Abstract Introduction Worldwide, health systems are improving access to empirically supported psychological therapies for anxiety and depression. Evaluations of this effort are limited by the cross ...sectional nature of studies, short implementation periods, poor data completeness rates and lack of clinically significant and reliable change metrics. Objective Assess the impact of implementing stepped care empirically supported psychological therapies by measuring the prospective outcomes of patients referred over a two year period to one Improving Access to Psychological Therapies service in the UK. Method We collected demographic, therapeutic and outcome data on depression (PHQ-9) and anxiety (GAD-7) from 7859 consecutive patients for 24 months between 1st July 2006 and 31st August 2008, following up these patients for a further one year. Results 4183 patients (53%) received two or more treatment sessions. Uncontrolled effect size for depression was 1.07 (95% CI: 0.88 to 1.29) and for anxiety was 1.04 (0.88 to 1.23). 55.4% of treated patients met reliable improvement or reliable and clinically significant change criteria for depression, 54.7% for anxiety. Patients received a mean of 5.5 sessions over 3.5 h, mainly low-intensity CBT and phone based case management. Attrition was high with 47% of referrals either not attending for an assessment or receiving an assessment only. Conclusions Recovery rates for patients receiving stepped care empirically supported treatments for anxiety and depression in routine practice are 40 to 46%. Only half of all patients referred go on to receive treatment. Further work is needed to improve routine engagement of patients with anxiety and depression.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Summary Background Depression is a common, debilitating, and costly disorder. Many patients request psychological therapy, but the best-evidenced therapy—cognitive behavioural therapy (CBT)—is ...complex and costly. A simpler therapy—behavioural activation (BA)—might be as effective and cheaper than is CBT. We aimed to establish the clinical efficacy and cost-effectiveness of BA compared with CBT for adults with depression. Methods In this randomised, controlled, non-inferiority trial, we recruited adults aged 18 years or older meeting Diagnostic and Statistical Manual of Mental Disorders IV criteria for major depressive disorder from primary care and psychological therapy services in Devon, Durham, and Leeds (UK). We excluded people who were receiving psychological therapy, were alcohol or drug dependent, were acutely suicidal or had attempted suicide in the previous 2 months, or were cognitively impaired, or who had bipolar disorder or psychosis or psychotic symptoms. We randomly assigned participants (1:1) remotely using computer-generated allocation (minimisation used; stratified by depression severity Patient Health Questionnaire 9 (PHQ-9) score of <19 vs ≥19, antidepressant use, and recruitment site) to BA from junior mental health workers or CBT from psychological therapists. Randomisation done at the Peninsula Clinical Trials Unit was concealed from investigators. Treatment was given open label, but outcome assessors were masked. The primary outcome was depression symptoms according to the PHQ-9 at 12 months. We analysed all those who were randomly allocated and had complete data (modified intention to treat mITT) and also all those who were randomly allocated, had complete data, and received at least eight treatment sessions (per protocol PP). We analysed safety in the mITT population. The non-inferiority margin was 1·9 PHQ-9 points. This trial is registered with the ISCRTN registry, number ISRCTN27473954. Findings Between Sept 26, 2012, and April 3, 2014, we randomly allocated 221 (50%) participants to BA and 219 (50%) to CBT. 175 (79%) participants were assessable for the primary outcome in the mITT population in the BA group compared with 189 (86%) in the CBT group, whereas 135 (61%) were assessable in the PP population in the BA group compared with 151 (69%) in the CBT group. BA was non-inferior to CBT (mITT: CBT 8·4 PHQ-9 points SD 7·5, BA 8·4 PHQ-9 points 7·0, mean difference 0·1 PHQ-9 points 95% CI −1·3 to 1·5, p=0·89; PP: CBT 7·9 PHQ-9 points 7·3; BA 7·8 6·5, mean difference 0·0 PHQ-9 points –1·5 to 1·6, p=0·99). Two (1%) non-trial-related deaths (one 1% multidrug toxicity in the BA group and one 1% cancer in the CBT group) and 15 depression-related, but not treatment-related, serious adverse events (three in the BA group and 12 in the CBT group) occurred in three 2% participants in the BA group (two 1% patients who overdosed and one 1% who self-harmed) and eight (4%) participants in the CBT group (seven 4% who overdosed and one 1% who self-harmed). Interpretation We found that BA, a simpler psychological treatment than CBT, can be delivered by junior mental health workers with less intensive and costly training, with no lesser effect than CBT. Effective psychological therapy for depression can be delivered without the need for costly and highly trained professionals. Funding National Institute for Health Research.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
