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.

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.

Functional somatic symptoms in preschool attention-deficit/hyperactivity disorder: a secondary analysis of data from a randomized controlled trial of parent training.

Children with attention-deficit/hyperactivity disorder (ADHD) can be more stress-vulnerable, and thereby, it has been suggested, prone to develop functional somatic symptoms (FSS) compared to their peers. In this paper, using data from 160 children aged 3-7 years with ADHD from the D'SNAPP study, a randomized controlled trial testing a parent training intervention, we addressed a number of questions about the role of FSS in ADHD. First, are FSS levels higher in an ADHD sample than in the children of the general population. Second, do FSS levels predict psychopathology and health-related quality of life (HRQoL) in ADHD samples. Third, does FSS levels moderate the effect of parent training on ADHD symptoms. We found that preschoolers with ADHD experienced more severe FSS than a general population-based sample (18.80% vs. 2.11%). Severe FSS were associated with increased psychopathology and impaired daily function and lower HRQoL. Level of baseline FSS did not moderate the effect of parent training on ADHD. FSS in preschool children with ADHD is associated with impaired daily functioning, but further research is warranted to determine the clinical impact of FSS in children with ADHD.

The management of ADHD in children and adolescents: bringing evidence to the clinic: perspective from the European ADHD Guidelines Group (EAGG).

ADHD is the most common neurodevelopmental disorder presenting to child and adolescent mental health, paediatric, and primary care services. Timely and effective interventions to address core ADHD symptoms and co-occurring problems are a high priority for healthcare and society more widely. While much research has reported on the benefits and adverse effects of different interventions for ADHD, these individual research reports and the reviews, meta-analyses and guidelines summarizing their findings are sometimes inconsistent and difficult to interpret. We have summarized the current evidence and identified several methodological issues and gaps in the current evidence that we believe are important for clinicians to consider when evaluating the evidence and making treatment decisions. These include understanding potential impact of bias such as inadequate blinding and selection bias on study outcomes; the relative lack of high-quality data comparing different treatments and assessing long-term effectiveness, adverse effects and safety for both pharmacological and non-pharmacological treatments; and the problems associated with observational studies, including those based on large national registries and comparing treatments with each other. We highlight key similarities across current international clinical guidelines and discuss the reasons for divergence where these occur. We discuss the integration of these different perspective into a framework for person/family-centered evidence-based practice approach to care that aims to achieve optimal outcomes that prioritize individual strengths and impairments, as well as the personal treatment targets of children and their families. Finally, we consider how access to care for this common and impairing disorder can be improved in different healthcare systems.

A self-help version of the New Forest Parenting Programme for parents of children with attention deficit hyperactivity disorder: a qualitative study of parent views and acceptability.

BACKGROUND: Although parent interventions are recommended as a frontline treatment approach for children with attention deficit hyperactivity disorder (ADHD), a number of practical and situational barriers can impact accessibility and availability. Self-help parent interventions offer a potential alternative to therapist-led interventions when barriers prevent access to face-to-face treatment. This qualitative study aims to explore participant views and acceptability of self-help parent interventions. METHOD: Semi-structured interviews were conducted with parents/carers of 12 children (age 6-10 years) with ADHD who received the self-help version of the New Forest Parenting Programme (NFPP-SH) as part of a randomised controlled trial. Thematic analysis (as proposed by Braun and Clarke) was used to analyse the data. RESULTS: Overall, participants had favourable views of the self-help intervention but also experienced some barriers to treatment adherence. Six key themes were identified in parent interviews related to parental desire to learn more; acquisition of new skills; the flexibility of the intervention; self-help intervention vs. traditional therapist-led formats; barriers to engagement in the home environment; and need for earlier access to help. CONCLUSIONS: NFPP-SH was an acceptable intervention for parents. However, some parents may need additional support to overcome barriers associated with completing an intervention at home. Implications for healthcare providers and researchers developing self-help parent interventions for ADHD and child behaviour are discussed.

Metal Ion Control of Photoinduced Electron Spin Polarization in Electronic Ground States.

