Chemokine Receptor Redundancy and Specificity Are Context Dependent.

Currently, we lack an understanding of the individual and combinatorial roles for chemokine receptors in the inflammatory process. We report studies on mice with a compound deletion of Ccr1, Ccr2, Ccr3, and Ccr5, which together control monocytic and eosinophilic recruitment to resting and inflamed sites. Analysis of resting tissues from these mice, and mice deficient in each individual receptor, provides clear evidence for redundant use of these receptors in establishing tissue-resident monocytic cell populations. In contrast, analysis of cellular recruitment to inflamed sites provides evidence of specificity of receptor use for distinct leukocyte subtypes and no indication of comprehensive redundancy. We find no evidence of involvement of any of these receptors in the recruitment of neutrophils or lymphocytes to resting or acutely inflamed tissues. Our data shed important light on combinatorial inflammatory chemokine receptor function and highlight Ccr2 as the primary driver of myelomonocytic cell recruitment in acutely inflamed contexts.

Parental awareness and attitudes towards prevention of respiratory syncytial virus in infants and young children in Australia.

AIM: To assess parental awareness of respiratory syncytial virus (RSV) and the level of acceptance of future RSV prevention strategies. METHODS: A cross-sectional online survey was implemented targeting "future" and "current" parents of children aged ≤5 years in Australia. RESULTS: From 1992 eligible participants, two non-mutually exclusive subgroups were formed: "current" parents (N = 1931) and "pregnant/planning" parents (N = 464: 403 also "current" parents and 61 "future" parents). Participants were predominantly (86.6%) aged 25-39 years and 68.5% with university education. The majority (89.6% current; 78.7% future) had heard of RSV. Of those, 64.2% (current) and 50.0% (future) were aware that pneumonia is associated with RSV; 71.8% (current) and 52.1% (future) were aware that bronchiolitis is associated with RSV. In multivariable logistic regression analyses, Australian-born parents (aOR = 2.47 [95% CI: 1.48-4.12]), living in the eastern states (e.g., New South Wales: aOR = 6.15 [95% CI:2.10-18.04]), with a university-level education (aOR = 2.61 [95% CI:1.38-4.94]) and being a current parent (aOR = 12.26 [95% CI:2.82-53.28]) were associated with higher RSV awareness. There was a high level of acceptance for maternal vaccines (future: 79.3%) and infant immunisation (all: 81.7%). CONCLUSION: While RSV awareness and immunisation acceptance were high, there was limited knowledge of severity of RSV, especially in future parents. Education campaigns need to be developed to increase RSV knowledge.

The association between proton pump inhibitors and hyperparathyroidism: a potential mechanism for increased fracture-results of a large observational cohort study.

Proton pump inhibitors (PPIs) are associated with increased risk of osteoporotic fracture; however, the mechanism is unclear. PPI users taking calcium supplements were more likely to have hyperparathyroidism compared to non-users (OR 1.56, CI 1.08-2.23, p = 0.018). This highlights the importance of monitoring PPI use, especially in older adults. PURPOSE: Proton pump inhibitors (PPIs) are associated with increased risk of osteoporotic fracture. Hyperparathyroidism may be implicated, but few studies have considered this relationship. This study evaluated the relationship between PPI use and hyperparathyroidism in older adults. METHODS: Participants were from the TUDA study, a large cross-sectional cohort of older Irish adults. Participants with an estimated glomerular filtration rate (eGFR) < 30 ml/min and serum calcium > 2.5 mmol/l were excluded to avoid hyperparathyroidism due to chronic renal disease and primary hyperparathyroidism. Hyperparathyroidism was defined as a parathyroid hormone (PTH) > 65 pg/ml. Multivariate regression models were used to analyse the relationship between PPI use and hyperparathyroidism. RESULTS: A total of 4139 participants met the inclusion criteria, of whom 37.8% (n = 1563) were taking PPI medication. PPI use was identified in 41.4% of calcium supplement users and 35.4% of non-calcium supplement users. Overall, compared to non-users of PPIs, those taking PPIs were older (74.8 vs 72.9 years, p < 0.001) and had a higher prevalence of hyperparathyroidism (17.8 vs 11.0%, p < 0.001). In those taking calcium supplements (but not in non-users), PPI use was significantly associated with hyperparathyroidism (OR 1.56, CI 1.08-2.23, p = 0.018) after adjusting for age, sex, body mass index, serum vitamin D, eGFR, timed-up-and-go, dairy intake, medications, and comorbidities. DISCUSSION: The results are consistent with the hypothesis of PPIs reducing calcium absorption, leading to a rise in PTH which could mediate increased fracture risk. No relationship of PPI use with hyperparathyroidism was observed in non-users of calcium supplements, possibly owing to lower dietary calcium intake. These results highlight the importance of monitoring PPI use, especially in older adults at risk of fracture.