In this article, we report the results of 2 studies that were conducted to investigate whether adult attachment theory explains employee behavior at work. In the first study, we examined the ...structure of a measure of adult attachment and its relations with measures of trait affectivity and the Big Five. In the second study, we examined the relations between dimensions of attachment and emotion regulation behaviors, turnover intentions, and supervisory reports of counterproductive work behavior and organizational citizenship behavior. Results showed that anxiety and avoidance represent 2 higher order dimensions of attachment that predicted these criteria (except for counterproductive work behavior) after controlling for individual difference variables and organizational commitment. The implications of these results for the study of attachment at work are discussed.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UPUK
Recently the UK Government announced an unprecedented, large-scale initiative for Improving Access to Psychological Therapies (IAPT) for depression and anxiety disorders. Prior to this development, ...the Department of Health established two pilot projects that aimed to collect valuable information to inform the national roll-out. Doncaster and Newham received additional funds to rapidly increase the availability of CBT-related interventions and to deploy them in new clinical services, operating on stepped-care principles, when appropriate. This article reports an evaluation of the new services (termed ‘demonstration sites’) during their first thirteen months of operation. A session-by-session outcome monitoring system achieved unusually high levels of pre to post-treatment data completeness. Large numbers of patients were treated, with low-intensity interventions (such as guided self-help) being particularly helpful for achieving high throughput. Clinical outcomes were broadly in line with expectation. 55–56% of patients who had attended at least twice (including the assessment interview) were classified as recovered when they left the services and 5% had improved their employment status. Treatment gains were largely maintained at 10 month follow-up. Opening the services to self-referral appeared to facilitate access for some groups that tend to be underrepresented in general practice referrals. Outcomes were comparable for the different ethnic groups who access the services. Issues for the further development of IAPT are discussed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The dentate gyrus is hypothesized to function as a “gate,” limiting the flow of excitation through the hippocampus. During epileptogenesis, adult-generated granule cells (DGCs) form aberrant neuronal ...connections with neighboring DGCs, disrupting the dentate gate. Hyperactivation of the mTOR signaling pathway is implicated in driving this aberrant circuit formation. While the presence of abnormal DGCs in epilepsy has been known for decades, direct evidence linking abnormal DGCs to seizures has been lacking. Here, we isolate the effects of abnormal DGCs using a transgenic mouse model to selectively delete PTEN from postnatally generated DGCs. PTEN deletion led to hyperactivation of the mTOR pathway, producing abnormal DGCs morphologically similar to those in epilepsy. Strikingly, animals in which PTEN was deleted from ≥9% of the DGC population developed spontaneous seizures in about 4 weeks, confirming that abnormal DGCs, which are present in both animals and humans with epilepsy, are capable of causing the disease.
► Direct evidence that selective disruption of the dentate gyrus causes epilepsy ► PTEN deletion from as few as 9% of granule cells is sufficient to cause epilepsy ► Findings suggest a plausible mechanism of epileptogenesis
Abnormal hippocampal granule cells are hypothesized to be critical for temporal lobe epileptogenesis, but direct supporting evidence has been limited. Here, Pun and colleagues demonstrate that selective disruption of granule cells by PTEN deletion is sufficient to cause the disease.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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).
