[Show abstract][Hide abstract] ABSTRACT: There is policy interest in the screening and treatment of mental health problems in young people who offend, but the value of such screening is not yet known.
To assess the diagnostic test accuracy of screening measures for mental health problems in young people who offend; to evaluate the clinical effectiveness and cost-effectiveness of screening and treatment; to model estimates of cost; to assess the evidence base for screening against UK National Screening Committee criteria; and to identify future research priorities.
In total, 25 electronic databases including MEDLINE, PsycINFO, EMBASE and The Cochrane Library were searched from inception until April 2011. Reverse citation searches of included studies were undertaken and reference list of included studies were examined.
Two reviewers independently examined titles and abstracts and extracted data from included studies using a standardised form. The inclusion criteria for the review were (1) population – young offenders (aged 10–21 years); (2) intervention/instrument – screening instruments for mental health problems, implementation of a screening programme or a psychological or pharmacological intervention as part of a clinical trial; (3) comparator – for diagnostic test accuracy studies, any standardised diagnostic interview; for trials, any comparator; (4) outcomes – details of diagnostic test accuracy, mental health outcomes over the short or longer term or measurement of cost data; and (5) study design – for diagnostic test accuracy studies, any design; for screening programmes, randomised controlled trials or controlled trials; for clinical effectiveness studies, randomised controlled trials; for economic studies, economic evaluations of screening strategies or interventions.
Of 13,580 studies identified, nine, including eight independent samples, met the inclusion criteria for the diagnostic test accuracy and validity of screening measures review. Screening accuracy was typically modest. No studies examined the clinical effectiveness of screening, although 10 studies were identified that examined the clinical effectiveness of interventions for mental health problems. There were too few studies to make firm conclusions about the clinical effectiveness of treatments in this population. No studies met the inclusion criteria for the assessment of the cost-effectiveness of screening or treatment. An exemplar decision model was developed for depression, which identified a number of the likely key drivers of uncertainty, including the prevalence of unidentified mental health problems, the severity of mental health problems and their relationship to generic measures of outcome and the impact of treatment on recidivism. The information evaluated as part of the review was relevant to five of the UK National Screening Committee criteria. On the basis of the above results, none of the five criteria was met.
The conclusions of the review are based on limited evidence. Conclusions are tentative and the decision model should be treated as an exemplar.
Evidence on the clinical effectiveness and cost-effectiveness of screening for mental health problems in young people who offend is currently lacking. Future research should consider feasibility trials of clinical interventions to establish important parameters ahead of conducting definitive trials. Future diagnostic studies should compare the diagnostic test accuracy of a range of screening instruments, including those recommended for use in the UK in this population. These studies should be designed to reduce the decision uncertainty identified by the exemplar decision model.
[Show abstract][Hide abstract] ABSTRACT: Self-management support interventions can improve health outcomes, but their impact is limited by the numbers of people able or willing to access them. Men's attendance at existing self-management support services appears suboptimal despite their increased risk of developing many of the most serious long term conditions. The aim of this review was to determine whether current self-management support interventions are acceptable and accessible to men with long term conditions, and explore what may act as facilitators and barriers to access of interventions and support activities.
A systematic search for qualitative research was undertaken on CINAHL, EMBASE, MEDLINE, PsycINFO and Social Science Citation Index, in July 2013. Reference lists of relevant articles were also examined. Studies that used a qualitative design to explore men's experiences of, or perceptions towards, self-management support for one or more long term condition were included. Studies which focused on experiences of living with a long term condition without consideration of self-management support were excluded. Thirty-eight studies met the inclusion criteria. A meta-ethnography approach was employed to synthesise the findings.
Four constructs associated with men's experience of, and perceptions towards, self-management support were identified: 1) need for purpose; 2) trusted environments; 3) value of peers; and 4) becoming an expert. The synthesis showed that men may feel less comfortable participating in self-management support if it is viewed as incongruous with valued aspects of their identity, particularly when activities are perceived to challenge masculine ideals associated with independence, stoicism, and control. Men may find self-management support more attractive when it is perceived as action-oriented, having a clear purpose, and offering personally meaningful information and practical strategies that can be integrated into daily life.