Both the sign and intensity of photoinduced electron spin polarization (ESP) in the electronic ground state doublet (2S0/D0) of chromophore-radical complexes can be controlled by changing the nature of the metal ion. The complexes consist of an organic radical (nitronyl nitroxide, NN) covalently attached to a donor-acceptor chromophore via a m-phenylene bridge, (bpy)M(CAT-m-Ph-NN) (1) (bpy = 4,4'-di-tert-butyl-2,2'-bipyridine, M = PdII (1-Pd) or PtII (1-Pt), CAT = 3-tert-butylcatecholate, m-Ph = meta-phenylene). In both complexes, photoexcitation with visible light produces an initial exchange-coupled, three-spin (bpy•-, CAT•+ = semiquinone (SQ), and NN•), charge-separated doublet 2S1 (S = chromophore excited spin singlet configuration) excited state that rapidly decays to the ground state via a 2T1 (T = chromophore excited spin triplet configuration) state. This process is not expected to be spin selective, and only very weak emissive ESP is found for 1-Pd. In contrast, strong absorptive ESP is generated in 1-Pt. It is postulated that zero-field-splitting-induced transitions between the chromophoric 2T1 and 4T1 states (1-Pd and 1-Pt) and spin-orbit-induced transitions between 2T1 and NN-based quartet states (1-Pt) account for the differences in polarization.

Efficacy of a self-help parenting intervention for parents of children with attention deficit hyperactivity disorder in adjunct to usual treatment-Small-scale randomized controlled trial.

BACKGROUND: Multimodal intervention incorporating psychosocial intervention and medication is recommended for school-aged children with attention deficit hyperactivity disorder (ADHD). This randomized controlled trial (RCT) investigates the adjunctive benefit of the self-help version of the New Forest Parenting Programme (NFPP-SH) when offered in addition to treatment as usual (TAU) compared with TAU alone. METHOD: Fifty-two children, receiving medication for ADHD as part of their usual care, were randomized to receive NFPP-SH + TAU or TAU alone. RESULTS: When used in adjunct to TAU, NFPP-SH may have beneficial effects for parenting efficacy (F = 6.28, p = 0.02), child social performance in school and negative comments made by parents during a recorded speech sample. However, the self-help intervention did not have any additional effect on child behaviour. CONCLUSIONS: This study provides further support for self-help interventions as potentially low-intensity and cost-effective alternatives to therapist-led parenting interventions. The findings require replication in larger samples before any firm conclusions about adjunctive efficacy of NFPP-SH can be drawn but underline the potential for self-help within routine treatment (ClinicalTrials.gov Identifier: NCT02174952).

Treatment of ADHD in adults - prevalence of discontinuation and associated factors - results from a cross-sectional analysis of Danish register data.

BACKGROUND: A growing number of adults are receiving pharmacological treatment for ADHD but a sizable proportion also discontinues or have gaps in treatment. The primary aims of this study were to identify how many patients treated for ADHD in adulthood, have at least one event of discontinuation in treatment and to identify possible associated variables. METHODS: Within the Danish population aged 18-60 years on the 1st of January 2013, we identified the number of individuals who had been prescribed ADHD-medication at least once during the 1st of January 2002-31st of December 2013 using Danish register data. Among those who filed more than one prescription, treatment discontinuation was defined as having more than 211 days between two prescriptions. In crude and adjusted logistic regression analysis, we explored potential associations to discontinuation for variables such as gender and age at treatment initiation. RESULTS: In a population, if N = 3,165,844 individuals, n = 42,892 had received at least one prescription for ADHD medication. Among those with more than one prescription (N = 38,289), 29.4% had discontinued their treatment at least once, according to our definition of treatment discontinuation. ADHD treatment discontinuation was associated with being male, unemployment, lower educational attainment, receiving incapacity benefits and younger age at treatment initiation (p < 0.001). CONCLUSIONS: A large proportion of individuals treated for ADHD had at least one discontinuation of treatment according to our definition. Although the present study does not allow for investigating the direction of these effects, nor whether some patients later resumed treatment, having at least one discontinuation was associated with a range of variables relating to e.g. age and gender, and provides an emerging profile for clinicians of patients more likely to discontinue.

Wave Function Control of Charge-Separated Excited-State Lifetimes.