West Australian parents' views on vaccinating their children against COVID-19: a qualitative study.

BACKGROUND: Australian children and adolescents were among the last local cohorts offered COVID-19 vaccines. Despite promising initial uptake, coverage subsequently plateaued, requiring further efforts to improve access and build parents' recognition of the importance of COVID-19 vaccination. We sought to understand West Australian (WA) parents' willingness to vaccinate their children to inform strategies for improving uptake at the time in which they were becoming eligible. METHODS: We undertook in-depth qualitative interviews with 30 parents of children aged 5-17 years from June - December 2021. During this period, children aged 12-15 years became eligible for vaccination; children aged 5-11 years became eligible shortly thereafter. Data were thematically analysed in NVivo. RESULTS: Most parents intended on vaccinating their children once eligible. Parents sought to protect their children, to protect the community, to resume travel, and to get back to "normal". They reflected that vaccination against key infectious threats is a routine activity in childhood. Some were concerned about the vaccine, particularly mRNA vaccines, being new technology or impacting fertility. "Wait-awhiles" wanted to see what other parents would do or were delaying until they felt that there was a higher risk of COVID-19 in WA. Most parents of younger children wanted their child to be vaccinated at the general practice clinic due to familiarity and convenience. Parents were particularly eager for clear and consistent messaging about vaccination of children and adolescents, including safety, importance, scientific evidence, and personal stories. CONCLUSION: For future pandemic vaccinations pertaining to children, governments and health officials need to address parents' concerns and meet their preferences for the delivery of the vaccine program to children and adolescents.

Reduced kidney function is associated with poorer domain-specific cognitive performance in community-dwelling older adults.

OBJECTIVES: Whilst chronic kidney disease has been associated with cognitive impairment, the association between reduced estimated Glomerular Filtration Rate (eGFR) and domain-specific cognitive performance is less clear and may represent an important target for the promotion of optimal brain health in older adults. METHODS: Participants aged >60 years from the Trinity-Ulster-Department of Agriculture study underwent detailed cognitive assessment using the Mini-Mental State Examination (Mini-Mental State Examination (MMSE)), Frontal Assessment Battery (FAB) and Repeatable Battery for Assessment of Neuropsychological Status (RBANS). Poisson and linear regression models assessed the relationship between eGFR strata and cognitive performance. RESULTS: In 4887 older adults (73.9 ± 8.3 years; 67.7% female), declining eGFR strata was associated with greater likelihood of error on the MMSE/FAB and poorer overall performance on the RBANS. Following robust covariate adjustment, findings were greatest for GFR <45 ml/ml/1.73 m2 (Incidence Rate Ratio: 1.17; 95% CI 1.08, 1.27; p < 0.001 for MMSE; IRR: 1.13; 95% CI 1.04, 1.13; p < 0.001 for FAB; ß: -3.66; 95% CI -5.64, -1.86; p < 0.001 for RBANS). Additionally, eGFR <45 ml/ml/1.73 m2 was associated with poorer performance on all five RBANS domains, with greatest effect sizes for immediate memory, delayed memory and attention. Associations were strongest in those aged 60-70, with no associations observed in those >80 years. CONCLUSIONS: Reduced kidney function was associated with poorer global and domain-specific neuropsychological performance. Associations were strongest with eGFR <45 ml/min/1.73 m2 and in those aged 60-70 years, suggesting that this population may potentially benefit from potential multi-domain interventions aimed at promoting optimal brain health in older adults.

