Legal capacity, developmental capacity, and impaired mental capacity in children under 16: Neurodevelopment and the law in Northern Ireland.

When people of any age, despite all possible support being provided, are unable to make a necessary decision, then it is important to have a legal framework which promotes and protects their rights. There is ongoing debate about how this can be achieved, in a non-discriminatory way, for adults but it is also an important consideration for children and young people. In Northern Ireland, the Mental Capacity Act (Northern Ireland) 2016, when fully implemented will provide a non-discriminatory framework for those aged 16 and over. Arguably this addresses discrimination based on disability but continues to discriminate based on age. This article explores some of the possible ways the rights of those aged under 16 could be further promoted and protected. These approaches may include: retaining the current combination of statute law but developing new guidance to inform practice for those aged under 16; codifying Gillick to clarify under what circumstances those aged under 16 can accept, and possibly also refuse, interventions; amend the Children (Northern Ireland) Order 1995 to provide a more comprehensive framework for health and welfare decision making; amend and extend the Mental Capacity Act (Northern Ireland) 2016 to apply to those aged under 16; or develop a new law specifically focused on the emerging capacity of those aged under 16. There are complex issues involved including how to consider emerging or developmental decision-making ability, and the role of those with parental responsibility, but the complexities involved should not prevent these issues being addressed.

Bioreactor-Grown Bacillus of Calmette and Guérin (BCG) Vaccine Protects Badgers against Virulent Mycobacterium bovis When Administered Orally: Identifying Limitations in Baited Vaccine Delivery.

Bovine tuberculosis (TB) in Great Britain adversely affects animal health and welfare and is a cause of considerable economic loss. The situation is exacerbated by European badgers (Meles meles) acting as a wildlife source of recurrent Mycobacterium bovis infection to cattle. Vaccination of badgers against TB is a possible means to reduce and control bovine TB. The delivery of vaccine in oral bait holds the best prospect for vaccinating badgers over a wide geographical area. There are practical limitations over the volume and concentration of Bacillus of Calmette and Guérin (BCG) that can be prepared for inclusion in bait. The production of BCG in a bioreactor may overcome these issues. We evaluated the efficacy of oral, bioreactor-grown BCG against experimental TB in badgers. We demonstrated repeatable protection through the direct administration of at least 2.0 × 108 colony forming units of BCG to the oral cavity, whereas vaccination via voluntary consumption of bait containing the same preparation of BCG did not result in demonstrable protection at the group-level, although a minority of badgers consuming bait showed immunological responses and protection after challenge equivalent to badgers receiving oral vaccine by direct administration. The need to deliver oral BCG in the context of a palatable and environmentally robust bait appears to introduce such variation in BCG delivery to sites of immune induction in the badger as to render experimental studies variable and inconsistent.

Internal validation of STRmix™ - A multi laboratory response to PCAST.

We report a large compilation of the internal validations of the probabilistic genotyping software STRmix™. Thirty one laboratories contributed data resulting in 2825 mixtures comprising three to six donors and a wide range of multiplex, equipment, mixture proportions and templates. Previously reported trends in the LR were confirmed including less discriminatory LRs occurring both for donors and non-donors at low template (for the donor in question) and at high contributor number. We were unable to isolate an effect of allelic sharing. Any apparent effect appears to be largely confounded with increased contributor number.

Low-Intensity Cognitive Behavioural Therapy-Based Music Group (CBT-Music) for the Treatment of Symptoms of Anxiety and Depression: A Feasibility Study.

BACKGROUND: Music has the potential to be an effective and engaging therapeutic intervention in the treatment of mental illness. This research area remains underdeveloped. AIMS: This paper reports the feasibility of an innovative low-intensity CBT-based music (CBT-Music) group targeted to symptoms of depression and anxiety. METHOD: A total of 28 participants with symptoms of depression and anxiety who were attending community mental health services were recruited for the study and randomized into TAU (treatment as usual) plus low-intensity CBT-Music (treatment) or to TAU alone (control). The treatment group consisted of a 9-week music group that incorporated various components of CBT material into a musical context. Feasibility was the primary outcome. The secondary outcomes were a reduction in depression, anxiety (Hospital Anxiety and Depression Scale) and disability (WHO Disability Assessment Schedule 2.0) assessed at baseline and 10 weeks. RESULTS: Recruitment proved feasible, retention rates were high, and the participants reported a high level of acceptability. A randomized control study design was successfully implemented as there were no significant differences between treatment and control groups at baseline. Participants in the treatment group showed improvement in disability (p = 0.027). Despite a reduction in depression and anxiety scores, these differences were not statistically significant. CONCLUSIONS: A low-intensity CBT-based music group can be successfully administered to clients of community mental health services. There are indications of effectiveness in reducing disability, although there appears to be negligible effect on symptoms of anxiety and depression. This is the first report of a trial of a low-intensity CBT-based music group intervention.

