Booster Vaccination Against SARS-CoV-2 Induces Potent Immune Responses in People With Human Immunodeficiency Virus.

BACKGROUND: People with human immunodeficiency virus (HIV) on antiretroviral therapy (ART) with good CD4 T-cell counts make effective immune responses following vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There are few data on longer term responses and the impact of a booster dose. METHODS: Adults with HIV were enrolled into a single arm open label study. Two doses of ChAdOx1 nCoV-19 were followed 12 months later by a third heterologous vaccine dose. Participants had undetectable viraemia on ART and CD4 counts >350 cells/µL. Immune responses to the ancestral strain and variants of concern were measured by anti-spike immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA), MesoScale Discovery (MSD) anti-spike platform, ACE-2 inhibition, activation induced marker (AIM) assay, and T-cell proliferation. FINDINGS: In total, 54 participants received 2 doses of ChAdOx1 nCoV-19. 43 received a third dose (42 with BNT162b2; 1 with mRNA-1273) 1 year after the first dose. After the third dose, total anti-SARS-CoV-2 spike IgG titers (MSD), ACE-2 inhibition, and IgG ELISA results were significantly higher compared to Day 182 titers (P < .0001 for all 3). SARS-CoV-2 specific CD4+ T-cell responses measured by AIM against SARS-CoV-2 S1 and S2 peptide pools were significantly increased after a third vaccine compared to 6 months after a first dose, with significant increases in proliferative CD4+ and CD8+ T-cell responses to SARS-CoV-2 S1 and S2 after boosting. Responses to Alpha, Beta, Gamma, and Delta variants were boosted, although to a lesser extent for Omicron. CONCLUSIONS: In PWH receiving a third vaccine dose, there were significant increases in B- and T-cell immunity, including to known variants of concern (VOCs).

Experiences of pain in paediatric chronic fatigue syndrome/myalgic encephalomyelitis: a single-centre qualitative study.

BACKGROUND: Moderate to severe pain affects up to two-thirds of children with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and is associated with worse fatigue and physical functioning. This research aims to gain a greater insight into pain experienced by these children. METHODS: Thematic analysis of qualitative data from semistructured interviews with 13 children with CFS/ME (mean age=15.3 years, 67% female) was completed. RESULTS: Thematic analysis enabled construction of three themes: children's wide-ranging experiences of pain, negative impact of pain and lack of effective treatment for pain and nine subthemes. The first theme demonstrated highly varied pain experiences, ranging from 'like [being]… on fire', like 'being stabbed' to 'like…lead'. Children experienced pain in multiple sites and with wide-ranging frequency and severity. The second theme highlighted the profound negative impact of pain on multiple aspects of children's lives. Physical activity was severely impaired; some children 'couldn't leave bed' or 'couldn't…brush [their] own hair'. Abdominal pain meant some would 'go…days without eating'. Pain substantially impacted on mental health, leaving children feeling 'agitated', experiencing 'really bad panic attacks' or making them '[want to] breakdown'. Children felt they 'can't do the things that everyone else can do', had 'missed out' and are 'behind everyone'. Some avoided socialising as they 'don't want to stop everyone else'. The final theme demonstrates the absence of adequate treatment for pain, with participants reporting 'nothing has ever really got rid of it' and only 'slightly [takes] the edge off' and other experiencing side effects. CONCLUSIONS: Pain in paediatric CFS/ME is highly variable, common and often results in severe physical limitation and poor mental health. Effective treatments for pain represent an unmet need.

Persistence of immunogenicity after seven COVID-19 vaccines given as third dose boosters following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK: Three month analyses of the COV-BOOST trial.