Control of excited-state processes is crucial to an increasing number of important device technologies that include displays, photocatalysts, solar energy conversion devices, photovoltaics, and photonics. However, the manipulation and control of electronic excited-state lifetimes and properties continue to be a challenge for molecular scientists. Herein, we present the results of ground-state and transient absorption spectroscopies as they relate to magnetic exchange control of excited-state lifetimes. We describe a novel mechanism for controlling these excited-state lifetimes that involves varying the magnetic exchange interaction between a stable organic radical and the unpaired electrons present in the open-shell configuration of a charge-separated excited state. Specifically, we show that the excited-state lifetime can be controlled in a predictable manner based on an a priori knowledge of the pairwise magnetic exchange interactions between excited-state spins. These magnetic exchange couplings affect the excited-state electronic structure in a manner that introduces variable degrees of spin forbiddenness into the nonradiative decay channel between the excited state and the electronic ground state.

Cognitive profile and determinants of poor cognition in people without dementia in Parkinson's disease.

Background: The Montreal Cognitive Assessment (MoCA) has been recommended as a cognitive screening tool for clinical practice and research in Parkinson's disease (PD), yet no normative data have been published for MoCA in PD without dementia. Methods: We undertook a pooled secondary analysis of data from two studies (one cross-sectional design and one clinical trial) conducted in the East of England region. All participants were aged 18 years or over, met UK Brain Bank criteria for PD and did not have clinical dementia. Cognitive status was assessed using MoCA at baseline in both studies. The influences of age, gender, disease duration, medication load (LEDD) and mood (HADS) on cognition were examined using regression analysis. Results: Data from 101 people with PD without dementia were available (mean age 71 years, 66% men). Median (IQR) MoCA was 25(22, 27). Age was found as the only predictor of MoCA in this sample. People aged over 71 had poorer MoCA (Beta=0.6 (95%CI 0.44, 0.82)) and an increased odds of MoCA <26 (Beta=0.29 (95%CI 0.12, 0.70)) as well as poorer scores on several MoCA sub-domains. Conclusion: We present the normative data for MoCA in people with PD without clinical dementia. Age appeared to be the only associated factor for lower level of cognition, suggestive of Mild cognitive impairment in PD (PD-MCI) in PD without clinical diagnosis of dementia.

A novel role for osteopontin in macrophage-mediated amyloid-ß clearance in Alzheimer's models.

Osteopontin (OPN), a matricellular immunomodulatory cytokine highly expressed by myelomonocytic cells, is known to regulate immune cell migration, communication, and response to brain injury. Enhanced cerebral recruitment of monocytes achieved through glatiramer acetate (GA) immunization or peripheral blood enrichment with bone marrow (BM)-derived CD115+ monocytes (MoBM) curbs amyloid ß-protein (Aß) neuropathology and preserves cognitive function in murine models of Alzheimer's disease (ADtg mice). To elucidate the beneficial mechanisms of these immunomodulatory approaches in AD, we focused on the potential role of OPN in macrophage-mediated Aß clearance. Here, we found extensive OPN upregulation along with reduction of vascular and parenchymal Aß burden in cortices and hippocampi of GA-immunized ADtg mice. Treatment combining GA with blood-grafted MoBM further increased OPN levels surrounding residual Aß plaques. In brains from AD patients and ADtg mice, OPN was also elevated and predominantly expressed by infiltrating GFP+- or Iba1+-CD45high monocyte-derived macrophages engulfing Aß plaques. Following GA immunization, we detected a significant increase in a subpopulation of inflammatory blood monocytes (CD115+CD11b+Ly6Chigh) expressing OPN, and subsequently, an elevated population of OPN-expressing CD11b+Ly6C+CD45high monocyte/macrophages in the brains of these ADtg mice. Correlogram analyses indicate a strong linear correlation between cerebral OPN levels and macrophage infiltration, as well as a tight inverse relation between OPN and Aß-plaque burden. In vitro studies corroborate in vivo findings by showing that GA directly upregulates OPN expression in BM-derived macrophages (MФBM). Further, OPN promotes a phenotypic shift that is highly phagocytic (increased uptake of Aß fibrils and surface scavenger receptors) and anti-inflammatory (altered cell morphology, reduced iNOS, and elevated IL-10 and Aß-degrading enzyme MMP-9). Inhibition of OPN expression in MФBM, either by siRNA, knockout (KOOPN), or minocycline, impairs uptake of Aß fibrils and hinders GA's neuroprotective effects on macrophage immunological profile. Addition of human recombinant OPN reverses the impaired Aß phagocytosis in KOOPN-MФBM. This study demonstrates that OPN has an essential role in modulating macrophage immunological profile and their ability to resist pathogenic forms of Aß.