Impact of the MTHFR C677T polymorphism on blood pressure and related central haemodynamic parameters in healthy adults.

BACKGROUND: The C677T polymorphism in the gene-encoding methylenetetrahydrofolate reductase (MTHFR) is associated with an increased risk of hypertension and cardiovascular disease. Riboflavin, the MTHFR cofactor, is an important modulator of blood pressure (BP) in adults homozygous for this polymorphism (TT genotype). The effect of this genetic variant on BP and related central haemodynamic parameters in healthy adults has not been previously investigated and was examined in this study. METHODS: Brachial BP, central BP and pulse wave velocity (PWV, SphygmoCor XCEL) were measured in adults aged 18-65 years prescreened for MTHFR genotype. Riboflavin status was assessed using the erythrocyte glutathione reductase activation coefficient assay. RESULTS: Two hundred and forty-two adults with the MTHFR 677TT genotype and age-matched non-TT (CC/CT) genotype controls were identified from a total cohort of 2546 adults prescreened for MTHFR genotype. The TT genotype was found to be an independent determinant of hypertension (p = 0.010), along with low-riboflavin status (p = 0.002). Brachial systolic and diastolic BP were higher in TT versus non-TT adults by 5.5 ± 1.2 and 2.4 ± 0.9 mmHg, respectively (both p < 0.001). A stronger phenotype was observed in women, with an almost 10 mmHg difference in mean systolic BP in TT versus non-TT genotype groups: 134.9 (95% confidence interval [CI] 132.1-137.6) versus 125.2 (95% CI 122.3-128.0) mmHg; p < 0.001. In addition, PWV was faster in women with the TT genotype (p = 0.043). CONCLUSION: This study provides the first evidence that brachial and central BP are significantly higher in adults with the variant MTHFR 677TT genotype and that the BP phenotype is more pronounced in women.

Dietary zinc and the control of Streptococcus pneumoniae infection.

Human zinc deficiency increases susceptibility to bacterial infection. Although zinc supplementation therapies can reduce the impact of disease, the molecular basis for protection remains unclear. Streptococcus pneumoniae is a major cause of bacterial pneumonia, which is prevalent in regions of zinc deficiency. We report that dietary zinc levels dictate the outcome of S. pneumoniae infection in a murine model. Dietary zinc restriction impacts murine tissue zinc levels with distribution post-infection altered, and S. pneumoniae virulence and infection enhanced. Although the activation and infiltration of murine phagocytic cells was not affected by zinc restriction, their efficacy of bacterial control was compromised. S. pneumoniae was shown to be highly sensitive to zinc intoxication, with this process impaired in zinc restricted mice and isolated phagocytic cells. Collectively, these data show how dietary zinc deficiency increases sensitivity to S. pneumoniae infection while revealing a role for zinc as a component of host antimicrobial defences.

Glycated haemoglobin (HbA1c ), diabetes and neuropsychological performance in community-dwelling older adults.

AIMS: Given that diabetes is associated with cognitive impairment and dementia in later life, we aimed to investigate the relationship between glycated haemoglobin (HbA1c ), diabetes and domain-specific neuropsychological performance in older adults. METHODS: Cross-sectional cohort study using data from the Trinity-Ulster-Department of Agriculture (TUDA) study. Participants underwent detailed cognitive and neuropsychological assessment using the Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB) and Repeatable Assessment for Neuropsychological Status (RBANS). Linear regression was used to assess associations between HbA1c , diabetes status and neuropsychological performance, with adjustment for important clinical covariates. RESULTS: Of 4938 older adults (74.1 ± 8.3 years; 66.9% female), 16.3% (n = 803) had diabetes (HbA1c  ≥ 6.5%; 48 mmol/mol), with prediabetes (HbA1c  ≥ 5.7%-6.4%; 39-47 mmol/mol) present in 28.3% (n = 1395). Increasing HbA1c concentration was associated with poorer overall performance on the FAB [ß: -0.01 (-0.02, -0.00); p = 0.04 per % increase] and RBANS [ß = -0.66 (-1.19, -0.13); p = 0.02 per % increase]. Increasing HbA1c was also associated with poorer performance on immediate memory, visuo-spatial, language and attention RBANS domains. Diabetes was associated poorer performance on neuropsychological tests of immediate memory, language, visual-spatial and attention. CONCLUSIONS: Both increasing HbA1c and the presence of diabetes were associated with poorer cognitive and domain-specific performance in older adults. HbA1c , and not just diabetes status per se, may represent an important target in the promotion of optimal brain health in older adults.