OBJECTIVES: To evaluate the persistence of immunogenicity three months after third dose boosters. METHODS: COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of seven COVID-19 vaccines used as a third booster dose. The analysis was conducted using all randomised participants who were SARS-CoV-2 naïve during the study. RESULTS: Amongst the 2883 participants randomised, there were 2422 SARS-CoV-2 naïve participants until D84 visit included in the analysis with median age of 70 (IQR: 30-94) years. In the participants who had two initial doses of ChAdOx1 nCov-19 (Oxford-AstraZeneca; hereafter referred to as ChAd), schedules using mRNA vaccines as third dose have the highest anti-spike IgG at D84 (e.g. geometric mean concentration of 8674 ELU/ml (95% CI: 7461-10,085) following ChAd/ChAd/BNT162b2 (Pfizer-BioNtech, hearafter referred to as BNT)). However, in people who had two initial doses of BNT there was no significant difference at D84 in people given ChAd versus BNT (geometric mean ratio (GMR) of 0.95 (95%CI: 0.78, 1.15). Also, people given Ad26.COV2.S (Janssen; hereafter referred to as Ad26) as a third dose had significantly higher anti-spike IgG at D84 than BNT (GMR of 1.20, 95%CI: 1.01,1.43). Responses at D84 between people who received BNT (15 µg) or BNT (30 µg) after ChAd/ChAd or BNT/BNT were similar, with anti-spike IgG GMRs of half-BNT (15 µg) versus BNT (30 µg) ranging between 0.74-0.86. The decay rate of cellular responses were similar between all the vaccine schedules and doses. CONCLUSIONS: 84 days after a third dose of COVID-19 vaccine the decay rates of humoral response were different between vaccines. Adenoviral vector vaccine anti-spike IgG concentrations at D84 following BNT/BNT initial doses were similar to or even higher than for a three dose (BNT/BNT/BNT) schedule. Half dose BNT immune responses were similar to full dose responses. While high antibody tires are desirable in situations of high transmission of new variants of concern, the maintenance of immune responses that confer long-lasting protection against severe disease or death is also of critical importance. Policymakers may also consider adenoviral vector, fractional dose of mRNA, or other non-mRNA vaccines as third doses.

Loneliness and mental health in children and adolescents with pre-existing mental health problems: A rapid systematic review.

OBJECTIVES: Periods of social isolation are associated with loneliness in children and young people, and loneliness is associated with poor mental and physical health. Children and young people with pre-existing mental health difficulties may be prone to loneliness. Containment of COVID-19 has necessitated widespread social isolation, with unprecedented school closures and restrictions imposed on social interactions. This rapid review aimed to establish what is known about the relationship between loneliness and mental health problems in children and young people with pre-existing mental health problems. METHODS: We sought to identify all primary research that examined the cross-sectional and longitudinal associations between loneliness/perceived social isolation and mental health in children and young people with pre-existing mental health problems. We also aimed to identify effective interventions that reduce the adverse impact of loneliness. A rapid systematic search was conducted using MEDLINE, PsycINFO, and Web of Science. RESULTS: Of 4,531 papers screened, 15 included children and young people with pre-existing mental health conditions. These 15 studies included 1,536 children and young people aged between 6 and 23 years with social phobia, anxiety and/or depression, and neurodevelopmental disorders. Loneliness was associated with anxiety and depression both cross-sectionally and prospectively in children and young people with mental health problems and neurodevelopmental conditions. We found preliminary evidence that psychological treatments can help to reduce feelings of loneliness in this population. CONCLUSIONS: Loneliness is associated with depression and anxiety in children and young people with pre-existing mental health conditions, and this relationship may be bidirectional. Existing interventions to address loneliness and/or mental health difficulties in other contexts may be applied to this population, although they may need adaptation and testing in younger children and adolescents. PRACTITIONER POINTS: Loneliness is common in children and young people, and during periods of enforced social isolation such as during COVID-19, children and young people report high levels of loneliness (or increased rates of loneliness). The review showed that loneliness is associated, both cross-sectionally and prospectively, in children and young people with mental health problems and also in children and young people with neurodevelopmental conditions, such as autism spectrum disorder. Thus, loneliness is a possible risk factor of which mental health providers should be aware. Maintaining social contact both by direct and by indirect means, especially through the Internet, could be important in mitigating loneliness. Interventions to address loneliness should be further developed and tested to help children and young people with pre-existing mental health problems who are lonely by preventing exacerbation of their mental health difficulties, in particular anxiety and depression.