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.

Practitioner Review: Current best practice in the use of parent training and other behavioural interventions in the treatment of children and adolescents with attention deficit hyperactivity disorder.

BACKGROUND: Behavioural interventions are recommended for use with children and young people with attention deficit hyperactivity disorder (ADHD); however, specific guidance for their implementation based on the best available evidence is currently lacking. METHODS: This review used an explicit question and answer format to address issues of clinical concern, based on expert interpretation of the evidence with precedence given to meta-analyses of randomised controlled trials. RESULTS: On the basis of current evidence that takes into account whether outcomes are blinded, behavioural intervention cannot be supported as a front-line treatment for core ADHD symptoms. There is, however, evidence from measures that are probably blinded that these interventions benefit parenting practices and improve conduct problems which commonly co-occur with ADHD, and are often the main reason for referral. Initial positive results have also been found in relation to parental knowledge, children's emotional, social and academic functioning - although most studies have not used blinded outcomes. Generic and specialised ADHD parent training approaches - delivered either individually or in groups - have reported beneficial effects. High-quality training, supervision of therapists and practice with the child, may improve outcomes but further evidence is required. Evidence for who benefits the most from behavioural interventions is scant. There is no evidence to limit behavioural treatments to parents with parenting difficulties or children with conduct problems. There are positive effects of additive school-based intervention for the inattentive subtype. Targeting parental depression may enhance the effects of behavioural interventions. CONCLUSIONS: Parent training is an important part of the multimodal treatment of children with ADHD, which improves parenting, reduces levels of oppositional and noncompliant behaviours and may improve other aspects of functioning. However, blinded evidence does not support it as a specific treatment for core ADHD symptoms. More research is required to understand how to optimise treatment effectiveness either in general or for individual patients and explore potential barriers to treatment uptake and engagement. In terms of selecting which intervention formats to use, it seems important to acknowledge and respond to parental treatment preferences.

Clearance of cerebral Aß in Alzheimer's disease: reassessing the role of microglia and monocytes.

Deficiency in cerebral amyloid ß-protein (Aß) clearance is implicated in the pathogenesis of the common late-onset forms of Alzheimer's disease (AD). Accumulation of misfolded Aß in the brain is believed to be a net result of imbalance between its production and removal. This in turn may trigger neuroinflammation, progressive synaptic loss, and ultimately cognitive decline. Clearance of cerebral Aß is a complex process mediated by various systems and cell types, including vascular transport across the blood-brain barrier, glymphatic drainage, and engulfment and degradation by resident microglia and infiltrating innate immune cells. Recent studies have highlighted a new, unexpected role for peripheral monocytes and macrophages in restricting cerebral Aß fibrils, and possibly soluble oligomers. In AD transgenic (ADtg) mice, monocyte ablation or inhibition of their migration into the brain exacerbated Aß pathology, while blood enrichment with monocytes and their increased recruitment to plaque lesion sites greatly diminished Aß burden. Profound neuroprotective effects in ADtg mice were further achieved through increased cerebral recruitment of myelomonocytes overexpressing Aß-degrading enzymes. This review summarizes the literature on cellular and molecular mechanisms of cerebral Aß clearance with an emphasis on the role of peripheral monocytes and macrophages in Aß removal.

A comparison of the clinical effectiveness and cost of specialised individually delivered parent training for preschool attention-deficit/hyperactivity disorder and a generic, group-based programme: a multi-centre, randomised controlled trial of the New Forest Parenting Programme versus Incredible Years.