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.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary Background Telephone triage is increasingly used to manage workload in primary care; however, supporting evidence for this approach is scarce. We aimed to assess the effectiveness and cost ...consequences of general practitioner-(GP)-led and nurse-led telephone triage compared with usual care for patients seeking same-day consultations in primary care. Methods We did a pragmatic, cluster-randomised controlled trial and economic evaluation between March 1, 2011, and March 31, 2013, at 42 practices in four centres in the UK. Practices were randomly assigned (1:1:1), via a computer-generated randomisation sequence minimised for geographical location, practice deprivation, and practice list size, to either GP-led triage, nurse-led computer-supported triage, or usual care. We included patients who telephoned the practice seeking a same-day face-to-face consultation with a GP. Allocations were concealed from practices until after they had agreed to participate and a stochastic element was included within the minimisation algorithm to maintain concealment. Patients, clinicians, and researchers were not masked to allocation, but practice assignment was concealed from the trial statistician. The primary outcome was primary care workload (patient contacts, including those attending accident and emergency departments) in the 28 days after the first same-day request. Analyses were by intention to treat and per protocol. This trial was registered with the ISRCTN register, number ISRCTN20687662. Findings We randomly assigned 42 practices to GP triage (n=13), nurse triage (n=15), or usual care (n=14), and 20 990 patients (n=6695 vs 7012 vs 7283) were randomly assigned, of whom 16 211 (77%) patients provided primary outcome data (n=5171 vs 5468 vs 5572). GP triage was associated with a 33% increase in the mean number of contacts per person over 28 days compared with usual care (2·65 SD 1·74 vs 1·91 1·43; rate ratio RR 1·33, 95% CI 1·30–1·36), and nurse triage with a 48% increase (2·81 SD 1·68; RR 1·48, 95% CI 1·44–1·52). Eight patients died within 7 days of the index request: five in the GP-triage group, two in the nurse-triage group, and one in the usual-care group; however, these deaths were not associated with the trial group or procedures. Although triage interventions were associated with increased contacts, estimated costs over 28 days were similar between all three groups (roughly £75 per patient). Interpretation Introduction of telephone triage delivered by a GP or nurse was associated with an increase in the number of primary care contacts in the 28 days after a patient's request for a same-day GP consultation, with similar costs to those of usual care. Telephone triage might be useful in aiding the delivery of primary care. The whole-system implications should be assessed when introduction of such a system is considered. Funding Health Technology Assessment Programme UK National Institute for Health Research.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Objectives. To determine the effects of implementing stepped care evidence‐based psychological treatments for anxiety and depression in routine practice using a collaborative care implementation ...model.
Design. Observational prospective cohort study/Phase IV field trial.
Methods. We collected data on depression and anxiety from a prospective cohort of 3,994 consecutive patients referred to the UK Improving Access to Psychological Therapies demonstration site in Doncaster for 12 months from August 2006 using PHQ‐9 and GAD‐7. We collected demographic and process information including the type and methods of treatments received. We calculated effect sizes, remission, and recovery rates for patients competing treatment and those who dropped out or were considered to be unsuitable.
Results. Two thousand seven hundred and ninety‐five patients received an assessment, out of which 2,017 received two or more appointments. Out of these, 869 had completed treatment by the census date, 743 remained in treatment, 319 had dropped out, and 85 had been found to be unsuitable. Pre–post treatment effect sizes for anxiety and depression in those patients completing treatment were 1.39 and 1.41, respectively, with post‐treatment relative risks of depression and anxiety 0.29 and 0.34. The combined remission and recovery rates were 76% for depression and 74% for anxiety. The mean number of treatment sessions was 5.15 in a mean time of 2 h and 45 min. On an average, patients received at least three of these contacts by telephone. Outcomes are comparable with benchmarked trials, reviews, and routine datasets.
Conclusions. Combining low‐intensity stepped care psychological treatment with a telephony‐based collaborative care organizational system can deliver good clinical outcomes in routine practice.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
PIP(2) and PIP(3) are implicated in a wide variety of cellular signaling pathways at the plasma membrane. We have used STORM imaging to localize clusters of PIP(2) and PIP(3) to distinct nanoscale ...regions within the plasma membrane of PC12 cells. With anti-phospholipid antibodies directly conjugated with AlexaFluor 647, we found that PIP(2) clusters in membrane domains of 64.5±27.558 nm, while PIP(3) clusters had a size of 125.6±22.408 nm. With two color direct STORM imaging we show that >99% of phospholipid clusters have only one or other phospholipid present. These results indicate that lipid nano-domains can be readily identified using super-resolution imaging techniques, and that the lipid composition and size of clusters is tightly regulated.
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