Self-management support is most likely to be successful in engaging men when it is congruent with key aspects of their masculine identity. In order to overcome barriers to access and fully engage with interventions, some men may need self-management support interventions to be delivered in an environment that offers a sense of shared understanding, connectedness, and normality, and involves and/or is facilitated by men with a shared illness experience.
BMC Public Health 11/2014; 14(1):1230. · 2.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Depression accounts for the greatest disease burden of all mental health disorders, contributes heavily to healthcare costs, and by 2020 is set to become the second largest cause of global disability. Although 10% to 16% of people aged 65 years and over are likely to experience depressive symptoms, the condition is under-diagnosed and often inadequately treated in primary care. Later-life depression is associated with chronic illness and disability, cognitive impairment and social isolation. With a progressively ageing population it becomes increasingly important to refine strategies to identity and manage depression in older people. Currently, management may be limited to the prescription of antidepressants where there may be poor concordance; older people may lack awareness of psychosocial interventions and general practitioners may neglect to offer this treatment option.Methods/design: CASPER Plus is a multi-centre, randomised controlled trial of a collaborative care intervention for individuals aged 65 years and over experiencing moderate to severe depression. Selected practices in the North of England identify potentially eligible patients and invite them to participate in the study. A diagnostic interview is carried out and participants with major depressive disorder are randomised to either collaborative care or usual care. The recruitment target is 450 participants.The intervention, behavioural activation and medication management in a collaborative care framework, has been adapted to meet the complex needs of older people. It is delivered over eight to 10 weekly sessions by a case manager liaising with general practitioners.The trial aims to evaluate the clinical and cost effectiveness of collaborative care in addition to usual GP care versus usual GP care alone. The primary clinical outcome, depression severity, will be measured with the Patient Health Questionnaire-9 (PHQ-9) at baseline, 4, 12 and 18 months. Cost effectiveness analysis will assess health-related quality of life using the SF-12 and EQ-5D and will examine cost-consequences of collaborative care.A qualitative process evaluation will be undertaken to explore acceptability, gauge the extent to which the intervention is implemented and to explore sustainability beyond the clinical trial.
Results will add to existing evidence and a positive outcome may lead to the commissioning of this model of service in primary care.Trial registration: ISRCTN45842879 (24 July 2012).
[Show abstract][Hide abstract] ABSTRACT: Major depressive disorder (MDD) may be present in 10%-20% of patients in medical settings. Routine depression screening is sometimes recommended to improve depression management. However, studies of the diagnostic accuracy of depression screening tools have typically used data-driven, exploratory methods to select optimal cutoffs. Often, these studies report results from a small range of cutoff points around whatever cutoff score is most accurate in that given study. When published data are combined in meta-analyses, estimates of accuracy for different cutoff points may be based on data from different studies, rather than data from all studies for each possible cutoff point. As a result, traditional meta-analyses may generate exaggerated estimates of accuracy. Individual patient data (IPD) meta-analyses can address this problem by synthesizing data from all studies for each cutoff score to obtain diagnostic accuracy estimates. The nine-item Patient Health Questionnaire-9 (PHQ-9) and the shorter PHQ-2 and PHQ-8 are commonly recommended for depression screening. Thus, the primary objectives of our IPD meta-analyses are to determine the diagnostic accuracy of the PHQ-9, PHQ-8, and PHQ-2 to detect MDD among adults across all potentially relevant cutoff scores. Secondary analyses involve assessing accuracy accounting for patient factors that may influence accuracy (age, sex, medical comorbidity).Methods/design: Data sources will include MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, PsycINFO, and Web of Science. We will include studies that included a Diagnostic and Statistical Manual or International Classification of Diseases diagnosis of MDD based on a validated structured or semi-structured clinical interview administered within 2 weeks of the administration of the PHQ. Two reviewers will independently screen titles and abstracts, perform full article review, and extract study data. Disagreements will be resolved by consensus. Risk of bias will be assessed with the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Bivariate random-effects meta-analysis will be conducted for the full range of plausible cutoff values.
