MCGT) designed specifically for prolonged grief symptomatology to reduce the psychological distress and impaired function resulting from bereavement. Design/participants: Twenty-two bereaved adult participants with prolonged grief symptomatology were randomised to a wait-list control (n=10) or an intervention condition (n=12) with a 3-month and 6-month follow-up. The wait-list control group was offered treatment after the post-test assessment. Intervention: Participants attended six group MCGT sessions that ran for 2 hours per week. Outcome measures: A primary outcome measure of prolonged grief symptomatology and secondary outcome measures of depression, anxiety, rumination, metacognitive beliefs and quality of life were taken pretreatment and post-treatment for both groups and at the 3-month and 6-month follow-up for the intervention group. A Generalised Linear Mixed Model was used to assess treatment efficacy. Results: Post-treatment intent-to-treat analyses showed MCGT reduced prolonged grief symptomatology (Cohen's d=1.7), depression (d=1.3), anxiety (d=0.8), stress (d=1.0), rumination (d=0.9) and increased quality of life (d=0.6), and these effects were maintained at the 3-month and 6-month follow-ups. No prepost between-group differences were found in metacognitive beliefs. However, a large significant effect was identified at the 3-month and 6-month follow-ups (d=1.0). Conclusion: The results show promise for the utility of group MCGT for reducing psychological distress and promoting quality of life. Additionally, the results underscore the need for a full randomised controlled trial of group MCGT, which may be an important addition to the treatment armamentarium available to support people with prolonged grief

Qualitative Parental Perceptions of a Paediatric Multidisciplinary Team Clinic for Prader-Willi Syndrome

Objective:This preliminary review was conducted to inform the design of a new service to support families with children with Prader-Willi syndrome (PWS). Families were invited to attend a pilot clinic at a hospital outpatient department, comprising appointments with a multi-disciplinary team (MDT).Methods:Following the clinic, families (n=6) were invited to take part in semi-structured qualitative interviews that were audio-recorded, transcribed and analysed using thematic analysis.Results:Families reported that the clinic offered enhanced support in the following categories: integrated care; professional input; signposting to social support (respite and financial); connection with the wider PWS community; and behavioural support.Conclusion:This is the first paper that documents the parental perspective of an MDT clinic for children with PWS. The families felt an MDT clinic was superior to current care, offering more convenient access to an enhanced service, which would provide integrated and consistent care for their children’s diverse, challenging and changing needs

Dapagliflozin-lowered blood glucose reduces respiratory Pseudomonas aeruginosa infection in diabetic mice.

BACKGROUND AND PURPOSE: Hyperglycaemia increases glucose concentrations in airway surface liquid and increases the risk of pulmonary Pseudomonas aeruginosa infection. We determined whether reduction of blood and airway glucose concentrations by the anti-diabetic drug dapagliflozin could reduce P. aeruginosa growth/survival in the lungs of diabetic mice. EXPERIMENTAL APPROACH: The effect of dapagliflozin on blood and airway glucose concentration, the inflammatory response and infection were investigated in C57BL/6J (wild type, WT) or leptin receptor-deficient (db/db) mice, treated orally with dapagliflozin prior to intranasal dosing with LPS or inoculation with P. aeruginosa. Pulmonary glucose transport and fluid absorption were investigated in Wistar rats using the perfused fluid-filled lung technique. KEY RESULTS: Fasting blood, airway glucose and lactate concentrations were elevated in the db/db mouse lung. LPS challenge increased inflammatory cells in bronchoalveolar lavage fluid from WT and db/db mice with and without dapagliflozin treatment. P. aeruginosa colony-forming units (CFU) were increased in db/db lungs. Pretreatment with dapagliflozin reduced blood and bronchoalveolar lavage glucose concentrations and P. aeruginosa CFU in db/db mice towards those seen in WT. Dapagliflozin had no adverse effects on the inflammatory response in the mouse or pulmonary glucose transport or fluid absorption in the rat lung. CONCLUSION AND IMPLICATIONS: Pharmacological lowering of blood glucose with dapagliflozin effectively reduced P. aeruginosa infection in the lungs of diabetic mice and had no adverse pulmonary effects in the rat. Dapagliflozin has potential to reduce the use, or augment the effect, of antimicrobials in the prevention or treatment of pulmonary infection