The objective of this study is to compare the efficacy and cost of specialised individually delivered parent training (PT) for preschool children with attention-deficit/hyperactivity disorder (ADHD) against generic group-based PT and treatment as usual (TAU). This is a multi-centre three-arm, parallel group randomised controlled trial conducted in National Health Service Trusts. The participants included in this study were preschool children (33-54 months) fulfilling ADHD research diagnostic criteria. New Forest Parenting Programme (NFPP)-12-week individual, home-delivered ADHD PT programme; Incredible Years (IY)-12-week group-based, PT programme initially designed for children with behaviour problems were the interventions. Primary outcome-Parent ratings of child's ADHD symptoms (Swanson, Nolan & Pelham Questionnaire-SNAP-IV). Secondary outcomes-teacher ratings (SNAP-IV) and direct observations of ADHD symptoms and parent/teacher ratings of conduct problems. NFPP, IY and TAU outcomes were measured at baseline (T1) and post treatment (T2). NFPP and IY outcomes only were measured 6 months post treatment (T3). Researchers, but not therapists or parents, were blind to treatment allocation. Analysis employed mixed effect regression models (multiple imputations). Intervention and other costs were estimated using standardized approaches. NFPP and IY did not differ on parent-rated SNAP-IV, ADHD combined symptoms [mean difference - 0.009 95% CI (- 0.191, 0.173), p = 0.921] or any other measure. Small, non-significant, benefits of NFPP over TAU were seen for parent-rated SNAP-IV, ADHD combined symptoms [- 0.189 95% CI (- 0.380, 0.003), p = 0.053]. NFPP significantly reduced parent-rated conduct problems compared to TAU across scales (p values < 0.05). No significant benefits of IY over TAU were seen for parent-rated SNAP, ADHD symptoms [- 0.16 95% CI (- 0.37, 0.04), p = 0.121] or parent-rated conduct problems (p > 0.05). The cost per family of providing NFPP in the trial was significantly lower than IY (£1591 versus £2103). Although, there were no differences between NFPP and IY with regards clinical effectiveness, individually delivered NFPP cost less. However, this difference may be reduced when implemented in routine clinical practice. Clinical decisions should take into account parental preferences between delivery approaches.

Study of user experience of an objective test (QbTest) to aid ADHD assessment and medication management: a multi-methods approach.

BACKGROUND: The diagnosis and monitoring of Attention deficit hyperactivity disorder (ADHD) typically relies on subjective reports and observations. Objective continuous performance tests (CPTs) have been incorporated into some services to support clinical decision making. However, the feasibility and acceptability of adding such a test into routine practice is unknown. The study aimed to investigate the feasibility and acceptability of adding an objective computerised test to the routine assessment and monitoring of attention deficit hyperactivity disorder (ADHD). METHODS: Semi-structured interviews were conducted with clinicians (n = 10) and families (parents/young people, n = 20) who participated in a randomised controlled trial. Additionally, the same clinicians (n = 10) and families (n = 76) completed a survey assessing their experience of the QbTest. The study took place in child and adolescent mental health and community paediatric clinics across the UK. Interview transcripts were thematically analysed. RESULTS: Interviewed clinicians and families valued the QbTest for providing an objective, valid assessment of symptoms. The QbTest was noted to facilitate communication between clinicians, families and schools. However, whereas clinicians were more unanimous on the usefulness of the QbTest, survey findings showed that, although the majority of families found the test useful, less than half felt the QbTest helped them understand the clinician's decision making around diagnosis and medication. The QbTest was seen as a potentially valuable tool to use early in the assessment process to streamline the care pathway. Although clinicians were conscious of the additional costs, these could be offset by reductions in time to diagnosis and the delivery of the test by a Healthcare Assistant. CONCLUSIONS: The findings indicate the QbTest is an acceptable and feasible tool to implement in routine clinical settings. Clinicians should be mindful to discuss the QbTest results with families to enable their understanding and engagement with the process. Further findings from definitive trials are required to understand the cost/benefit; however, the findings from this study support the feasibility and acceptability of integrating QbTest in the ADHD care pathway. TRIAL REGISTRATION: The findings form the implementation component of the Assessing QbTest Utility in ADHD (AQUA) Trial which is registered with the ISRCTN registry ( ISRCTN11727351 , retrospectively registered 04 July 2016) and clinicaltrials.gov ( NCT02209116 , registered 04 August 2014).

Impulsivity and self-harm in adolescence: a systematic review.