Long-term anticholinergic, benzodiazepine and Z-drug use in community-dwelling older adults: What is the impact on cognitive and neuropsychological performance?

BACKGROUND: Long-term use of anticholinergics, benzodiazepines and related drugs (or "Z-drugs") have been associated with cognitive impairment and dementia. However, the relationship of these medications with cognitive function and domain-specific neuropsychological performance in older adults without dementia, is unclear. METHODS: 5135 older adults (74.0 ± 8.3 years; 67.4% female) without a diagnosis of dementia were recruited in Ireland to the Trinity-Ulster-Department of Agriculture (TUDA) study. Detailed cognitive and neuropsychological assessment was conducted using the Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB) and Repeatable Battery for Assessment of Neuropsychological Status (RBANS). RESULTS: A total of 44% (2259 of 5153) used either a potential or definite anticholinergic medication. Overall, 9.7% (n = 500) used a definite anticholinergic medication. Regular benzodiazepine use was reported by 7% (n = 363), whilst 7.5% (n = 387) used a "Z-drug". Use of definite, but not potential anticholinergic medication was associated with poorer performance on all three assessments (ß: -0.09; 95% CI: -0.14, -0.03, p = 0.002 for MMSE; ß: -0.04; 95% CI: -0.06, -0.02; p < 0.001 for FAB; ß: -4.15; 95% CI: -5.64, -2.66; p < 0.001 for RBANS) in addition to all domains of the RBANS. Regular benzodiazepine use was also associated with poorer neuropsychological test performance, especially in Immediate Memory (ß: -4.98; 95% CI: -6.81, -3.15; p < 0.001) and Attention (ß: -6.81; 95% CI: -8.60, -5.03; p < 0.001) RBANS domains. CONCLUSIONS: Regular use of definite anticholinergic medications and benzodiazepines, but not potential anticholinergics or "Z-drugs", was associated with poorer overall and domain-specific neuropsychological performance in older adults.

A qualitative systematic review and thematic synthesis exploring the impacts of clinical academic activity by healthcare professionals outside medicine.

BACKGROUND: There are increasing opportunities for healthcare professionals outside medicine to be involved in and lead clinical research. However, there are few roles within these professions that include time for research. In order to develop such roles, and evaluate effective use of this time, the range of impacts of this clinical academic activity need to be valued and understood by healthcare leaders and managers. To date, these impacts have not been comprehensively explored, but are suggested to extend beyond traditional quantitative impact metrics, such as publications, citations and funding awards. METHODS: Ten databases, four grey literature repositories and a naïve web search engine were systematically searched for articles reporting impacts of clinical academic activity by healthcare professionals outside medicine. Specifically, this did not include the direct impacts of the research findings, rather the impacts of the research activity. All stages of the review were performed by a minimum of two reviewers and reported impacts were categorised qualitatively according to a modified VICTOR (making Visible the ImpaCT Of Research) framework. RESULTS: Of the initial 2704 identified articles, 20 were eligible for inclusion. Identified impacts were mapped to seven themes: impacts for patients; impacts for the service provision and workforce; impacts to research profile, culture and capacity; economic impacts; impacts on staff recruitment and retention; impacts to knowledge exchange; and impacts to the clinical academic. CONCLUSIONS: Several overlapping sub-themes were identified across the main themes. These included the challenges and benefits of balancing clinical and academic roles, the creation and implementation of new evidence, and the development of collaborations and networks. These may be key areas for organisations to explore when looking to support and increase academic activity among healthcare professionals outside medicine. The modified VICTOR tool is a useful starting point for individuals and organisations to record the impact of their research activity. Further work is needed to explore standardised methods of capturing research impact that address the full range of impacts identified in this systematic review and are specific to the context of clinical academics outside medicine.

