GrOW National Study of Grandfamilies During COVID-19: Wave I and Wave II Results and Recommendations

The COVID-19 pandemic has impacted families across the globe. This study highlights how a multidisciplinary workgroup, Grandfamilies Outcome Workgroup (GrOW) operationalized a caregiver-centered data cycle to learn how COVID-19 has impacted grandfamilies across the United States. The National Grandfamilies and COVID-19 Wave I (n=600, June 2020) and Wave II (n=225, July 2021) surveys recruited grandfamilies nationwide through GrOW’s network of kinship community partners. Wave I survey results illuminated that all sources of social support were reduced for grandfamilies during the pandemic, except for online support groups. Wave II provided an opportunity to revise the survey to capture emergent issues relevant to a later stage of the pandemic for grandfamilies. Results indicated that 73% of caregivers were vaccinated. Results also identified gaps in caregiver knowledge of kinship navigator programs and supports in their communities. Recommendations for future research are provided. Keywords Kinship, COVID-19, Grandfamilies’ Outcome Workgroup, Culturally Responsive Research, Translational Disseminatio

'Relieved to be seen'-patient and carer experiences of psychosocial assessment in the emergency department following self-harm: qualitative analysis of 102 free-text survey responses.

From Europe PMC via Jisc Publications RouterHistory: ppub 2021-05-01, epub 2021-05-23Publication status: PublishedObjectivesWe sought to explore patient and carer experiences of psychosocial assessments following presentations to hospital after self-harm.DesignThematic analysis of free-text responses to an open-ended online survey.SettingBetween March and November 2019, we recruited 88 patients (82% women) and 14 carers aged ≥18 years from 16 English mental health trusts, community organisations, and via social media.ResultsPsychosocial assessments were experienced as helpful on some occasions but harmful on others. Participants felt better, less suicidal and less likely to repeat self-harm after good-quality compassionate and supportive assessments. However, negative experiences during the assessment pathway were common and, in some cases, contributed to greater distress, less engagement and further self-harm. Participants reported receiving negative and stigmatising comments about their injuries. Others reported that they were refused medical care or an anaesthetic. Stigmatising attitudes among some mental health staff centred on preconceived ideas over self-harm as a 'behavioural issue', inappropriate use of services and psychiatric diagnosis.ConclusionOur findings highlight important patient experiences that can inform service provision and they demonstrate the value of involving patients/carers throughout the research process. Psychosocial assessments can be beneficial when empathetic and collaborative but less helpful when overly standardised, lacking in compassion and waiting times are unduly long. Patient views are essential to inform practice, particularly given the rapidly changing service context during and after the COVID-19 emergency

Evaluating the impact of patient and carer involvement in suicide and self‐harm research: A mixed‐methods, longitudinal study protocol

From Wiley via Jisc Publications RouterHistory: received 2019-04-30, rev-recd 2019-10-16, accepted 2019-10-25, pub-electronic 2019-12-05, pub-print 2021-05Article version: VoRPublication status: PublishedFunder: National Institute for Health Research; Id: http://dx.doi.org/10.13039/100009250; Grant(s): PSTRC‐2016‐003Abstract: Background: Patient and public involvement (PPI) is becoming more commonplace in mental health research. There are strong moral and ethical arguments for good quality PPI. Few studies have documented and evaluated PPI in self‐harm and suicide research. Inconsistent reporting of PPI makes it difficult to discern practices that deliver quality, effective and meaningful involvement. It is important to understand and address emotional support needs of PPI members contributing to sensitive topics such as suicide and self‐harm. Therefore, this study will examine the effect of PPI on self‐harm and suicide research and explore patients', carers' and researchers' experiences and views in relation to the quality of PPI practice and provision of appropriate support for PPI members. Methods: This protocol outlines the longitudinal, mixed methodological approach that will be taken. Qualitative and quantitative data will be collected via baseline and repeated questionnaires, document review and semi‐structured interviews. Both PPI members and researchers will be invited to participate in this study. The two‐year data collection period will enable evaluation of PPI throughout the entire research cycle. An integrated approach will be taken to data analysis, using inductive thematic analysis and descriptive and repeated measures analyses, to address specified study aims. Dissemination: Findings from this study will inform practical guidance to support self‐harm and suicide researchers in effectively involving people with experiential knowledge in their research. Analyses will offer insight into the effect of PPI throughout the research process and assess changes in PPI members' and researchers' experiences of involvement across a two‐year period

Mitochondrial Structure, Function and Dynamics Are Temporally Controlled by c-Myc

Although the c-Myc (Myc) oncoprotein controls mitochondrial biogenesis and multiple enzymes involved in oxidative phosphorylation (OXPHOS), the coordination of these events and the mechanistic underpinnings of their regulation remain largely unexplored. We show here that re-expression of Myc in myc−/− fibroblasts is accompanied by a gradual accumulation of mitochondrial biomass and by increases in membrane polarization and mitochondrial fusion. A correction of OXPHOS deficiency is also seen, although structural abnormalities in electron transport chain complexes (ETC) are not entirely normalized. Conversely, the down-regulation of Myc leads to a gradual decrease in mitochondrial mass and a more rapid loss of fusion and membrane potential. Increases in the levels of proteins specifically involved in mitochondrial fission and fusion support the idea that Myc affects mitochondrial mass by influencing both of these processes, albeit favoring the latter. The ETC defects that persist following Myc restoration may represent metabolic adaptations, as mitochondrial function is re-directed away from producing ATP to providing a source of metabolic precursors demanded by the transformed cell

Clinical outcomes and response to treatment of patients receiving topical treatments for pyoderma gangrenosum: a prospective cohort study