Preliminary evaluation of a "formulation-driven cognitive behavioral guided self-help (fCBT-GSH)" for crisis and transitional case management clients.

BACKGROUND: Cognitive behavioral therapy (CBT) is found to be effective for common mental disorders and has been delivered in self-help and guided self-help formats. Crisis and transitional case management (TCM) services play a vital role in managing clients in acute mental health crises. It is, therefore, an appropriate setting to try CBT in guided self-help format. METHODS: This was a preliminary evaluation of a formulation-driven cognitive behavioral guided self-help. Thirty-six (36) consenting participants with a diagnosis of nonpsychotic illness, attending crisis and the TCM services in Kingston, Canada, were recruited in this study. They were randomly assigned to the guided self-help plus treatment as usual (TAU) (treatment group) or to TAU alone (control group). The intervention was delivered over 8-12 weeks. Assessments were completed at baseline and 3 months after baseline. The primary outcome was a reduction in general psychopathology, and this was done using Clinical Outcomes in Routine Evaluation - Outcome Measure. The secondary outcomes included a reduction in depression, measured using the Hospital Anxiety and Depression Scale, and reduction in disability, measured using the World Health Organization Disability Assessment Schedule 2.0. FINDINGS: Participants in the treatment group showed statistically significant improvement in overall psychopathology (P<0.005), anxiety and depression (P<0.005), and disability (P<0.005) at the end of the trial compared with TAU group. CONCLUSION: A formulation-driven cognitive behavioral guided self-help was feasible for the crisis and TCM clients and can be effective in improving mental health, when compared with TAU. This is the first report of a trial of guided self-help for clients attending crisis and TCM services.

Lack of breaks is a safety risk.

Your story about staff working long shifts without breaks is nothing new (news online, 19 January, news page 9 ). It's been happening for years, because nurses let it continue.

Cognitive Behavior Therapy for psychosis based Guided Self-help (CBTp-GSH) delivered by frontline mental health professionals: Results of a feasibility study.

Availability of Cognitive Behavior Therapy for psychosis (CBTp) is limited in spite of strong evidence base. The purpose of this study was to determine the feasibility of a CBTp based Guided Self-help (CBTp-GSH) in comparison to Treatment As Usual (TAU). The secondary outcomes were a reduction of symptoms of schizophrenia using Positive and Negative Symptom Scale (PANSS) & Disability (WHO DAS 2.0). A total of 33 adults with a DSM-IV diagnosis of schizophrenia was recruited from community mental health services in Kingston, ON, Canada, and randomly assigned to the 12-16week intervention with TAU (Treatment), or TAU alone (Control). End of therapy (16weeks) comparisons between the two groups were made on an Intention To Treat (ITT) basis. Post-intervention scores on measures of psychopathology were compared using Analysis of Covariance (ANCOVA) to adjust for baseline measurements. Recruitment proved feasible, retention rates were high and participants reported a high level of acceptability. There was significant "treatment group by outcome interaction" for Positive and Negative Symptoms, General Psychopathology, measures of disability, such that individuals who received the Treatment improved more than those in Control group. The results of this feasibility study indicate that CBTp based Guided Self-help is feasible and acceptable to the participants, and it can lead to improvement in psychopathology and the level of disability. Individuals in this study had a moderate degree of psychopathology and relatively low level of disability and, therefore, caution is warranted in applying these results to individuals with severe symptoms and with high levels of disability. An adequately powered randomized controlled trial of the intervention is warranted.

Methods to place a value on additional evidence are illustrated using a case study of corticosteroids after traumatic brain injury.