Correction: A Direct-to-Public Peer Support Program (Big White Wall) Versus Web-Based Information to Aid the Self-management of Depression and Anxiety: Results and Challenges of an Automated Randomized Controlled Trial.

[This corrects the article DOI: 10.2196/23487.].

A Direct-to-Public Peer Support Program (Big White Wall) Versus Web-Based Information to Aid the Self-management of Depression and Anxiety: Results and Challenges of an Automated Randomized Controlled Trial.

BACKGROUND: Effective help for depression and anxiety reaches a small proportion of people who might benefit from it. The scale of the problem suggests the need for effective, safe web-based public health services delivered directly to the public. One model, the Big White Wall (BWW), offers peer support at low cost. As these interventions are delivered digitally, we tested whether a randomized controlled trial (RCT) intervention could also be fully delivered and evaluated digitally. OBJECTIVE: This study aims to determine the reach, feasibility, acceptability, baseline costs, and outcomes of a public health campaign for an automated RCT of the BWW, providing digital peer support and information, compared with a standard website used by the National Health Service Moodzone (MZ), to people with probable mild-to-moderate depression and anxiety disorder. The primary outcome was the change in self-rated well-being at 6 weeks, measured using the Warwick-Edinburgh Mental Well-Being Scale. METHODS: An 18-month campaign was conducted across Nottinghamshire, the United Kingdom (target population 914,000) to advertise the trial directly to the public through general marketing, web-based and social media sources, health services, other public services, and third-sector groups. The population reach of this campaign was examined by the number of people accessing the study website and self-registering to the study. A pragmatic, parallel-group, single-blind RCT was then conducted using a fully automated trial website in which eligible participants were randomized to receive either 6 months of access to BWW or signposted to MZ. Those eligible for participation were aged >16 years with probable mild-to-moderate depression or anxiety disorders. RESULTS: Of 6483 visitors to the study website, 1510 (23.29%) were eligible. Overall, 790 of 1510 (52.32%) visitors participated. Of 790 visitors, 397 (50.3%) were randomized to BWW and 393 (49.7%) to MZ. Their mean age was 38 (SD 13.8) years, 81.0% (640/790) were female, 93.4% (738/790) were White, and 47.4% (271/572) had no contact with health services in the previous 3 months. We estimated 3-month productivity losses of £1001.01 (95% CI 868.75-1133.27; US $1380.79; 95% CI 1198.35-1563.23) per person for those employed. Only 16.6% (131/790) participants completed the primary outcome assessment. There were no differences in the primary or secondary outcomes between the 2 groups. CONCLUSIONS: Most participants reached and those eligible for this trial of digital interventions were White women not in recent contact with health services and whose productivity losses represent a significant annual societal burden. A fully automated RCT recruiting directly from the public failed to recruit and retain sufficient participants to test the clinical effectiveness of this digital intervention, primarily because it did not personally engage participants and explain how these unfamiliar interventions might benefit them. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN) 12673428; https://www.isrctn.com/ISRCTN12673428. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/resprot.8061.

Impact of the common MTHFR 677C→T polymorphism on blood pressure in adulthood and role of riboflavin in modifying the genetic risk of hypertension: evidence from the JINGO project.