Voltammetric behaviour of hydrogen peroxide at a silver electrode fabricated from a rewritable digital versatile disc (DVD) and its determination in water samples

In this study we investigated the possibility of applying Ag electrodes manufactured from recordable rewritable digital versatile discs (DVD-RW) for the voltammetric determination of hydrogen peroxide. The calibration plot was linear from 0.087 mM to 3.41 mM hydrogen peroxide with a sensitivity of 58.7 μA mM-1 over this range. A corresponding detection limit of 78.35 μM, based on a signal-to-noise-ratio of 3 was recorded. No interferences were observed by 500 mg L-1 chloride, 50 mg L-1 nitrate, 700 mg L-1 sulphate or 700 mg L-1 carbonate which are found in swimming pool water at these concentrations. Using the multiple standard addition method a percentage recovery of 90.67% with a coefficient of variation of 4.69% (n = 5) was found for a representative swimming pool water concentration of 1.2 mM hydrogen peroxide. Therefore, the performance data suggests that the method is reliable at the concentrations examined in this study and that a rapid, simple, economical and precise method of monitoring hydrogen peroxide in swimming pool and aquaculture applications is possible. © 2013 The Royal Society of Chemistry

Autistic perspectives on the future of clinical autism research

The Lancet Commission on the Future of Care and Clinical Research in Autism recently published their recommendations for what should be done in the next 5 years to address the current needs of autistic individuals and families. Although the Commission includes many prominent clinicians and researchers from around the world, as well as some autistic advocates and parents of autistic people, there have been widespread expressions of dissatisfaction among autistic people and communities regarding these recommendations. We, the Global Autistic Task Force on Autism Research are a group of autistic professionals and representatives of organizations run by and for autistic people. We are autistic clinicians, therapists, educators and researchers, parents, and family members of autistic people of all ages and with all types of support needs, as well as individuals with high support needs. Among us are also autistic people of color, autistic people from the Global South and Asia, autistic women, and autistic people belonging to gender minorities. Despite aiming at bringing together different stakeholders, representation within the Lancet Commission was limited in these respects. We hope to bring more voices to the discourse. We previously wrote an open letter to the Commission to draw attention to our main concerns. In this editorial, we offer a more detailed discussion of the Commission's report, as well as our own recommendations for future directions in autism research and care

Increased serum miR-193a-5p during non-alcoholic fatty liver disease progression: Diagnostic and mechanistic relevance

Background & Aims: Serum microRNA (miRNA) levels are known to change in non-alcoholic fatty liver disease (NAFLD) and may serve as useful biomarkers. This study aimed to profile miRNAs comprehensively at all NAFLD stages. Methods: We profiled 2,083 serum miRNAs in a discovery cohort (183 cases with NAFLD representing the complete NAFLD spectrum and 10 population controls). miRNA libraries generated by HTG EdgeSeq were sequenced by Illumina NextSeq. Selected serum miRNAs were profiled in 372 additional cases with NAFLD and 15 population controls by quantitative reverse transcriptase PCR. Results: Levels of 275 miRNAs differed between cases and population controls. Fewer differences were seen within individual NAFLD stages, but miR-193a-5p consistently showed increased levels in all comparisons. Relative to NAFL/non-alcoholic steatohepatitis (NASH) with mild fibrosis (stage 0/1), 3 miRNAs (miR-193a-5p, miR-378d, and miR378d) were increased in cases with NASH and clinically significant fibrosis (stages 2–4), 7 (miR193a-5p, miR-378d, miR-378e, miR-320b, miR-320c, miR-320d, and miR-320e) increased in cases with NAFLD activity score (NAS) 5–8 compared with lower NAS, and 3 (miR-193a-5p, miR-378d, and miR-378e) increased but 1 (miR-19b-3p) decreased in steatosis, activity, and fibrosis (SAF) activity score 2–4 compared with lower SAF activity. The significant findings for miR-193a-5p were replicated in the additional cohort with NAFLD. Studies in Hep G2 cells showed that following palmitic acid treatment, miR-193a-5p expression decreased significantly. Gene targets for miR-193a-5p were investigated in liver RNAseq data for a case subgroup (n = 80); liver GPX8 levels correlated positively with serum miR-193a-5p. Conclusions: Serum miR-193a-5p levels correlate strongly with NAFLD activity grade and fibrosis stage. MiR-193a-5p may have a role in the hepatic response to oxidative stress and is a potential clinically tractable circulating biomarker for progressive NAFLD. Lay summary: MicroRNAs (miRNAs) are small pieces of nucleic acid that may turn expression of genes on or off. These molecules can be detected in the blood circulation, and their levels in blood may change in liver disease including non-alcoholic fatty liver disease (NAFLD). To see if we could detect specific miRNA associated with advanced stages of NAFLD, we carried out miRNA sequencing in a group of 183 patients with NAFLD of varying severity together with 10 population controls. We found that a number of miRNAs showed changes, mainly increases, in serum levels but that 1 particular miRNA miR-193a-5p consistently increased. We confirmed this increase in a second group of cases with NAFLD. Measuring this miRNA in a blood sample may be a useful way to determine whether a patient has advanced NAFLD without an invasive liver biopsy