Research supports an association between impulsivity and self-harm, yet inconsistencies in methodology across studies have complicated understanding of this relationship. This systematic review examines the association between impulsivity and self-harm in community-based adolescents aged 11-25 years and aims to integrate findings according to differing concepts and methods. Electronic searches of EMBASE, MEDLINE, PsychINFO, CINAHL, PubMed and The Cochrane Library, and manual searches of reference lists of relevant reviews identified 4496 articles published up to July 2015, of which 28 met inclusion criteria. Twenty-four of the studies reported an association between broadly specified impulsivity and self-harm. However, findings varied according to the conception and measurement of impulsivity and the precision with which self-harm behaviours were specified. Specifically, lifetime non-suicidal self-injury was most consistently associated with mood-based impulsivity-related traits. However, cognitive facets of impulsivity (relating to difficulties maintaining focus or acting without forethought) differentiated current self-harm from past self-harm. These facets also distinguished those with thoughts of self-harm (ideation) from those who acted on thoughts (enaction). The findings suggested that mood-based impulsivity is related to the initiation of self-harm, while cognitive facets of impulsivity are associated with the maintenance of self-harm. In addition, behavioural impulsivity is most relevant to self-harm under conditions of negative affect. Collectively, the findings indicate that distinct impulsivity facets confer unique risks across the life-course of self-harm. From a clinical perspective, the review suggests that interventions focusing on reducing rash reactivity to emotions or improving self-regulation and decision making may offer most benefit in supporting those who self-harm.

Therapeutic effects of glatiramer acetate and grafted CD115⁺ monocytes in a mouse model of Alzheimer's disease.

Weekly glatiramer acetate immunization of transgenic mice modelling Alzheimer's disease resulted in retained cognition (Morris water maze test), decreased amyloid-ß plaque burden, and regulation of local inflammation through a mechanism involving enhanced recruitment of monocytes. Ablation of bone marrow-derived myeloid cells exacerbated plaque pathology, whereas weekly administration of glatiramer acetate enhanced cerebral recruitment of innate immune cells, which dampened the pathology. Here, we assessed the therapeutic potential of grafted CD115(+) monocytes, injected once monthly into the peripheral blood of transgenic APPSWE/PS1ΔE9 Alzheimer's disease mouse models, with and without weekly immunization of glatiramer acetate, as compared to glatiramer acetate alone. All immune-modulation treatment groups were compared with age-matched phosphate-buffered saline-injected control transgenic and untreated non-transgenic mouse groups. Two independent cohorts of mice were assessed for behavioural performance (6-8 mice/group); treatments started in 10-month-old symptomatic mice and spanned a total of 2 months. For all three treatments, our data suggest a substantial decrease in cognitive deficit as assessed by the Barnes maze test (P < 0.0001-0.001). Improved cognitive function was associated with synaptic preservation and reduction in cerebral amyloid-ß protein levels and astrogliosis (P < 0.001 and P < 0.0001), with no apparent additive effects for the combined treatment. The peripherally grafted, green fluorescent protein-labelled and endogenous monocytes, homed to cerebral amyloid plaques and directly engulfed amyloid-ß; their recruitment was further enhanced by glatiramer acetate. In glatiramer acetate-immunized mice and, moreover, in the combined treatment group, monocyte recruitment to the brain was coupled with greater elevation of the regulatory cytokine IL10 surrounding amyloid-ß plaques. All treated transgenic mice had increased cerebral levels of MMP9 protein (P < 0.05), an enzyme capable of degrading amyloid-ß, which was highly expressed by the infiltrating monocytes. In vitro studies using primary cultures of bone marrow monocyte-derived macrophages, demonstrated that glatiramer acetate enhanced the ability of macrophages to phagocytose preformed fibrillar amyloid-ß1-42 (P < 0.0001). These glatiramer acetate-treated macrophages exhibited increased expression of the scavenger receptors CD36 and SCARA1 (encoded by MSR1), which can facilitate amyloid-ß phagocytosis, and the amyloid-ß-degrading enzyme MMP9 (P < 0.0001-0.001). Overall, our studies indicate that increased cerebral infiltration of monocytes, either by enrichment of their levels in the circulation or by weekly immunization with glatiramer acetate, resulted in substantial attenuation of disease progression in murine Alzheimer's models by mechanisms that involved enhanced cellular uptake and enzymatic degradation of toxic amyloid-ß as well as regulation of brain inflammation.