BACKGROUND: Genome-wide and clinical studies have linked the 677C→T polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR) with hypertension, whilst limited evidence shows that intervention with riboflavin (i.e. the MTHFR co-factor) can lower blood pressure (BP) in hypertensive patients with the variant MTHFR 677TT genotype. We investigated the impact of this common polymorphism on BP throughout adulthood and hypothesised that riboflavin status would modulate the genetic risk of hypertension. METHODS: Observational data on 6076 adults of 18-102 years were drawn from the Joint Irish Nutrigenomics Organisation project, comprising the Trinity-Ulster Department of Agriculture (TUDA; volunteer sample) and the National Adult Nutrition Survey (NANS; population-based sample) cohorts. Participants were recruited from the Republic of Ireland and Northern Ireland (UK) in 2008-2012 using standardised methods. RESULTS: The variant MTHFR 677TT genotype was identified in 12% of adults. From 18 to 70 years, this genotype was associated with an increased risk of hypertension (i.e. systolic BP ≥ 140 and/or a diastolic BP ≥ 90 mmHg): odds ratio (OR) 1.42, 95% confidence interval (CI) 1.07 to 1.90; P = 0.016, after adjustment for antihypertensive drug use and other significant factors, namely, age, male sex, BMI, alcohol and total cholesterol. Low or deficient biomarker status of riboflavin (observed in 30.2% and 30.0% of participants, respectively) exacerbated the genetic risk of hypertension, with a 3-fold increased risk for the TT genotype in combination with deficient riboflavin status (OR 3.00, 95% CI, 1.34-6.68; P = 0.007) relative to the CC genotype combined with normal riboflavin status. Up to 65 years, we observed poorer BP control rates on antihypertensive treatment in participants with the TT genotype (30%) compared to those without this variant, CT (37%) and CC (45%) genotypes (P < 0.027). CONCLUSIONS: The MTHFR 677TT genotype is associated with higher BP independently of homocysteine and predisposes adults to an increased risk of hypertension and poorer BP control with antihypertensive treatment, whilst better riboflavin status is associated with a reduced genetic risk. Riboflavin intervention may thus offer a personalised approach to prevent the onset of hypertension in adults with the TT genotype; however, this requires confirmation in a randomised trial in non-hypertensive adults.

Riboflavin Is an Important Determinant of Vitamin B-6 Status in Healthy Adults.

BACKGROUND: Riboflavin is required to generate the active form of vitamin B-6 (pyridoxal 5'-phosphate; PLP) in tissues, but the relevance of this metabolic interaction for nutritional status of vitamin B-6 is unclear because riboflavin biomarkers are rarely measured in human studies. OBJECTIVES: The purpose of this study was to identify the determinants of biomarkers of vitamin B-6 and riboflavin status and to examine the relationship between these nutrients in healthy adults. METHODS: Multiple linear regression was performed on observational data in 407 healthy adults aged 18-92 y who did not use B-vitamin supplements. Vitamin B-6 status was assessed by plasma PLP concentrations and erythrocyte glutathione reductase activation coefficient (EGRac) was used as a functional indicator of riboflavin status. RESULTS: Dietary intakes of vitamin B-6 and riboflavin were below the average requirements in 10% and 29% of participants, respectively. Suboptimal status of vitamin B-6 (PLP ≤30.0 nmol/L) was more prevalent in adults aged ≥60 y than in younger participants (i.e., 14% compared with 5%), whereas a high proportion (i.e., overall 37%) of both age groups had deficient riboflavin status (EGRac ≥1.40). In multiple regression analysis, EGRac (P = 0.019) was a significant determinant of plasma PLP, along with dietary vitamin B-6 intake (P = 0.003), age (P < 0.001), BMI (kg/m2) (P = 0.031), and methylenetetrahydrofolate reductase gene (MTHFR) genotype (P < 0.001). Significant determinants of EGRac were dietary riboflavin intake (P < 0.001), age (P < 0.001) and MTHFR genotype (P = 0.020). Plasma PLP showed a stepwise decrease across riboflavin status categories from optimal (EGRac ≤1.26) to low (EGRac 1.27-1.39) to deficient status (P = 0.001), independent of dietary vitamin B-6 intake. CONCLUSIONS: The findings are consistent with the known metabolic dependency of vitamin B-6 on riboflavin status and indicate that riboflavin may be the limiting nutrient, particularly in older people, for maintaining adequate vitamin B-6 status.

GRAPPA Trainees Symposium 2019: A Report from the GRAPPA 2019 Annual Meeting.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) held a trainees symposium at its 2019 annual meeting in Paris, France. Rheumatology and dermatology trainees engaged in psoriasis or psoriatic arthritis research presented their work. This report briefly reviews 5 oral presentations and 19 posters presented at the meeting.