[Show abstract][Hide abstract] ABSTRACT: The 1 year prevalence of depression in adolescents is about 2%. Treatment with antidepressant medication is not recommended for initial treatment in young people due to concerns over high side effects, poor efficacy and addictive potential. Evidence suggests that cognitive behaviour therapy (CBT) is an effective treatment for depression and is currently one of the main treatment options recommended in adolescents. Given the affinity young people have with information technology they may be treated effectively, more widely and earlier in their illness evolution using computer-administered CBT (CCBT). Currently little is known about the clinical and resource implications of implementing CCBT within the National Health Service for adolescents with low mood/depression. We aim to establish the feasibility of running a fully powered randomised controlled trial (RCT).
BMJ Open 10/2014; 4(10):e006488. · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Self-harm is common among prisoners, particularly female prisoners. In 2007, concerned about the rising incidence, the prison service introduced a care-planning system called Assessment, Care in Custody, and Teamwork (ACCT). To date, it does not incorporate a standardised diagnostic test to estimate the risk of future self-harm.
[Show abstract][Hide abstract] ABSTRACT: Background
Collaborative care is a complex intervention based on chronic disease management models and is effective in the management of depression. However, there is still uncertainty about which components of collaborative care are effective. We used meta-regression to identify factors in collaborative care associated with improvement in patient outcomes (depressive symptoms) and the process of care (use of anti-depressant medication).
Methods and Findings
Systematic review with meta-regression. The Cochrane Collaboration Depression, Anxiety and Neurosis Group trials registers were searched from inception to 9th February 2012. An update was run in the CENTRAL trials database on 29th December 2013. Inclusion criteria were: randomised controlled trials of collaborative care for adults ≥18 years with a primary diagnosis of depression or mixed anxiety and depressive disorder. Random effects meta-regression was used to estimate regression coefficients with 95% confidence intervals (CIs) between study level covariates and depressive symptoms and relative risk (95% CI) and anti-depressant use. The association between anti-depressant use and improvement in depression was also explored. Seventy four trials were identified (85 comparisons, across 21,345 participants). Collaborative care that included psychological interventions predicted improvement in depression (β coefficient −0.11, 95% CI −0.20 to −0.01, p = 0.03). Systematic identification of patients (relative risk 1.43, 95% CI 1.12 to 1.81, p = 0.004) and the presence of a chronic physical condition (relative risk 1.32, 95% CI 1.05 to 1.65, p = 0.02) predicted use of anti-depressant medication.
Trials of collaborative care that included psychological treatment, with or without anti-depressant medication, appeared to improve depression more than those without psychological treatment. Trials that used systematic methods to identify patients with depression and also trials that included patients with a chronic physical condition reported improved use of anti-depressant medication. However, these findings are limited by the observational nature of meta-regression, incomplete data reporting, and the use of study aggregates.
[Show abstract][Hide abstract] ABSTRACT: Background
The depression module of the Patient Health Questionnaire (PHQ-9) is a widely used depression screening instrument in non-psychiatric settings. The PHQ-9 can be scored using different methods, including an algorithm based on DSM-IV criteria and a cut-off based on summed item scores. The algorithm was the originally proposed scoring method to screen for depression. We summarised the diagnostic test accuracy of the PHQ-9 using the algorithm scoring method across a range of validation studies and compared the diagnostic properties of the PHQ-9 using the algorithm and summed scoring method at the proposed cut-off point of 10.
We performed a systematic review of diagnostic accuracy studies of the PHQ-9 using the algorithm scoring method to detect major depressive disorder. We used meta-analytic methods to calculate summary sensitivity, specificity, likelihood ratios and diagnostic odds ratios for diagnosing major depressive disorder of the PHQ-9 using algorithm scoring method. In studies that reported both scoring methods (algorithm and summed item scoring at proposed cut-off point of ≥ 10) we compared the diagnostic properties of the PHQ-9 using these methods.
We found 27 validation studies that validated the algorithm scoring method of the PHQ-9 in various settings. There was substantial heterogeneity across studies, which makes the pooled results difficult to interpret. In general, sensitivity was low whereas specificity was good. Thirteen studies reported the diagnostic properties of the PHQ-9 for both scoring methods. Pooled sensitivity for algorithm scoring method was lower while specificities were good for both scoring methods. Heterogeneity was consistently high; therefore caution should be used when interpreting these results.