OBJECTIVES: To establish whether evidence about the effectiveness of a health care intervention is sufficient to justify the use of the intervention in practice and show how value of information (VOI) analysis can be used to place a value on the need for additional evidence and inform research prioritization decisions. STUDY DESIGN AND SETTING: Meta-analysis provides an estimate of the effect of an intervention with uncertainty. VOI analysis determines the adverse health consequences of not resolving this uncertainty. A case study examining the evidence before the high profile trial of Corticosteroid Randomisation After Significant Head injury (CRASH) shows the consequences on patient outcomes if this trial had not been successfully funded. RESULTS: The consequences of uncertainty before CRASH were high at 40 deaths and 1,067 years of full health per annum. VOI analysis indicates that CRASH was worthwhile and the UK National Health Service would have had to spend an additional £205 million elsewhere to generate health benefits similar to CRASH. CONCLUSIONS: VOI analysis can be integrated with the results of meta-analysis to help inform whether a particular research proposal is potentially worthwhile and whether it should be prioritized over other research topics that could be commissioned with the same resources.

The Person and the Partner: Individual Differences Moderate the Relationship Between Partner Feedback and Condom Use.

Attachment anxiety is negatively associated with condom use; however, little research has assessed mechanisms underlying this relationship. In two studies we assessed the relationships among attachment orientations, perceived partner rejection, and condom use. In Study 1 we used a survey methodology and found that a measure of perceived partner rejection mediated the relationship between attachment anxiety and reported condom use behavior. In Study 2, women responded to condom use scenarios in which rejection was manipulated. We found a three-way interaction among attachment anxiety, attachment avoidance, and condom use intentions, such that perceived rejection from a potential sexual partner was associated with greater intentions to engage in unprotected sexual intercourse among women high in attachment anxiety and low in attachment avoidance, and among those high in attachment avoidance and low in attachment anxiety.

Unifying Research and Reimbursement Decisions: Case Studies Demonstrating the Sequence of Assessment and Judgments Required.

BACKGROUND: The key principles regarding what assessments lead to different types of guidance about the use of health technologies (Only in Research, Approval with Research, Approve, or Reject) provide an explicit and transparent framework for technology appraisal. OBJECTIVE: We aim to demonstrate how these principles and assessments can be applied in practice through the use of a seven-point checklist of assessment. METHODS: The value of access to a technology and the value of additional evidence are explored through the application of the checklist to the case studies of enhanced external counterpulsation for chronic stable angina and clopidogrel for the management of patients with non-ST-segment elevation acute coronary syndromes. RESULTS: The case studies demonstrate the importance of considering 1) the expected cost-effectiveness and population net health effects; 2) the need for evidence and whether the type of research required can be conducted once a technology is approved for widespread use; 3) whether there are sources of uncertainty that cannot be resolved by research but only over time; and 4) whether there are significant (opportunity) costs that once committed by approval cannot be recovered. CONCLUSIONS: The checklist demonstrates that cost-effectiveness is a necessary but not sufficient condition for approval. Only in Research may be appropriate when a technology is expected to be cost-effective due to significant irrecoverable costs. It is only approval that can be ruled out if a technology is not expected to be cost-effective. Lack of cost-effectiveness is not a necessary or sufficient condition for rejection.

Ipilimumab for Previously Untreated Unresectable Malignant Melanoma: A Critique of the Evidence.