Late unexpected complete fracture of a right ventricular lead still capturing the myocardium.

A 72-year-old man presented for routine dual chamber pacemaker interrogation 13 years following insertion for sick sinus syndrome. Increased noise, impedance and threshold of the right ventricular (RV) lead were identified. RV capture was maintained with an overall RV pacing burden of 47%. A routine generator replacement was scheduled alongside RV lead replacement. Fluoroscopy at the start of the procedure revealed an unexpected striking fracture of the RV pacing lead with complete separation of the proximal and distal portions within the RV. The patient was asymptomatic and described no predisposing factors. He underwent implantation of a new ventricular lead and generator and has remained well. This case demonstrates clear RV lead fracture as a late complication of pacemaker implantation despite maintained capture. This emphasises the need for a chest X-ray when a change in device parameters is noted at device interrogation even in the absence of symptoms.

Recovery from chronic fatigue syndrome: a systematic review-heterogeneity of definition limits study comparison.

BACKGROUND: Paediatric chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) is a common illness with a major impact on quality of life. Recovery is poorly understood. Our aim was to describe definitions of recovery in paediatric CFS/ME, the rate of recovery and the time to recovery. METHODS: This systematic review included a detailed search of MEDLINE, EMBASE, PsycInfo and Cochrane Library between 1994 and July 2018. Inclusion criteria were (1) clinical trials and observational studies, (2) participants aged <19 years with CFS/ME, (3) conducted in Western Healthcare systems and (4) studies including a measure of recovery and time taken to recover. RESULTS: Twelve papers (10 studies) were identified, involving 826 patients (range 23-135). Recovery rates were highly varied, ranging between 4.5% and 83%.Eleven distinct definitions of recovery were used; six were composite outcomes while five used unidimensional outcomes. Outcome measures used to define recovery were highly heterogeneous. School attendance (n=8), fatigue (n=6) and physical functioning (n=4) were the most common outcomes included in definition of recovery. Only five definitions included a personal measure of recovery. IMPLICATIONS: Definitions of recovery are highly variable, likely secondary to differences in study design, outcomes used, follow-up and study populations. Heterogeneous definitions of recovery limit meaningful comparison between studies, highlighting the need for a consensus definition going forward. Recovery is probably best defined from the child's own perspective with a single self-reported measure. If composite measures are used for research, there should be agreement on the core outcome set used.

Who should we ask about mental health symptoms in adolescents with CFS/ME? Parent-child agreement on the revised children's anxiety and depression scale.

BACKGROUND: One in three adolescents with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) have mental health problems. Multi-informant perspectives are key to psychological assessment. Understanding parent-child agreement is crucial to accurate diagnosis, particularly where severe fatigue limits self-report. METHODS: Agreement on the revised children's anxiety and depression scale (RCADs) was assessed between parents and children with CFS/ME (n = 93) using Bland-Altman plots, cross tabulations and regression analyses. RESULTS: Diagnostic thresholds were met more frequently based on child-report. Parent- and child-report had similar sensitivity and specificity on RCADS compared to gold-standard diagnostic interviews. Regression analysis found similar accuracy between both reports. For anxiety diagnoses, odds ratio (OR) for child-report was 1.10 (CI = 1.06-1.14), and 1.10 (CI = 1.05-1.14) for parent-report. For depression, OR for child report was 1.26 (CI = 1.11-1.43), while for parent-report is was 1.25 (CI = 1.10-1.41). For total score, OR for child-report was 1.10 (CI = 1.05-1.13) while OR for parent-report was 1.09 (CI = 1.05-1.13). CONCLUSIONS: Reasonable agreement was observed between parent- and child-report of mental health symptoms in paediatric CFS/ME. While parent-report can facilitate psychological evaluation in CFS/ME, this is not a substitute for a child's own report.

Digital Behavior Change Interventions for Younger Children With Chronic Health Conditions: Systematic Review.