The clinical utility of the continuous performance test and objective measures of activity for diagnosing and monitoring ADHD in children: a systematic review.

Attention-deficit hyperactivity disorder (ADHD) is typically diagnosed using clinical observation and subjective informant reports. Once children commence ADHD medication, robust monitoring is required to detect partial or non-responses. The extent to which neuropsychological continuous performance tests (CPTs) and objective measures of activity can clinically aid the assessment and titration process in ADHD is not fully understood. This review describes the current evidence base for the use of CPTs and objectively measured activity to support the diagnostic procedure and medication management for children with ADHD. Four databases (PsycINFO, Medline, Allied and Complementary Medicine (AMED), and PsycARTICLES) were systematically searched to understand the current evidence base for (1) the use of CPTs to aid clinical assessment of ADHD; (2) the use of CPTs to aid medication management; and (3) the clinical utility of objective measures of activity in ADHD. Sixty relevant articles were identified. The search revealed six commercially available CPTs that had been reported on for their clinical use. There were mixed findings with regard to the use of CPTs to assess and manage medication, with contrasting evidence on their ability to support clinical decision-making. There was a strong evidence base for the use of objective measures of activity to aid ADHD/non-ADHD group differentiation, which appears sensitive to medication effects and would also benefit from further research on their clinical utility. The findings suggest that combining CPTs and an objective measure of activity may be particularly useful as a clinical tool and worthy of further pursuit.

The impact of ADHD on the health and well-being of ADHD children and their siblings.

Childhood attention-deficit/hyperactivity disorder (ADHD) has been associated with reduced health and well-being of patients and their families. The authors undertook a large UK survey-based observational study of the burden associated with childhood ADHD. The impact of ADHD on both the patient (N = 476) and their siblings (N = 337) on health-related quality of life (HRQoL) and happiness was quantified using multiple standard measures [e.g. child health utility-9D (CHU-9D), EuroQol-5D-Youth]. In the analysis, careful statistical adjustments were made to ensure a like-for-like comparison of ADHD families with two different control groups. We controlled for carers' ADHD symptoms, their employment and relationship status and siblings' ADHD symptoms. ADHD was associated with a significant deficit in the patient's HRQoL (with a CHU-9D score of around 6 % lower). Children with ADHD also have less sleep and were less happy with their family and their lives overall. No consistent decrement to the HRQoL of the siblings was identified across the models, except that related to their own conduct problems. The siblings do, however, report lower happiness with life overall and with their family, even when controlling for the siblings own ADHD symptoms. We also find evidence of elevated bullying between siblings in families with a child with ADHD. Overall, the current results suggest that the reduction in quality of life caused by ADHD is experienced both by the child with ADHD and their siblings.

Practitioner Review: Pathways to care for ADHD - a systematic review of barriers and facilitators.

BACKGROUND: Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder starting in childhood that may persist into adulthood. It can be managed through carefully monitored medication and nonpharmacological interventions. Access to care for children at risk of ADHD varies both within and between countries. A systematic literature review was conducted to investigate the research evidence related to factors which influence children accessing services for ADHD. METHOD: Studies investigating access to care for children at risk of ADHD were identified through electronic searches of the international peer-reviewed and grey literature. Databases were searched from inception till 30th April 2012. This identified 23,156 articles which were subjected to three levels of screening (title, abstract and full text) by a minimum of two independent reviewers. Due to the heterogeneity in the study designs, a narrative approach was used to present the findings. RESULTS: Twenty-seven papers met the inclusion criteria; these were grouped into four main themes, with some papers being included in more than one. These were wider determinants (10 papers); identification of need (9 papers); entry and continuity of care (13 papers) and interventions to improve access (4 papers). Barriers and facilitators to access were found to operate at the individual, organisational and societal level. Limited evidence of effective interventions to improve access was identified. CONCLUSION: This review explored the multilayered obstacles in the pathway to care for children at risk of ADHD and the lack of evidence-based interventions designed to address these issues, thereby indicating areas for service development and further evaluative research.