This review shows that if the algorithm scoring method is used the PHQ-9 has a low sensitivity for detecting major depressive disorder. This could be due to the rating scale categories of the measure, higher specificity, or other factors which warrant further research. The summed item score method at proposed cut-off point of ≥ 10 has better diagnostic performance for screening purposes or where a high sensitivity is needed.
General Hospital Psychiatry 09/2014; · 2.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Variability in patient-reported outcomes of psychological treatments has been partly attributed to therapists – a phenomenon commonly known as therapist effects. Meta-analytic reviews reveal wide variation in therapist-attributable variability in psychotherapy outcomes, with most studies reporting therapist effects in the region of 5% to 10% and some finding minimal to no therapist effects. However, all except one study to date have been conducted in high-intensity or mixed intervention groups; therefore, there is scarcity of evidence on therapist effects in brief low-intensity psychological interventions.
To examine therapist effects in low-intensity interventions for depression and anxiety in a naturalistic setting.
Data and Analysis
Session-by-session data on patient-reported outcome measures were available for a cohort of 1,376 primary care psychotherapy patients treated by 38 therapists. Outcome measures included PHQ-9 (sensitive to depression) and GAD-7 (sensitive to general anxiety disorder) measures. Three-level hierarchical linear modelling was employed to estimate therapist-attributable proportion of variance in clinical outcomes. Therapist effects were evaluated using the intra-cluster correlation coefficient (ICC) and Bayesian empirical predictions of therapist random effects. Three sensitivity analyses were conducted: 1) using both treatment completers and non-completers; 2) a sub-sample of cases with baseline scores above the conventional clinical thresholds for PHQ-9 and GAD-7; and 3) a two-level model (using patient-level pre- and post-treatment scores nested within therapists).
The ICC estimates for all outcome measures were very small, ranging between 0% and 1.3%, although most were statistically significant. The Bayesian empirical predictions showed that therapist random effects were not statistically significantly different from each other. Between patient variability explained most of the variance in outcomes.
Consistent with the only other study to date in low intensity interventions, evidence was found to suggest minimal to no therapist effects in patient-reported outcomes. This draws attention to the more prominent source of variability which is found at the between-patient level.
PLoS ONE 09/2014; 9(9):e99658. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Sudden gains have been linked to improved outcomes in cognitive behaviour therapy for depression. The relationship between sudden gains and outcome is less clear in other treatment modalities, including interpersonal psychotherapy and supportive expressive therapy, which may indicate different mechanisms of change between treatment modalities. The current study examined sudden gains in adults meeting diagnostic criteria for depression (N = 40) offered up to 12 sessions of behavioural activation treatment. Sudden gains were found in 42.5% of the sample. Sudden gains occurred early (median pre-gain session 2) and were related to outcome: those who experienced a sudden gain had significantly lower post-treatment scores on the PHQ-9. Furthermore, the proportion meeting the reliable and clinically significant change criteria at end of treatment was higher in the sudden gain group. These findings highlight the importance of understanding the mechanisms by which sudden gains relate to therapy outcome in behavioural activation.
Behaviour Research and Therapy 09/2014; · 3.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: UK National Institute of Health and Clinical Excellence guidelines for obsessive compulsive disorder (OCD) specify recommendations for the treatment and management of OCD using a stepped care approach. Steps three to six of this model recommend treatment options for people with OCD that range from low-intensity guided self-help (GSH) to more intensive psychological and pharmacological interventions. Cognitive behavioural therapy (CBT), including exposure and response prevention, is the recommended psychological treatment. However, whilst there is some preliminary evidence that self-managed therapy packages for OCD can be effective, a more robust evidence base of their clinical and cost effectiveness and acceptability is required.Methods/design: Our proposed study will test two different self-help treatments for OCD: 1) computerised CBT (cCBT) using OCFighter, an internet-delivered OCD treatment package; and 2) GSH using a book. Both treatments will be accompanied by email or telephone support from a mental health professional. We will evaluate the effectiveness, cost and patient and health professional acceptability of the treatments.