BACKGROUND: The prevalence of chronic health conditions in childhood is increasing, and behavioral interventions can support the management of these conditions. Compared with face-to-face treatment, the use of digital interventions may be more cost-effective, appealing, and accessible, but there has been inadequate attention to their use with younger populations (children aged 5-12 years). OBJECTIVE: This systematic review aims to (1) identify effective digital interventions, (2) report the characteristics of promising interventions, and (3) describe the user's experience of the digital intervention. METHODS: A total of 4 databases were searched (Excerpta Medica Database [EMBASE], PsycINFO, Medical Literature Analysis and Retrieval System Online [MEDLINE], and the Cochrane Library) between January 2014 and January 2019. The inclusion criteria for studies were as follows: (1) children aged between 5 and 12 years, (2) interventions for behavior change, (3) randomized controlled trials, (4) digital interventions, and (5) chronic health conditions. Two researchers independently double reviewed papers to assess eligibility, extract data, and assess quality. RESULTS: Searches run in the databases identified 2643 papers. We identified 17 eligible interventions. The most promising interventions (having a beneficial effect and low risk of bias) were 3 targeting overweight or obesity, using exergaming or social media, and 2 for anxiety, using web-based cognitive behavioral therapy (CBT). Characteristics of promising interventions included gaming features, therapist support, and parental involvement. Most were purely behavioral interventions (rather than CBT or third wave), typically using the behavior change techniques (BCTs) feedback and monitoring, shaping knowledge, repetition and substitution, and reward. Three papers included qualitative data on the user's experience. We developed the following themes: parental involvement, connection with a health professional is important for engagement, technological affordances and barriers, and child-centered design. CONCLUSIONS: Of the 17 eligible interventions, digital interventions for anxiety and overweight or obesity had the greatest promise. Using qualitative methods during digital intervention development and evaluation may lead to more meaningful, usable, feasible, and engaging interventions, especially for this underresearched younger population. The following characteristics could be considered when developing digital interventions for younger children: involvement of parents, gaming features, additional therapist support, behavioral (rather than cognitive) approaches, and particular BCTs (feedback and monitoring, shaping knowledge, repetition and substitution, and reward). This review suggests a model for improving the conceptualization and reporting of behavioral interventions involving children and parents.

Interventions to treat pain in paediatric CFS/ME: a systematic review.

BACKGROUND: Paediatric chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is common (prevalence 1%-2%). Two-thirds of children experience moderate or severe pain, which is associated with increased fatigue and poorer physical function. However, we do not know if treatment for CFS/ME improves pain. OBJECTIVE: Identify whether specialist treatment of paediatric CFS/ME improves pain. METHODS: We conducted a detailed search in MEDLINE, EMBASE, PsycINFO and the Cochrane Library. Two researchers independently screened texts published between 1994 and 24 January 2019 with no language restrictions. Inclusion criteria were (1) randomised controlled trials and observational studies; (2) participants aged <19 years with CFS/ME; and (3) measure of pain before and after an intervention. RESULTS: Of 1898 papers screened, 26 studies investigated treatment for paediatric CFS/ME, 19 of which did not measure pain at any time point. Only five treatment studies measured pain at baseline and follow-up and were included in this review. None of the interventions were specifically targeted at treating pain. Of the included studies, two showed no improvement in pain scores, one suggested an improvement in one subgroup and two studies identified improvements in pain measures in 'recovered' patients compared with 'non-recovered' patients. CONCLUSIONS: Despite the prevalence and impact of pain in children with CFS/ME surprisingly few treatment studies measured pain. In those that did measure pain, the treatments used focused on overall management of CFS/ME and we identified no treatments that were targeted specifically at managing pain. There is limited evidence that treatment helps improve pain scores. However, patients who recover appear to have less pain than those who do not recover. More studies are needed to determine if pain in paediatric CFS/ME requires a specific treatment approach, with a particular focus on patients who do not recover following initial treatment. PROSPERO REGISTRATION NUMBER: CRD42019117540.