Clinical and economic outcomes of remotely delivered cognitive behaviour therapy versus treatment as usual for repeat unscheduled care users with severe health anxiety: a multicentre randomised controlled trial.

BACKGROUND: It is challenging to engage repeat users of unscheduled healthcare with severe health anxiety in psychological help and high service costs are incurred. We investigated whether clinical and economic outcomes were improved by offering remote cognitive behaviour therapy (RCBT) using videoconferencing or telephone compared to treatment as usual (TAU). METHODS: A single-blind, parallel group, multicentre randomised controlled trial was undertaken in primary and general hospital care. Participants were aged ≥18 years with ≥2 unscheduled healthcare contacts within 12 months and scored >18 on the Health Anxiety Inventory. Randomisation to RCBT or TAU was stratified by site, with allocation conveyed to a trial administrator, research assessors masked to outcome. Data were collected at baseline, 3, 6, 9 and 12 months. The primary outcome was change in HAI score from baseline to six months on an intention-to-treat basis. Secondary outcomes were generalised anxiety, depression, physical symptoms, function and overall health. Health economics analysis was conducted from a health service and societal perspective. RESULTS: Of the 524 patients who were referred and assessed for trial eligibility, 470 were eligible and 156 (33%) were recruited; 78 were randomised to TAU and 78 to RCBT. Compared to TAU, RCBT significantly reduced health anxiety at six months, maintained to 9 and 12 months (mean change difference HAI -2.81; 95% CI -5.11 to -0.50; P = 0.017). Generalised anxiety, depression and overall health was significantly improved at 12 months, but there was no significant change in physical symptoms or function. RCBT was strictly dominant with a net monetary benefit of £3,164 per participant at a willingness to pay threshold of £30,000. No treatment-related adverse events were reported in either group. CONCLUSIONS: RCBT may reduce health anxiety, general anxiety and depression and improve overall health, with considerable reductions in health and informal care costs in repeat users of unscheduled care with severe health anxiety who have previously been difficult to engage in psychological treatment. RCBT may be an easy-to-implement intervention to improve clinical outcome and save costs in one group of repeat users of unscheduled care. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov on 19 Nov 2014 with reference number NCT02298036.

Feasibility of a randomised controlled trial of remotely delivered problem-solving cognitive behaviour therapy versus usual care for young people with depression and repeat self-harm: lessons learnt (e-DASH).

BACKGROUND: Self-harm and depression are strong risk factors for repeat self-harm and suicide. We aimed to investigate the feasibility of a randomised controlled trial (RCT) of remotely delivered problem-solving cognitive behaviour therapy (PSCBT) plus treatment as usual (TAU) versus TAU in young people with repeat self-harm and depression. METHODS: Single-blind multi-centre RCT with an internal pilot, pre-set stop-go criteria and qualitative semi-structured interviews. Eligible participants (aged 16-30 years) were recruited from 9 adult or child and adolescent self-harm and crisis services; had ≥ 2 lifetime self-harm episodes, one in the preceding 96 h; and Beck Depression Inventory-II (BDI-II) score ≥ 17. Participants were randomised (1:1) to either TAU or TAU and 10-12 sessions of PSCBT delivered by mobile phone or video-calling. RESULTS: Twenty-two participants were recruited (11 in each arm), 10 (46%) completed follow-up at 6 months, 9 (82%) started the PSCBT and 4 (36%) completed it. The study did not meet three of its four stop-go criteria, reflecting considerable barriers to recruitment and retention. Participants had severe depression symptoms: with mean BDI-II 38.9 in the PSCBT and 37.2 in TAU groups, respectively. Three (14%) unblindings occurred for immediate safety concerns. Barriers to recruitment and retention included lack of agency for participants, severity of depression, recency of crisis with burden for participants and clinicians who diagnosed depression according to pervasiveness. CONCLUSIONS: RCTs of PSCBT for young people with depression and self-harm are not feasible using recruitment through mental health services that conduct assessments following self-harm presentations. Clinician assessment following self-harm presentation mainly identifies those with severe rather than mild-moderate depression. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT02377011 ); Date of registration: March 3rd 2015. Retrospectively registered: within 21 days of recruitment of the first participant.