An unbiased ranking of murine dietary models based on their proximity to human metabolic dysfunction-associated steatotic liver disease (MASLD)

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease, encompasses steatosis and metabolic dysfunction-associated steatohepatitis (MASH), leading to cirrhosis and hepatocellular carcinoma. Preclinical MASLD research is mainly performed in rodents; however, the model that best recapitulates human disease is yet to be defined. We conducted a wide-ranging retrospective review (metabolic phenotype, liver histopathology, transcriptome benchmarked against humans) of murine models (mostly male) and ranked them using an unbiased MASLD ‘human proximity score’ to define their metabolic relevance and ability to induce MASH-fibrosis. Here, we show that Western diets align closely with human MASH; high cholesterol content, extended study duration and/or genetic manipulation of disease-promoting pathways are required to intensify liver damage and accelerate significant (F2+) fibrosis development. Choline-deficient models rapidly induce MASH-fibrosis while showing relatively poor translatability. Our ranking of commonly used MASLD models, based on their proximity to human MASLD, helps with the selection of appropriate in vivo models to accelerate preclinical research

Diagnostic accuracy of non-invasive tests for advanced fibrosis in patients with NAFLD: An individual patient data meta-analysis

Objective Liver biopsy is still needed for fibrosis staging in many patients with non-alcoholic fatty liver disease. The aims of this study were to evaluate the individual diagnostic performance of liver stiffness measurement by vibration controlled transient elastography (LSM-VCTE), Fibrosis-4 Index (FIB-4) and NAFLD (non-alcoholic fatty liver disease) Fibrosis Score (NFS) and to derive diagnostic strategies that could reduce the need for liver biopsies. Design Individual patient data meta-analysis of studies evaluating LSM-VCTE against liver histology was conducted. FIB-4 and NFS were computed where possible. Sensitivity, specificity and area under the receiver operating curve (AUROC) were calculated. Biomarkers were assessed individually and in sequential combinations. Results Data were included from 37 primary studies (n=5735; 45% women; median age: 54 years; median body mass index: 30 kg/m2; 33% had type 2 diabetes; 30% had advanced fibrosis). AUROCs of individual LSM-VCTE, FIB-4 and NFS for advanced fibrosis were 0.85, 0.76 and 0.73. Sequential combination of FIB-4 cut-offs (<1.3; ≥2.67) followed by LSM-VCTE cut-offs (<8.0; ≥10.0 kPa) to rule-in or rule-out advanced fibrosis had sensitivity and specificity (95% CI) of 66% (63-68) and 86% (84-87) with 33% needing a biopsy to establish a final diagnosis. FIB-4 cut-offs (<1.3; ≥3.48) followed by LSM cut-offs (<8.0; ≥20.0 kPa) to rule out advanced fibrosis or rule in cirrhosis had a sensitivity of 38% (37-39) and specificity of 90% (89-91) with 19% needing biopsy. Conclusion Sequential combinations of markers with a lower cut-off to rule-out advanced fibrosis and a higher cut-off to rule-in cirrhosis can reduce the need for liver biopsies