[Show abstract][Hide abstract] ABSTRACT: Depression is a common, disabling condition for which psychological treatments are recommended. Behavioural activation has attracted increased interest in recent years. It has been over 5 years since our meta-analyses summarised the evidence supporting and this systematic review updates those findings and examines moderators of treatment effect.
PLoS ONE 06/2014; 9(6):e100100. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective
Clinical practice guidelines disagree on whether health care professionals should screen women for depression during pregnancy or postpartum. The objective of this systematic review was to determine whether depression screening improves depression outcomes among women during pregnancy or the postpartum period.
Searches included the CINAHL, EMBASE, ISI, MEDLINE, and PsycINFO databases through April 1, 2013; manual journal searches; reference list reviews; citation tracking of included articles; and trial registry reviews. RCTs in any language that compared depression outcomes between women during pregnancy or postpartum randomized to undergo depression screening versus women not screened were eligible.
There were 9,242 unique titles/abstracts and 15 full-text articles reviewed. Only 1 RCT of screening postpartum was included, but none during pregnancy. The eligible postpartum study evaluated screening in mothers in Hong Kong with 2-month-old babies (N = 462) and reported a standardized mean difference for symptoms of depression at 6 months postpartum of 0.34 (95% confidence interval = 0.15 to 0.52, P < 0.001). Standardized mean difference per 44 additional women treated in the intervention trial arm compared to the non-screening arm was approximately 1.8. Risk of bias was high, however, because the status of outcome measures was changed post-hoc and because the reported effect size per woman treated was 6–7 times the effect sizes reported in comparable depression care interventions.
There is currently no evidence from any well-designed and conducted RCT that screening for depression would benefit women in pregnancy or postpartum. Existing guidelines that recommend depression screening during pregnancy or postpartum should be re-considered.
Journal of Psychosomatic Research 06/2014; · 2.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Generic preference-based measures of health like the EQ-5D and SF-6D(®) are increasingly being used in economic evaluation and outcome assessment. However, there are concerns as to whether or not these generic measures are appropriate for use in people with mental health problems.
[Show abstract][Hide abstract] ABSTRACT: People diagnosed with severe mental illness (SMI) are at greater risk of HIV than the general population. However, little attention has been given to how best to reduce sexual risk taking in this group. The aim of the review was to evaluate the effectiveness of behavioural interventions to promote sexual safety behaviour in people diagnosed with SMI. A comprehensive search of relevant databases was undertaken, and studies were included if they were randomized, controlled trials; behavioural intervention related to sexual behaviour; included adults diagnosed with SMI; and if a behavioural outcome was reported. The Cochrane Assessment of Bias Tool was used. Of the initial 515 papers identified, 11 trials were included for quality assessment and data extraction. The studies were heterogeneous in content and dose of intervention, as well as outcome measure and follow-up periods, and all had some risk of bias. Four of the studies demonstrated significant improvement in safer sexual behaviour at follow up, but this effect diminished over time. The effect sizes were extremely variable. There is emerging evidence to suggest that a behavioural intervention has the potential to reduce sexual risks in people diagnosed with SMI. However, further high-quality research is needed in this area.
International journal of mental health nursing 04/2014; · 2.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES: To investigate if early symptom changes in brief low intensity psychological interventions (guided self-help and psycho-education using cognitive behavioural therapy principles) are predictive of final treatment outcome.
DESIGN: Retrospective cohort data analysis.
METHOD: Clinical records for 1,850 patients who screened positive for depression and/or an anxiety disorder were analysed. Reliable and clinically significant improvement (RCSI) on depression (Patient Health Questionnaire-9: PHQ-9) or anxiety (generalized anxiety disorder-7: GAD-7) outcome measures after treatment was the primary outcome. Change scores ≥6 on PHQ-9 and ≥5 on GAD-7 were taken as indicative of reliable improvement (RI). The model assumed that RI in the earliest treatment sessions would be predictive of RCSI post-treatment. Predictive accuracy was assessed by calculating the area under the curve (AUC), as well as positive and negative predictive values. Diagnostic odds ratios were also estimated, adjusting for confounders such as baseline severity, use of medication, and pre-treatment symptom change.