Background: pyoderma gangrenosum (PG) is an uncommon dermatosis with a limited evidence base for treatment. Objective: to estimate the effectiveness of topical therapies in the treatment of PG. Methods: prospective cohort study of UK secondary care patients with a clinical diagnosis of PG suitable for topical treatment (recruited July 2009 to June 2012). Participants received topical therapy following normal clinical practice (mainly Class I-III topical corticosteroids, tacrolimus 0.03% or 0.1%). Primary outcome: speed of healing at 6 weeks. Secondary outcomes: proportion healed by 6 months; time to healing; global assessment; inflammation; pain; quality-of-life; treatment failure and recurrence. Results: Sixty-six patients (22 to 85 years) were enrolled. Clobetasol propionate 0.05% was the most commonly prescribed therapy. Overall, 28/66 (43.8%) of ulcers healed by 6 months. Median time-to-healing was 145 days (95% CI: 96 days, ∞). Initial ulcer size was a significant predictor of time-to-healing (hazard ratio 0.94 (0.88;80 1.00); p = 0.043). Four patients (15%) had a recurrence. Limitations: No randomised comparator Conclusion: Topical therapy is potentially an effective first-line treatment for PG that avoids possible side effects associated with systemic therapy. It remains unclear whether more severe disease will respond adequately to topical therapy alone

Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial

Background Some high-income countries have deployed fourth doses of COVID-19 vaccines, but the clinical need, effectiveness, timing, and dose of a fourth dose remain uncertain. We aimed to investigate the safety, reactogenicity, and immunogenicity of fourth-dose boosters against COVID-19.Methods The COV-BOOST trial is a multicentre, blinded, phase 2, randomised controlled trial of seven COVID-19 vaccines given as third-dose boosters at 18 sites in the UK. This sub-study enrolled participants who had received BNT162b2 (Pfizer-BioNTech) as their third dose in COV-BOOST and randomly assigned them (1:1) to receive a fourth dose of either BNT162b2 (30 µg in 0·30 mL; full dose) or mRNA-1273 (Moderna; 50 µg in 0·25 mL; half dose) via intramuscular injection into the upper arm. The computer-generated randomisation list was created by the study statisticians with random block sizes of two or four. Participants and all study staff not delivering the vaccines were masked to treatment allocation. The coprimary outcomes were safety and reactogenicity, and immunogenicity (antispike protein IgG titres by ELISA and cellular immune response by ELISpot). We compared immunogenicity at 28 days after the third dose versus 14 days after the fourth dose and at day 0 versus day 14 relative to the fourth dose. Safety and reactogenicity were assessed in the per-protocol population, which comprised all participants who received a fourth-dose booster regardless of their SARS-CoV-2 serostatus. Immunogenicity was primarily analysed in a modified intention-to-treat population comprising seronegative participants who had received a fourth-dose booster and had available endpoint data. This trial is registered with ISRCTN, 73765130, and is ongoing.Findings Between Jan 11 and Jan 25, 2022, 166 participants were screened, randomly assigned, and received either full-dose BNT162b2 (n=83) or half-dose mRNA-1273 (n=83) as a fourth dose. The median age of these participants was 70·1 years (IQR 51·6–77·5) and 86 (52%) of 166 participants were female and 80 (48%) were male. The median interval between the third and fourth doses was 208·5 days (IQR 203·3–214·8). Pain was the most common local solicited adverse event and fatigue was the most common systemic solicited adverse event after BNT162b2 or mRNA-1273 booster doses. None of three serious adverse events reported after a fourth dose with BNT162b2 were related to the study vaccine. In the BNT162b2 group, geometric mean anti-spike protein IgG concentration at day 28 after the third dose was 23 325 ELISA laboratory units (ELU)/mL (95% CI 20 030–27 162), which increased to 37 460 ELU/mL (31 996–43 857) at day 14 after the fourth dose, representing a significant fold change (geometric mean 1·59, 95% CI 1·41–1·78). There was a significant increase in geometric mean anti-spike protein IgG concentration from 28 days after the third dose (25 317 ELU/mL, 95% CI 20 996–30 528) to 14 days after a fourth dose of mRNA-1273 (54 936 ELU/mL, 46 826–64 452), with a geometric mean fold change of 2·19 (1·90–2·52). The fold changes in anti-spike protein IgG titres from before (day 0) to after (day 14) the fourth dose were 12·19 (95% CI 10·37–14·32) and 15·90 (12·92–19·58) in the BNT162b2 and mRNA-1273 groups, respectively. T-cell responses were also boosted after the fourth dose (eg, the fold changes for the wild-type variant from before to after the fourth dose were 7·32 [95% CI 3·24–16·54] in the BNT162b2 group and 6·22 [3·90–9·92] in the mRNA-1273 group).Interpretation Fourth-dose COVID-19 mRNA booster vaccines are well tolerated and boost cellular and humoral immunity. Peak responses after the fourth dose were similar to, and possibly better than, peak responses after the third dose

Is there a role for sleep medicine in suicide prevention?

Suicide is a leading cause of preventable death worldwide, accounting for approximately 800,000 deaths per year [1]. Deaths by suicide represent only the “tip of the iceberg” of suicidal experiences, with an even larger proportion of the population reporting having attempted suicide, or thought about doing so [2]. Given the scale of the problem, suicide prevention research has sought to identify psychosocial and demographic factors that are associated with suicidal thoughts and behaviours. In recent years, growing evidence has highlighted links between sleep disorders and suicide [3] as well as non-fatal self-harm [4]. Notably, these relationships remain significant after controlling for symptoms of co-morbid mental illness. The association between sleep disorders and suicidal experiences has been replicated in a wide range of studies; in both clinical [5] and non-clinical populations [3], spanning wide age-ranges including adolescents [6] to older adults [7], and using subjective and objective assessment of sleep disturbance [8]