The impact of a computerised test of attention and activity (QbTest) on diagnostic decision-making in children and young people with suspected attention deficit hyperactivity disorder: single-blind randomised controlled trial.

BACKGROUND: Diagnosis of attention deficit hyperactivity disorder (ADHD) relies on subjective methods which can lead to diagnostic uncertainty and delay. This trial evaluated the impact of providing a computerised test of attention and activity (QbTest) report on the speed and accuracy of diagnostic decision-making in children with suspected ADHD. METHODS: Randomised, parallel, single-blind controlled trial in mental health and community paediatric clinics in England. Participants were 6-17 years-old and referred for ADHD diagnostic assessment; all underwent assessment-as-usual, plus QbTest. Participants and their clinician were randomised to either receive the QbTest report immediately (QbOpen group) or the report was withheld (QbBlind group). The primary outcome was number of consultations until a diagnostic decision confirming/excluding ADHD within 6-months from baseline. Health economic cost-effectiveness and cost utility analysis was conducted. Assessing QbTest Utility in ADHD: A Randomised Controlled Trial was registered at ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT02209116). RESULTS: One hundred and thirty-two participants were randomised to QbOpen group (123 analysed) and 135 to QbBlind group (127 analysed). Clinicians with access to the QbTest report (QbOpen) were more likely to reach a diagnostic decision about ADHD (hazard ratio 1.44, 95% CI 1.04-2.01). At 6-months, 76% of those with a QbTest report had received a diagnostic decision, compared with 50% without. QbTest reduced appointment length by 15% (time ratio 0.85, 95% CI 0.77-0.93), increased clinicians' confidence in their diagnostic decisions (odds ratio 1.77, 95% CI 1.09-2.89) and doubled the likelihood of excluding ADHD. There was no difference in diagnostic accuracy. Health economic analysis showed a position of strict dominance; however, cost savings were small suggesting that the impact of providing the QbTest report within this trial can best be viewed as 'cost neutral'. CONCLUSIONS: QbTest may increase the efficiency of ADHD assessment pathway allowing greater patient throughput with clinicians reaching diagnostic decisions faster without compromising diagnostic accuracy.

The relationship between adiposity and cognitive function in a large community-dwelling population: data from the Trinity Ulster Department of Agriculture (TUDA) ageing cohort study.

Previous reports investigating adiposity and cognitive function in the population allude to a negative association, although the relationship in older adults is unclear. The aim of this study was to investigate the association of adiposity (BMI and waist:hip ratio (WHR)) with cognitive function in community-dwelling older adults (≥60 years). Participants included 5186 adults from the Trinity Ulster Department of Agriculture ageing cohort study. Neuropsychological assessment measures included the Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB) and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Multi-variable linear regression models were used to assess the association between adiposity and cognitive function adjusting for insulin resistance, inflammation and cerebrovascular disease. The mean ages were 80·3 (sd 6·7), 71·0 (sd 7·3) and 70·2 (sd 6·3) years on the cognitive, bone and hypertensive cohorts, respectively. In the cognitive cohort, BMI was positively associated with immediate and delay memory, visuospatial/constructional ability, language and MMSE, and negatively with FAB (log-transformed), whereas WHR was negatively associated with attention. In the bone cohort, BMI was not associated with any cognitive domain, whereas WHR was negatively associated with visuospatial/constructional ability, attention and MMSE. In the hypertensive cohort, BMI was not associated with any cognitive domain, whereas WHR was negatively associated with immediate and delayed memory, visuospatial/constructional ability, language and MMSE and positively with FAB (log-transformed). In the cognitive and bone cohorts, the association of WHR and attention disappeared by further controlling for C-reactive protein and HbA1C. In this study of older adults, central adiposity was a stronger predictor of poor cognitive performance than BMI. Older adults could benefit from targeted public health strategies aimed at reducing obesity and obeseogenic risk factors to avoid/prevent/slow cognitive dysfunction.