RESULTS: The AUC estimates for session-to-session change scores ranged between .62 and .88, indicative of modest to high predictive reliability. Predictive accuracy was higher for patients who had four or more treatment sessions, with more than 70% of patients with RCSI being accurately identified as early as sessions 1-3. Attrition rates were significantly associated with poor outcomes. Results suggest that at least four therapy sessions are necessary to achieve more than 50% RCSI rates, and the dose-response effect appears to decline in treatments longer than six sessions.
CONCLUSIONS: Patients showing RI early in treatment were at least twice as likely to fully recover compared to those without early RI.
ACCESS FULL ARTICLE AT: http://onlinelibrary.wiley.com/doi/10.1111/bjc.12031/full
British Journal of Clinical Psychology 03/2014; 53(1):114-130. · 1.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cognitive behaviour therapy (CBT) is an effective treatment for depression. However, CBT is a complex therapy that requires highly trained and qualified practitioners, and its scalability is therefore limited by the costs of training and employing sufficient therapists to meet demand. Behavioural activation (BA) is a psychological treatment for depression that may be an effective alternative to CBT and, because it is simpler, might also be delivered by less highly trained and specialised mental health workers.
COBRA is a two-arm, non-inferiority, patient-level randomised controlled trial, including clinical, economic, and process evaluations comparing CBT delivered by highly trained professional therapists to BA delivered by junior professional or para-professional mental health workers to establish whether the clinical effectiveness of BA is non-inferior to CBT and if BA is cost effective compared to CBT. Four hundred and forty patients with major depressive disorder will be recruited through screening in primary care. We will analyse for non-inferiority in per-protocol and intention-to-treat populations. Our primary outcome will be severity of depression symptoms (Patient Health Questionnaire-9) at 12 months follow-up. Secondary outcomes will be clinically significant change and severity of depression at 18 months, and anxiety (General Anxiety Disorder-7 questionnaire) and health-related quality of life (Short-Form Health Survey-36) at 12 and 18 months. Our economic evaluation will take the United Kingdom National Health Service/Personal Social Services perspective to include costs of the interventions, health and social care services used, plus productivity losses. Cost-effectiveness will explored in terms of quality-adjusted life years using the EuroQol-5D measure of health-related quality of life.
The clinical and economic outcomes of this trial will provide the evidence to help policy makers, clinicians and guideline developers decide on the merits of including BA as a first-line treatment of depression.Trial registration: Current Controlled Trials ISRCTN27473954.
Trials 01/2014; 15(1):29. · 2.12 Impact Factor
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[Show abstract][Hide abstract] ABSTRACT: Computerised therapies play an integral role in efforts to improve access to psychological treatment for patients with depression and anxiety. However, despite recognised problems with uptake, there has been a lack of investigation into the barriers and facilitators of engagement. We aimed to systematically review and synthesise findings from qualitative studies of computerised therapies, in order to identify factors impacting on engagement.
Systematic review and meta-synthesis of qualitative studies of user experiences of computer delivered therapy for depression and/or anxiety.
8 studies were included in the review. All except one were of desktop based cognitive behavioural treatments. Black and minority ethnic and older participants were underrepresented, and only one study addressed users with a co-morbid physical health problem. Through synthesis, we identified two key overarching concepts, regarding the need for treatments to be sensitive to the individual, and the dialectal nature of user experience, with different degrees of support and anonymity experienced as both positive and negative. We propose that these factors can be conceptually understood as the 'non-specific' or 'common' factors of computerised therapy, analogous to but distinct from the common factors of traditional face-to-face therapies.
Experience of computerised therapy could be improved through personalisation and sensitisation of content to individual users, recognising the need for users to experience a sense of 'self' in the treatment which is currently absent. Exploiting the common factors of computerised therapy, through enhancing perceived connection and collaboration, could offer a way of reconciling tensions due to the dialectal nature of user experience. Future research should explore whether the findings are generalisable to other patient groups, to other delivery formats (such as mobile technology) and other treatment modalities beyond cognitive behaviour therapy. The proposed model could aid the development of enhancements to current packages to improve uptake and support engagement.
PLoS ONE 01/2014; 9(1):e84323. · 3.53 Impact Factor