The National Institute for Health and Care Excellence (NICE) invited the manufacturer of ipilimumab (Bristol-Myers Squibb Pharmaceuticals Limited) to submit clinical and cost-effectiveness evidence for previously untreated advanced (unresectable or metastatic) melanoma as part of the Institute's Single Technology Appraisal process. The Centre for Reviews and Dissemination and Centre for Health Economics at the University of York were commissioned to act as the independent Evidence Review Group (ERG). This article presents a summary of the manufacturer's submission of ipilimumab, the ERG review and the resulting NICE guidance TA319, issued in July 2014. Ipilimumab at a recommended dose of 3 mg/kg monotherapy was previously granted marketing authorisation by the European Medicines Agency in adult patients who had received prior therapy and was recommended by NICE in guidance TA268. In October 2013, the EMA approved the extension of this indication to previously untreated advanced melanoma patients. NICE decisions are bound by the marketing authorisation; therefore, the decision problem faced by the NICE Appraisal Committee was whether ipilimumab at a recommended dose of 3 mg/kg monotherapy was effective and cost effective compared with first-line standard of care involving dacarbazine (DTIC) and vemurafenib (for BRAF V600 mutation-positive patients). The CA184-024 trial was the primary source of clinical evidence for ipilimumab. However, this was based on a dose of 10 mg/kg with concomitant DTIC. The results over a 5-year period indicated that ipilimumab 10 mg/kg plus DTIC demonstrated a significant increase in median overall survival (OS) of 2.1 months compared with DTIC plus placebo (11.2 vs. 9.1 months). The BRIM-3 trial, which was an open-label randomised controlled trial (RCT) in BRAF V600 mutation-positive patients, was the primary source of evidence for an indirect comparison with vemurafenib. The results showed that vemurafenib increased median OS by 3.6 months compared with DTIC (13.2 vs. 9.6 months). The economic evaluation compared the costs and outcomes of ipilimumab by assuming that the 3 mg/kg dosing regimen was clinically equivalent in efficacy to an ipilimumab 10 mg/kg dosing regimen plus DTIC and by using a treatment sequencing approach that incorporated second-line active therapy and third-line best supportive care (BSC). In the first appraisal meeting, the committee recommended ipilimumab only in the context of research as part of a clinical study. This was primarily based on the lack of robust evidence to support the assumption of clinical equivalence between dosages and the absence of evidence available to inform the sequential use of treatments. Following the consultation, the manufacturer submitted additional analyses and evidence to support the cost effectiveness of ipilimumab at first line. The manufacturer's response was based on concerns relating to uncertainty surrounding the relative efficacy of ipilimumab 3 mg/kg monotherapy compared with DTIC and vemurafenib, comparability of the patient populations at first and second line, and the effects of concomitant DTIC. These additional analyses indicated that the incremental cost-effectiveness ratio (ICER) was £ 47,900 per quality-adjusted life-year (QALY) gained for ipilimumab compared with DTIC and £ 28,600 per QALY gained for ipilimumab compared with vemurafenib. Following consideration of the additional evidence and the responses from a large number of consultees and commentators, the committee recommended ipilimumab as an option for adults with previously untreated advanced melanoma.

Optimizing the position and use of omalizumab for severe persistent allergic asthma using cost-effectiveness analysis.

BACKGROUND: There has been some controversy on whether the costs of omalizumab outweigh its benefits for severe persistent allergic asthma. OBJECTIVES: This study aimed to resolve the uncertainties and limitations of previous analyses and establish the cost-effectiveness of omalizumab under the list price and Patient Access Scheme (PAS) discounted price for the UK National Health Service. METHODS: A decision-analytic model was developed to evaluate the long-term cost-effectiveness of omalizumab under the perspective of the National Health Service. Outcomes were expressed as quality-adjusted life-years (QALYs). Patient subgroups were defined post hoc on the basis of data collected in clinical trials: previous hospitalization, on maintenance oral corticosteroids, and three or more previous exacerbations. RESULTS: The incremental cost-effectiveness ratio varied from £30,109 to £57,557 per QALY gained depending on the population considered using the PAS price; incremental cost-effectiveness ratios were over a third higher using the list price. Omalizumab is likely to be cost-effective at the threshold of £30,000 per QALY gained in the severe subgroups if the improvement in health-related quality of life from omalizumab is mapped from an asthma-specific measure to the EuroQol five-dimensional questionnaire (vs. the EuroQol five-dimensional questionnaire directly collected from patients) or asthma mortality refers to death after hospitalization from asthma (vs. asthma-mortality risk in the community). CONCLUSIONS: Although the cost-effectiveness of omalizumab is more favorable under the PAS price, it represents good value for money only in severe subgroups and under optimistic assumptions regarding asthma mortality and improvement in health-related quality of life. For these reasons, omalizumab should be carefully targeted to ensure value for money.

Early childhood housing instability and school readiness.

This study assesses the consequences of housing instability during the first 5 years of a child's life for a host of school readiness outcomes. Using data from the Fragile Families and Child Wellbeing Study (n = 2,810), this study examines the relation between multiple moves and children's language and literacy and behavior problems at age 5. The moderating role of poverty is further tested in this relation. The findings show that moving three or more times in a child's first 5 years is significantly associated with increases in attention problems, and internalizing and externalizing behavior, but only among poor children.